Background Diagnosis of liver cirrhosis in patients with chronic hepatitis B is challenging given rare use of biopsy. In low and middle-income countries, transient elastography (TE), a recommended noninvasive imaging test for cirrhosis is rarely accessible. We therefore investigated the performance of multiple low-cost and more accessible blood-based liver fibrosis markers in patients with chronic hepatitis B infection in Zambia. As alcohol use complicates the assessment and outcomes of hepatitis B, we also considered alcohol use patterns in our evaluation. Methods We performed a hospital-based cross-sectional study, in Lusaka, Zambia, among consecutive treatment-naive adults with chronic hepatitis B mono-infection (i.e., HIV-negative) presenting to our hospital. The reference test for cirrhosis was TE of >/=9.6 kPa. Low-cost markers were the AST-to-platelet ratio index (APRI) at recommended threshold >2, as well as lower proposed alternative thresholds for Africa, >0.5 and >0.65, AST/ALT ratio and FIB-4 index >3.25. We evaluated the performance of each marker versus TE. In a secondary analysis, we evaluated marker performance in participants with current alcohol use versus lifetime abstinence. Results Among 239 adults with HBV mono-infection analyzed, the mean age was 34.7 years and 53 (22.2%) reported current alcohol use. The prevalence of cirrhosis by TE was 16.3% (95% CI: 11.87-21.63). The area under the receiver operating characteristic curve was 0.83, 0.80, 0.79 and 0.73 for FIB-4, APRI >0.5, APRI >0.65 and APRI >2 respectively. Virtually all indices performed less well in people with current alcohol use. Conclusion These data support the adoption of a lower APRI threshold in Africa, and the use of the FIB-4 index, for diagnosis of cirrhosis among patients with chronic hepatitis B infection. The currently-recommended APRI threshold may exclude people with cirrhosis who need antiviral therapy. Clinicians adopting these markers should screen for alcohol use and consider reassessment of cirrhosis after alcohol reduction.

The authors have declared no competing interest.

The project was not funded.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

NATIONAL HEALTH RESEARCH AUTHORITY Paediatric Centre of Excellence, University Teaching Hospital, P.O. Box 30075, LUSAKA Chalala Office Lot No. 18961/M, Off Kasama Road, P.O. Box 30075, LUSAKA Tell: +260211 250309 | Email: znhrasec@nhra.org.zm | www.nhra.org.zm

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data from this study are a property of the government of Zambia and cannot be made publicly available. All interested readers can access the data set from the Chairperson of the Zambia Biomedical Research Ethics Committee or the National Health research Authority from the following contact details: The chairperson of the University of Zambia Biomedical Research Ethics Committee contact details: Ridgeway campus P.O Box 50110, Lusaka: Telephone:260-1-256067Fax:+260-1-250753 E-mail:unzarec@unza.zm and the chairperson of the National Health research Authority contact details:Paediatric Centre of Excellence, University Teaching Hospital, P.O. Box 30075, LUSAKAChalala Office Lot No. 18961/M, Off Kasama Road, P.O. Box 30075, LUSAKA Tell: +260211 250309 | Email: znhrasec@nhra.org.zm | www.nhra.org.zm