Co-infection with hepatitis B virus and hepatitis C virus

Abstract

The hepatitis B virus (HBV) and the hepatitis C virus (HCV) share common transmission pathways. Therefore, co-infection can be expected. The World Health Organization estimates that, worldwide, 170 million people are infected with HCV, and 350 million people are infected with HBV. However, the number of individuals co-infected with both viruses is unknown. Although various studies have evaluated small numbers of co-infected individuals, the inclusion criteria, parameters assessed, and study designs are not uniform. In addition, ethnicity, local epidemiology, and viral genotypes are also diverse. Therefore, the conclusions of a specific study, in principle, should not be widespread. In cases of co-infection with HBV and HCV, the replication of either virus can be inhibited, just as either virus can be dominant or the dominance can alternate between the two. It is more common for HBV to appear to be suppressed by HCV. The chronologies of the two infections have an influence on which virus will be dominant. Molecular biology techniques (to determine levels of HCV RNA and HBV DNA) have facilitated the definition of the interaction between the two viruses. Co-infections can appear in various manners: a) Simultaneous acute infection with HBV and HCV: presupposes same source and transmission pathway. The number of studies is small, but indicates that the interaction between the two viruses is similar to that which occurs in chronic infections. There are descriptions of cases in which there is a delay in the identification of the Hepatitis B surface antigen (HBsAg), lower levels of alanine aminotransferase (ALT), and lower HBV antigenemia, which can be attributed to suppression of HBV activity by HCV. b) Superinfection by one virus, the other virus being chronically present: it should be suspected above all in individuals with risk factors, such as the use of illicit intravenous drugs, multi-transfused individuals, and those living in areas of high HBV prevalence. Superinfection by HCV: infection by HCV in a patient that is already infected with HBV. This is known in Asian countries, where the prevalence of HBV is high. The viral suppression of the HCV may occur, although the viral suppression of the HBV is more frequent, noted by lower levels of HBV DNA and lower DNA polymerase activity, as well as by the hepatic expression of HBsAg and hepatitis B core antigen (HBcAg), clearance of the hepatitis B e antigen (HBeAg) or even of the HBsAg. The HCV core antigen seems to affect the transcription of HBV and, as a result, its replication, which is reported to be more accentuated for the HCV genotype 1. After HBV clearance, HCV can persist, resulting in chronic hepatitis. In addition, there is the possibility of evolution to severe disease, with a risk of death. Superinfection by HBV: infection by HBV in an individual that is already chronically infected with HCV. The HCV RNA levels are lower, and, in a study conducted in Italy, HCV clearance was higher in co-infected individuals (71%) than in mono-infected individuals (14%). However, the HBV DNA levels can be lower than those of mono-infected individuals, indicating HCV interference. Therefore, one virus can induce the clearance of another. The evolution to severe forms of the disease, with fulminant hepatitis profiles, has also been described. c) Asymptomatic infection with HBV: there are reports of patients infected with HCV, with low levels of HBV DNA, reactive anti-HBc, however, non-reactive HBsAg, HBeAg, anti-HBe, and anti-HBs, configuring co-infection with HCV with asymptomatic HBV. These individuals evolve with high ALT levels and high histological activity. There are reports in which biopsies from such patients were evaluated, and cirrhosis was found in 33% of the cases, compared with 19% for patients presenting chronic mono-infections. The data suggest that the evolution of the disease is more severe in co-infected individuals. There are various potential outcomes: