Steatohepatitis in Chronic Hepatitis B

NCT05317260 | Completed

• 1 other identifier: 043/2560(EC2)
• Study Type: observational
• Target: 408
• Locations: 1 country
• Sites: 1

Brief Summary

Fatty liver disease is increasingly recognized in patients with chronic hepatitis B (CHB). Whether concurrent fatty liver disease affects the long-term outcomes of CHB is unclear. The investigators performed a longitudinal study to investigate the prognostic relevance of concurrent fatty liver disease for patients with CHB receiving antiviral therapy.

Conditions

Fatty Liver; Chronic Hepatitis b

Outcome Measures

Primary Outcomes (1)

• Overall mortality

  Death from any cause

  From date of liver biopsy until the date of liver transplantation or date of death from any cause, whichever came first, assessed up to 22 years

Secondary Outcomes (1)

• Liver-related complications

  From date of liver biopsy until the date of first documented liver-related complications, whichever came first, assessed up to 22 years

Study Arms (3)

Chronic hepatitis B patients without hepatic steatosis

Patients with chronic hepatitis B will be defined as the non-steatosis group if they had histological evidence of visible lipid droplets in hepatocytes less than 5%.

Drug: Antiviral Agents

Chronic hepatitis B with steatosis but no steatohepatitis

Patients with chronic hepatitis B will be categorized as the steatosis but not steatohepatitis group if they had histological evidence of visible lipid droplets in hepatocytes more than 5% in the absence of steatohepatitis feature.

Drug: Antiviral Agents

Chronic hepatitis B patients with steatohepatitis

Patients with chronic hepatitis B will be classified as the steatohepatitis group if they had histological evidence of steatosis, hepatocyte ballooning, mixed lobular acute and chronic inflammation, and intra-acinar perisinusoidal fibrosis according to Brunt's classification.

Drug: Antiviral Agents

Interventions

Antiviral Agents DRUG

The type of antiviral agents for the individual patient was selected by physicians based on a policy to reimburse a patient's health and comorbidity.

Also known as: Nucleoside analogue, Nucleotide analogue, Peginterferon

Chronic hepatitis B patients with steatohepatitis; Chronic hepatitis B patients without hepatic steatosis; Chronic hepatitis B with steatosis but no steatohepatitis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Chronic hepatitis B patients who underwent liver biopsy during 2002-2008 and then received antiviral therapy. The studied patients had achieved undetectable HBV DNA or hepatitis B surface antigen (HBsAg) loss during antiviral therapy, and those who had hepatitis B e antigen (HBeAg) seroconversion with serum HBV DNA persistently \<2,000 IU/ml and normalization of aminotransferase levels after discontinuing antiviral therapy. According to Brunt's classification, patients will be categorized into three groups, including non-steatosis, steatosis but no steatohepatitis, and steatohepatitis groups based on the histological features of the liver specimens.

You may qualify if:

• All CHB patients who had significant histologic features, defined as at least moderate necroinflammation and/or liver fibrosis stage 2 or higher according to the METAVIR system, required antiviral therapy and have been managed in our institution.
• HBV-treated patients who had achieved undetectable HBV DNA or hepatitis B surface antigen (HBsAg) loss during antiviral therapy, and those who had hepatitis B e antigen (HBeAg) seroconversion with serum HBV DNA persistently \<2,000 IU/ml and normalization of aminotransferase levels after discontinuing antiviral therapy.

You may not qualify if:

• Patients who had viremia \>2000 IU/ml after stopping antiviral agents will be excluded.
• Patients with a history of alcohol dependence or co-infections with hepatitis C virus or human immunodeficiency virus before liver biopsy will be excluded.

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Faculty of Medicine Siriraj Hospital

Bangkoknoi, Bangkok, 10700, Thailand

Location

Related Publications (12)

• Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 28.

  PMID: 26231459 BACKGROUND

• European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.

  PMID: 28427875 BACKGROUND

• Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.

  PMID: 29405329 BACKGROUND

• Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.

  PMID: 26563120 BACKGROUND

• Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021 Jun 5;397(10290):2212-2224. doi: 10.1016/S0140-6736(20)32511-3. Epub 2021 Apr 21.

  PMID: 33894145 BACKGROUND

• Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020 May;158(7):1999-2014.e1. doi: 10.1053/j.gastro.2019.11.312. Epub 2020 Feb 8.

  PMID: 32044314 BACKGROUND

• Charatcharoenwitthaya P, Pongpaibul A, Kaosombatwattana U, Bhanthumkomol P, Bandidniyamanon W, Pausawasdi N, Tanwandee T. The prevalence of steatohepatitis in chronic hepatitis B patients and its impact on disease severity and treatment response. Liver Int. 2017 Apr;37(4):542-551. doi: 10.1111/liv.13271. Epub 2016 Oct 31.

  PMID: 27740738 BACKGROUND

• Mak LY, Seto WK, Hui RW, Fung J, Wong DK, Lai CL, Yuen MF. Fibrosis evolution in chronic hepatitis B e antigen-negative patients across a 10-year interval. J Viral Hepat. 2019 Jul;26(7):818-827. doi: 10.1111/jvh.13095. Epub 2019 Apr 16.

  PMID: 30895682 BACKGROUND

• Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Aguilar Schall R, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchison JG, Heathcote EJ. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013 Feb 9;381(9865):468-75. doi: 10.1016/S0140-6736(12)61425-1. Epub 2012 Dec 10.

  PMID: 23234725 BACKGROUND

• Seto WK, Fung J, Cheung KS, Mak LY, Hui RW, Liu KS, Lai CL, Yuen MF. Body-mass index is associated with fibrosis regression during long-term nucleoside analogue therapy in chronic hepatitis B. Aliment Pharmacol Ther. 2016 Nov;44(10):1071-1079. doi: 10.1111/apt.13804. Epub 2016 Sep 22.

  PMID: 27659292 BACKGROUND

• Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21. doi: 10.1002/hep.20701.

  PMID: 15915461 BACKGROUND

• Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999 Sep;94(9):2467-74. doi: 10.1111/j.1572-0241.1999.01377.x.

  PMID: 10484010 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

All liver biopsies were stained with Hematoxylin and Eosin, and Masson's trichrome. In cases of faded tissue slides, stored paraffin-embedded tissue block will be cut and re-stained.

MeSH Terms

Conditions

Fatty Liver; Hepatitis B, Chronic

Interventions

Antiviral Agents; Nucleosides

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Glycosides; Carbohydrates; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Phunchai Charatcharoenwitthaya, MD.

  Siriraj Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated Professor

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: April 7, 2022
• Study Start: January 1, 2002
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2021
• Last Updated: April 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)