Disease Management

Long-Term Consequences of Hepatitis C

Progression of Liver Damage

Patients with chronic HCV infection can succumb to liver damage, which can progress over a period of 10 to 50 years: fibrosis can develop into cirrhosis, with those with severe liver damage or even hepatic carcinoma requiring a liver transplant, as illustrated in the figure below.

Figure 2-1: Demonstrating hepatitis C disease progression without treatment

Figure demonstrating hepatitis C disease progression without treatment

Click image to enlarge

Cirrhosis (scarring of the liver tissue)

Cirrhosis of the liver is the term used when hardened, diseased liver cells replace healthy liver cells. This blocks the passage of blood and prevents the liver from working normally. Although cirrhosis has numerous causes, the most common are alcoholism and hepatitis C. About 5–30% of people initially infected will develop cirrhosis within 20 years and a percentage of these are consequently at high risk of developing hepatocellular carcinoma. The only treatment option for people with end-stage liver disease or hepatocellular carcinoma is liver transplantation.1

The early stages of cirrhosis are not usually apparent. However, as the proportion of hardened scar tissue offsets healthy tissue, symptoms emerge including:

The physical findings of cirrhosis may include:

Established cirrhosis can develop into what is known as decompensated liver disease, with complications such as jaundice, ascites, bleeding from oesophageal varices (swollen veins in the oesophagus) and encephalopathy (brain disease), rapidly resulting in end-stage liver disease requiring a liver transplant.

Figure 2-2: Photograph of a healthy and diseased liver

Photograph of a health and a disease liver

Initially, patients with cirrhosis had a poor response to antiviral therapy. More recent medications, however, have improved response rates dramatically.2

Figure 2-3: Development of cirrhosis

Development of cirrhosis

Recent studies suggest that treating patients with cirrhosis with antiviral  drug therapies can result in improved liver health. This in turn results in fewer complications, less recurrence of liver cancer and prolonged survival,3 thereby highlighting the importance of treatment in this challenging patient group.

Liver Cancer

Liver cancer (or hepatocellular carcinoma, HCC) is the fifth most common cancer in the world. It develops in 1 to 5 per cent of people per year who have cirrhosis due to chronic hepatitis C.7 Several studies have reported that the incidence of HCC in people with HCV and cirrhosis ranges from 2 to 5 per cent per year.4 In Japan, 75 per cent of patients with HCC test positive for HCV.The average time to develop HCC after HCV exposure is 30 years.34 However, patients with liver cancer typically do not live for more than 2 years after diagnosis.5

Damage to Other Parts of the Body

Although hepatitis C is most often associated with damage to the liver, up to 38 per cent of patients suffer symptoms related to other parts of the body.6 Incidence appears to vary with genotype. Called extrahepatic manifestations, these disorders are thought to arise from an interaction between the hepatitis C virus and the patient’s immune system, although scientists do not yet know exactly what is involved. Extrahepatic disorders include:8

1. Hoofnagle JH. Hepatitis C: the clinical spectrum of disease. Hepatology 1997;26 (3 Suppl 1):15S-20S.
2. Houghton M. Hepatitis C viruses. 3rd ed. Philadelphia: Lippincott-Raven; 1996. 
3. Bruno S, Stroffolini T, Bollani S. Long-term outcome of patients with HCV-related, Child’s class A cirrhosis treated with interferon-Alpha (IFN): the impact of sustained virologic response (SVR) on hepatocellular carcinoma (HCC) occurrence and mortality. Hepatology 2005;42:229A-30A.
4. Marcellin P. Hepatitis C: the clinical spectrum of the disease. J Hepatol 1999;31 (Suppl 1):9-16.
5. Colombo M. The role of hepatitis C virus in hepatocellular carcinoma. Recent Results Cancer Res 1998;154:337-44.
6. Mayo MJ. Extrapepatic manifestations of hepatitis C infection. Am J Med Sci 2003;325(3):135-48.
7. Global surveillance and control of hepatitis C. Report of a WHO consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hepat 1999;6(1):35-47.
8. National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C; June 10-12, 2002. Hepatology 2002;36 (5 Suppl 1):S3-20.