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. 2024 Dec 27;16(12):1395-1406.
doi: 10.4254/wjh.v16.i12.1395.

Influence of nonalcoholic fatty liver disease on the therapeutic effect of nucleoside (acid) analogs for hepatitis B virus

Hua-Dong Li  1   2 , Ya-Nan Liu  1 , Shuang Wu  2 , Xu-Feng Quan  1 , Xiao-Yan Wang  1 , Tian-Dan Xiang  1 , Shu-Meng Li  1 , Ling Xu  1 , Tong Wang  1 , Hua Wang  1 , Xin Zheng  3
Affiliations

Influence of nonalcoholic fatty liver disease on the therapeutic effect of nucleoside (acid) analogs for hepatitis B virus

Hua-Dong Li et al. World J Hepatol. .

Abstract

Background: The effect of nonalcoholic fatty liver disease (NAFLD) on the efficacy of nucleoside analogues (NAs) in antiviral therapy for patients with chronic hepatitis B (CHB) remains controversial.

Aim: To investigate the influence of NAFLD on virological response in CHB patients undergoing NAs treatment.

Methods: Logistic regression analysis was conducted on a cohort of 465 CHB patients from two hospitals to determine whether NAFLD was a risk factor for adverse reactions to NAs. CHB patients were followed up for more than 28 months after initial antiviral treatment, and further validation was performed using different viral load populations.

Results: NAFLD was identified as an independent risk factor for partial virological response following antiviral therapy with NAs (odds ratio = 1.777, P = 0.017). In our subsequent analysis focusing on CHB patients with high viral load, the NAFLD group exhibited significantly longer virus shedding time and lower proportion of the complete virological response compared with the non-NAFLD group (16.8 ± 6.1 vs 13.0 ± 6.8, P < 0.05). During the 24-month period of antiviral treatment with NAs, hepatitis B virus (HBV) DNA levels decreased slowly in the NAFLD group, and the negative conversion rate of HBV was notably lower than that observed in non-NAFLD group (P = 0.001). Similar results were obtained when analyzing patients with low baseline HBV viral load within the NAFLD group.

Conclusion: Coexistence of NAFLD may diminish virological response among CHB patients receiving antiviral treatment with NAs.

Keywords: Antiviral therapy; Chronic hepatitis B; Nonalcoholic fatty liver disease; Nucleoside analogues; Virological response.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the chronic hepatitis B subjects enrolled in the study. A total of 1405 adults with chronic hepatitis B (CHB) were assessed during the study period, and 465 met the inclusion criteria. Among those who received antiviral therapy with NAs, 139 subjects obtained complete virological response, 326 subjects got partial virological response (PVR), and the risk factors of PVR were observed. Subsequently, to verify the relationship between nonalcoholic fatty liver disease coexisting with CHB and virological response, we conducted a dynamic analysis of viral response to NAs antiviral treatment from patients with hepatitis B virus DNA high viral load and low viral load. CHB: Chronic hepatitis B; NAs: Nucleos(t)ide analogues; NAFLD: Nonalcoholic fatty liver disease; ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; TAF: Tenofovir alafenamide fumarate.
Figure 2
Figure 2
Dynamics of virological response to antiviral therapy over time in chronic hepatitis B patients with and without nonalcoholic fatty liver disease. A: Dynamic change trend of hepatitis B virus viral load; B: Cumulative negative conversion rate of hepatitis B virus. NAFLD: Nonalcoholic fatty liver disease; CHB: Chronic hepatitis B; HBV: Hepatitis B virus; HBV DNA: Hepatitis B virus deoxyribonucleic acid.
Figure 3
Figure 3
Biochemical response of chronic hepatitis B patients with and without nonalcoholic fatty liver disease by antiviral therapy at 24 months. A: Normalization rate of alanine aminotransferase (≤ 30 U/L and ≤ 19 U/L for males and females); B: Normalization rate of aspartate aminotransferase (≤ 40 U/L for males and females). NAFLD: Nonalcoholic fatty liver disease.
Figure 4
Figure 4
Virological response of chronic hepatitis B patients with and without nonalcoholic fatty liver disease at different antiviral treatment duration. A: Dynamic change trend of hepatitis B virus low viral load; B: Cumulative negative conversion rate of hepatitis B virus low viral load. NAFLD: Nonalcoholic fatty liver disease; HBV: Hepatitis B virus; HBV DNA: Hepatitis B virus deoxyribonucleic acid.
Figure 5
Figure 5
Virological response of chronic hepatitis B patients with different grades of nonalcoholic fatty liver disease at different antiviral treatment duration. Dynamic change trend of hepatitis B virus viral load. NAFLD: Nonalcoholic fatty liver disease; CHB: Chronic hepatitis B; HBV DNA: Hepatitis B virus deoxyribonucleic acid.
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