Hepatitis B Virus PreS-Mutated Strains in People Living with HIV: Long-Term Hepatic Outcomes Following ART Initiation

Abstract

In the modern era of HIV treatment, people co-infected with HIV and HBV still face poor liver outcomes, including liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. We investigated baseline characteristics and long-term liver function outcomes in 435 people living with HIV and HBV co-infection, focusing on HCC-associated point mutations (PMs) and PreS region deletion mutations. PMs were present in 72.9% of participants and were associated with male predominance, lower HBV genotype C prevalence, reduced HBV DNA and HBeAg levels, and higher HBsAg and HBeAb positivity. However, PMs did not significantly impact liver function or fibrosis progression over six years of ART follow-up. In contrast, PreS deletions were found in 21.8% of cases and stratified into PreS1, PreS2, and PreS1+2 deletions. PreS2 and PreS1+2 deletions were linked to older age, higher HBsAg and AFP levels, elevated liver enzymes, and lower platelet counts. These groups also exhibited significantly worse liver fibrosis markers (APRI and FIB-4), with PreS2 deletions consistently showing the highest values throughout the follow-up. Despite the initial improvement with ART, patients with PreS2 and PreS1+2 deletions maintained higher fibrosis and cirrhosis risks over six years. In summary, while PMs were not predictive of liver disease progression, PreS deletion mutations (especially in the PreS2 region) were associated with poorer liver outcomes, indicating their potential as biomarkers for fibrosis risk in co-infected individuals with long-term ART.

Keywords: HBV; HIV; PreS deletion; hepatic outcomes; point mutation.

Figure 1

The impact of HBV PreS point mutations on hepatic outcomes in people living with HIV and HBV co-infection. (A,B) Longitudinal changes in liver fibrosis and cirrhosis risk scores (APRI/FIB-4) over six years after treatment; (C–G) longitudinal changes in liver function indicators (AFP, PLT, AST, ALT, and T.BIL) over six years after treatment; The dashed lines represent the reference range. Mann–Whitney U test for comparison between groups. p < 0.05 shows the difference is statistically significant. * p < 0.05, ** p < 0.01.

Figure 2

The impact of HBV PreS deletion mutations on hepatic outcomes in people living with HIV and HBV co-infection. (A,B) Longitudinal changes in liver fibrosis and cirrhosis risk scores (APRI/FIB-4) over six years after treatment; (C–G) longitudinal changes in liver function indicators (AFP, PLT, AST, ALT, and T.BIL) over six years after treatment; The dashed lines represent the reference range. Mann–Whitney U test for comparison between groups. p < 0.05 shows the difference is statistically significant. * p < 0.05, ** p < 0.01, and *** p < 0.001. Blue asterisks indicate the comparison between “PreS1 del” and “w/o del”; red asterisks indicate the comparison between “PreS2 del” and “w/o del”; purple asterisks indicate the comparison between “PreS1+2 del” and “w/o del”.