Hepatitis C in Uganda: Identification of infected blood donors for micro-elimination.

BACKGROUND: The drive to eliminate viral hepatitis by 2030 is underway. However, locally generated data on active infection is required to focus such efforts. We performed a regionally-inclusive survey to determine prevalence of active HCV, genotypes and related factors among Ugandan blood donors. METHODS: Participants from regional blood banks and blood collection centers were surveyed for information on demographic, clinical and lifestyle factors. Blood was assayed for HCV infection, HCV genotypes and subtypes. Logistic regression was performed to determine factors associated with active HCV infection. RESULTS: Of 1243 participants, 1041 (83.7%) were male, average age (SD), 27.7 (9.8). Prevalence of active HCV infection was 7.8% and we identified 3 genotypes. Median age (adj. OR (95% CI) = 1.03 (1.01-1.06), p-value = 0.040)), Northern region of birth versus Central or Eastern (adj. OR (95% CI) = 10.25 (2.65-39.68), p-value = 0.001)), Northern residence, versus Central or Eastern (adj. OR (95% CI) = 0.23 (0.08-0.65), p-value = 0.006)), and being married (versus single/divorced) adj. OR 2.49(1.3-4.79), p-value = 0.006 were associated with active HCV infection. CONCLUSION: Targeted interventions in at-risk populations coupled with linkage to care and treatment will help achieve the WHO elimination goals in this setting.

Hepatitis B in sub-Saharan Africa: strategies to achieve the 2030 elimination targets.

The WHO global health sector strategy on viral hepatitis, created in May, 2016, aims to achieve a 90% reduction in new cases of chronic hepatitis B and C and a 65% reduction in mortality due to hepatitis B and C by 2030. Hepatitis B virus (HBV) is endemic in sub-Saharan Africa, and despite the introduction of universal hepatitis B vaccination and effective antiviral therapy, the estimated overall seroprevalence of hepatitis B surface antigen remains high at 6·1% (95% uncertainty interval 4·6-8·5). In this Series paper, we have reviewed the literature to examine the epidemiology, burden of liver disease, and elimination strategies of hepatitis B in sub-Saharan Africa. This paper reflects a supranational perspective of sub-Saharan Africa, and recommends several priority elimination strategies that address the need both to prevent new infections and to diagnose and treat chronic infections. The key to achieving these elimination goals in sub-Saharan Africa is the effective prevention of new infections via universal implementation of the HBV birth-dose vaccine, full vaccine coverage, access to affordable diagnostics to identify HBV-infected individuals, and to enable linkage to care and antiviral therapy.

Hepatitis C in sub-Saharan Africa: the current status and recommendations for achieving elimination by 2030.

In 2016, WHO adopted a strategy for the elimination of viral hepatitis by 2030. Africa, and more specifically, sub-Saharan Africa, carries a substantial portion of the global burden of viral hepatitis, especially chronic hepatitis B and hepatitis C virus infections. The task that lies ahead for sub-Saharan Africa to achieve elimination is substantial, but not insurmountable. Major developments in the management of hepatitis C have put elimination within reach, but several difficulties will need to be navigated on the path to elimination. Many of the challenges faced are unique to sub-Saharan Africa and the development of strategies is complicated by a scarcity of good data from countries and regions within sub-Saharan Africa. However, this hindrance should not act as a barrier to delay interventions in screening, detection, and linkage to care. Moreover, by sharing experiences from across sub-Saharan Africa, countries can create supranational synergies to develop their programmes and work together in a more cohesive manner to tackle the burden of hepatitis C in sub-Saharan Africa. In this Series paper, several issues related to hepatitis C in sub-Saharan Africa are addressed, including prevalence, risk factors, and fibrosis assessment, and recommendations are given by experts from across the region. Simplified diagnostic algorithms and treatment regimens for both HIV co-infected and hepatitis C mono-infected patients are suggested. The recommendations are consensus based and provided to guide the development of programmes in sub-Saharan Africa. Political will and appropriate funding will be required to provide impetus to implement these recommendations.

The burden, pattern and factors that contribute to periportal fibrosis in HIV-infected patients in an S. mansoni endemic rural Uganda.

INTRODUCTION: Both Human Immunodeficiency Virus (HIV) and S.mansoni infections are common in Uganda and can cause liver disease. No study has determined co-infection significance in Uganda. We carried out a study on the burden, pattern and factors that contribute to peri-portal fibrosis (PPF) in HIV infected patients attending a Primary healthcare setting at Pakwach. METHODOLOGY: We conducted a cross-sectional study in the HIV clinic at Pakwach health centre IV. Data on demographics, contact with the Nile, CD4+ cell count, ART and alcohol use were collected. Urinary Circulating Cathodic Antigen (CCA), was done for S. Mansoni detection. Liver scan was done for presence and pattern of PPF. HBsAg testing was performed on all participants. Data was analyzed using Stata Version 10. RESULTS: We enrolled 299 patients, median age 39 years (IQR 16), most were female, 210 (73%). Overall, 206 (68.9%) had PPF, majority 191 (92.7%) had pattern c, either alone (63 participants) or in combination with pattern d (128 participants). Age of 30-50 years was significantly associated with PPF (OR 2.28 p-value-0.003). CONCLUSION: We found high prevalence of S. mansoni and PPF in the HIV infected population and age was a significant factor for PPF. We recommend all HIV infected patients be examined routinely for S. mansoni infection for early anti-schistosomal treatment.

Hepatitis B virus genotypes A and D in Uganda.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection in Uganda is 10%. Hepatitis B virus genotypes impact on treatment response, rate of spontaneous recovery and progression of chronic HBV infection and hepatocellular carcinoma. There is little information on the HBV genotypic distribution in Uganda. OBJECTIVES: To determine HBV genotypes in Uganda. METHODS: The MBN clinical laboratory performs HBV viral load and genotype testing in Uganda. It receives hepatitis B surface antigen (HBsAg)-positive samples from all over the country for additional HBV testing. Samples are stored for 6 months before being discarded. Our study used delinked stored samples. PCR-positive samples had DNA extracted and used as template for HBV genome amplification by nested PCR. Reverse hybridisation was performed and genotypes were determined by the line probe assay method (INNO-LiPA). RESULTS: One hundred stored HBsAg-positive plasma samples with detectable viral loads were analysed. Of these, 93 samples showed PCR amplification products and gave genotype-specific probe lines on the INNO-LiPA assay. Of the patients, where gender was recorded, 60.9% were female, and the overall median age (IQR) was 25 (2-60) years. There was a predominance of HBV genotype D (47 patients; 50.5%), followed by genotype A, (16 patients; 17.2%). One patient (1.1%) had genotype E. In 28% of the samples mixed infections were detected with genotypes A/E (9.7%) and A/D (6.5%) being most common. Genotypes B, C, E and H only occurred as part of mixed infections. CONCLUSION: Hepatitis B genotypes D and A were predominant in our study population.

High prevalence of occult hepatitis B infection in an African urban population.

Occult hepatitis B infection (OBI), the presence of low hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels in patients without detectable hepatitis B surface antigen (HBsAg), has significant implications for understanding the natural history of hepatitis B infection. We determined the prevalence of OBI in African patients using a sensitive polymerase chain reaction (PCR) assay and describe here the characteristics of OBI in an urban African hospital population. Routine serological testing as well as molecular studies were performed on sera from 314 patients who were part of a previous study from an urban hospital emergency room in Kampala, Uganda, detecting HBV DNA using a nested PCR with amplification of two regions of the HBV genome. HBV viral loads (VL) were determined by real-time PCR (rtPCR) and sequencing performed to determine HBV genotype and S gene mutations. Among 314 subjects tested, 50 (16%) had chronic HBV infection, 94 (30%) had detectable HBV DNA despite testing HBsAg negative (OBI), and 170 (54%) were not infected. VLs of OBI subjects were relatively low although 19 (20%) had VL exceeding 10(4) IU ml(-) . Subjects with chronic HBV infection had a higher median VL compared to OBI patients (P < 0.001). All chronic HBV sequenced (10) and 83/89 OBI sequences were genotype A, the remaining six being genotype D. S-gene mutations were present in some but not all OBI patients (48%). OBI is more prevalent among African patients than previously thought. This may have implications for clinical management and transfusion-related HBV transmission.

Hepatitis B and HIV co-infection is still treated using lamivudine-only antiretroviral therapy combination in Uganda.

BACKGROUND: Hepatitis B virus (HBV) and HIV are endemic in Uganda. Co-infection is common and leads to rapid progression of liver disease. Burden of co-infection is unknown yet most patients are on lamivudine-only ART where resistance is frequent. Most patients are initiated on antiretroviral therapy (ART) without knowing their HBV status. OBJECTIVES: To determine burden of co-infection and HBV viral suppression among patients on ART in Northern Uganda. METHODS: We recruited HIV infected adult patients on ART in a cross-sectional study. Age, sex, ART regimen and duration were recorded. Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBcAb) and liver panel were performed. For those HBsAg+, hepatitis B e antigen (HBeAg) and HBV DNA were performed. CD4 cell count was recorded. RESULTS: Three hundred patients were recruited. Twenty (6.7%) were co-infected, while 41% were anti-HBcAb+. Overall 188 (62.7%) were on lamivudine- only HBV active drug. Median ART duration 2 years (IQR 1-5), mean CD4+ cell count 317 cells/microlitre (SD 255-557). Of 20 HIV/HBV co-infected, 11/20 (55%) were on lamivudine-only ART, median duration 1.5 years. Nineteen (95%) had undetectable HBV DNA. Seventeen (85%) were HBeAg negative. Mean CD4+ cell count 327 cells/microlitre (SD 197-482). CONCLUSION: A large proportion of patients were on lamivudine- only HBV-active ART. Resistance may occur long term thus testing for HBV and correct ART is recommended.

A small percentage of patients with hepatitis C receive triple therapy with boceprevir or telaprevir.

BACKGROUND & AIMS: Protease inhibitor triple therapy for hepatitis C virus (HCV) infection (boceprevir or telaprevir with pegylated interferon and ribavirin) has been shown to increase rates of sustained virologic response in phase 3 trials. We investigated the proportion of patients who began therapy with this regimen in the 12 months after the Food and Drug Administration approval of boceprevir and telaprevir in the United States. METHODS: We performed a retrospective cross-sectional study of 487 patients with HCV genotype 1 infection (396 did not receive triple therapy, and 91 had begun triple therapy with boceprevir or telaprevir), who were seen at hepatology practices in Dallas and Miami from June 2011 through February 2012. The subjects were predominantly middle-aged, non-Hispanic white, and privately insured; 50% were treatment-naive, and most had advanced fibrosis. We compared features of patients who initiated triple therapy with those who deferred it. Treated patients were followed to determine the discontinuation rate in the first 12 weeks of treatment. RESULTS: Of patients assessed, only 18.7% began triple therapy, the same percentage as those receiving dual therapy (pegylated interferon and ribavirin) before boceprevir or telaprevir was approved for treatment of HCV infection in the United States. Reasons for deferring treatment included relative contraindications (50.5%), patient choice (22.5%), and less advanced liver disease (17.4%). Among treated patients, 15% discontinued prematurely because of serious adverse events. On the basis of multivariate analysis, factors associated with initiation of triple therapy included prior treatment relapse (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.1-9.9) and liver fibrosis of stage 3 (OR, 9.1; 95% CI, 3.1-27) or stage 4 (OR, 9.0; 95% CI, 3.3-25) but not hepatic decompensation. CONCLUSIONS: Only 18.7% of patients with HCV genotype 1 infection received triple therapy in the 12 months after Food and Drug Administration approval of boceprevir and telaprevir. This low percentage might result from concerns of side effects and recognition that more effective medications could be available in the future.