The impact of antiviral therapy and the influence of metabolic cofactors on the outcome of chronic HCV infection.

Marcello Persico,Andrea Costantino,Piero Luigi Almasio,Savino Bruno,Marta Mazza

doi:10.4061/2011/314301

Abstract

Natural history of HCV related chronic hepatitis is influenced and modified by many factors: virus features, coinfections and host characteristics. In particular, a peculiar genetic background of the host by conditioning the occurrence of intracellular metabolic derangements (i.e., insulin resistance) might contribute to accelerate the rate of progression to cirrhosis and eventually the occurrence of hepatocellular carcinoma (HCC) and death. Likely, direct interplays between virus genotype and host genetic background might be hypothesized at this level. Morbidity and mortality in cirrhosis is primarily associated with complications of liver cirrhosis (ascites, hepatic encephalopathy, jaundice, and gastroesophageal bleeding) and HCC occurrence. Therefore the main goal of therapy is to clear viral infection and decrease liver necro-inflammation that directly relates to development of cirrhosis and HCC. Among patients treated with Interferon-based therapy, those with sustained viral response showed a significant reduction of progression to cirrhosis and development of HCC. However, a residual risk of hepatocellular carcinoma still remains indicating the need for careful follow-up using ultrasonography every six months in cirrhotic patients, even in those showing persistently normal ALT and undetectable HCV RNA levels after antiviral therapy.

Highlights

IntroductionThe natural history of HCV infection is usually characterized by the transition from no perceivable acute to chronic infection, which may progress from a long-lasting asymptomatic condition up to a decompensated hepatic disease and/or hepatocellular carcinoma (HCC) development, which represents the main cause of liver-related death and liver transplantation in the Western World [1,2,3,4,5] (Figure 1)
Direct interplays between virus genotype and host genetic background might be hypothesized at this level
Morbidity and mortality in cirrhosis is primarily associated with complications of liver cirrhosis and hepatocellular carcinoma (HCC) occurrence

Summary

Introduction

The natural history of HCV infection is usually characterized by the transition from no perceivable acute to chronic infection, which may progress from a long-lasting asymptomatic condition up to a decompensated hepatic disease and/or hepatocellular carcinoma (HCC) development, which represents the main cause of liver-related death and liver transplantation in the Western World [1,2,3,4,5] (Figure 1). Since the availability of effective therapies has led to treat patients, the outcome and natural history of untreated people in order to analyse the events, their timing, and type of evolution has not been fully evaluated [6,7,8,9,10,11,12]. Another essential phenomenon that has hampered the difficulty to obtain reliable information of the progression of the disease is because many cofactors can change the rate of progression of the disease. Based on the statistical concept of “analysis by segments,” a typical approach for the cohort studies, the progression of HCV infection can be designed as the sequence of different, limited, and of presumably known duration stages of the disease

Natural History of HCV Infection

The Natural Course of HCV-Induced Cirrhosis

The Impact of Antiviral Therapy on Natural Course of the Disease

Findings

Summary