Diagnosis and treatment of hepatitis C
Authors: R. D'Souza, G. R Foster
Journal: Journal of the Royal Society of Medicine (2004)

The identification of hepatitis C virus (HCV) in 19891 illuminated many dark corners in the natural history of the infection formerly known as non-A, non-B hepatitis. Chronic infection with HCV, we now know, affects more than 170 million people worldwide, and up to 90% of these will progress to chronic liver disease.2 Prevalence rates of infection range from 0.5-2% in the developed world, through 6.5% in parts of equatorial Africa, to as high as 20% in Egypt. The virus is transmitted by blood-to-blood contact and most infections in the Western world were acquired either through intravenous drug abuse or, before the advent of anti-HCV screening in 1992, through transfusion of blood or blood products. A high proportion of individuals with HCV infection in the USA3 and the UK were infected 20-25 years ago by sharing of drug injection equipment, so we face a substantial rise in the prevalence of end-stage liver disease. In the UK, between 200 000 and 400 000 individuals are believed to harbour the infection, most of whom have yet to be diagnosed. In developing countries the principal vehicle of transmission is inadequately sterilized medical equipment,4,5 and the high prevalence in Egypt may be attributable to lack of hygiene in schistosomiasis prevention programmes after the Second World War.6 Sexual transmission contributes few cases,7 and vertical transmission is likewise uncommon (< 6% of children becoming HCV-positive) unless the mother has high viraemia or is coinfected with HIV.8 The virus has not been shown to be transmitted by breast feeding.

Within 30 years after HCV infection nearly one-third of patients have developed cirrhosis. Independent factors associated with rapid progression to fibrosis include age at infection greater than 40 years, daily alcohol consumption 50 g or more and male sex.9 Other possible factors are immunodeficiency (for example due to HIV) and coinfection with hepatitis B virus.

Infection with the hepatitis C virus results in extrahepatic as well as hepatic diseases. In a minority of patients the first sign is an acute syndrome resembling other forms of acute hepatitis. The mean incubation period is 7 weeks and symptoms last 2-12 weeks. Patients with chronic HCV are often symptom-free, but fatigue, muscle aches, anorexia, and right upper quadrant pain do occur. Disorders linked to the infection include autoimmune hepatitis, Sjogren's syndrome, lichen planus, thyroiditis, membranous glomerulonephritis, polyarteritis nodosa, and essential mixed cryoglobulinaemia.10,11 Hepatocellular carcinoma is commonly associated with chronic HCV infection—probably as a consequence of cirrhosis or chronic necroinflammation rather than a direct carcinogenic effect.12

Individuals with suspected HCV infection should be tested for virus antibody by enzyme-linked immunosorbent assay (ELISA).13 If antibody is detected or the patient is thought to be at risk despite negative or indeterminate serological tests, viraemia should be sought by polymerase chain reaction (PCR). A liver biopsy provides the best measure of the extent of disease—routine liver tests correlate poorly with both necroinflammatory and fibrosis scores—and is also useful for excluding other diagnoses such as alcohol-induced liver disease. All patients with chronic HCV should be considered for treatment. The goal of treatment is to achieve a sustained virological response (PCR-negativity 6 months after the end of treatment).14 In the first interferon trials, subcutaneous interferon alpha three times a week achieved sustained virological responses in 12-16% of patients. Addition of ribavirin then raised response rates to 35-45%,15,16 and the results have since been further improved (50-60%) by use of pegylated interferons.17 Variables that favour a sustained response to therapy include low pretreatment HCV RNA levels, HCV genotype 2 or 3, female sex, younger age, less hepatic fibrosis on liver biopsy and lower body weight.18 Patients with chronic HCV infection should be warned that alcohol abuse speeds progression to cirrhosis and hepatocellular carcinoma.10