Long-term health outcomes of chronic hepatitis C patients: A review of findings from REVEAL-HCV cohort study

Chronic hepatitis C affects more than 180 million people worldwide. As one of the most important infectious diseases, it causes around 250,000 deaths per year. A long-term follow-up cohort study is essential for evaluating health outcomes associated with virus infection, and for exploring potential seromarkers that have high predictability for risk of developing various diseases. However, the prospective cohorts consisted of individuals with chronic hepatitis C virus (HCV) infection are still rare. The Risk Elevation of Viral Load Elevation and Associated Liver Disease/Cancer in HCV (REVEAL-HCV) study has followed a cohort of 1095 residents seropositive for anti-HCV antibodies lived in seven townships in Taiwan for 15 years. These anti-HCV seropositives were asymptomatic and relatively more healthy than chronic hepatitis C patients cared in clinics and hospitals. Most of them acquired HCV infection through iatrogenic transmission routes in study townships. The epidemiological characteristics of HCV infection were very similar to those in countries with high prevalence such as Japan, Korea, Italy, and India. As the participants in the REVEAL-HCV study rarely received antiviral therapies, it provided an exceptional opportunity to study the natural history of chronic HCV infection. In this review article, we describe the details of participant enrollment, laboratory tests, follow-up procedures, and major recent findings. Anti-HCV seropositives with elevated serum HCV RNA levels were found to have an increasing risk of developing hepatocellular carcinoma in a dose-response relationship. In addition to the serum HCV RNA level, serum alanine aminotransferase levels and HCV genotype also had long-term predictability for the risk of hepatocellular carcinoma. Moreover, anti-HCV seropositives with detectable serum HCV RNA levels had an increased mortality from extrahepatic diseases such as cerebrovascular and renal diseases. Our study revealed that anti-HCV seropositives with detectable serum HCV RNA levels had an increased risk of hepatic and extrahepatic diseases.