Hepatitis C virus, which, before its identification was labeled “non-A, non-B hepatitis,” is a linear, single-stranded enveloped RNA virus belonging to the flavivirus family.
Clinical Course of Hepatitis C Infection
Hepatitis C infection is usually acquired through infected syringes and needles, and transfusion of infected blood. Sexual transmission of HCV occurs infrequently in heterosexual couples. It is reported to be more common in HIV-positive persons, particularly in MSM. The risk of transmission of HCV from a mother to her child occurs in 4–8% of births to women with HCV infection, and in 10.8–25% of births to women with HIV and HCV co-infection.
HCV causes both acute and chronic hepatitis. Acute hepatitis is often clinically mild and marked by fluctuating elevations of serum aminotransferase levels; greater than 50% likelihood of chronicity, leading to cirrhosis in greater than 20%.
Chronic infection with HCV is usually clinically silent, and is only very rarely associated with life-threatening disease. Spontaneous clearance of acute HCV infection occurs within six months of infection in 15–45% of infected individuals in the absence of treatment. Almost all the remaining 55–85% of persons will harbor HCV for the rest of their lives (if not treated) and are considered to have chronic HCV infection.
Left untreated, chronic HCV infection can cause liver cirrhosis, liver failure and HCC. Of those with chronic HCV infection, the risk of cirrhosis of the liver is 15–30% within 20 years. The risk of HCC in persons with cirrhosis is approximately 2–4% per year.
Following an initial eclipse phase of 1–2 weeks when no virological or serological markers of infection may be detected, the natural course of HCV infection is characterized by the appearance of HCV RNA, then HCV core p22 Ag in the absence of an antibody response for a further 6–10 weeks. During this serological window, it has been shown that free (i.e. not complexed with antibody) HCV core antigen (HCVcAg) can be detected in a proportion of individuals. Following the development of the antibody response, HCVcAg becomes complexed with these antibodies specific for HCV.
The standard method of diagnosis is by detection of anti-HCV antibody. Third generation immunoassays, which incorporate proteins from the core, NS3, and NS5 regions, can detect anti-HCV antibodies usually within 6 – 8 weeks of infection, i.e., from the initial phase of elevation of aminotransferases.
Both rapid diagnostic tests (RDTs) and Immunoassays are available, with comparable sensitivity and specificity. This test does not differentiate between current and past infection. The test may also be false positive in some situations and the diagnosis of an individual patient should be confirmed by HCV RNA detection prior to considering treatment.
Since anti-HCV antibodies from an infected mother may persist in children less than 18 months of age, HCV RNA detection is also used to diagnose HCV infection in this age group (after 2 months of age)
Window period. Assays designed solely to detect antibodies to HCV inevitably have a window period of infectivity in early infection, during which antibodies may be undetectable.
HCV RNA is typically not used to determine exposure to HCV, in spite of its short window period (1–2 weeks after the onset of acute infection) primarily because of cost. There are some situations with occult HCV infection, i.e. HCV RNA detectable in the absence of any serological markers (i.e. HCV seronegative), which may be due to underlying immunosuppression in, for example, HIV-infected populations.
Treatment of Viral Hepatitis C in Adults
The spectrum of disease in persons infected with HCV extends from mild fibrosis to cirrhosis and HCC. Compensated cirrhosis may progress over time to decompensated cirrhosis associated with ascites, oesophageal and gastric varices, and eventually to liver failure, renal failure and sepsis, all of which are life-threatening.
HCC may also occur at a rate of 2–4% per year in persons with cirrhosis. The diagnosis of decompensated liver disease is based on both clinical examination and laboratory monitoring, and therefore a careful medical examination of patients must be made prior to commencing therapy. The stage of disease may be assessed by liver biopsy or by using a variety of non-invasive methods.
Chronic HCV infection is the leading cause for end-stage liver disease (cirrhosis) and its complications including development of ascites, variceal bleeding, severe infections, etc, HCC and liver-related deaths worldwide. There is substantial economic burden if HCV patients are not treated. HCV is a major cause of morbidity globally, with estimated 495,000 deaths; in India, HCV infection was estimated to be responsible for 37,000 deaths in the year 2015.