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Natural history of hepatitis C
K Kiyosawa1, E Tanaka, T Sodeyama
1Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Insights
Most adult hepatitis C virus (HCV) infections become chronic, rarely resolving spontaneously. Understanding HCV
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Hepatitis C virus (HCV) infection often progresses from acute to chronic hepatitis in adults.
- Spontaneous clearance of chronic hepatitis C is rare (less than 2%).
- HCV chronicity can lead to liver cirrhosis and hepatocellular carcinoma over decades.
Purpose of the Study:
- To describe the natural history and phases of hepatitis C virus (HCV) infection.
- To explore potential mechanisms behind HCV chronicity.
Main Methods:
- Review of diagnostic tools for evaluating HCV natural course.
- Analysis of clinical phases: acute, silent, and reactivated.
- Consideration of molecular mechanisms, including viral mutations.
Main Results:
- Acute hepatitis C progresses to chronic in 68% of adult cases.
- The disease progresses through distinct phases: acute (2-3 years), silent (10-15 years), and reactivated.
- Elevated aminotransferase levels characterize the reactivated phase, preceding liver cancer.
Conclusions:
- The long-term clinical course of hepatitis C is characterized by distinct phases.
- The precise mechanism of HCV chronicity remains under investigation.
- Viral mutations in the E2/NS1 hypervariable domain may facilitate immune evasion and chronicity.
Abstract:
With advances in tools for the diagnosis of hepatitis C virus (HCV) infection, it has become easier to evaluate the natural course of hepatitis C. Although HCV infection initially occurs in adult individuals, in most patients with acute hepatitis C (68%) it develops into chronic hepatitis. Once chronic hepatitis is established, the rate of spontaneous cure of the liver disease is very rare (below 2%). The duration from the onset of acute hepatitis until the time of diagnosis of cirrhosis of the liver and of hepatocellular carcinoma is about 20 and 30 years, respectively. The long-term clinical course of hepatitis C is divided into the three phases of acute, silent, and reactivated. The acute phase lasts from the onset of disease until 2-3 years thereafter, and the silent phase which follows lasts for 10-15 years. In the silent phase, the serum transferase level remains relatively low, below 100 IU/l, and is sometimes within the normal range. In the reactivated phase, the level of serum aminotransferase increases and remains at a high or moderate level until hepatocellular carcinoma develops. The mechanism of the chronicity of hepatitis C is unknown. However, recent advances in molecular analysis may soon elucidate this. Successive antigenic change of the HCV E2/NS1 hypervariable domain as a result of mutations may represent a mechanism by which this virus escapes the host immunosurveillance system, as well as a mechanism of its chronicity.