Association between hepatitis B co-infection and elevated liver stiffness among HIV-infected adults in Lusaka, Zambia.

OBJECTIVE: To describe liver disease epidemiology among HIV-infected individuals in Zambia. METHODS: We recruited HIV-infected adults (≥18 years) at antiretroviral therapy initiation at two facilities in Lusaka. Using vibration controlled transient elastography, we assessed liver stiffness, a surrogate for fibrosis/cirrhosis, and analysed liver stiffness measurements (LSM) according to established thresholds (>7.0 kPa for significant fibrosis and >11.0 kPa for cirrhosis). All participants underwent standardised screening for potential causes of liver disease including chronic hepatitis B (HBV) and C virus co-infection, herbal medicine, and alcohol use. We used multivariable logistic regression to identify factors associated with elevated liver stiffness. RESULTS: Among 798 HIV-infected patients, 651 had a valid LSM (median age, 34 years; 53% female). HBV co-infection (12%) and alcohol use disorders (41%) were common and hepatitis C virus co-infection (<1%) was rare. According to LSM, 75 (12%) had significant fibrosis and 13 (2%) had cirrhosis. In multivariable analysis, HBV co-infection as well as male sex, increased age and WHO clinical stage 3 or 4 were independently associated with LSM >7.0 kPa (all P < 0.05). HBV co-infection was the only independent risk factor for LSM >11.0 kPa. Among HIV-HBV patients, those with elevated ALT and HBV viral load were more likely to have significant liver fibrosis than patients with normal markers of HBV activity. CONCLUSIONS: HBV co-infection was the most important risk factor for liver fibrosis and cirrhosis and should be diagnosed early in HIV care to optimise treatment outcomes.

Hepatosplenic schistosomiasis in Zambian adults is characterized by increased liver stiffness: A nested case-control study.

Cirrhosis commonly complicates portal hypertension worldwide but in Zambia hepatosplenic schistosomiasis (HSS) dominates as the cause of portal hypertension. We need easier and non-invasive ways to assess HSS. Transient elastography (TE), a measure of liver stiffness can diagnose liver cirrhosis. TE remains unexplored in HSS patients, who generally have normal liver parenchyma. We aimed to explore liver stiffness in HSS. This nested case control study was conducted at the University Teaching Hospital, Lusaka, Zambia between January 2015 and January 2016. We enrolled 48 adults with HSS and 22 healthy controls. We assessed liver stiffness using TE while plasma hyaluronan was used to assess liver fibrosis. Plasma tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) were used to assess inflammation. The median (interquartile range) liver stiffness was higher in patients, 9.5 kPa (7.8, 12.8) than in controls, 4.7 kPa (4.0, 5.4), P < 0.0001. We noted linear correlations of hyaluronan and TNFR1 with the liver stiffness, P = 0.0307 and P = 0.0003 respectively. HSS patients seem to have higher liver stiffness than healthy controls. TE may be useful in identifying fibrosis in HSS. The positive correlations of inflammatory markers with TE suggest that HSS has both periportal and parenchymal pathophysiology.

Field performance of the Determine HBsAg point-of-care test for diagnosis of hepatitis B virus co-infection among HIV patients in Zambia.

BACKGROUND: We evaluated the field performance of a rapid point-of-care (POC) test for hepatitis B surface antigen (HBsAg) that could support decentralization and scale-up of hepatitis B virus (HBV) diagnosis in Africa. OBJECTIVE: To determine the field performance of the Determine HBsAg POC test for diagnosis of HBV co-infection among HIV patients in Zambia. STUDY DESIGN: Between 2013-2014, we screened HIV-infected adults for HBsAg at two urban clinics in Zambia. A subset were tested with the POC Determine HBsAg (Alere, USA) by finger prick in the clinic and HBsAg serology (Access2Analyzer, Beckman Coulter) at a reference laboratory. If either test was reactive, we determined HBV viral load (VL) and genotype. We described patient demographic and clinical characteristics (including liver fibrosis) and assessed the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the Determine test. In secondary analyses, we assessed sensitivity among patients with replicating HBV (i.e., VL>20 IU/ml) and with high HBV VL (i.e.,>20,000IU/ml). RESULTS: Among 412 participants with both HBsAg tests, median age was 34 years, 51% were women, and median CD4 was 208 cells/mm3. By serology, 66 (16%) were HBsAg-positive. Overall Determine had 87.9% sensitivity, 99.7% specificity, 98.3% PPV, and 97.7% NPV. Six of 8 patients with false negative results had undetectable HBV VL and no evidence of significant liver fibrosis. Test sensitivity was 95.9% among the 51 with replicating HBV and 100% among the 28 with high HBV VL. CONCLUSIONS: Determine HBsAg is a cheaper alternative HBV testing option compared to the gold standard ELISA and has high specificity and good sensitivity in the field among HIV-infected individuals.