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Impact of nucleos(t)ide analog treatment on the development of malignancy in patients with chronic hepatitis B.

ABSTRACT: We evaluated whether nucleos(t)ide analog (NA) influences the risk of non-hepatocellular carcinoma (non-HCC) malignancies in patients with chronic hepatitis B (CHB). A total of 9867 patients with CHB were followed up for ?12 months for the occurrence of any type of malignancy between 1998 and 2013. Patients who received NA for ?180 days were defined as the NA group. Propensity score matching produced the control (n?=?2220) and NA groups (n?=?2220) after adjustment for age, sex, and the presence of diabetes mellitus and liver cirrhosis. The National Health Insurance Service sample cohort dataset was used for external validation. Regarding non-HCC malignancies, only old age was an independent risk factor (>50 years; hazard ratio 3.17, 95% confidence interval 1.71-5.88, P?50 years old are encouraged to undergo surveillance for malignancies similar to the general population.

SUBMITTER: Kim SS

PROVIDER: S-EPMC6023687 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Impact of nucleos(t)ide analog treatment on the development of malignancy in patients with chronic hepatitis B.

Kim Soon Sun SS Ahn Eun Kyoung EK Cho Soo Yeon SY Park Rae Woong RW Cho Hyo Jung HJ Kim Ji-Hyun JH Kim Han Gyeol HG Lee Ga Ram GR Hwang Sun Hyuk SH Yang Min Jae MJ Cheong Jae Youn JY Cho Sung Won SW

Medicine 20180601 24

We evaluated whether nucleos(t)ide analog (NA) influences the risk of non-hepatocellular carcinoma (non-HCC) malignancies in patients with chronic hepatitis B (CHB). A total of 9867 patients with CHB were followed up for ≥12 months for the occurrence of any type of malignancy between 1998 and 2013. Patients who received NA for ≥180 days were defined as the NA group. Propensity score matching produced the control (n = 2220) and NA groups (n = 2220) after adjustment for age, sex, and the presence ...[more]

PMID: 29901622

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Project description:BackgroundChronic hepatitis B (CHB) patients have a high virological relapse rate after cessation of nucleos(t)ide analog (NA) treatment, but the clinical outcome remains unclear. This study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of NAs.MethodsThis study was a prospective trial; 74 eligible patients were enrolled. The patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver Guideline. Symptoms, biochemical (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, urea nitrogen, creatinine), virological data (hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B virus [HBV] DNA levels), and color Doppler ultrasound examination results were recorded and analysed.ResultsAfter NA cessation, 19 cases were HBsAg-negative without relapse during the 96-week follow-up. Of the 55 cases of HBsAg-positive after cessation, four types of clinical outcomes were observed. Twelve patients had no relapse during the 96-week follow-up (type A, 21.8%), 7 patients underwent virological relapses but spontaneously had a non-virological relapse (type B, 12.7%), 10 patients maintained virological relapse (type C, 18.2%), and 26 patients turned to clinical relapse, received NA retreatment, and achieved ALT normalization and negative conversion of HBV DNA within 12 months (type D, 47.3%). The 2-year overall cumulative rates of virological and clinical relapses were 58.1% and 24.3%, respectively. Independent factors associated with virological relapse were duration of negative HBV DNA, EOT (end of treatment) HBsAg, and original status of HBeAg. The EOT HBsAg was also an independent factor for clinical relapse.ConclusionsThere are four types of clinical outcomes in patients with CHB after cessation of NA treatment. Further research is needed to explore the mechanism of different clinical outcomes. The EOT HBsAg level is an independent factor associated with both virological and clinical relapse.

Project description:BackgroundGut dysbiosis is present in chronic hepatitis B virus (HBV) infection. In this study, we integrated microbiome and metabolome analysis to investigate the role of gut microbiome in virological response to nucleos(t)ide analogues (NAs) treatment.MethodsChronic HBV patients were prospectively recruited for steatosis and fibrosis assessments via liver elastography, with full-length 16S sequencing performed to identify the compositional gut microbiota differences. Fasting plasma bile acids were quantified by liquid chromatography-tandem mass spectrometry.FindingsAll patients (n = 110) were characterized into three distinct microbial clusters by their dominant genus: c-Bacteroides, c-Blautia, and c-Prevotella. Patients with c-Bacteroides had a higher plasma ursodeoxycholic acids (UDCA) level and an increase in 7-alpha-hydroxysteroid dehydrogenase (secondary bile acid biotransformation) than other clusters. In NAs-treated patients (n = 84), c-Bacteroides was associated with higher odds of plasma HBV-DNA undetectability when compared with non-c-Bacteroides clusters (OR 3.49, 95% CI 1.43-8.96, p = 0.01). c-Blautia was positively associated with advanced fibrosis (OR 2.74, 95% CI 1.09-7.31, p = 0.04). No such associations were found in treatment-naïve patients. Increased Escherichia coli relative abundance (0.21% vs. 0.03%, p = 0.035) was found in on-treatment patients (median treatment duration 98.1 months) with advanced fibrosis despite HBV DNA undetectability. An enrichment in l-tryptophan biosynthesis was observed in patients with advanced fibrosis, which exhibited a positive correlation with Escherichia coli.InterpretationCollectively, unique bacterial signatures, including c-Bacteroides and c-Blautia, were associated with virological undetectability and fibrosis evolution during NAs therapy in chronic HBV, setting up intriguing possibilities in optimizing HBV treatment.FundingThis study was supported by the Guangdong Natural Science Fund (2019A1515012003).

Dataset Information

Impact of nucleos(t)ide analog treatment on the development of malignancy in patients with chronic hepatitis B.

Publications

Impact of nucleos(t)ide analog treatment on the development of malignancy in patients with chronic hepatitis B.

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