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

ABSTRACT: 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.

SUBMITTER: Vinikoor MJ

PROVIDER: S-EPMC5467871 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Vinikoor Michael J MJ Mulenga Lloyd L Siyunda Alice A Musukuma Kalo K Chilengi Roma R Moore Carolyn Bolton CB Chi Benjamin H BH Davies Mary-Ann MA Egger Matthias M Wandeler Gilles G

Tropical medicine & international health : TM & IH 20160830 11

<h4>Objective</h4>To describe liver disease epidemiology among HIV-infected individuals in Zambia.<h4>Methods</h4>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 partic ...[more]

PMID: 27499385

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Project description:(1) Background: The role of hepatitis C virus (HCV) co-infection on the T-cell homeostasis disturbances in human immunodeficiency virus (HIV)-infected patients as well as its reversion after HCV eradication with direct acting antivirals (DAAs) therapy has not been yet clarified. We extensively analyzed the effect of HCV co-infection on immune parameters of HIV pathogenesis and its evolution after HCV eradication with DAAs. (2) Methods: Seventy individuals were included in the study-25 HIV-monoinfected patients, 25 HIV/HCV-coinfected patients and 20 HIV and HCV seronegative subjects. All patients were on antiretroviral therapy and undetectable HIV-viremia. Immune parameters, such as maturation, activation, apoptosis, senescence and exhaustion of T-cells were assessed by flow cytometry. Cross-sectional and longitudinal (comparing pre- and post-DAAs data in HIV/HCV coinfected patients) analyses were performed. Univariate and multivariate (general linear model and canonical discriminant analysis -CDA-) analyses were used to assess differences between groups. (3) Results-The CDA was able to clearly separate HIV/HCV coinfected from HIV-monoinfected patients, showing a more disturbed T-cells homeostasis in HIV/HCV patients, especially activation and exhaustion of T-cells. Interestingly, those perturbations were more marked in HIV/HCV patients with increased liver stiffness. Eradication of HCV with DAAs restored some but not all the T-cells homeostasis disturbances, with activation and exhaustion of effector CD8 T-cells remaining significantly increased three months after HCV eradication. (4) Conclusions-HCV co-infection significantly impacts on several immune markers of HIV pathogenesis, especially in patients with increased liver stiffness. Eradication of HCV with DAAs ameliorates but does not completely normalize these alterations. It is of utmost relevance to explore other mechanisms underlying the immune damage observed in HIV/HCV coinfected patients with control of both HIV and HCV replication.

Project description:OBJECTIVES:The aim of this study was to estimate the frequency of disclosure to and testing of contacts of patients with hepatitis B virus (HBV) in Zambia. DESIGN:We used a convergent parallel mixed-method research design including a quantitative survey and focus group discussions with patients with HBV. SETTING:A university hospital in Lusaka, Zambia. PARTICIPANTS:79 hepatitis B surface antigen (HBsAg)-positive, HIV-negative, adults (18+ years) receiving HBV care completed a quantitative survey and 32 also participated in a focus group discussion. OUTCOMES AND ANALYSIS:Contacts of patients with HBV were enumerated and patient-reported disclosure, contact testing and contact HBV test results were used to develop a testing cascade. Using multivariable logistic regression, we identified factors associated with disclosure of HBV status. In focus groups, we explored how index patient knowledge and awareness of their condition shaped perspectives on contact disclosure and testing. Focus groups coding and analysis followed a thematic analysis approach. RESULTS:Among 79 patients with HBV (median age 35 years; 26.6% women), the majority reported disclosure to ?1 contact. According to the index patients' knowledge, of 776 contacts enumerated, 326 (42.1%) were disclosed to, 77 (9.9%) were tested, 67 (8.6%) received results and 8 (11.9%) were HBsAg-positive. Increased stigma score was associated with reduced disclosure. In focus groups, HBV awareness, knowledge and stigma emerged as barriers to disclosure and referral of contacts for testing. Association of HBV with HIV-related stigma was also reported as a strong barrier to contact disclosure and testing and to taking antivirals for HBV monoinfection. CONCLUSIONS:HBV contact disclosure and testing were feasible and yielded new diagnoses in Zambia. A better understanding of barriers to seeking HBV testing and treatment is needed to scale-up this important intervention in Africa. TRIALS REGISTRATION NUMBER:NCT03158818.

Project description:Many patients in HIV care in Africa considered lost to follow up (LTFU) at one facility are reportedly accessing care in another. The success of these unofficial transfers as measured by time to re-entry at the new-facility, prevalence of treatment interruptions, speed of ART-initiation, and overall continuity of care is not well characterized but may reveal opportunities for improvement. We traced a random sample of LTFU HIV-infected patients in Zambia. Among those found alive and reported in care at a new-facility, we reviewed records at the receiving facility to verify transfer; and when verified, documented the transfer experience. We used Kaplan-Meier methods to examine incidence of ART-initiation after transfer to new clinic. We assessed demographic and clinical characteristics, official and cross-provincial transfer for associations with HIV treatment re-engagement using Poisson regression models and associations between official-transfer and same-day ART initiation at the new-facility. Among 350 LTFU-patients, 178 (51%) were successfully verified through chart review at the new-facility. 132 (74.2%) were female, 72 (40.4%) aged 25-35, and 51% were ever recorded as previously being on ART. 110 patients (61.8%) were registered under new ART-IDs and 97 (54.5%) received a new HIV test. 54% of those previously on ART-initiated on the same-day. Using the same ART-ID was associated with same-day initiation compared to those receiving a new ART-ID (p = 0.07). 80% (n = 91) of those ever on ART had evidence of medication initiation at new clinic. Among these, initiation reached 66% (95% CI: 56-75) by 30 days, 77.5% (95% CI: 68-86) by 90 days after new-facility presentation. Many patients use new identifiers at new facilities, indicative of inefficiencies. Re-entry into new facilities among the unofficial-transfer population is often delayed and timely treatment initiation is inconsistent, suggesting interruptions in treatment. Health systems innovations to ensure smooth and safe transfers are needed to maintain quality HIV care.

Project description:Noninvasive biomarkers are used increasingly to assess fibrosis in patients with chronic liver disease. We determined the utility of dual cutoffs for noninvasive biomarkers to exclude and confirm advanced fibrosis in hepatitis B virus (HBV)-human immunodeficiency virus (HIV) co-infected patients receiving combined antiretroviral therapy. Participants were anti-HIV/hepatitis B surface antigen-positive adults from eight clinical sites in the United States and Canada of the Hepatitis B Research Network. Fibrosis was staged by a central pathology committee using the Ishak fibrosis score (F). Clinical, laboratory, and vibration-controlled transient elastography (VCTE) data were collected at each site. Dual cutoffs for three noninvasive biomarkers (aspartate aminotransferase-to-platelet ratio index, Fibrosis-4 index [FIB-4], and liver stiffness by VCTE) with the best accuracy to exclude or confirm advanced fibrosis (F ≥ 3) were determined using established methodology. Of the 139 enrolled participants, 108 with a liver biopsy and having at least one noninvasive biomarker were included: 22% had advanced fibrosis and 54% had normal alanine aminotransferase. The median (interquartile range) of APRI (n = 106), FIB-4 (n = 106), and VCTE (n = 63) were 0.34 (0.26-0.56), 1.35 (0.99-1.89), and 4.9 (3.8-6.8) kPa, respectively. The area under the curve for advanced fibrosis was 0.69 for APRI, 0.66 for FIB-4, and 0.87 for VCTE. VCTE cutoffs of 5.0 kPa or less (to exclude) and 8.8 kPa or greater (to confirm) advanced fibrosis had a sensitivity of 92.3% and specificity of 96.0%, respectively, and accounted for 65.1% of participants. Among the 34.9% with values between the cutoffs, 26.1% had advanced fibrosis. Considering APRI or FIB-4 jointly with VCTE did not improve the discriminatory capacity. Conclusion: VCTE is a better biomarker of advanced fibrosis compared with APRI or FIB-4 in HBV/HIV co-infected adults on combined antiretroviral therapy. Using VCTE dual cutoffs, approximately two-thirds of patients could avoid biopsy to determine advanced fibrosis.

Project description:IntroductionSub-Saharan Africa has the highest global incidence of cervical cancer. Cervical cancer is the most common cause of cancer morbidity and mortality among women in Zambia. HIV increases the risk for cervical cancer and with a national Zambian adult HIV prevalence of 16%, it is important to investigate the impact of HIV on the progression of cervical cancer. We measured differences in cervical cancer progression between HIV-positive and HIV-negative patients in Zambia.MethodsThis study included 577 stage I and II cervical cancer patients seen between January 2008 and December 2012 at the Cancer Diseases Hospital in Lusaka, Zambia. The inclusion criteria for records during the study period included known HIV status and FIGO stage I and II cervical cancer at initial date of registration in the Cancer Diseases Hospital. Medical records were abstracted for clinical and epidemiological data. Cancer databases were linked to the national HIV database to assess HIV status among cervical cancer patients. Logistic regression examined the association between HIV and progression, which was defined as metastatic or residual tumor after 3 months of initial treatment.ResultsA total of 2451 cervical cancer cases were identified, and after exclusion criteria were performed the final analysis population totaled 537 patients with stage I and II cervical cancer with known HIV status (224 HIV-positive and 313 HIV-negative). HIV-positive women were, on average, 10 years younger than HIV-negative women who had a median age of 42, ranging between 25 and 72. A total of 416 (77.5%) patients received external beam radiation, and only 249 (46.4%) patients received the recommended treatment of chemotherapy, external beam radiation, and brachytherapy. Most patients were stage II (85.7%) and had squamous cell carcinoma (74.7%). HIV-positive patients were more likely to receive lower doses of external beam radiation than HIV-negative patients (47% vs 37%; P<0.05, respectively). The median total dose of external beam radiation for HIV-positive and HIV-negative patients was 46 Gy and 50 Gy, respectively. HIV positivity did not lead to tumor progression (25.4% in HIV-positive vs 23.9% in HIV-negative, OR 1.04, 95% CI [0.57, 1.92]). However, among a subset of HIV-positive patients, longer duration of infection was associated with lower odds of progression.ConclusionThere was no significant impact on non-metastatic cervical cancer progression by HIV status among patients in Lusaka, Zambia. The high prevalence of HIV among cervical cancer patients suggest that HIV-positive patients should be a primary target group for HPV vaccinations, screening, and early detection.

Dataset Information

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

Publications

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

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