Is genotype 3 of the hepatitis C virus the new villain?

Abstract

Genotype 3 of the hepatitis C virus (HCV) has been long considered an easy-to-treat infection, with higher cure rates ( 70%) than other viral genotypes with the standard combination of pegylated interferon-a and ribavirin. However, the relative insensitivity of this genotype to most protease inhibitors and the recent unexpected data on decreased effectiveness of sofosbuvir have raised questions on how to achieve universal cure, a goal that seems reasonable for other genotypes. In addition, increasing clinical and experimental data show that HCV genotype 3 may be associated not only with severe steatosis, but also with accelerated fibrosis progression rate and increased oncogenesis. Conclusion: Currently available data suggest that we should increase our efforts to understand the virology and pathogenesis of HCV genotype 3, aiming at better and more potent, genotype-targeted treatments. (HEPATOLOGY 2014;59:2403-2412 A pproximately 185 million people are infected worldwide with the hepatitis C virus (HCV). 1 HCV is a major human pathogen causing progressive liver damage, culminating in cirrhosis and hepatocellular carcinoma (HCC), and various extrahepatic complications, ranging from type 2 diabetes to cardiovascular disorders. 2 HCV has a positive singlestranded RNA genome, characterized by a high heterogeneity, leading to classification of HCV isolates in at least seven genotypes and several subtypes. 3,4 Genotype 1 is the most prevalent genotype worldwide, accounting for 60% of the global infections, with a higher proportion of subtype 1b in Europe and 1a in the USA. Genotype 2 is found in the Mediterranean region and in some parts of Africa and the Americas. Genotype 3 is highly prevalent in the European population of intravenous drug users, and in a large proportion of patients-irrespective of risk factor-in Southern Asia. Overall, it is estimated that about 10-15% of the world HCV reservoir is accounted for by genotype 3. 5 Genotype 4 is the most prevalent type in the Middle East and in sub-Saharan Africa, and has spread to a significant proportion of infected persons across Europe, especially in drug users. Genotypes 5 and 6 are rare and concentrated in isolated clusters in France, Belgium, Syria, and Southern Africa. 6 The novel genotype 7 was identified in rare patients from Canada and Belgium, possibly infected in Central Africa. 4 The identification of HCV genotypes and subtypes is of obvious epidemiological interest. In addition, genotyping is critical to select the type and duration of antiviral therapy, due to a different response to antiviral therapy. Thus, genotype 1 has been considered, until now, the most difficult to treat genotype, with sustained virological response (SVR) rates of 50% with a dual therapy based on the combination of pegylated interferon-a and ribavirin, 7-9 only recently increasing to 70% with the addition of a protease inhibitor. 10,11 Dual therapy reaches higher SVR rates in genotypes 2 and 3 ( 70-80%) and intermediate rates in patients with genotype 4. Finally, some viral gen...

Concurrent Obesity, Diabetes, and Steatosis Increase Risk of Advanced Fibrosis Among HCV Patients: A Systematic Review

“…However, the impact of increasing BMI on risk of obesityrelated diseases is not uniform across all populations, and the definition of obesity differs by race/ethnicity, reflecting differences in fat deposition and degree of visceral adiposity associated with weight gain [27]. While many guidelines, including US guidelines, utilize a BMI cutoff of 30 kg/m 2 to define obesity, it is well recognized that the Previous studies have reported on the association of HCV genotype 3 with concurrent HCV-related steatosis [29,30]. More recently, it is becoming evident that HCV genotype 3 is also associated with higher risk of progression to cirrhosis and hepatocellular carcinoma [31,32].…”

PCSK9, apolipoprotein E and lipoviral particles in chronic hepatitis C genotype 3: Evidence for genotype-specific regulation of lipoprotein metabolism

“…HCV genotype 3 (HCV-G3) is the dominant genotype circulating in the UK and Southern Asia, and is most commonly found in European intravenous drug users [2]. Globally, it is estimated to account for 10-15% of the total number of HCV infections [3].…”

Factors Associated with Failure to Achieve SVR in Hepatitis C Genotype 3 Patients Within an Integrated Care Delivery System

“…16 It is increasingly reported that HCV genotype 3 is more difficult to treat than previously thought and is associated with higher rates of complications than most other genotypes. 9,26,27 Two recent reviews that focused exclusively on HCV genotype 3 concluded that these patients are at increased risk for rapid progression of liver disease (steatosis, fibrosis, and hepatocellular cancer) and that efforts should be made for more efficacious and targeted genotype 3 treatments. 26,27 The results of our study, which evaluated dual therapy with PegINF and ribavirin …”