Genotype may correlate with liver carcinogenesis and tumor characteristics in cirrhotic patients infected with hepatitis B virus subtype adw

Abstract

To identify the influence of hepatitis B virus (HBV) genotype on development of hepatocellular carcinoma (HCC) and clinical outcome in chronic HBV infection, 26 consecutive cirrhotic patients infected with HBV subtype adw were investigated prospectively. HBV serology was undertaken using subtype-specific antibodies against hepatitis B surface antigens. The HBV genotype was determined by sequencing directly the polymerase chain reaction products of the HBV S gene. When HCC occurred, patients underwent transcatheter arterial embolization therapy. If tumor necrosis was incomplete, additional embolization therapy was carried out after a 3- to 4-month interval. At a median follow-up of 14.1 years (range 2.2 to 31.7), HCC occurred in 9 (35%) of 26 patients. Nineteen patients were infected with genotype B and 7 with genotype C. Four of the 19 genotype B patients (21%) and 5 of the 7 genotype C patients (71%) developed HCC (P = 0.058). Patient age (<45 years or 45 < or = ) at diagnosis of cirrhosis was the only significant independent factor influencing liver carcinogenesis by multiple logistic regression analysis and Cox's regression analysis (P = 0.0069 and 0.029, respectively). When analysis was limited to the age of 45 years or more at the last visit, genotype was the only contributory factor to HCC development by univariate analysis (P = 0.038). Whereas genotype B patients responded well to embolization therapy and had no recurrence of HCC for a prolonged period of time, genotype C patients showed poor responses and died of hepatic failure due to rapid HCC progression despite embolization therapy. The cumulative incidence of survival was significantly higher in the genotype B group (P = 0.0049). The HBV genotype correlated with the development of HCC, response to embolization therapy, and recurrence of HCC. Determination of HBV genotype may be useful in predicting outcomes in HBV subtype adw-related cirrhosis.

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

“…For example, HBV genotypes C and D are more difficult to treat than genotypes A and B [113,114]. There is also some evidence suggesting an increased pathogenicity of genotype C over B, with a greater likelihood of developing HCC [115,116].…”

Prevalence of HBV-genotypes in immigrants affected by HBV-related chronic active hepatitis

“…Some studies have recently suggested that the HBV genotype is correlated with the clinical features of HBV infection and with the response to antiviral treatments. In fact, with regard to genotypes B and C, which are prevalent in Asia, genotype C has been shown to be more frequently found in severe liver disease and in hepatocellular carcinoma and it presents a lower response rate to interferon alfa therapy, while genotype B is associated with faster HbeAg/antiHBe seroconversion (4,5,6,8,18,20) . During treatment with lamivudine, YMDD variants seem to appear faster in genotype A patients than genotype D but appear earlier in genotype D (19) .…”

Construction and expression of eukaryotic plasmids containing lamivudine-resistant or wild-type strains of Hepatitis B Virus genotype C

“…HBV genotype C is associated with more severe histological liver damage and low-grade responses to interferon therapy [22] . Moreover, patients with genotype C show poor responses to embolization therapy and may die from hepatic failure because of rapid hepatocellular carcinoma (HCC) progression [23] . Another study has reported that HBV genotype C has more rapid selection of lamivudine resistance than genotype B [17] .Therefore, further studies of HBV YMDD mutants with genotype C are of great significance.…”