What is Viral Hepatitis C?
Viral hepatitis C is an anthroponotic viral infection from the conditional group of transfusion hepatitis, characterized by liver damage, anicteric, mild and moderate course in the acute phase and a frequent tendency to chronicity, development of liver cirrhosis and primary hepatocarcinoma.
When deciphering the etiology of post-transfusion viral hepatitis after B. Blumberg discovered the “Australian” antigen, methods of immunodiagnostics of viral hepatitis C were used. However, in a sufficiently large number of cases, the markers of viral hepatitis B were not found, which gave grounds to distinguish an independent group of hepatitis, called “hepatitis Ni, nor in. In 1989, it was possible to create a test system for detecting antibodies to a new virus, and then detect its RNA, which made it possible to isolate a new independent nosological form, the hepatitis C group of hepatitis.
Causes of Viral Hepatitis C
The causative agent of viral hepatitis C is an RNA genomic virus included in the nameless genus of the family Flaviviridae. Spherical virions surrounded by supercapsid; The genome contains single-stranded RNA. There are 6 serotypes and more than 90 subtypes of the virus, each of which is “tied” to certain countries, for example, viral hepatitis C-1 is common in the US, viral hepatitis C-2 is prevalent in Japan, while viral hepatitis C-2 and -3 are more common They are met in northern and central Europe, and viral hepatitis C-4 in the Middle East and Africa. These serotypes do not provide cross-immunity. A number of studies have shown that the lb subtype is combined with a more severe course of the disease, higher RNA levels of viral hepatitis C in the blood, greater resistance to antiviral drugs and a greater likelihood of serious relapse.
A distinctive feature of the virus of hepatitis C is the ability for long-term persistence in the body, which leads to a high level of chronic infection. The mechanisms underlying the ineffective elimination of the virus are not well understood. The main significance is attached to the high variability of the pathogen. Like other flaviviruses, the daughter populations of viral hepatitis C form quasi-tams — immunologically distinct antigenic variants that elude immune surveillance, which complicates vaccine development.
Since the virus of hepatitis C does not multiply in cell cultures, information about the sensitivity of the virus to environmental factors is scarce. The virus is resistant to heat up to 50 ° C, and is inactivated by UVA. The resistance of the pathogen in the external environment is more pronounced than in HIV.
The reservoir and source of infection – patients with chronic and acute forms of the disease, occurring with both clinical manifestations and asymptomatic. Serum and blood plasma of an infected person are contagious for a period starting from one or several weeks before the onset of clinical signs of the disease, and may contain the virus for an indefinite long time.
The mechanism of transmission of hepatitis C. It is similar to viral hepatitis B, but the structure of the routes of infection has its own characteristics. This is due to the relatively low resistance of the virus in the external environment and a rather large infectious dose required for infection. The virus of hepatitis C is transmitted primarily through infected blood and to a lesser extent through other human biological fluids. RNA virus found in saliva, urine, seminal and ascitic fluids.
High-risk groups include people who have been repeatedly transfused with blood and its drugs, as well as people with a history of massive medical interventions, organ transplants from donors with HCV-positive reactions and repeated parenteral manipulations, especially when re-using non-sterile syringes and needles. The prevalence of viral hepatitis C among drug addicts is very high (70-90%); This mode of transmission represents the greatest risk in the spread of the disease.
The risk of transmitting the virus is increased by hemodialysis procedures, tattooing, and skin integrity during injections. However, 40-50% of patients fail to identify any parenteral risk factors, and the method of transmission of the virus in these “sporadic” cases remains unknown. The frequency of detection of antibodies to the viral hepatitis C virus among medical personnel exposed to the danger of contact with infected blood is not higher than in the general population. As a result of mandatory testing of all transfused doses of preserved blood, a reduction in the number of cases of post-transfusion viral hepatitis C has been achieved. Persistent minimal risk associated mainly with the possible presence of an acute period of infection in the donor, not diagnosed using screening methods of detection antibodies to the virus hepatitis C. At the same time, the risk of transmission of viral hepatitis C with a single random injection made by medical personnel is insignificant, which is explained by the low concentration of the virus in small volumes of blood.
Vertical transmission of viral hepatitis C from pregnant to the fetus is rare, but possible with high concentrations of the virus in the mother or with concurrent infection with the human immunodeficiency virus. The role of sexual contacts in the transmission of viral hepatitis C is quite small and amounts to about 5-10% (with the transmission of viral hepatitis B – 30%). The frequency of sexual transmission of the pathogen increases with concomitant HIV infection, a large number of sexual partners. The identification of identical genotypes of viral hepatitis C in families confirms the possibility (although unlikely) of its household transmission.
Natural susceptibility is high and to a large extent determined by the infectious dose. The intensity and duration of post-infectious immunity are unknown. In experiments on monkeys, the possibility of recurring disease was shown.
Major epidemiological signs. Infection is common everywhere. According to WHO, at the end of the 1990s, about 1% of the world’s population was infected with viral hepatitis C. In Europe and North America, the prevalence of infection is 0.5-2%, in some regions of Africa – 4% and higher.
The main group of cases are, as in viral hepatitis B, adolescents and people 20-29 years old. The number of people infected in medical institutions is 1-2% of all infections. Viral hepatitis C is one of the main causes of chronic diffuse liver diseases and hepatocellular carcinoma (primary liver cancer). Cirrhosis of the liver, caused by viral hepatitis C, is one of the main places in the series of indications for liver transplantation.
Pathogenesis During Viral Hepatitis C
Pathogenesis remains poorly understood. The direct cytopathic effect of the virus on hepatocytes is assigned an insignificant role, and only during the primary infection. The main lesions of various organs and tissues in viral hepatitis C are caused by immunological reactions. Proof of viral replication outside the liver – in the tissues of lymphoid and non-lymphoid origin. Reproduction of the virus in immunocompetent cells (monocytes) leads to a violation of their immunological functions.
High chronicity of viral hepatitis C, obviously, is primarily due to the lack of formation of a sufficient protective immune response, i.e. the formation of specific antibodies, which is a consequence of the high frequency of transcriptional failures of viral hepatitis C RNA. In infected individuals, there is a constant rapid mutation of viral hepatitis C, especially in the surface proteins of the virus, which does not allow for complete cellular immunity (antibody-dependent and T-cell-mediated killing virus infected cells).
All this suggests the presence of two leading factors in the pathogenesis of viral hepatitis C:
- Permanent uncontrolled replication of the virus;
- Active, but ineffective humoral immune response. These factors contribute to the formation of a significant amount of cross-reactive autoantibodies and polyclonal gamma globulinopathy, which is realized as a large number of autoimmune diseases associated with the persistence of viral hepatitis C or triggered by viral hepatitis C with subsequent elimination of the virus.
Symptoms of Viral Hepatitis C
Incubation period. Makes 2-13 weeks, however, depending on the route of transmission can be extended up to 26 weeks.
Acute infection is mostly not clinically diagnosed, occurs predominantly in subclinical anicteric form, accounting for up to 95% of all cases of acute viral hepatitis C. Late laboratory diagnosis of acute infection is due to the existence of the so-called “antibody window”: when examined with test systems of the first and second generations of antibodies 61% of patients with viral hepatitis C appear in the period up to 6 months from the initial clinical manifestations, and in many cases much later.
In the clinically manifest form of acute viral hepatitis C, the classic signs of the disease are mild or absent. Patients noted weakness, lethargy, fatigue, loss of appetite, reduced tolerance to food stress. Sometimes in the pre-jaundice period there is a heaviness in the right hypochondrium, fever, arthralgia, polyneuropathy, dyspeptic manifestations. In general, blood tests can detect leuko- and thrombocytopenia. Jaundice is found in 25% of patients, mainly in individuals with post-transfusion infection. The course of the icteric period is most often easy, ikterichnost quickly disappears. The disease is prone to exacerbations, in which the icteric syndrome reappears and the activity of aminotransferases increases.
However, rarely occurring (no more than 1% of cases) fulminant forms of viral hepatitis C are currently described.
In some cases, the manifestation of acute infection is accompanied by severe autoimmune reactions – aplastic anemia, agranulocytosis, peripheral neuropathy. These processes are associated with extrahepatic replication of the virus and can result in the death of patients before the appearance of significant antibody titers.
A distinctive feature of viral hepatitis C is a perennial latent or oligosymptomatic course of the type of so-called slow viral infection. In such cases, the disease for the most part remains unrecognized for a long time and is diagnosed at advanced clinical stages, including against the background of the development of cirrhosis of the liver and primary hepatocellular carcinoma.
Symptoms of hepatitis C reflect mainly damage and impaired liver function.
The most common symptoms of developing hepatitis include:
- weakness and fatigue
- loss of appetite
- heaviness or discomfort in the abdomen (on the right, where the liver is located)
- dark urine
- discoloration of feces (becomes light)
The above signs are presented in chronological order. This means that jaundice (changes in skin color, eye protein, tongue) in acute hepatitis appears last, when the patient’s condition improves.
The period before the development of jaundice is called preicteric (prodromal, presicteric).
Jaundice in the usual sense is one of the synonyms of hepatitis, but it can also be caused by other reasons.
Signs of Chronic Hepatitis C
For chronic hepatitis C is characterized by mild symptoms and even their long absence. The most typical long-term weakness and fatigue, asthenic syndrome.
Sometimes chronic hepatitis is noticed only when its irreversible outcomes have already developed.
The terrible consequence of chronic viral hepatitis – cirrhosis of the liver can manifest itself as a worsening condition of the patient, development of jaundice and the appearance of ascites (an increase in the abdomen).
Hepatic encephalopathy, a lesion of the brain with impairment of its activity, may develop.
Often, chronic hepatitis is detected by chance, during examination for other diseases or clinical examination.
Diagnosis of Viral Hepatitis C
Differential diagnosis of hepatitis C is similar to that in hepatitis A and B. It should be noted that the icteric form of hepatitis C, as a rule, occurs with mild intoxication. The only reliable confirmation of hepatitis C are the results of marker diagnosis. Given the large number of anicteric forms of hepatitis C, it is necessary to carry out a marker diagnosis of persons systematically receiving a large number of injections (primarily, intravenous drug users).
Laboratory diagnosis of the acute phase of hepatitis C
Based on the detection of viral RNA in PCR and specific IgM by various serological methods. When RNA of hepatitis C virus is detected, it is desirable to conduct genotyping. Detection of serum IgG to antigens of viral hepatitis C indicates either a previously transferred disease, or the continued persistence of the virus.
Treatment of Viral Hepatitis C
Currently, the standard of treatment of viral hepatitis C, adopted by a number of countries, is a combination antiviral therapy (PVT) with interferon alfa and ribavirin preparations. PVT is indicated in patients with constantly elevated serum ALT levels, in the determination of hepatitis C virus RNA (HCV) and the presence of marked histological changes in the patient’s liver biopath. The duration of therapy may range from 24 to 48 weeks, depending on the genotype of the hepatitis C virus.
Interferon alfa preparations are divided into short-lived and pegylated IFN. The latter, when used in conjunction with ribavirin, have shown greater efficacy compared with standard INF. The criterion for the effectiveness of treatment is persistent biochemical remission (normalization of the level of alanine aminotransferase for a long time after HTT) and the absence of viremia (undetectable level of HCV RNA after 6 months or more after completion of treatment).
Individualization and optimization of the management strategy for a patient infected with hepatitis C virus, who is in standard antiviral treatment using a combination of interferon and ribavirin, is as follows:
- Tracking the presence of the definition of RNA of the hepatitis C virus using the “qualitative” PCR test at 4 weeks and the size of the reduction in viral load using “quantitative PCR analysis at 12 weeks from the start of treatment.
- Extension of the combined treatment to 72 weeks in patients with genotype 1 of the hepatitis C virus who did not achieve a rapid virological response (RVR) at 4 weeks from the start of treatment.
- Repeated combined treatment with pegylated interferon and ribavirin is not recommended if the first course of treatment was insufficient due to the low level of sustained virological response (SVR). Another option for these patients is Interferon Consensus. A longer duration of the re-“standard” treatment can bring additional benefits.
- The results of monitoring the long-term effect of maintenance treatment with pegylated interferon (without ribavirin) on clinical results and histology in patients with advanced fibrosis due to hepatitis C do not confirm the effectiveness of using pegylated interferon in treating people with advanced fibrosis who do not respond to a course of standard antiviral treatment with a combination of interferon and ribavirin.
Hepatitis C Prediction
The combination of hepatitis C with other forms of viral hepatitis, dramatically aggravates the disease and is fatal. The treatment of hepatitis C is complex and in many respects similar to therapy for hepatitis B. In recent years, the detection of the hepatitis C virus from a blood test is not difficult. The danger of hepatitis C is that an effective vaccine that can protect against infection with hepatitis C does not yet exist.
Prevention of Viral Hepatitis C
A health policy aimed at reducing the transmission of HIV infection, such as promoting safer sex advertising among young people and using individual syringes and needles among drug addicts, helps reduce the transmission of viral hepatitis C in high-risk groups. Preventive measures to prevent instrumental infection with viral hepatitis C, as well as measures aimed at neutralizing the natural routes of transmission, are the same as in viral hepatitis B. Creating a HCV vaccine is hampered by the presence of a large number of subtypes (more than 90) and mutant varieties of viral hepatitis C , as well as the short duration of the effect of neutralizing antibodies.
Interesting facts about the disease Viral Hepatitis C
Hepatitis C and liver cancer
Hepatitis C virus is also associated with liver cancer. For example, in Japan, in 75% of cases, hepatitis C is found in patients with liver cancer. Like with the hepatitis B virus, cirrhosis preceded the hepatitis C virus in patients with liver cancer. In several retrospective-prospective studies (study of the time before and after the disease) of the history of hepatitis C, the average time for the development of liver cancer after infection with the hepatitis C virus was about 28 years. The time of cancer development after the onset of cirrhosis in patients with hepatitis C was 8-10 years. Some promising studies by European scientists prove that the incidence of liver cancer in patients with hepatitis C and liver cirrhosis is 1.4% to 2.5% each year.
For patients who suffer from the hepatitis C virus, risk factors for liver cancer include cirrhosis, old age, male gender, elevated levels of alpha-fetoproteins (cancer markers), alcohol consumption, hepatitis B virus infection. Some scientists suggested that the risk factor also hepatitis C virus genotype 1b, however, recent studies do not support this statement.
Scientists are still not fully clear how the hepatitis C virus causes liver cancer. Unlike the hepatitis B virus, the genetic material of the hepatitis C virus is not directly introduced into the genetic material of the liver cells. However, it is certain that cirrhosis is a serious risk factor for liver cancer. Consequently, there is controversy as to whether the hepatitis C virus, which causes cirrhosis, is an indirect cause of liver cancer.
However, in some patients with hepatitis C and liver cancer, cirrhosis did not develop at all. Thus, scientists have suggested that the central protein of the hepatitis C virus is the cause of liver cancer. It is believed that the central protein of the hepatitis C virus interferes with the natural process of cell death or the functioning of the gene (p53), which is responsible for the suppression of tumor cells. The result of these processes is the functioning of the liver without natural limiters, which causes cancer.