Impact of Antiretroviral Therapy on Liver Fibrosis Among Human Immunodeficiency Virus-Infected Adults With and Without HBV Coinfection in Zambia

Abstract

Background. We investigated changes in hepatic fibrosis, based on transient elastography (TE), among human immunodeficiency virus (HIV)-infected patients with and without hepatitis B virus (HBV) coinfection on antiretroviral therapy (ART) in Zambia.Methods. Patients' liver stiffness measurements (LSM; kiloPascals [kPa]) at ART initiation were categorized as no or minimal fibrosis (equivalent to Metavir F0-F1), significant fibrosis (F2-F3), and cirrhosis (F4). TE was repeated following 1 year of ART. Stratified by HBV coinfection status (hepatitis B surface antigen positive at baseline), we described LSM change and the proportion with an increase/decrease in fibrosis category. Using multivariable logistic regression, we assessed correlates of significant fibrosis/ cirrhosis at 1 year on ART.Results. Among 463 patients analyzed (61 with HBV coinfection), median age was 35 years, 53.7% were women, and median baseline CD4+ count was 240 cells/mm 3 . Nearly all (97.6%) patients received tenofovir disoproxil fumarate-containing ART, in line with nationally recommended first-line treatment. The median LSM change was −0.70 kPa (95% confidence interval, −3.0 to +1.7) and was similar with and without HBV coinfection. Significant fibrosis/cirrhosis decreased in frequency from 14.0% to 6.7% (P < .001). Increased age, male sex, and HBV coinfection predicted significant fibrosis/cirrhosis at 1 year (all P < .05).Conclusion. The percentage of HIV-infected Zambian adults with elevated liver stiffness suggestive of significant fibrosis/cirrhosis decreased following ART initiation-regardless of HBV status. This suggests that HIV infection plays a role in liver inflammation. HBV-coinfected patients were more likely to have significant fibrosis/cirrhosis at 1 year on ART.Clinical Trials Registration. NCT02060162.

Adherence to Nucleos(t)ide Analogue Therapies for Chronic Hepatitis B Infection: A Systematic Review and Meta‐Analysis

“…From an initial screen of 878 titles, 30 studies providing data for 23,823 patients met our eligibility criteria and were taken through for review (Fig. ) . The majority (23 studies, 17,057 patients) were from high‐income settings, mainly the United States (seven studies), Australia (four studies), and France (three studies).…”

“…The majority (23 studies, 17,057 patients) were from high‐income settings, mainly the United States (seven studies), Australia (four studies), and France (three studies). Studies from low‐income and middle‐income settings were carried out in Brazil, China, The Gambia, India, and Zambia . Twelve studies were prospective cohorts, 11 were retrospective cohorts, and seven were cross‐sectional surveys.…”

“…Studies from low-income and middle-income settings were carried out in Brazil, (15,29) China, (31,33) The Gambia, (40) India, (24) and Zambia. (36) Twelve studies were prospective cohorts, 11 were retrospective cohorts, and seven were cross-sectional surveys. Most studies used self-report (11 studies) as the main adherence measure.…”

Eligibility for hepatitis B antiviral therapy among adults in the general population in Zambia

“…However, we also noted that our HBV monoinfected sample had higher proportions with ALT >40 U/L and HBV DNA >2,000 IU/ml than the Gambian sample. Differences in the proportion needing therapy may be due to the sample age, as PROLIFICA recruited a slightly older population (median age of 38 years) or due to HBV genotype, since A1 is more common in Zambia [23,24] than the Gambia where E predominates, and genotype A1 was linked with more severe disease compared to E [11]. Treatment of HBV in those who need it is one of the 2030 global hepatitis targets [25]; therefore, estimates around the proportion who need therapy are critical to inform global strategies to diagnose and link individuals to care and AVT.…”

HIV-hepatitis B virus coinfection

“…However, recent studies continue to report that overall mortality, liver related mortality and hospital utilization rates and risk of hepatocellular carcinoma (HCC) remain elevated in HIV-HBV co-infected individuals compared to HIV mono- or HBV mono-infected individuals [2, 3, 5, 6, 8, 70, 95–99] . Furthermore, liver disease progression continues to occur in 10–20% of individuals on tenofovir-containing HBV-active ART [5, 100, 101] (summarized in Table 1). …”