List of Abbreviations
Anti-NS3, -NS4, -NS5 – Anti-HCV-NS3, Anti-HCV-NS4, Anti-HCV-NS5 – antibodies to non-structural proteins NS3, NS4, NS5, NS4a, NS4b, NS5a, NS5b
Anti-core, Anti-HCV-core IgG – antibodies to hepatitis C virus core protein class G
Anti-HCV IgM – IgM class antibodies to hepatitis C virus antigens
Anti-HCV Anti-HCV-total – antibodies to hepatitis C virus (total)
ALT – alanine aminotransferase
AST – aspartate aminotransferase
HBV – hepatitis B virus
HCV – hepatitis C virus
HIV – human immunodeficiency virus
VL – viral load – quantitative content of viral nucleic acid in 1 µl of blood/plasma (copies/µl, IU/µl/IU/ml)
WHO – World Health Organization
GGT – gamma-glutamyl transferase
DIC – disseminated intravascular coagulation
DNA – deoxyribonuclease
GI – gastrointestinal tract
EIA – enzyme immunoassay
LDH – lactate dehydrogenase
IU – international units
Russian Ministry of Health – Ministry of Health of the Russian Federation
ICD-10 — International Statistical Classification of Diseases and Related Health Problems, 10th Revision
INR – international normalized ratio
MRI – magnetic resonance imaging
CBC – complete blood count
UA – urinalysis
AHC – acute hepatitis C
ICU – intensive care unit
AVT – antiviral therapy
DAA – direct-acting antivirals
PT – prothrombin index
PCR – polymerase chain reaction
RCT – randomized controlled trial
RNA – ribonucleic acid
RF – Russian Federation
ESR – erythrocyte sedimentation rate
US – ultrasound examination
UVR – ultraviolet radiation
EGD – esophagogastroduodenoscopy
FZ – federal law
CHC – chronic hepatitis C virus infection
CLIA – chemiluminescent immunoassay
RR – respiratory rate
HR – heart rate
ALP – alkaline phosphatase
CD – human leukocyte differentiation antigens
HAV – hepatitis A virus
HBV — hepatitis B virus
HCV – hepatitis C virus
IgM, G – immunoglobulin classes M and G
Th – T-helper cells
l – liter
µl – microliter
µmol – micromol
Terms and Definitions
Evidence-based medicine is the conscientious, explicit, and judicious use of current best evidence (clinical research results) in making decisions about the care and treatment of individual patients.
Disease – a disturbance of bodily function, working capacity, and the ability to adapt to changing environmental conditions arising from the impact of pathogenic factors, accompanied by alterations in the body's protective-compensatory and protective-adaptive reactions and mechanisms.
Instrumental diagnostics – diagnostics using various devices, apparatuses, and instruments to examine a patient.
Disease outcomes – the medical and biological consequences of a disease.
Quality of medical care – a set of characteristics reflecting the timeliness of medical care, the correctness of the choice of prevention, diagnosis, treatment, and rehabilitation methods in providing medical care, and the degree of achievement of the planned result.
Clinical guidelines are documents based on proven clinical experience that describe a physician's actions regarding the diagnosis, treatment, rehabilitation, and prevention of diseases, helping them make correct clinical decisions.
Clinical situation refers to a case requiring the regulation of medical care regardless of the specific disease or syndrome.
Laboratory diagnostics is a set of methods aimed at analyzing test material using various specialized equipment.
Medical intervention encompasses types of medical examinations and/or medical manipulations performed by a medical professional in relation to a patient, affecting their physical or mental state and having a preventive, exploratory, diagnostic, therapeutic, or rehabilitative purpose, as well as artificial termination of pregnancy.
Level of certainty of evidence – reflects the degree of confidence that the found effect of a medical intervention is true.
Level of recommendation certainty – reflects not only the degree of confidence in the validity of the intervention's effect, but also the degree of confidence that following the recommendations will bring more benefit than harm in a specific situation.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Acute hepatitis C (AHC) is an anthroponotic infectious disease caused by the hepatitis C virus (HCV) with a parenteral, predominantly hemotransmissive transmission mechanism. It clinically manifests with symptoms of liver damage (hepatitis) of varying severity. It is characterized by a high rate of progression to the chronic form.
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
Hepatitis C virus (HCV) was discovered in 1989 [1]. For the discovery and study of this virus, H.J. Alter (USA), M. Houghton (UK), and C.M. Rice (USA) were awarded the Nobel Prize in 2020. HCV contains single-stranded RNA and belongs to the Flaviviridae family, representing the third, independent genus Hepacivirus within it. The HCV genome encodes structural and non-structural proteins. Structural proteins include the C-core protein and envelope glycoproteins E1 and E2; non-structural proteins include a complex of proteins with specific enzymatic activity (NS2-3 – NS-5: NS2, NS3, NS4a, NS4b, NS5a, NS5b). Antibodies are produced against each of the structural and non-structural viral proteins, but they lack virus-neutralizing properties. A feature of HCV is its ability to rapidly substitute nucleotides, leading to the formation of a large number of genotypes, subtypes, and mutant strains [2]. There are 8 genotypes of the virus. Genotypes are further subdivided into subtypes with nucleotide sequence divergence of more than 15%. To date, over 90 confirmed HCV subtypes have been described, and even more genotypes and subtypes may be identified. In addition, in infected patients, the virus exists as a set of virions containing slightly altered but closely related genomes, so-called quasispecies [3]. Such variability of the viral genome leads to changes in the structure of antigenic determinants that determine the production of specific antibodies, which are unable to eliminate the virus from the body and prevent the creation of an effective hepatitis C vaccine. Until recently, HCV was classified into seven different genotypes, which differ in nucleotide sequence by more than 30% [4]. A new HCV genotype 8, which forms a distinct phylogenetic group from previously described sequences, was recently identified in four epidemiologically unrelated patients from India [5]. In the Russian Federation (RF), genotypes 1, 2, 3 and subtypes 1b and 3a are most widespread. Other viral genotypes are practically not found in the territory of the RF [6]. HCV genotyping (determination of the hepatitis C virus genotype) with the identification of the virus genotype and subtype is mandatory in children with CHC, because it not only has diagnostic value (recognizing reinfection with another viral genotype), but also allows determining predictors of response to therapy, selecting the drug, and determining the necessary doses and duration of treatment.
HCV, compared to HAV and HBV, is unstable in the external environment and against physical and chemical factors. It is sensitive to chloroform, formalin, and UV irradiation; it is inactivated at 60°C in 30 minutes, and upon boiling (100°C) within 2 minutes [2, 7].
Pathogenesis. The virus enters the body of a susceptible person along with infected blood. An indispensable condition for the development of the infectious process is the penetration of HCV into hepatocytes, where its replication and interaction with the immune system take place. Damage to hepatocytes is caused by the activation of cellular and humoral reactions of the immune system aimed ultimately at eliminating HCV. Cellular cytotoxic reactions mediated by various classes of effector cells work towards HCV elimination. Disruption of the balance in Th1/Th2 cytokine production plays a crucial role in the development of various forms of HCV infection. Enhanced production of IL-4 and IL-10 inhibits Th1 function, suppresses the production of IFN-γ and IL-2, and promotes a chronic course of the disease [8, 9].
Target cells for HCV are not only hepatocytes, but also immunocompetent peripheral blood cells PBMC/WBC (Peripheral Blood Mononuclear Cells I White Blood cells). To date, two specific lymphotropic strains of the hepatitis C virus have been verified (Ly-HCV and SB-HCV). In case of infection of a susceptible organism with one of these lymphotropic strains, the pathological (inflammatory) process in the liver is minimal, since the HCV virus delivers its main "blow" not to liver cells (hepatocytes), but to peripheral blood immune cells (PBMC/WBC) with all ensuing adverse clinical consequences (autoimmune, lymphoproliferative, etc.) [10].
HCV is capable of suppressing CD4+ activation by disrupting the interaction between antigen-presenting cells and T lymphocytes. The ability of the virus to replicate in immune-privileged sites (immune system cells, brain tissues) makes it inaccessible to cytotoxic T lymphocytes (CTLs). The humoral response in HCV is less pronounced.
In addition to the direct cytopathic effect, the leading mechanisms of liver damage are immune cytolysis, apoptosis, and an autoimmune mechanism, which is associated with the high frequency of extrahepatic manifestations in HCV infection (vasculitis, glomerulonephritis, peripheral neuropathy, polyarteritis nodosa, arthritis, Sjögren's syndrome). These diseases are based on immunocellular and immune complex processes. Therefore, HCV infection can be considered a multisystem disease. However, in childhood, multiorgan involvement in HCV is practically not observed [2, 10, 11].
In intrauterine infection during the first 12 weeks (mainly 15–75 days) with a high viral load (VL) and the presence of fetoplacental complex pathology (chronic intrauterine fetal hypoxia, intrauterine growth restriction, placentitis), pregnancy termination is possible in early terms. With ongoing maternal infection and high VL at 75 to 180 days of the intrauterine period, early fetopathies may develop, leading to late pregnancy termination or developmental anomalies of the liver and biliary tract. With ongoing maternal infection and high VL at more than 180 days of the intrauterine period, fetal HCV hepatitis or—which is extremely rare in the absence of comorbid pathology—fetal HCV liver cirrhosis may develop [2, 11].
1.3 Epidemiology of the Disease or Condition
The source of infection includes individuals infected with HCV who are in the incubation period (14–180 days), as well as patients with an asymptomatic acute or chronic form of HCV. The transmission mechanism is parenteral (blood-borne), which is realized through natural and artificial routes of pathogen transmission [2, 7, 12].
Among natural transmission routes, vertical transmission is of paramount importance (more than 95% of cases) in childhood, involving transplacental, intranatal, and postnatal infection of the child from the mother, as well as horizontal transmission, which in some cases occurs in adolescents through sexual contact [2, 7, 11, 12]. The artificial (blood-borne) route of infection, in which CHC develops as a healthcare-associated infection (HAI)—post-transfusion, catheter-associated, post-injection, and associated with other invasive interventions—can occur in children of any age.
The main medical procedures during which HCV infection can occur include blood or blood component transfusions, organ or tissue transplantation, hemodialysis procedures (high risk), as well as various parenteral interventions [13]. In Western European countries and the USA, HCV accounts for 75–95% of post-transfusion hepatitis cases. Among patients receiving blood infusions as part of complex treatment, the highest HCV infection rate is registered in patients with hemophilia—at 45–80% [14]. Children with oncohematological diseases are also a risk group. However, currently, after the introduction of routine screening for HCV infection in blood transfusion services, the frequency of this transmission route has dropped sharply and does not exceed 2–3% [15, 16].
In adolescents, artificial routes of pathogen transmission can be of epidemiological importance, occurring during non-medical and medical procedures accompanied by damage to the skin or mucous membranes, as well as procedures associated with the risk of such damage. Non-medical procedures include: injection drug use (highest risk), paramedical interventions—tattooing, piercing, cosmetic, manicure, pedicure, and other procedures using instruments contaminated with HCV, and occasionally specific ritual practices among certain ethnic groups. In addition, adolescents are at risk of infection as a result of unprotected sexual practices, especially among men who have sex with men [2, 11, 12].
Considerable attention of researchers is directed to studying the realization of natural routes of HCV transmission. The main factor in pathogen transmission is blood or its components, and to a lesser extent, other human biological fluids (semen, vaginal secretions, tear fluid, saliva, etc.). It has been established that the infectious dose of HCV is 2–3 orders of magnitude higher than that of HBV; accordingly, the probability of infection upon contact is lower. However, most authors indicate the possibility of HCV infection through hetero- and homosexual sexual contacts—the risk of infection among regular heterosexual partners, one of whom has chronic HCV infection, is 1.5% (in the absence of other risk factors) [2, 6, 7, 11, 12]. However, in childhood, these routes are of practically no significance. These epidemiological factors must be taken into account when assessing the epidemiological situation of HCV infection within a family, especially in cases of infection in a mother caring for a child [17].
To date, sufficient information has also been accumulated regarding HCV transmission through everyday household contact within a family—hidden blood-borne infection via microtraumas of the integument. According to WHO data, the probability of household transmission can reach 7% [14].
Transmission of the virus from an infected mother to her child is possible during pregnancy and childbirth (risk 1–5%). The probability of infecting a newborn increases significantly at high concentrations of HCV in the mother's blood serum (7–12%), as well as in the presence of HIV co-infection (14–16%) [11, 12, 18]. The frequency of HCV transmission increases with prolonged labor, the use of amniocentesis, or fetal scalp blood monitoring and a prolonged dry period. Recent studies have shown that breastfeeding does not affect the rate of infection in children [19, 20, 21, 58, 59].
In Russia, the incidence of acute hepatitis C (AHC) in children is low, at 0.18 cases per 100,000 children, and in the structure of all acute hepatitis cases, the proportion of children with acute HCV does not exceed 1–2%. However, a negative trend in AHC incidence is noteworthy—a progressive increase has been observed since 2021: 853 cases (incl. 30 in children) in 2021, 1,094 (53) in 2022, 1,391 (39) in 2023, 1,451 (53) in 2024. Thus, over 4 years, the rate has almost doubled [23]. A significant proportion (25–30%) of the patients are adolescents older than 14 years, which is likely associated with high-risk behavior in this cohort of children.
In 90–95% of cases in early childhood, the disease presents in anicteric, subclinical, and inapparent forms with a high rate of chronic progression—according to various authors, ranging from 40–56% to 81% or more [2, 18–20].
1.4 Features of Coding the Disease or Condition
B17.1 – Acute hepatitis C.
1.5 Classification of the disease or condition
Clinical classification of “Acute hepatitis C”
By clinical presentation [7, 25–31]:
Typical (manifest):
- icteric;
- anicteric;
Atypical:
subclinical;
inapparent;
By severity [7, 25–31]:
Mild;
Moderate;
Severe;
By duration of the course [7, 25–31]:
Acute – up to 3 months;
Acute protracted (progredient) – 3–6 months;
The icteric form is characterized by the presence of intoxication, dyspeptic disorders, cytolysis, elevated bilirubin due to the direct fraction, and hepatomegaly. Impairment of the protein-synthesizing function of the liver is possible, with corresponding dysproteinemia and a decrease in the prothrombin index. The severity of symptoms and laboratory abnormalities is variable and correlates with the severity of the disease.
The anicteric form is characterized by symptoms of intoxication and dyspeptic disorders. Liver enlargement may be minimal, but both hepatomegaly and hyperfermentemia are mandatory symptoms of this form. The disease generally runs a mild course, but has a protracted, progredient character.
Asymptomatic forms are diagnosed during immunobiochemical studies in infection foci and scheduled examinations of specific categories of citizens (donors, medical personnel, public catering workers, military personnel, and others). Patients with the subclinical form exhibit moderate hyperfermentemia. Hepatomegaly is observed. In the inapparent form, clinical and biochemical symptoms are absent. Serological markers of viral replicative activity serve to confirm the diagnosis [7, 25–31].
Criteria for assessing the severity of the disease include both clinical indicators (severity of intoxication, jaundice, hepatomegaly) and laboratory abnormalities (levels of hepatic transaminases, bilirubin, impairment of the protein-synthesizing liver function) [7, 25–31]. Severity criteria are described in detail in Appendix A3.
Examples of diagnosis formulation:
Preliminary diagnosis (first-time detected disease – a case suspected of AHC / probable case of AHC): Acute viral hepatitis C, typical icteric form of moderate severity?
Clinical diagnosis (confirmed case of AHC): B17.1 Acute viral hepatitis C (total anti-HCV positive; HCV RNA positive), caused by genotype 1a virus, typical icteric form of moderate severity.
1.6 Clinical presentation of the disease or condition
The incubation period ranges from 3 weeks to 4 months, averaging 2–3 months. Its duration depends on the route of viral entry, the infectious dose, and the patient's age. In massive blood transfusions, it is shortened [7, 25–31].
The following periods of the disease are distinguished:
Prodromal (pre-icteric) period – 4–7 days, in some patients up to 3 weeks. However, in 80–90% of cases of AHC, jaundice does not develop. The disease is characterized by a gradual onset. The main symptoms and syndromes of this period are:
intoxication (flu-like)
asthenovegetative
catarrhal
dyspeptic
mixed (dyspeptic/catarrhal)
arthralgic
However, all symptoms may be mild. In children, asthenovegetative and dyspeptic syndromes are most commonly recorded. Dyspeptic syndrome is marked by decreased appetite to the point of complete anorexia, discomfort in the right upper quadrant, dull abdominal pain, nausea, and possible 1–2 episodes of vomiting [7, 25, 28–31].
Period of parenchymal hepatitis (icteric). When jaundice appears, intoxication symptoms persist or intensify. Clinical manifestations are often limited to lethargy, weakness, decreased appetite, and a sensation of heaviness and discomfort in the right upper quadrant. The leading clinical symptoms and syndromes of this period are:
intoxication
yellowing of the skin and mucous membranes
hepatomegaly
splenomegaly
choluria
acholic stools
Leading laboratory syndromes:
cytolysis syndrome (elevated ALT, AST, LDH)
jaundice (hyperbilirubinemia due to the direct fraction, detection of bile pigments and urobilin in urine, disappearance of stercobilin and stercobilinogen in stool)
cholestasis syndrome (hyperbilirubinemia due to the direct fraction, elevated levels of GGT, ALP)
mesenchymal inflammation syndrome (accelerated ESR, elevated total protein, gamma-globulins, acute-phase proteins)
hepatocellular insufficiency syndrome (decreased albumin, total protein, prothrombin, fibrinogen, clotting factors)
The completion of this period is associated with a reduction in the leading clinical and laboratory symptoms and syndromes [7, 25, 28–31].
Convalescence period – the duration of this period is from 3 to 6 months. During this period, there is a complete disappearance of the clinical symptoms of the disease, and restoration of the functional activity and morphological structure of the liver [7].
In 90–95% of cases in early childhood, the disease proceeds in anicteric, subclinical, and inapparent forms. A protracted course may arise in any period of the disease. There is a high frequency of chronic progression of HCV infection, ranging from 40 to 81%. In adults, the frequency of progression to chronic HCV infection is similar to that in children, at 50–85% [7, 25–31].
Probability of spontaneous recovery
In patients with the manifest form of AHC, the probability of spontaneous recovery is higher than in patients with the asymptomatic form [32, 35, 37, 38]. It is believed that the development of symptoms reflects a more robust antiviral immune response, leading to a rapid decline in HCV RNA and increasing the likelihood of viral clearance [33, 34, 36, 39].
The severity of AHC depends on the intensity and duration of the syndromes and symptoms of the disease [7, 25–31].
Complications
Acute liver failure in acute HCV infection is extremely rare, occurring in less than 1% of cases. However, this critical condition should not be overlooked at the preliminary diagnosis stage.
HCV is rarely an independent cause of acute liver failure. Co-infection or superinfection with hepatitis B frequently contributes to this complication [40].
Acute liver failure is a severe acute liver injury accompanied by encephalopathy and impaired protein-synthetic function of the liver (INR >1.5) in a patient without cirrhosis or pre-existing liver disease, as well as in patients with previously undiagnosed liver disease, provided that the condition was recognized within <26 weeks [7, 25, 27, 31].
2. Diagnostics, medical indications and contraindications for diagnostic methods
The diagnosis is established based on pathognomonic findings:
Anamnestic data — perinatal contact with an HCV-infected mother, blood transfusions, parenteral interventions (including surgical treatment, dental care, tattoos, piercings, manicures using non-sterile instruments, injection drug use), contact with the blood of an HCV-infected person (including household contact such as sharing razors, manicure tools, etc.), unprotected sexual intercourse, etc., weeks to 6 months prior to the onset of symptoms;
Physical examination — jaundice of the skin and sclera, changes in stool and urine color, discomfort and/or tenderness in the right upper quadrant; hepatomegaly upon palpation;
Laboratory tests — elevated liver transaminases (ALT, AST), and bilirubin due to the direct fraction;
The definitive diagnosis of acute HCV infection is established based on the detection of HCV RNA in the patient's blood, regardless of the presence or absence of characteristic symptoms and/or abnormal laboratory findings, since both clinically manifest and latent forms of the disease are possible. The criterion for differential diagnosis between acute and chronic hepatitis is the duration of the disease. If the disease duration is less than 6 months, the diagnosis is formulated as acute hepatitis C.
2.1 Complaints and Anamnesis
It is recommended that all patients with suspected viral hepatitis undergo a thorough collection of complaints and medical history to assess the patient's condition, determine the examination and treatment plan, and establish a preliminary diagnosis [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comment: when taking complaints and medical history, it is recommended to carefully question the patient about the nature of the disease onset, the presence or absence of complaints of fever, fatigue, decreased appetite, drowsiness, etc., in order to identify the primary symptoms of the prodromal period. The exact timing of the onset of jaundice of the skin, sclera, and changes in the color of urine and stool (if any) should be specifically clarified [7, 25, 28-31, 42-43].
It is recommended that all patients with suspected hepatitis C be questioned about their epidemiological history to identify risk factors for hepatitis C virus infection [7, 25, 28–31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comment: During the interview, attention should be paid to gathering epidemiological history data. An epidemiological contact (perinatal, sexual, household) with an HCV-infected person, as well as a history of parenteral exposure (surgeries, blood transfusions, injections), are key diagnostic features for viral hepatitis C. The epidemiological history for acute HCV requires information on transfusions, surgical interventions, injections, instrumental examinations, dental treatment, and other medical procedures within the 6 months prior to the disease onset, as well as data on sexual and household contacts with patients having acute and chronic forms of viral hepatitis C, unprotected sexual intercourse, and injection drug use. For infants and young children, information regarding maternal infection is of paramount importance [7, 25, 28–31, 42-43].
2.2 Physical Examination
It is recommended that all patients undergo a general physical examination to assess their overall condition and well-being, the color of the skin, oral mucosa, and sclera, in order to identify symptoms characteristic of the prodromal period and indicative of liver involvement in the pathological process [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
It is recommended that all patients undergo a visual and manual examination of the abdomen and abdominal organs to assess the degree of liver damage and disease severity: the size and shape of the abdomen are evaluated, as well as its involvement in the respiratory act; the liver and spleen are palpated and their borders are determined. Percussion (A01.15.004 Percussion in diseases of the liver and biliary tract) is used to determine the presence or absence of fluid in the abdominal cavity (ascites may develop in severe cases), peritoneal signs are checked, and peristalsis is evaluated [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: Hepatomegaly may be mildly expressed or be the only clinical sign in the anicteric form of acute HCV. In the typical form, the enlargement of the liver size and density peaks during the icteric period. The younger the child, the more frequently splenomegaly is registered. The severity of hepatomegaly and splenomegaly correlates with the severity of the disease. A decrease in liver size (compared to normal) can be a prognostically dangerous sign indicating a malignant course of the process.
It is recommended to evaluate the color of urine and stool in all examined children for the timely detection of cholestasis [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: In children, dark urine and "spotted" followed by acholic (light gray) stool appear 2–3 days before the onset of jaundice. In mild cases, the disease may begin directly with dark urine and jaundice. The appearance of "mottled" stool after acholic stool indicates the restoration of bile secretion and corresponds to the crisis of the disease, after which a regression of all symptoms is observed [7, 25, 28-31, 42-43].
It is recommended to assess the state of the cardiovascular and respiratory systems — measure heart rate, examine the pulse, measure blood pressure in peripheral arteries, and measure respiratory rate in all examined children for the timely detection of cardiovascular system involvement [7, 25, 28-31, 42-43].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: The cardiovascular, nervous, urinary, and other systems are frequently involved in the process, but these changes are never predominant.
It is recommended for patients with a severe course of the disease to determine signs of liver function decompensation: the appearance of symptoms of encephalopathy, peripheral edema, and hemorrhagic syndrome — for the timely diagnosis of liver failure [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
It is recommended for patients with severe acute HCV, in the presence of signs of acute liver failure (development of encephalopathy, edema syndrome, hemorrhagic syndrome), to assess the degree of consciousness impairment and coma using the Glasgow Coma Scale for timely transfer and further specialized care in an intensive care unit [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: Criteria for assessing the degree of consciousness impairment and coma using the Glasgow Coma Scale are presented in Appendix A3.
2.3 Laboratory Diagnostics
Laboratory research methods, including biochemical and hematological parameters, make it possible to diagnose the acute phase of the disease and its severity; the etiological verification of hepatitis is carried out exclusively using serological and molecular genetic methods.
The diagnosis of acute HCV is confirmed exclusively upon the detection of HCV RNA or HCV core Ag in blood serum (plasma), taking into account epidemiological history data and the results of clinical and laboratory examinations (determination of alanine aminotransferase activity in the blood, bilirubin concentration (determination of total bilirubin level in the blood and/or free and conjugated bilirubin levels in the blood), determination of liver size, etc.), paragraph 721 of the Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021, "On approval of sanitary rules and norms SanPiN 3.3686-21 'Sanitary and epidemiological requirements for the prevention of infectious diseases'" (registered with the Ministry of Justice of Russia on February 15, 2021, No. 62500).
At the diagnostic stage
It is recommended that all patients undergo a complete blood count (CBC) to assess the severity of the condition — the degree of inflammatory changes and to rule out anemia and thrombocytopenia [7, 25, 28-31, 42-43, 48].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: In mild and moderate acute HCV, peripheral blood tests reveal leukopenia or a tendency toward it, lymphocytosis, whereas in severe cases, leukopenia is replaced by leukocytosis with a left shift, along with a slowed ESR, thrombocytopenia, and possible development of anemia.
It is recommended that all patients undergo a urinalysis to assess bilirubin metabolism disorders and involvement of the urinary system in the pathological process [7, 25, 28-31, 42-43, 48].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: Elevated levels of urobilin and bile pigments in the urine are characteristic of the onset of the icteric period of hepatitis and indicate the initial signs of pigment metabolism disorders and intrahepatic cholestasis.
It is recommended that all patients undergo blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity testing to assess the degree of liver damage and disease severity [7, 25, 28-31, 42-43, 48].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: Detection of elevated serum ALT and AST levels indicates hepatocyte cytolysis and highly confirms the diagnosis of acute hepatitis. Characteristically, ALT predominates over AST.
It is recommended that all patients undergo a blood test for free and conjugated bilirubin to assess the degree of impaired bilirubin metabolism and disease severity concordance [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: Signs of impaired pigment metabolism and intrahepatic cholestasis include rising levels of total serum bilirubin with a predominance of the direct fraction, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and cholesterol.
It is recommended that all patients undergo alkaline phosphatase activity testing in the blood to assess the degree of cholestasis and disease severity [7, 25, 28-31, 42-43, 48].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
It is recommended that all patients undergo gamma-glutamyl transferase activity testing in the blood to assess the degree of cholestasis and disease severity [1-6, 8, 10, 48].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: Signs of impaired pigment metabolism and intrahepatic cholestasis include rising levels of total bilirubin with a predominance of the direct fraction in the blood serum, ALP, GGT, and cholesterol.
It is recommended that all patients undergo blood total protein and albumin testing to evaluate the protein-synthetic function of the liver [7, 25, 28-31, 42-43].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
It is recommended that all patients undergo a coagulogram (screening hemostasis test) to assess the severity of the disease and for early detection of signs of acute liver failure [7, 25, 28-31, 42-43, 48].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: Proteinogram and coagulogram data are necessary to assess disease severity. Decreased levels of total protein, albumin, fibrinogen, and prothrombin index (PTI) indicate impaired protein-synthetic liver function (signs of hepatocellular failure) and the potential development of disseminated intravascular coagulation (DIC) syndrome, which is accompanied by phase changes in the blood coagulation system [7, 25, 28-31, 42-43].
It is recommended for all patients with suspected acute hepatitis C (AHC), to clarify the diagnosis, to perform serological tests using ELISA or CLIA – Determination of antibodies to Hepatitis C virus (HCV) in the blood [14].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
It is recommended to determine Hepatitis C virus (HCV) RNA in the blood by qualitative PCR testing to confirm the etiology of hepatitis in all patients with suspected AHC, regardless of the presence or absence of anti-HCV antibodies. If the qualitative test result is positive, quantitative PCR testing for Hepatitis C virus (HCV) RNA in the blood should be performed [44-46].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: In patients with AHC in early stages, HCV RNA may be detected in the absence of antibodies. This clinical situation is characteristic of the acute course, as viremia can be detected as early as 14 days after infection, whereas antibodies typically appear much later [64-66].
An important feature of the course of HCV infection in children in the first 3 years of life is a fairly high percentage of spontaneous viral clearance (35-45%). However, this largely applies to transfusion-associated HCV. In perinatal hepatitis, the rate of spontaneous viral clearance, according to various authors, is 2.4-18%, with isolated studies indicating higher figures of up to 50% [11, 18-20, 47].
Only the detection of specific HCV markers provides absolute etiological confirmation of the diagnosis of HCV. HCV RNA is an indicator of viral replication; it can be detected during the incubation and icteric periods, as well as at later stages of the disease. HCV RNA begins to be detected in the blood on average one month after infection and serves as the first diagnostic marker of HCV. Testing for HCV RNA allows for early diagnosis of AHC and the detection of occult (latent) forms. In protracted hepatitis, quantitative PCR testing for Hepatitis C virus (HCV) RNA in the blood is advisable to assess the dynamics of viral activity and predict disease outcome.
It is recommended for patients with a severe disease course to determine ABO blood groups and Rh factor (D antigen) for timely blood transfusion in case of hemorrhagic syndrome development [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: performed in patients with severe and fulminant forms of hepatitis.
At the stage of pathogenetic and symptomatic therapy
It is recommended that all hospitalized patients with AHC undergo serial complete blood count (CBC) monitoring with differential to detect complications and comorbid conditions [1-6, 8-10, 48, 65].
GPP CLoE 5Level of Evidence/Grade of Recommendation C (level of evidence - 5).
Comments: Allows for assessing the severity of the inflammatory process (by leukocyte count, differential, and ESR) and evaluating bleeding risk (by platelet count). Performed every 7-14 days. If clinically indicated, frequency is at the discretion of the attending physician.
It is recommended for patients with elevated ALT, AST, alkaline phosphatase, gamma-glutamyl transferase, increased bilirubin levels, and abnormalities in other general biochemical blood test parameters during diagnosis and treatment, to undergo serial monitoring of these parameters for the timely detection of a severe and complicated course of the disease [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: performed on average every 7-14 days. If clinically indicated, the frequency of the general biochemical blood test is at the discretion of the attending physician.
For patients with abnormalities in coagulogram parameters (screening hemostasis test), total protein, and albumin at the diagnostic and treatment stages, as well as patients with clinical signs of decreased protein-synthetic liver function (edema, hemorrhagic syndrome), serial monitoring of these parameters is recommended [7, 25, 28-31, 42-43].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: performed every 7-14 days. If clinically indicated, the frequency is at the discretion of the attending physician [7, 25, 28-31, 42-43].
Hepatitis C screening:
Due to the potential latent and inapparent course of HCV infection and the social significance of the disease, HCV screening is advisable. Individuals with a mild or subclinical course pose an epidemiological threat to the population as an undiagnosed source of infection. Certainly, most such patients are more likely to have a chronic disease course, though diagnosis of the acute period of the disease is also possible.
It is recommended to determine total IgM and IgG antibodies (anti-HCV IgG and anti-HCV IgM) to Hepatitis C virus in the blood to rule out HCV infection in the following population groups:
1) Children under 12 months of age born to HCV-infected mothers (at age ≥ 2 months, 6 months [if HCV RNA is negative at 2 months], and 12 months) [44, 47, 48, 68]
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
2) Children of any age from an HCV family cluster [41, 42, 55].
GCR CLEL 4Grade of Recommendation C (Level of Evidence - 4)
Children with liver disease of unknown etiology (during the initial clinical and laboratory evaluation) [11, 12, 14].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Individuals belonging to HCV risk groups (adolescents with a tendency to vagrancy, injection drug users, those with early sexual debut, individuals with tattoos) [2, 20, 55, 56].
GCR CLEL 4Grade of Recommendation C (Level of Evidence - 4)
3) Children with immunodeficiencies (patients with oncological diseases, patients on hemodialysis, patients receiving immunosuppressive therapy, etc.) [11, 41, 42].
4) Individuals in closed institutions (orphanages, penitentiary institutions
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: Screening of children with perinatal exposure to hepatitis C virus should be performed at the age older than 2 months. Qualitative PCR assay for hepatitis C virus RNA in the blood is required. If HCV RNA is not detected in the child's blood, follow-up is continued up to 18 months with testing every 6 months. In case of persistently negative PCR results and absence of anti-HCV in blood EIA, the child is deregistered as healthy. If blood anti-HCV EIA is already negative by 12 months of age, deregistration at this age is acceptable. Blood anti-HCV EIA (determination of antibodies to hepatitis C virus in the blood) is advisable at 12 and 18 months of age to make a decision on perinatal contact deregistration. Blood HCV RNA PCR (qualitative determination of hepatitis C virus RNA in the blood by PCR) is performed at 2 months, 6 months, 12 months, and 18 months of age. If HCV RNA is detected in the child's blood under the age of 6 months, the diagnosis of "Acute viral hepatitis C" is established, and at the age older than 6 months – "Chronic viral hepatitis C". In case of infection and confirmation of the diagnosis (acute hepatitis C or chronic hepatitis C), dispensary follow-up is carried out similarly to older age groups.
In immunocompromised patients, an immune response to HCV infection may be absent, as a result of which anti-HCV antibodies may be undetectable. In addition to antibody testing, patients in this group need to undergo blood HCV RNA PCR (qualitative determination of hepatitis C virus RNA in the blood by PCR).
2.4 Instrumental Diagnostics
It is recommended that all patients at the stage of diagnosis undergo a comprehensive ultrasound examination (ultrasonography) of the abdominal cavity and retroperitoneal space to characterize the condition of the liver and spleen and to rule out concomitant gastrointestinal pathology [7, 25, 28-31, 42-43].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comment: hepatomegaly without changes in liver structure is characteristic; splenomegaly is possible. If marked changes are present during the initial examination, repeat examination may be performed according to clinical indications to assess disease dynamics [7, 25, 28].
It is recommended in diagnostically unclear cases, with prolonged persistence of hyperbilirubinemia or cholestasis syndrome, to perform magnetic resonance imaging of the abdominal cavity or computed tomography of the abdominal cavity for differential diagnosis [1-6, 30, 47].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
2.5 Other Procedures
It is recommended for patients with severe acute hepatitis C in the presence of emergency conditions to have an initial examination (consultation) by an anesthesiologist-resuscitologist to determine indications for transfer to the intensive care unit (ICU) [25, 31, 42, 43].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
It is recommended for patients with severe acute hepatitis C with suspected encephalopathy to have an initial examination (evaluation, consultation) by a neurologist to adjust therapy [25, 31, 42, 43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
The choice of treatment tactics is influenced by the following factors:
variant of the initial period of the disease;
severity of the disease;
clinical form of the disease;
patient's age;
presence and nature of complications;
availability and feasibility of treatment in accordance with the required type and conditions of medical care.
The volume of drug therapy correlates with the severity of the disease: in mild cases, it is limited to baseline therapy with a sufficient level of patient hydration and nutritional support. As the severity increases, the spectrum of prescribed drugs expands. Unjustified prescription of medications should be avoided due to potential risks of drug-induced liver injury.
3.1 Conservative Treatment
3.1.1 Basic therapy:
It is recommended to prescribe a protective regimen for patients with moderate and severe disease [7, 27, 31, 49, 50].
GPP CLoE 5Level of Evidence/Grade of Recommendation C (level of evidence - 5).
Comments: During the peak period of the disease, bed rest must be prescribed, and patients with severe, malignant courses of the disease require strict bed rest. During the periods of jaundice subsidence and convalescence, patients are switched to a ward-based regimen.
It is recommended to prescribe a diet variant with mechanical and chemical sparing for all patients. Alcohol is strictly prohibited [7, 27, 31, 49, 50].
GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)
3.1.2 Etiotropic therapy
Most patients do not need etiotropic therapy. A rational approach is observation for 6 months, with the prompt prescription of antiviral therapy if the development of chronic hepatitis C is confirmed. Prescription of antiviral therapy for acute hepatitis C is possible for vital indications in life-threatening conditions during a severe course of acute hepatitis C. In the adult population, the main motivation for initiating etiotropic therapy for acute hepatitis C is high-risk behavior accompanied by the risk of infection spread. In such a situation in a pediatric patient, it is advisable to use a similar approach. There are no studies on antiviral therapy for acute hepatitis C in children. Due to the lack of alternatives, approaches to treating adult patients with acute hepatitis C can be extrapolated. For etiotropic therapy of acute hepatitis C, direct-acting antivirals used in the treatment of chronic hepatitis C can be used according to similar regimens [67-69].
3.1.3 Pathogenetic therapy
It is recommended to perform detoxification therapy via oral and/or infusion routes according to clinical indications, taking into account the severity of the disease, to relieve intoxication syndrome. The choice of drugs and the volume of this therapy depend on the severity of the disease [7, 27, 31, 42, 49, 50].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: Mild course – oral detoxification. Moderate severity – infusion therapy using solutions affecting water-electrolyte balance, carbohydrates: electrolyte solutions, electrolytes in combination with carbohydrates, carbohydrates (ATC V06DC) (taking into account the age of children, indications, and contraindications). Parenteral fluid administration is carried out based on physiological needs, ongoing pathological losses, and existing fluid deficit.
It is recommended for all patients with moderate and severe disease to prescribe liver disease drugs (glycyrrhizic acid + phospholipids**, phospholipids) to more rapidly restore liver function, improve tissue metabolism, and stabilize cell membranes [25, 27-30, 50, 51, 53, 60, 62].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: Drugs are prescribed taking into account age restrictions in accordance with the instructions for medical use of medicinal products. Therapy can be started with intravenous forms followed by switching to oral ones.
It is recommended for patients with acute hepatitis C in the event of cholestasis development to conduct therapy aimed at normalizing bile formation and excretion functions using liver and biliary tract drugs (#ursodeoxycholic acid** at a dose of 10 mg/kg of body weight once a day in the evening, for a course of 15-30 days) [25, 27-30, 50, 53].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
It is recommended in cases of severe disease with the development of liver failure, or fulminant course of acute hepatitis C, to prescribe glucocorticoids. The duration of therapy is determined individually, according to clinical indications [31, 42, 50-52].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: the prescription of glucocorticoids is necessary for patients with any manifestations of the fulminant form of acute hepatitis C (precoma, coma, signs of massive liver necrosis), with severe forms of hepatitis with signs of acute liver failure, as well as severe forms without signs of hepatic precoma-coma, but with pronounced manifestations of intoxication and their progression, despite ongoing active infusion therapy, in order to suppress immunopathological, inflammatory reactions and prevent brain swelling and edema. The drug of choice is prednisolone** in a dosage corresponding to the instructions, taking into account age contraindications [31, 42, 50-51].
It is recommended in severe acute hepatitis C with the development of liver failure accompanied by a decrease in the protein-synthesizing function of the liver and serum albumin levels, as a replacement therapy, to prescribe 10% human albumin solution**, aimed at maintaining the circulating blood volume. In case of liver failure development – therapy according to ICU protocols [25, 31, 42, 50, 51].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
It is recommended for patients with the icteric form of acute hepatitis C to conduct therapy aimed at normalizing gastrointestinal tract function (prevention of constipation) for bowel evacuation in accordance with the age-related physiological norm [25, 27-30, 52].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: When treating patients with acute hepatitis C, it is necessary to monitor regular bowel evacuation in accordance with the physiological norm. Laxatives (lactulose**) are used for this purpose.
It is recommended for patients with symptoms of pancreatic enzyme insufficiency to prescribe multienzyme preparations (including those containing lipase, protease) (ATC A09AA) to normalize digestion [25, 27-30, 52].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
It is recommended upon the development of ascites and/or peripheral edema to use diuretics to relieve edema syndrome [25, 27-30, 52].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
Comments: if tense ascites develops, paracentesis with controlled removal of peritoneal transudate (large-volume paracentesis) is recommended.
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Specialized rehabilitation measures have not been developed for patients with acute severe hepatitis.
5. Prevention and Dispensary Observation
5.1 Prevention
Specific prophylaxis for viral hepatitis C has not been developed to date.
Non-specific prophylaxis
Prophylaxis of hepatitis C is carried out in accordance with the Sanitary Rules and Norms SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" (approved by the Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021).
It is recommended to actively detect sources of infection (screening individuals at increased risk of infection and/or with special epidemiological significance) [6] (see Screening in the Diagnostics section).
GCR CLEL 4Grade of Recommendation C (Level of Evidence - 4)
It is recommended to prevent artificial routes of HCV transmission (blood transfusion and its components only for vital indications, justification of invasive diagnostic methods, use of disposable instruments, strict adherence to disinfection and sterilization regimens for medical instruments and equipment, use of personal protective equipment by medical personnel) [6].
GCR CLEL 4Grade of Recommendation C (Level of Evidence - 4)
It is recommended, for the prevention of perinatal HCV transmission, that women of reproductive age with CHC undergo antiviral therapy (AVT) aimed at complete eradication of the pathogen at the preconception planning stage [14].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
It is recommended to maintain breastfeeding in newborns and infants born to HCV-infected women, since refraining from it is not a method of preventing infection [19, 20, 21, 58, 59].
GCR CLEL 4Grade of Recommendation C (Level of Evidence - 4)
Comments: Numerous studies have shown that breastfeeding is not a risk factor for infection and does not increase the likelihood of mother-to-child transmission [19, 20, 21, 58, 59].
5.2. Dispensary follow-up
All individuals who have recovered from acute hepatitis C are subject to mandatory follow-up (dispensary observation) by an infectious disease specialist (pediatrician, gastroenterologist) at the medical organization at their place of residence or at a territorial hepatological (specialized) center.
It is recommended that all patients with acute hepatitis C undergo dispensary observation—clinical examination and laboratory testing with mandatory qualitative detection of Hepatitis C virus RNA in the blood by PCR—6 months after the diagnosis of the disease. In this case, if Hepatitis C virus RNA is detected, these individuals are considered to have chronic hepatitis C. If Hepatitis C virus RNA is not detected after 6 months, these individuals are considered convalescents of acute hepatitis C and are subject to dynamic follow-up for 2 years and examination with qualitative detection of Hepatitis C virus RNA in the blood by PCR at least once every 6 months [7, 25, 28-31, 42-44, 47, 48, 54].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
It is recommended that all patients undergo a complete blood count (CBC) with differential leukocyte count to assess the severity of the condition—the degree of inflammatory changes, rule out anemia and thrombocytopenia—1 month after discharge from the hospital, and repeatedly over time if abnormalities are detected. The frequency and timing of follow-up examinations depend on the severity and specifics of the abnormalities and are determined by the attending physician [7, 25, 28-31, 42-43, 48].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
It is recommended that patients with elevated ALT, AST, alkaline phosphatase, gamma-glutamyl transferase, bilirubin levels, and abnormalities in other routine biochemical blood tests at the time of hospital discharge undergo dynamic monitoring of these parameters 1 month after discharge, and repeatedly after 1-3 months if abnormalities are detected, in order to assess liver recovery [7, 25, 28-31, 42-43].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
6. Organization of Medical Care
Indications for hospital admission:
1) Suspected/confirmed acute hepatitis C
Treatment of acute hepatitis C with moderate and severe courses is carried out in a hospital setting. Hospitalization is carried out in infectious disease hospitals or departments; treatment and monitoring are performed by an infectious disease specialist (or, in their absence, by a pediatrician or general practitioner [family physician]) [26, 27, 30, 31, 43].
Indications for discharge from the hospital:
1) Reduction of intoxication symptoms
2) Reduction of jaundice
3) Reduction in the severity of hepatomegaly
4) Bilirubin level <40 µmol/L
5) ALT and AST levels <150 IU/L
6) Prothrombin index (PTI) >70%
In mild disease, these criteria are achieved on average by days 10–15, in moderate disease by days 15–20, and in severe disease by days 25–30. The timeframe for full recovery and admission to childcare facilities and school is determined by the physician on an individual basis, taking into account the dynamics of clinical and laboratory parameters, the presence/absence of complications, and comorbid somatic diseases [26, 27, 30, 31, 43].
7. Additional Information
Children born to mothers infected with the hepatitis C virus are subject to dispensary observation at the medical organization at their place of residence with mandatory testing of blood serum (plasma) for the presence of anti-HCV IgG and HCV RNA (determination of class G antibodies [anti-HCV IgG] to Hepatitis C virus in the blood and qualitative detection of Hepatitis C virus RNA in the blood by PCR). The detection of anti-HCV IgG in such children has no independent diagnostic value, as antibodies to the hepatitis C virus acquired from the mother during pregnancy may be detected. The first examination of the child is carried out at the age of 2 months. If Hepatitis C virus RNA is absent at this age, a re-examination of the child is performed—determination of class G antibodies (anti-HCV IgG) to Hepatitis C virus in the blood and qualitative detection of Hepatitis C virus RNA in the blood by PCR.
of the hepatitis C virus at the age of 6 months. Detection of Hepatitis C virus RNA in a child at the age of 2 or 6 months indicates the presence of acute hepatitis C. Further examination of the child is carried out at the age of 12 months. Repeated detection of Hepatitis C virus RNA at this age indicates chronic hepatitis C. When Hepatitis C virus RNA is first detected at the age of 12 months, it is necessary to rule out infection of the child at a later date through other routes of hepatitis C virus transmission. In the absence of Hepatitis C virus RNA at the age of 12 months (if Hepatitis C virus RNA was previously detected at 2 or 6 months), the child is considered an acute hepatitis C convalescent and is subject to examination—determination of class G antibodies (anti-HCV IgG) to Hepatitis C virus in the blood and qualitative detection of Hepatitis C virus RNA in the blood by PCR at the age of 18 and 24 months. A child in whom Hepatitis C virus RNA is not detected at 2, 6, and 12 months is discharged from dispensary observation if anti-HCV IgG is absent at 12 months of age. A child in whom Hepatitis C virus RNA is not detected at 2, 6, and 12 months, but anti-HCV IgG is detected at 12 months of age, is subject to additional examination—determination of class G antibodies (anti-HCV IgG) to Hepatitis C virus in the blood and qualitative detection of Hepatitis C virus RNA in the blood by PCR at 18 months of age. In the absence of anti-HCV IgG and Hepatitis C virus RNA at 18 months of age, the child is discharged from dispensary observation. The detection of anti-HCV IgG at the age of 18 months and older (in the absence of Hepatitis C virus RNA) may be a sign of past acute hepatitis C in the first months of life. Diagnosis of hepatitis C in children born to hepatitis C virus-infected mothers who have reached the age of 18 months is carried out in the same way as in adults [54].
Recent studies have shown that breastfeeding does not affect the rate of infection in children [19, 20, 21, 58, 59]. Data have been published indicating that breast milk contains free fatty acids that destroy the lipid envelope of the virus, thereby causing its inactivation [21]. These findings confirm that even if HCV penetrates into milk, the virus will be inactivated. Thus, preventing breastfeeding is not a means of preventing vertical transmission of HCV. In the absence of other contraindications, such as HIV coinfection, women with HCV infection are recommended to practice breastfeeding.
Criteria for Evaluating the Quality of Medical Care
№ | Quality criteria | Performance evaluation (yes/no) |
|---|---|---|
1 | Complete blood count (CBC) performed | Yes/no |
2 | Determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in the blood performed | Yes/no |
3 | Investigation of free and conjugated bilirubin levels in the blood performed | Yes/no |
4 | Determination of alkaline phosphatase activity in the blood performed | Yes/no |
5 | Determination of gamma-glutamyl transferase activity in the blood performed | Yes/no |
6 | Investigation of total protein and albumin levels in the blood performed | Yes/no |
7 | Coagulogram (exploratory assessment of hemostasis) performed | Yes/no |
8 | Serological testing performed to establish the etiology of hepatitis C using enzyme-linked immunosorbent assay (ELISA) or chemiluminescence immunoassay (CLIA): total antibodies of classes M and G (anti-HCV IgG and anti-HCV IgM) to Hepatitis C virus | Yes/no |
9 | Qualitative detection of Hepatitis C virus RNA in the blood by PCR performed | Yes/no |
10 | Dynamic monitoring of laboratory parameters was performed in inpatients with elevated activity of ALT, AST, alkaline phosphatase, gamma-glutamyl transferase, bilirubin levels, and abnormalities in other parameters of general general-clinical blood biochemistry at the time of hospital discharge at least once every 14 days | Yes/no |
11 | Dynamic monitoring of parameters was performed in inpatients with abnormalities in coagulogram parameters (orienting hemostasis test), total protein and albumin, as well as in patients with clinical signs of decreased protein-synthesizing liver function | Yes/no |
12 | Ultrasound examination of the abdominal organs (complex) and retroperitoneal space was performed | Yes/no |
14 | Initial examination (consultation, assessment) by a neurologist was performed for patients with severe acute viral hepatitis C (AHCV) presenting with suspected encephalopathy | Yes/no |
15 | Detoxification therapy was administered | Yes/no |
16 | Glucocorticoids were prescribed in cases of severe disease with the development of liver failure or fulminant course | Yes/no |
References
Show references
Choo Q.-L., Kuo G., Weiner A. J. Isolation of a cDNA clone derived from a blood-borne non- A, non-B viral hepatitis genome. Science. 1989; 244: P. 359 - 362.
Volynets G.V., Panfilova V.N., Zhavoronok S.V. Chronic Viral Hepatitis in Children. Textbook. - M.: Tonchu Publishing House, 2020. - 376 p.
International Committee on Taxonomy of Viruses (ICTV): [https://talk.ictvonline.Org/ictv_wikis/flaviviridae/w/sg_flavi/56/hcv-classification] Accessed December 6, 2021
Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection.JHepatol 2014;61:S45-57
Borgia, S. M., Hedskog, C., Parhy, B., Hyland, R. H., Stamm, L. M., Brainard, D. M., Subramanian, M. G., McHutchison, J. G., Mo, H., Svarovskaia, E. & Shafran, S. D. (2018). Identification of a novel hepatitis C virus genotype from Punjab, India: expanding classification of hepatitis C virus into 8 genotypes. J Infect Dis 2018,17221729.
Pimenov N.N., Chulanov V.P., Komarova S.V. et al. Hepatitis C in Russia: epidemiological characteristics and ways to improve diagnostics and surveillance. Epidemiology and Infectious Diseases. 2012; 3: P. 4 - 9.
Zhdanov, K.V., Lobzin, Yu.V., Gusev, D.A., Kozlov, K.V. Viral Hepatitis. St. Petersburg: Foliant, 2011. - 304 p.
Larrubia J.R., Moreno-Cubero E., Lokhande M.U., Garcia-Garzon S., Lazaro A., Miquel J., et al. Adaptive immune response during hepatitis C virus infection. World J Gastroenterol. 2014;20(13):3418-30. doi: 10.3748/wjg.v20.i13.3418.
Urbani S., Amadei B., Fisicaro P., Tola D., Orlandini A., Sacchelli L., et al. Outcome of acute hepatitis C is related to virusspecific CD4 function and maturation of antiviral memory CD8 responses. Hepatology. 2006;44:126-39. DOI: 10.1002/hep.21242
Cacoub P., Gragnani L., Comarmond C., Zignego A.L. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis. 2014;46(5): 165-73. doi: 10.1016/j.dld. 2014.10.005
Indolfi G, Easterbrook P, Dusheiko G, et al. Hepatitis C virus infection in children and adolescents. Lancet Gastroenterol Hepatol 2019; 4: 477-87
Nwaohiri, A., Schillie, S., Bulterys, M., & Kourtis, A. P. Towards elimination of hepatitis C virus infection in children. The Lancet Child & Adolescent Health. 2018. 2(4). 235237. doi: 10.1016/s2352-4642(18)30069-5
Layden JE, Phillips RO, Owusu-Ofori S, et al. High frequency of active HCV infection among seropositive cases in West Africa and evidence for multiple transmission pathways. Clin Infect Dis 2015;60:1033-41
WHO Global hepatitis report 2024: action for access in low- and middle-income countries ISBN 978-92-4-009167-2 (electronic version)
Marie-Claude Pelland-Marcotte, Jeremiah Hwee, Jason D. Pole, Paul C. Nathan; Lillian Sung (2019): Incidence of infections after therapy completion in children with acute lymphoblastic leukemia or acute myeloid leukemia: a systematic review of the literature, Leukemia & Lymphoma, DOI: 10.1080/10428194.2019.1573369
Gubanova M.N., Madzaev S.R., Zhiburt E.B. Prevalence and occurrence of infections in blood donors in Russia. / Voprosy Virusologii. 2015; 60 (5): 29-31.
Indolfi G., Nesi A., Resti M. Intrafamilial transmission of hepatitis C virus. J Med Virol. 2013;85(4):608-14. doi: 10.1002/jmv.23522.
Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis. 2014;59(6):765- 73.
Volynets G.V. et al. Chronic hepatitis C in children in the Russian Federation: a multicenter study. Journal of Hepatology. 2017; V66 (1), 316 - 317.
Greshnyakova V.A., Goryacheva L.G., Skripchenko N.V. Viral hepatitis C with perinatal transmission route: epidemiology and clinical features. Pediatrics. 2019; 98 (2): 203-208.
Pfaender S. Heyden J, Friesland M, Ciesek W, Ejaz A, Steinmann J, Steinmann J, Malarski A, Stoiber H, Tsiavaliaris G, Bader W, Jahreis G, Pietschmann T, Steinmann E. Inactivation of hepatitis C virus infectivity by human breast milk. The Journal of Infectious Diseases. 2013; 208 (12): 1943-1952. doi: 10.1093/infdis/jit519.
Viral Hepatitis in the Russian Federation. Analytical Review. Issue 11 / Ed. by V.I. Pokrovsky, A.A. Totolian. — St. Petersburg: Pasteur Research Institute of Epidemiology and Microbiology, 2018. — 112 p.
On the state of sanitary and epidemiological welfare of the population in the Russian Federation in 2024: State Report. Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 2025. 424 p.
European Paediatric Hepatitis C Virus Network. Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis. 2005;41(1):45-51. Doi: 10.1086/430601.
Tsyrkunov V.M., Matievskaya N.V., Lukashik S.P. HCV infection. Minsk: Asar. 2012. - 480 p.
Infectious Diseases. National Guidelines. 3rd edition, revised and expanded / ed. Yushchuk N.D., Vengerov Yu.Ya. Moscow: GEOTAR-Media. 2021. 1104 p.
Yushchuk N.D., Znoyko O.O., Bely P.A. Viral Hepatitis. Clinic, Diagnosis, Treatment. Specialist Physician Library / ed. Yushchuk N.D. Moscow: GEOTAR-Media, 2018. 368 p.
Pokrovsky V.I. Infectious Diseases and Epidemiology: Textbook— 3rd ed., rev. and add. Moscow: GEOTAR-Media, 2018. 1008 p.
Guide to Infectious Diseases in Children / ed. Lobzin Yu.V. Saint Petersburg: SpetsLit, 2013. 591 p.
Lobzin Yu.V. Viral Hepatitis. St. Petersburg: FOLIANT, 2011. 304 p.
Shamsheva O.V. Parenteral Viral Hepatitis in Children: Study Guide [for medical university students]. Moscow: Pirogov Russian National Research Medical University, 2021. 108 p.
Gerlach JT, Diepolder HM, Zachoval R, et al. Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology 2003; 125:80.
Santantonio T, Sinisi E, Guastadisegni A, et al. Natural course of acute hepatitis C: a longterm prospective study. Dig Liver Dis 2003; 35:104.
Hofer H, Watkins-Riedel T, Janata O, et al. Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load. Hepatology 2003; 37:60.
Kenny-Walsh E. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group. N Engl J Med 1999; 340:1228.
Kamal SM, Kassim SK, Ahmed Al, et al. Host and viral determinants of the outcome of exposure to HCV infection genotype 4: a large longitudinal study. Am J Gastroenterol 2014; 109:199.
Missale G, Bertoni R, Lamonaca V, et al. Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response. J Clin Invest 1996; 98:706.
Diepolder HM, Zachoval R, Hoffmann RM, et al. Possible mechanism involving T- lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 1995; 346:1006
Page K, Mirzazadeh A, Rice TM, et al. Interferon Lambda 4 Genotype Is Associated With Jaundice and Elevated Aminotransferase Levels During Acute Hepatitis C Virus Infection: Findings From the InC3 Collaborative. Open Forum Infect Dis 2016;
Chu CM, Yeh CT, Liaw YF. Fulminant hepatic failure in acute hepatitis C: increased risk in chronic carriers of hepatitis B virus. Gut 1999; 45:613.
Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United kingdom. J Pediatr Gastroenterol Nutr 2005; 40:575.
Cherednichenko T.V., Moskovskaya I.A. Viral hepatitis in infants in the first year of life // Detskie Infektsii. 2003. Vol. 3. P. 11-14.
Uchaykin V.F., Cherednichenko G.V., Smirnov A.V. Infectious Hepatology. Guide for Physicians. Moscow: GEOTAR-Media, 2014. 608 p.
Kamili S., Drobeniuc J., Araujo A.C. et al. Laboratory diagnostics for hepatitis C virus infection. Clin Infect Dis. 2012;55: S43-S48
Smith BD, Yartel AK, Krauskopf K, et al. Hepatitis C virus antibody positivity and predictors among previously undiagnosed adult primary care outpatients: cross-sectional analysis of a multisite retrospective cohort study. Clin Infect Dis. 2015;60(8):l 145-1152.
Rein DB, Wagner LD, Brown KA, et al. Current practices of hepatitis C antibody testing and follow-up evaluation in primary care settings: a retrospective study of four large, primary care service centers. Hepatology. 2012;56:1094
Goryacheva L.G., Greshnyakova V.A., Rogozina N.V., Ivanova V.V. [Perinatal viral hepatitis C and possibilities of its treatment]. Epidemiologiya i infektsionnye bolezni. 2014; (3): 4–8. (In Russ.).
Leung DH, Squires JE, Jhaveri R, Kerkar N, Lin CH, Mohan P, Murray KF, Gonzalez- Peralta RP, Roberts EA, Sundaram SS. Hepatitis C in 2020: A North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper. J Pediatr Gastroenterol Nutr. 2020 Sep;71(3):407-417. doi: 10.1097/MPG.0000000000002814. PMID: 32826718.
Enaleeva D.Sh., Fazylov V.Kh., Sozinov A.S. Chronic Viral Hepatitis B, C, and D. Guide for Physicians. Moscow: GEOTAR-Media, 2015. 194 p.
Kramar L.V. Features of the treatment of viral hepatitis in children // Lekarstvenny Vestnik. 2018. Vol. 4, № 72. P. 34-40.
Goryacheva L.G. Neonatal hepatitis: prognosis of the course and management tactics. Methodological guide // Modern approaches to the diagnosis, therapy, and prevention of infectious diseases in children. St. Petersburg: Taktik-Studio, 2013. P. 531-548.
Korchinsky N.Ch. The use of enterosorbents in the treatment of patients with acute viral hepatitis // Klinicheskaya Infektologiya i Parazitologiya. 2014. Vol. 3, № 10. P. 125-136.
Sundukov A.V. Herbal hepatoprotectors in the complex therapy of viral hepatitis. // Infectious Diseases. 2008. Vol. 6, № 1. P. 47-50.
Sanitary Rules and Norms SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" (approved by the Resolution of the Chief State Sanitary Doctor of the Russian Federation dated January 28, 2021, No. 4).
Jafri W. et al. Hepatitis B and C: prevalence and risk factors associated with seropositivity among children in Karachi, Pakistan // BMC Infectious Diseases. – 2006. – Vol. 6. – No. 1. – P. 1-10.
Fernandes N. D. et al. Hepatitis C virus screening among adolescents attending a drug rehabilitation center // Journal of the Pediatric Infectious Diseases Society. – 2020. – Vol. 9. – No. 4. – P. 437-441.
Rauf A. et al. Tuberculosis and hepatitis infections among the underprivileged orphan children of Northern Pakistan // Pakistan Journal of Zoology. – 2013. – Vol. 45. – No. 6.
Greshnyakova V.A. Clinical and laboratory risk factors for infection and prognosis of viral clearance in children with perinatal contact regarding hepatitis C: Abstract of Thesis ... Candidate of Medical Sciences. St. Petersburg, 2018:
Epstein RL, Sabharwal V, Wachman EM, Saia KA, Vellozzi C, Hariri S, Linas BP. Perinatal Transmission of Hepatitis C Virus: Defining the Cascade of Care. J. Pediatr. 2018; 203: 34–40.e1. doi: 10.1016/j.jpeds.2018.07.006.
Uchaykin V.F., Kovalev O.B. Use of phosphogliv in acute and chronic viral hepatitis in children // Detskie Infektsii. 2006. No. 1. P.35-43
Order of the Ministry of Health of the Russian Federation dated September 28, 2020, No. 1029n “On approval of lists of medical indications and contraindications for sanatorium-resort treatment”. Registered with the Ministry of Justice of the Russian Federation on October 27, 2020. Registration No. 60589
Grishchenko E.B., Shchekina M.I. The use of essential phospholipids in the treatment of acute and chronic liver diseases. Consilium Medicum. 2011. Vol. 13. N 8. P. 38 - 41.
Order of the Ministry of Health of the Russian Federation dated September 28, 2020, No. 1029n “On approval of lists of medical indications and contraindications for sanatorium-resort treatment”. Registered with the Ministry of Justice of the Russian Federation on October 27, 2020. Registration No. 60589
Wang TY, Kuo HT, Chen LC, Chen YT, Lin CN, Lee MM. Use of polymerase chain reaction for early detection and management of hepatitis C virus infection after needlestick injury. Ann Clin Lab Sci. 2002 Spring;32(2):137-41. PMID: 12017194.
Hoofnagle JH. Hepatitis C: the clinical spectrum of disease. Hepatology. 1997 Sep;26(3 Suppl 1):15S-20S. doi: 10.1002/hep.510260703. PMID: 9305658.
Farci P, Alter HJ, Wong D, Miller RH, Shih JW, Jett B, Purcell RH. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med. 1991 Jul 11;325(2):98-104. doi: 10.1056/NEJM199107113250205. PMID: 1646962.
Fasano M, Ieva F, Ciarallo M, Caccianotti B, Santantonio TA. Acute Hepatitis C: Current Status and Future Perspectives. Viruses. 2024 Nov 6;16(11):1739. doi: 10.3390/v16111739. PMID: 39599853; PMCID: PMC11599108.
Martinello M, Naggie S, Rockstroh JK, Matthews GV. Direct-Acting Antiviral Therapy for Treatment of Acute and Recent Hepatitis C Virus Infection: A Narrative Review. Clin Infect Dis. 2023 Aug 14;77(Suppl 3):S238-S244. doi: 10.1093/cid/ciad344. PMID: 37579203.
Kerkar N, Hartjes K. Hepatitis C Virus-Pediatric and Adult Perspectives in the Current Decade. Pathogens. 2024 Dec 29;14(1):11. doi: 10.3390/pathogens14010011. PMID: 39860972; PMCID: PMC11769290.
Appendix A1. Working Group Composition
Greshnyakova Vera Aleksandrovna, Candidate of Medical Sciences, Head of the Research Department of Viral Hepatitis and Liver Diseases at the Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies of the Federal Medical-Biological Agency (FSCC EID FMBA). Member of the "Euro-Asian Society of Infectious Diseases" (ROO "EASID"), member of the Union of Pediatrists of Russia, member of the Russian Study of the Liver Association.
Lobzin Yuriy Vladimirovich, Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Honorary President of the FSCC EID FMBA. Chairman of the "Euro-Asian Society of Infectious Diseases" (ROO "EASID").
Zhdanov Konstantin Valeryevich, Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Director of the Scientific and Clinical Center for Infectious Diseases of the FSCC EID FMBA.
Goryacheva Larisa Georgievna, Doctor of Medical Sciences, Leading Researcher at the Research Department of Viral Hepatitis and Liver Diseases of the FSCC EID FMBA. Member of the "Euro-Asian Society of Infectious Diseases" (ROO "EASID").
Rychkova Svetlana Vladislavovna, Doctor of Medical Sciences, Associate Professor, Head of the Department of Organization of Medical Care for Children, FSCC EID FMBA. Member of the "Euro-Asian Society of Infectious Diseases" (ROO "EASID").
Conflict of interest:
The clinical practice guideline developers reported no conflict of interest
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
Infectious disease specialist;
Pediatrician;
General practitioner (family physician);
Gastroenterologist;
Medical students, residents, postgraduate students.
Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Scale for grading levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)
LoE | Definition |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 3. Scale for grading grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
These clinical guidelines were developed taking into account the following regulatory legal documents:
Federal Law No. 157-FZ of September 17, 1998 (as amended on June 11, 2021) "On Immunoprophylaxis of Infectious Diseases"
Federal Law No. 326-FZ of November 29, 2010 (as amended on February 24, 2021) "On Compulsory Health Insurance in the Russian Federation".
Federal Law No. 323-FZ of November 21, 2011 (as amended on July 2, 2021) "The Fundamentals of Healthcare Protection in the Russian Federation."
Order of the Ministry of Health and Social Development of Russia No. 494 of August 9, 2005, "On the Procedure for the Use of Medicinal Products in Patients for Vital Indications".
Order of the Russian Ministry of Health No. 804n of October 13, 2017 "On Approval of the Nomenclature of Medical Services" (as amended on September 24, 2020)
Order of the Russian Ministry of Health No. 125n of March 21, 2014 (as amended on February 3, 2021) "On Approval of the National Schedule of Preventive Vaccinations and the Schedule of Preventive Vaccinations by Epidemiological Indications" (Registered with the Ministry of Justice of Russia on April 25, 2014, No. 32115)
Order of the Russian Ministry of Health No. 1183n of December 20, 2012 (as amended on September 4, 2020) "On Approval of the Nomenclature of Positions of Medical Workers and Pharmaceutical Workers" (Registered with the Ministry of Justice of Russia on March 18, 2013, No. 27723)
Order of the Russian Ministry of Health No. 700n of October 7, 2015 (as amended on December 9, 2019) "On the Nomenclature of Specialties of Specialists with Higher Medical and Pharmaceutical Education" (Registered with the Ministry of Justice of Russia on November 12, 2015, No. 39696)
Order of the Russian Ministry of Health No. 203n of May 10, 2017 "On Approval of Criteria for Assessing the Quality of Medical Care" (Registered with the Ministry of Justice of Russia on May 17, 2017, No. 46740)
Sanitary Rules and Norms SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" (approved by the Resolution of the Chief State Sanitary Doctor of the Russian Federation dated January 28, 2021, No. 4).
Order of the Ministry of Health and Social Development of Russia No. 521n of May 5, 2012 (as amended on February 21, 2020) "On Approval of the Procedure for Providing Medical Care to Children with Infectious Diseases" (Registered with the Ministry of Justice of Russia on July 10, 2012, No. 24867)
Order of the Ministry of Health of the Russian Federation No. 1008n of September 23, 2020 "On Approval of the Procedure for Providing Patients with Therapeutic Nutrition" (Registered with the Ministry of Justice of the Russian Federation on September 30, 2020, No. 60137)
Order of the Ministry of Health of the Russian Federation No. 330 of August 5, 2003 "On Measures to Improve Therapeutic Nutrition in Medical and Preventive Treatment Institutions of the Russian Federation" Registered with the Ministry of Justice of the Russian Federation on September 12, 2003, registration No. 5073 (as amended on February 19, 2024)
Criteria for the severity of AHCV
Symptom complex | Characteristic of symptoms | ||
|---|---|---|---|
Disease severity | Mild | Moderate | Severe |
Severity and duration of intoxication | Absent or mildly expressed weakness, nausea, decreased appetite, 5-7 days. | Moderate intoxication (anorexia, weakness, sleep disturbances, nausea, vomiting, etc.) | Pronounced symptoms of intoxication (progressive general weakness, drowsiness, dizziness, anorexia, recurrent vomiting) |
Intensity and duration of skin jaundice | Mild to moderate, 2–3 weeks. | Intensely expressed, 3-4 weeks, in cholestatic syndrome up to 40-45 days. | Pronounced, may progress against the background of increasing intoxication, exceeding 4 weeks. |
Tachycardia | Absent | Absent, tendency to bradycardia. | Appears against the background of the development and progression of jaundice. |
Hemorrhagic syndrome | Absent | Absent or mild – isolated skin petechiae and epistaxis | Petechial skin rash, epistaxis, "coffee ground" emesis, injection site hemorrhages, "tarry" stools. |
Liver size | Normal or enlarged up to 3 cm | Enlarged by 3–4 cm | Sharp decrease in size with disease progression, tenderness of the edge |
Bilirubin, µmol/L | <100 | 100-170 | >170 |
Prothrombin index, % | >60 | 50-60 | <50 |
Differential diagnosis of viral hepatitis A, B, C [1–6, 8, 10, 48].
Signs | Hepatitis A | Hepatitis B | Hepatitis C |
|---|---|---|---|
Epidemiological background | History of being in an HA focus 15-40 days before the disease onset | Blood transfusions, surgeries, parenteral interventions (including IV drug use), sexual or close contact with an HBV patient | Blood transfusions, surgeries, parenteral interventions (including drug injection), sexual or close contact with a patient with viral hepatitis |
Initial (pre-icteric) period | Acute onset of the disease, short prodromal (pre-jaundiced) period up to 4-7 days (usually influenza-like type) | Gradual onset of the disease, prolonged prodromal period up to 7-14 days (usually mixed type with possible polyarthralgia) | Typically absent. When present, it is characterized by mild intoxication symptoms lasting 1–4 days. |
Iteric (jaundiced) period | Rapid onset of jaundice, the appearance of which generally coincides with an improvement in well-being. Short icteric period (average of 2 weeks) | Gradual development of jaundice, upon the appearance of which well-being generally does not improve or worsens. Prolonged jaundiced period with slow disappearance of symptoms during the convalescence period | As a rule, absent. If present, it is characterized by minor, transient jaundice and disappearance of symptoms during convalescence |
Laboratory diagnostics | Presence of hepatitis A virus IgM antibodies (anti-HAV IgM) | Presence of hepatitis B surface antigen (HBsAg), IgM antibodies to hepatitis B core antigen (anti-HBc IgM), and hepatitis B virus DNA | Presence of IgM antibodies to hepatitis C core antigen (anti-HCVc IgM), HCV RNA, and total antibodies (anti-HCV) |
Chronification | Not characteristic | in 5-10% | in 80-90% |
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Acute hepatitis C is an infectious disease caused by the hepatitis C virus. The primary organ affected by this infection is the liver. AHG is typically characterized by a mild or subclinical course, a high rate of progression to chronic forms (55–85%), and the potential subsequent development of liver cirrhosis and hepatocellular carcinoma in some patients. The disease affects both adults and children, regardless of sex. Currently, about 71 million people worldwide are infected. In Russia, approximately 55,000 new infection cases are registered annually. In the Russian Federation, a steady annual decrease in the incidence of acute hepatitis C has been observed since 2014. From 2011 to 2020, the incidence rate decreased by 2.8 times. In 2020, a total of 964 cases of AHG were registered. The proportion of children among all infected individuals was 3.1%. The proportion of children under 1 year of age among all children with AHG in 2020 was 46.7% (14 cases), and in 2019 – 54.3% (19 cases).
A child can contract the hepatitis C virus during procedures involving skin integrity compromise if infected instruments are used—surgical interventions, reuse of syringes, as well as hemodialysis, dental procedures, sharing razors, acupuncture, tattoos, piercings, manicures, and pedicures. In adolescents, infection is also associated with intravenous drug use, and the virus can be sexually transmitted. Transmission of the virus from an infected mother to her child during pregnancy and childbirth is also possible. This route of infection is the primary one for children. Mother-to-child transmission during pregnancy and delivery does not always occur; about 5–10% of newborns become infected. Co-existing HIV infection, obstetric manipulations, and a prolonged anhydrous period significantly increase the risk of infection. Currently, there are no medical methods for preventing mother-to-child transmission of the virus. Research on developing a hepatitis C vaccine is underway worldwide, but has not yet been successful.
In accordance with current legislation, you are not obligated to inform others about your infection status. However, you should strive to prevent infecting other people. Ensure that you have your own individual toothbrush, razors, and manicure/pedicure tools. Alcoholic beverages should be avoided. Sports activities may be continued. In general, a normal healthy lifestyle is recommended.
In the case of an acute course of infection, the prescription of antiviral therapy is not indicated, as the disease resolves spontaneously. Despite the relatively mild course, hepatitis C very frequently transitions into a chronic form. HCV infection is currently completely curable. Hepatitis C is treated with medications, including oral antiviral drugs. Modern antiviral therapy for CHC allows for the cure of the disease and does not affect a person's lifestyle or personality. It does not cause numerous adverse events or psychological changes associated with the necessity of undergoing treatment. Anxiety, tension, fear, agitation, depression, and hope are common reactions for many patients.
To prevent infection in a future child, it is strongly recommended to undergo treatment for CHC at the pregnancy planning stage, before conception occurs. The medications used to treat hepatitis will not have any impact on reproductive health or the developing fetus. Nevertheless, the use of these agents is not recommended during pregnancy, so contraception methods must be used during therapy.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Glasgow Coma Scale (Teasdale G.M., Jennett B., 1974) [66]
Russian name: Glasgow Coma Scale
Original name: Glasgow Coma Scale
Source: Teasdale G.M., Jennett B., 1974
Type: rating scale
Purpose: A criterion for assessing the level of consciousness, correlating with the severity of cerebral injury and prognosis.
Content: The scale consists of three tests assessing eye-opening response, verbal response, and motor response. A specific number of points is awarded for each test. The eye-opening test ranges from 1 to 4 points, the verbal response test from 1 to 5 points, and the motor response test from 1 to 6 points. The level of consciousness is expressed as the sum of points for each parameter.
Sign | Score |
|---|---|
1. Eye opening: | |
Spontaneous | 4 |
To verbal stimuli | 3 |
To pain | 2 |
None | 1 |
2. Verbal response: | |
Oriented | 5 |
Confused | 4 |
Incoherent words | 3 |
incomprehensible sounds | 2 |
None | 1 |
3. Motor response: | |
Obeys commands | 6 |
localizes pain | 5 |
Withdrawal response to pain | 4 |
Flexion response to pain (decorticate posturing) | 3 |
Extension response to pain (decerebrate posturing) | 2 |
None | 1 |
The initial Glasgow score correlates with the severity of cerebral injury and prognosis. Thus, the Glasgow scale is an important criterion for assessing the level of consciousness. Each individual response is scored in points, and the level of consciousness is expressed as the sum of points for each parameter.
Key (interpretation): The lowest score is 3 points, and the highest score is 15 points. A score of 8 points or lower is defined as a coma.
Notes: A score of 3–5 points carries an extremely unfavorable prognosis, especially when combined with dilated pupils and the absence of the oculocephalic/oculovestibular reflex.