Viral hepatitis update: Progress and perspectives.

Viral hepatitis, secondary to infection with hepatitis A, B, C, D, and E viruses, are a major public health problem and an important cause of morbidity and mortality. Despite the huge medical advances achieved in recent years, there are still points of conflict concerning the pathogenesis, immune response, development of new and more effective vaccines, therapies, and treatment. This review focuses on the most important research topics that deal with issues that are currently being solved, those that remain to be solved, and future research directions. For hepatitis A virus we will address epidemiology, molecular surveillance, new susceptible populations as well as environmental and food detections. In the case of hepatitis B virus, we will discuss host factors related to disease, diagnosis, therapy, and vaccine improvement. On hepatitis C virus, we will focus on pathogenesis, immune response, direct action antivirals treatment in the context of solid organ transplantation, issues related to hepatocellular carcinoma development, direct action antivirals resistance due to selection of resistance-associated variants, and vaccination. Regarding hepatitis D virus, we describe diagnostic methodology, pathogenesis, and therapy. Finally, for hepatitis E virus, we will address epidemiology (including new emerging species), diagnosis, clinical aspects, treatment, the development of a vaccine, and environmental surveillance.

Chronic hepatitis B: The interplay between intrahepatic lymphocyte population and viral antigens in relation to liver damage.

In Chronic hepatitis B (CHB) infection, virus and immune response interplay is thought to be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (T-bet+)] and viral antigen expression (HBsAg and HBcAg). Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system. All studied populations were identified in the portal-periportal (P-P) areas with a CD4+ lymphocyte predominance, while only CD8+ and FoxP3+ cells were observed in the intralobular area. Both P-P CD4+ and intralobular CD8+ cell frequencies were increased among severe hepatitis cases. Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was observed. HBcAg was mainly detected among HBeAg-positive patients and was associated with hepatitis severity and higher frequency of P-P FoxP3+, intralobular CD8+ and FoxP3+ cells. HBsAg was identified among HBeAg-negative cases with less severe hepatitis grade and lower frequency of P-P CD4+ and intralobular FoxP3+ lymphocytes. In conclusion, the HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication which impacts the host immune response and liver damage process. While HBcAg might be an inducer of a regulatory microenvironment, the intralobular CTL population seemed to have a key role in hepatitis severity.