MANAGEMENT OF HEPATITIS C

DR. MAZLAM MOHD. ZAWAWI

Hepatitis C virus (HCV) has an estimated prevalence of 3% globally, and approximately 170 million individuals are infected worldwide. It is the leading cause of known liver disease in Western countries giving rise to the most common cause of cirrhosis and hepatocellular carcinoma (HCC). In Malaysia the prevalence of hepatitis C is about 1.5% and amongst blood donors 0.3% is positive for anti-HCV. Screening for blood donation has been carried out since 1991 in the National Blood Bank(1). HCV is a RNA virus of the Flaviviridae family. There are 6 HCV genotypes (namely genotype 1,2, 3, 4, 5 & 6) and more than 50 subtypes. There are 4 genotypes found in Malaysia, with a distribution of genotype 1 (39%), genotype 2 (4%), genotype 3 (56%) and genotype 4 (1%)(2).

Hepatitis C virus has a high propensity to mutate. The lack of vigorous T-lymphocyte response appears to promote a high rate of chronic infection. The extensive genetic heterogeneity of HCV has important diagnostic and clinical implications; perhaps explaining difficulties in vaccine development and lack of response to therapy. HCV replicates primarily in hepatocytes but not directly cytopathic, thus leading to persistent infection (Figure 1).

The Natural History of Hepatitis C

After the exposure of the virus, patients are often asymptomatic. However, about 20% will develop acute hepatitis, some of whom will experience malaise, weakness and anorexia. Up to 85% of those exposed fail to clear the virus and go on to develop chronic hepatitis C. The ability of patients to rid themselves of the virus is partly related to the genotype of the virus, which affects the ability of the immune system to mount an effective response. The rate of progression of the disease is slow and variable, over 20-50 years.

About 20-30% of those infected developed advanced liver disease or cirrhosis within 20 years and a small percentage of these patients developed hepatocellular carcinoma. Patients with cirrhosis develop severe symptoms and complications. Patients with end stage liver disease or hepatocellular carcinoma (HCC) may require liver transplantation(3). (Figure 2).

Transmission of HCV

HCV transmission occurs primarily through exposure to infected blood. This exposure exists in the context of:
- Intravenous drug use (IVDU)
- Blood transfusion
- Solid organ transplantation from infected donors
- Unsafe medical practices
- Occupational exposure to infected blood
- Birth to an infected mother
- Multiple heterosexual partners or high-risk sexual practices

An audit of 119 hepatitis C cases seen in Hospital Kuala Lumpur during the years 1990-2000 indicated that the majority of patients (48.7%) were infected through blood transfusion(4).

Clinical Manifestation of Hepatitis C

After initial exposure, HCV RNA can be detected in blood in 1 to 3 weeks and is present at the onset of symptoms; usually manifested as malaise, weakness, anorexia and jaundice. Antibodies to HCV are detected by enzyme immunoassay (EIA) in only 50% to 70% of patients at the onset of symptoms. Within 2 to 8 weeks, elevation of serum alanine aminotransferase (ALT) is seen due to liver cell injury. Acute infection can be severe but rarely fulminant. Symptoms usually subside after several weeks as ALT declines (Figure 3).

Chronic HCV infection is diagnosed by the detection of HCV RNA at least intermittently in the blood by either qualitative or quantitative tests for a period of at least 6 months.

Diagnosis of patients with HCV
Most of the time, patients with hepatitis C is diagnosed by chance. Detection of antibodies against HCV (anti-HCV) in the circulating blood system indicates the patient has been infected. These antibodies are not the protecting antibodies, thus does not produce immunity to the patients against the virus. The diagnosis can be reconfirmed using qualitative or quantitative polymerase chain reaction (PCR) or transcription-mediated amplification (TMA) techniques to detect the presence of HCV RNA. Thus a patient with elevated ALT but is hepatitis B negative should warrant testing for hepatitis C.

Genotyping of virus
Genotyping the virus that the patients had is warranted before any initiation of therapy. This is due to different virus type responds differently to antiviral therapy. It was found that patients with genotype 2 or 3 virus have a better prognosis than those with genotype 1 or 4 virus. Thus, patients with genotype 2 or 3 viruses will only require 24 weeks of combination interferon-ribavirin or pegylated interferon-ribavirin treatment as compare to 48 weeks of antiviral treatment for patients with genotype 1 or 4 virus(8)

page 1 of 3

next page