HBsAg seroclearance in chronic hepatitis B in the Chinese: Virological, histological, and clinical aspects (original) (raw)
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Clinical microbiology, 2012
The ultimate goal of antiviral treatment is prevention of hepatocellular carcinoma (HCC). Currently the end point of successful antiviral treatment for patients with chronic hepatitis B is to achieve HBsAg loss or HBsAg seroconversion. We report two patients who successfully developed anti-HBs with or without antiviral therapy and yet developed HCC. Initial commercial assay showed negative HBV DNA for both patients. However, they were found to have detectable HBV DNA by a new laboratory-developed HBV DNA assay. These cases show that patients with HBsAg seroclearance continue to be at risk for HCC and surveillance for HCC should be continued. The diagnosis of occult hepatitis B with an improved HBV DNA assays is also necessary as it is important for treatment for chronic HBV and prevention of HCC.
Journal of hepatology, 2014
Little is known about whether surveillance for hepatocellular carcinoma (HCC) is worthwhile in chronic hepatitis B virus (HBV)-infected patients who have achieved HBsAg seroclearance. A retrospective analysis of 829 patients (mean age, 52.3 years; 575 male; 98 with cirrhosis) achieving HBsAg seroclearance was performed at a tertiary hospital in Korea between 1997 and 2012. We evaluated incidence rates of HCC, and validated CU-HCC score based on data at the time of HBsAg seroclearance. During a follow-up of 3,464 patients-years, 19 patients developed HCC (annual rate: 0.55%). Liver cirrhosis (hazard ratio [HR], 10.80; 95% confidence interval [CI], 4.25-27.43), male gender (HR, 8.96; 95% CI, 1.17-68.80), and age ⩾ 50 years at the time of HBsAg seroclearance (HR, 12.14; 95% CI, 1.61-91.68) were independently associated with HCC. The estimated annual incidence of HCC was 2.85% and 0.29% in patients with and without cirrhosis, respectively. Among the non-cirrhotic patients, the annual ra...
Hepatology, 2007
Nine HBeAg+ and 24 anti-HBe+ subjects with chronic hepatitis B virus (HBV) infection were studied for HBV DNA in the serum by molecular hybridization, for HBcAg in the liver by immunofluorescence, and for histologic evidence of liver disease. All HBeAg+ patients had underlying chronic liver disease (chronic persistent hepatitis, chronic active hepatitis, or cirrhosis with or without hepatocellular carcinoma), and all were found positive for both HBV DNA in the serum and HBcAg in the nucleus of hepatocytes. Of the 24 anti-HBe+ individuals, 18 had various forms of chronic liver disease. Six HBsAg+/anti-HBe+ patients had normal liver histology except for numerous "ground-glass" hepatocytes with abundant cytoplasmic HBsAg. All six were negative for nuclear HBcAg and serum HBV DNA, but three showed HBV DNA which appeared to be integrated into unique sites in host liver DNA by hybridization analysis. In contrast, 14/18 (78%) of HBsAg+/anti-HBe' patients with chronic liver disease were positive for nuclear HBcAg, serum HBV DNA, or both of these markers of HBV replication. It is suggested that in long-term HBsAg carriers with serum anti-HBe and normal liver histology, viral replication is suppressed or inactive and HBV potential infectivity is presumably very low or absent. However, when viral replication is present in HBsAg+/anti-HBe+ carriers (as demonstrated by serum HBV DNA and/or nuclear HBcAg) active liver disease is often found. In these individuals, active chronic liver disease appears to be related to continued replication and secretion of HBV and may occur in a much higher proportion of HBsAg+/anti-HBe+ carriers than was previously suspected.
Euroasian Journal of Hepato-Gastroenterology, 2011
Background: There is lack of consensus if hepatitis B virus (HBV) DNA can be regarded as a surrogate marker of liver damages in patients with chronic hepatitis B (CHB). Methods: A total of 77 patients with CHB were enrolled in this study. The sera of the patients were tested for HBV DNA and hepatitis B e antigen (HBeAg). The extent of hepatitis and hepatic fibrosis was assessed by liver biopsy. Results: Out of total of 77 patients with CHB, 29 were HBeAg-positive and 48 were HBeAg-negative. Twenty-seven of 29 HBeAg-positive patients and eight of 48 HBeAg-negative patients had high levels of HBV DNA (HBV DNA>10 5 copies/ml). The extent of hepatitis was minimal or mild in most HBeAg-positive CHB patients (27 of 29) irrespective of the levels of HBV DNA in the sera. Moderate levels of hepatitis were seen in two HBeAg-positive patients and five HBeAg-negative patients. Moderate levels of hepatic fibrosis were seen in four of eight HBeAg-negative patients with high HBV DNA. Conclusion: This study shows that HBV DNA and HBeAg do not reflect the extent of hepatitis or hepatic fibrosis in CHB patients of Bangladesh. Combination of different HBV-related markers with liver biopsy is required for proper diagnosis and management of CHB in Bangladesh.
Clinical Gastroenterology and Hepatology, 2019
BACKGROUND & AIMS: In some individuals with undetectable serum levels of hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA can still be detected in serum or hepatocytes and HBV replicates at low levels-this is called occult HBV infection (OBI). OBI has been associated with increased risk of hepatocellular carcinoma (HCC). We investigated the incidence of OBI in patients with HCC and other liver diseases. We also investigated whether, in patients with OBI and HCC, HBV DNA has integrated into the DNA of hepatocytes. METHODS: We collected clinical information and liver tissues from 110 HBsAg-negative patients (90 with HCC and 20 without HCC; median ages at surgical resection and biopsy collection, 64.1 and 48.6 years, respectively) who underwent liver resection or liver biopsy from November 2002 through July 2017 in Hong Kong. HBV DNA and covalently closed circular DNA (cccDNA) were analyzed and quantified by PCR in liver tissues. Integration of HBV DNA into the DNA of liver cells was detected by Alu-PCR. RESULTS: Of the 90 HBsAg-negative patients with HCC, 18 had alcoholic liver disease (20%), 14 had nonalcoholic fatty liver disease or steatohepatitis (16%), 2 had primary biliary cholangitis, 2 had recurrent pyogenic cholangitis, 1 had autoimmune hepatitis, and 53 had none of these (59%). Among the 20 patients without HCC, 7 had non-alcoholic fatty liver disease or steatohepatitis, 7 had primary biliary cholangitis, and 6 had autoimmune hepatitis. OBI was detected in 62/90 patients with HCC (69%) and 3/20 patients without HCC (15%) (P < .0001). cccDNA was detectable in liver cells of 29 patients with HCC and OBI (47%) and HBV DNA had integrated into DNA of liver cells of 43 patients with HCC and OBI (69%); cccDNA and integrated HBV DNA were not detected in the 3 patients who had OBI without HCC. There were 29 patients with integration of HBV DNA among 33 patients with undetectable cccDNA in liver tissues (88%) and 14 patients with integration of HBV DNA among the 29 patients with cccDNA in liver tissues (48%) (P [ .001). HBV DNA was found to integrate near genes associated with hepatocarcinogenesis, such as those encoding telomerase reverse transcriptase, lysine methyltransferase 2B, and cyclin A2. Among the 43 patients with integration of HBV DNA, 39 (91%) did not have cirrhosis. CONCLUSIONS: In an analysis of clinical data and liver tissues from 90 HBsAg-negative patients with HCC, we found that almost 70% had OBI, of whom 70% had integration of HBV DNA into liver cell DNA; 90% of these patients did not have cirrhosis. HBV DNA integrated near hepatic oncogenes; these integrations might promote development of liver cancer.
Hepatology, 2003
The pathologic role of hepatitis B virus (HBV) genotype in Chinese patients with HBV infection is largely unknown. We examined the relationship between HBV genotypes, and hepatitis B e antigen (HBeAg) seroconversion, acute exacerbation, cirrhosis-related complications, and precore/core promoter mutations. Three hundred forty-three HBV patients (288 were asymptomatic, 55 presented with cirrhosis-related complications) were recruited. HBV genotypes and precore/core promoter mutations were determined by line probe assays. Genotypes B and C were the 2 most common genotypes, contributing 28% and 60%, respectively. The median age of HBeAg seroconversion for patients with genotype B was 9 years earlier than patients with genotype C (P ؍ .011). There were no differences in the liver biochemistry, HBV DNA level, and cumulative risk of acute exacerbation (defined as increased alanine aminotransferase level >1.5 ؋ upper limit of normal) between patients with genotypes B and C. There was a trend for patients with genotype B to have a higher cumulative rate of HBeAg seroconversion compared with patients with genotype C at the initial follow-up of 6 years (P ؍ .053), but this difference became insignificant during subsequent follow-up. The prevalence of both genotypes was the same in patients with and without cirrhosis-related complications and/or hepatocellular carcinoma. Genotype B was associated with precore mutations (P < .0001), whereas genotype C was associated with core promoter mutations (P < .0001). In conclusion, although patients with genotype B had earlier HBeAg seroconversion, there was no significant reduction in the risk of development of complications. Genotypes B and C are associated with high prevalence of precore and core promoter mutations, respectively. (HEPATOLOGY 2003;37:562-567.) Abbreviations: HBV, hepatitis B virus; HBeAg, hepatitis B e antigen; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface antigen; anti-HBe, antibody to HBeAg; ALT, alanine aminotransferase; ULN, upper limit of normal. From the