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Background Gastroenterologists of Mulago hospital noted that many patients with gastrointestinal bleeding are transferred to their ward from the emergency ward without adequate resuscitation. They recommended that blood should be ring fenced for patients with gastrointestinal bleeding (GI) on the emergency ward so that urgent resuscitation can be done. There was however no current data on the prevalence of GI bleeding in the emergency ward to provide a guide of how much blood should be ring fenced. This was partly because the medical records are not adequately completed as designed. We thus undertook a study to estimate the prevalence of GI bleeding on the emergency ward by incorporating quality improvement methods in the process of data collection to improve the documentation practice on the Casualty assessment form (CAF).Methods This was a cross sectional study incorporating quality improvement methods in the process of data collection from the CAF for patients attending the emergency ward. Focus group discussions and key informant interviews were conducted to ascertain the root causes of inadequate completion of this form. The health care team was educated on documentation of GI bleeding while being assessed weekly for knowledge and practice of completion of the CAF. The filled CAF were assessed for adequate completion while looking out for a documented diagnosis of GI bleeding and selected predictors of mortality.Results Of the 1881 CAF assessed, 278 had a documented diagnosis of GI bleeding, resulting in a prevalence of 6.8%. Of the patients with GI bleeding, 14.1% of them had age greater than 60 years old, 24.0% had a systolic blood pressure less than 100mmHg and 44.5% had a heart rate greater than 100 beats per minute.Conclusion The prevalence of GI bleeding on the medical emergency ward of Mulago hospital is high, with 1 in every 15 patients having this condition. This calls for strategies for resuscitative management of this potentially life threatening condition. Among the selected predictors of mortality, tachycardia was most frequent followed by hypotension. These should always be assessed in a patient with GI bleeding and resuscitative measures with blood transfusion and intravenous fluids undertaken to correct them.

Background Decompensated cirrhosis is a major cause of morbidity and mortality globally affecting close to 10.6 million people of which an estimated 28,877 are in Uganda. Bacterial infections including urinary tract infections (UTIs) are an increasing cause of short-term mortality in this sub-population. Data on UTIs among patients with cirrhosis are scarce in Uganda and other settings in sub-Saharan Africa (SSA) which suffer a high burden of liver diseases. We determined the prevalence, microbiologic spectrum and antibacterial sensitivity patterns of UTIs among patients with decompensated cirrhosis at a large urban health facility in Uganda. Methods Patients with decompensated cirrhosis presenting to a tertiary care centre in Uganda were enrolled in the study. Demographic and clinical features of UTI were captured and urine samples collected. Urinalysis and urine culture studies were conducted to determine presence of UTIs and antibacterial susceptibility patterns. Urinalysis results of ≥ 5 white cells per high power field and or culture findings of ≥ 104CFUs/ml defined UTI. Analysis was done using STATA 16.0 and findings summarized in percentages. Results Irrespective of symptomatology, prevalence of UTI was 37.1% (106/286) on either urinalysis alone 11/286 (3.9%), urine culture alone 77/286 (26.9%) or both 18/286 (6.3%). The most common bacteria isolated were Escherichia coli (40.1%) and Enterococcus spp (22.9%). The majority of isolates were resistant to fluoroquinolones, penicillins and third generation cephalosporins. Multidrug resistant organisms particularly ESBL and MRSA constituted 32.7% of the bacterial isolates. Conclusion Urinary tract infection is common among patients with decompensated cirrhosis, occurring in one third of patients with cirrhosis and are commonly caused by gram negative bacteria resistant to commonly recommended antibacterial agents in Uganda. Regardless of symptomatology, we recommend screening of patients with decompensated cirrhosis for UTI at presentation.

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.

Introduction The “2for1” project is a demonstration project to examine the feasibility and effectiveness of HBV care integrated into an HIV clinic and service. An initial phase in implementation of this project was the development of a specific training program. Our objective was to describe key features of this integrated training curriculum and evaluation of its impact in the initial cohort of health care workers (HCWs). Methods A training curriculum was designed by experts through literature review and expert opinion. Key distinctive features of this training program (compared to standard HBV training provided in the Government program) were; (i) Comparison of commonalities between HIV and HBV (ii) Available clinic- and community-level infrastructure, and the need to strengthen HBV care through integration (iii) Planning and coordination of sustained service integration. The training was aided by a power-point guided presentation, question and answer session and discussion, facilitated by physicians and hepatologists with expertise in viral hepatitis. Assessment approach used a self-administered questionnaire among a cohort of HCWs from 2 health facilities to answer questions on demographic information, knowledge and attitudes related to HBV and its prevention, before and after the training. Knowledge scores were generated and compared using paired t- tests. Results A training curriculum was developed and delivered to a cohort of 44 HCWs including medical and nursing staff from the two project sites. Of the 44 participants, 20 (45.5%) were male, average age (SD) was 34.3 (8.3) with an age range of 22–58 years. More than half (24, 54.5%) had been in service for fewer than 5 years. Mean correct knowledge scores increased across three knowledge domains (HBV epidemiology and transmission, natural history and treatment) post-intervention. However, knowledge related to diagnosis and prevention of HBV did not change. Conclusion A structured HBV education intervention conducted as part of an HIV/HBV care integration training for health care workers yielded improved knowledge on HBV and identified aspects that require further training. This approach may be replicated in other settings, as a public health strategy to heighten HBV elimination efforts.

BackgroundHepatitis B and HIV care share health system challenges in the implementation of primary prevention, screening, early linkage to care, monitoring of therapeutic success and long-term medication adherence.SettingArua regional referral hospital (RRH) and Koboko district hospital (DH), the West Nile region of Uganda.DesignA cross-sectional hospital-based cost minimisation study from the providers’ perspective considers financial costs to measure the amount of money spent on resources used in the stand-alone and integrated pathways.Data sourcesClinic inputs and procurement invoices, budgetary documents, open market information and expert opinion. Data were extracted from 3121 files of HIV and hepatitis B virus (HBV) monoinfected patients from the two study sites.ObjectiveTo estimate provider costs associated with running an integrated HBV and HIV clinical pathway for patients on lifelong treatment in low-resource setting in Uganda.Outcome measuresThe annual cost per patient was simulated based on the total amount of resources spent for all the expected number of patient visits to the facility for HBV or HIV care per year.ResultsFindings showed that Arua hospital had a higher cost per patient in both clinics than did Koboko Hospital. The cost per HBV patient was US$163.59 in Arua and US$145.76 in Koboko while the cost per HIV patient was US$176.52 in Arua and US$173.23 in Koboko. The integration resulted in a total saving of US$36.73 per patient per year in Arua RRH and US$17.5 in Koboko DH.ConclusionThe application of the integrated Pathway in HIV and HBV patient management could improve hospital cost efficiency compared with operating stand-alone clinics.

The development of direct-acting antivirals against hepatitis C virus (HCV) has transformed the treatment landscape and underpinned the WHO goal of HCV elimination by 2030. However, as of 2021, few countries remain on track to achieve this goal. Reliable data remain scarce, especially those on national plans for HCV elimination in many regions of the world and particularly in sub-Saharan Africa, which accounts for around 11 million of 71 million people estimated to be living with HCV.

Background: In recent years there has been growing interest in exploring methods by which the care pathways for people with comorbid physical and health problems may be integrated. The success of such an integration however would depend on several factors including feasibility, acceptability and costs involved. Therefore, this report presents estimated provider costs associated with managing an integrated HBV and HIV clinical pathway for patients on life-long treatment in low resource setting in Uganda.Methods: A cost minimisation analysis from the providers perspective was done by considering financial costs as a measure of the amount of money spent on resources used in the clinical pathways. The annual cost per patient was simulated based on total amount of resources spent for all the patient visits to the facility for HBV or HIV care per year.Results: Findings showed that drugs and laboratory tests were the main drivers of costs in the pathways. A high-volume facility (Arua regional referral hospital- ARRH) had a higher cost per patient in both clinics than did the low volume facility (Koboko District Hospital- KDH). Variations occurred due to differences in the carders of health workers, the infrastructure, the amounts of consumables used in the facilities. Cost per HBV patient was $163.59 in ARRH and $145.76 in K DH while the cost per HIV patient was $176.52 in ARRH and $173.23 in KDH. The integration resulted into total saving of $36.73 per patient per year in Arua RRH and $17.5 in Koboko DH. The cost saving accrued from savings from personnel, fixed costs, consumables and utilities incurred in running the standalone Hepatitis B clinic and the reduction in per HIV patient costs from sharing of resources in the integrated pathway. Conclusion: This analysis showed that the application of the integrated Pathway in HIV and HBV patient management could improve hospital cost efficiency compared to operating stand-alone clinics. This could further improve adherence to treatment by Hepatitis B patients and improve patient outcomes as HBV patients get access to counselling services.

Background Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common in sub-Saharan Africa (SSA) and can rapidly progress to cirrhosis and hepatocellular carcinoma. Recent data demonstrate ongoing HBV transmission among HIV-infected adults in SSA, suggesting that complications of HIV/HBV co-infection could be prevented with HBV vaccination. Because HBV vaccine efficacy is poorly understood among HIV-infected persons in SSA, we sought to characterize the humoral response to the HBV vaccine in HIV-seropositive Ugandan adults. Methods We enrolled HIV-infected adults in Kampala, Uganda without serologic evidence of prior HBV infection. Three HBV vaccine doses were administered at 0, 1 and 6 months. Anti-HBs levels were measured 4 weeks after the third vaccine dose. “Response” to vaccination was defined as anti-HBs levels ≥ 10 IU/L and “high response” as ≥ 100 IU/L. Regression analysis was used to determine predictors of response. Results Of 251 HIV-positive adults screened, 132 (53%) had no prior HBV infection or immunity and were enrolled. Most participants were women [89 (67%)]; median (IQR) age was 32 years (27–41), and 68 (52%) had received antiretroviral therapy (ART) for > 3 months. Median (IQR) CD4 count was 426 (261–583), and 64 (94%) of the 68 receiving ART had undetectable plasma HIV RNA. Overall, 117 (92%) participants seroconverted to the vaccine (anti-HBs ≥ 10 IU/L), with 109 (86%) participants having high-level response (anti-HBs ≥ 100 IU/L). In multivariate analysis, only baseline CD4 > 200 cells/mm3 was associated with response [OR = 6.97 (1.34–34.71), p = 0.02] and high-level response [OR = 4.25 (1.15–15.69)], p = 0.03]. Conclusion HBV vaccination was effective in eliciting a protective humoral response, particularly among those with higher CD4 counts. Half of the screened patients did not have immunity to HBV infection, suggesting a large at-risk population for HBV infection among HIV-positive adults in Uganda. Our findings support including HBV vaccination as part of routine care among HIV-positive adults.

Author(s): Musisi, Emmanuel; Matovu, Denis Kasozi; Bukenya, Andrew; Kaswabuli, Sylvia; Zawedde, Josephine; Andama, Alfred; Byanyima, Patrick; Sanyu, Ingvar; Sessolo, Abdul; Seremba, Emmanuel; Davis, J Lucian; Worodria, William; Huang, Laurence; Walter, Nicholas D; Mayanja-Kizza, Harriet | Abstract: BackgroundHIV infection and opportunistic infections cause oxidative stress (OS), which is associated with tissue damage. Anti-retroviral therapy (ART) is used to treat HIV and decrease the risk of opportunistic infections, but it is unclear whether ART reduces OS. Association of ART with OS was investigated.MethodsWe stratified a convenience sample of frozen serum or plasma from HIV-infected, ART-naive (n=21); HIV-infected, ART-treated (n=14); HIV and PTB co-infected, ART-naive (n=21); HIV and PTB co-infected, ART-treated (n=25) patients. Controls (n=21) were HIV-negative adults without TB symptoms. Concentration of OS markers namely: transaminases (ALT and AST), gamma glutamyl transpeptidase (GGT), albumin, total protein, malondialdehyde (MDA), vitamin C, and total anti-oxidant status (TAS) were determined.ResultsAST (pl0.001), GGT (pl0.001), total protein (p=0.001) and MDA (pl0.001) were higher in HIV patients compared to controls. Vitamin C (Pl0.0001) and albumin (pl0.01) were lower in HIV-patients relative to controls. ART was only associated with higher albumin (p=0.001), higher GGT (p=0.02) and lower vitamin C (p=0.009). HIV and PTB co-infection was only significantly associated with higher GGT (p=0.01) and AST (p=0.03).ConclusionWe identified severe OS among HIV-patients. ART was associated with both increased and reduced markers of OS hence suggesting that ART may not attenuate OS.

Antiretroviral therapy (ART) may interfere with replication of hepatitis B virus (HBV), raising the hypothesis that HBV infection might be prevented by ART. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda.We screened stored sera from 944 HIV-infected adults enrolled in the Rakai Community Cohort Study between September 2003 and March 2015 for evidence of HBV exposure. Serum from participants who tested anti-hepatitis B core-negative (497) at baseline were tested over 3-7 consecutive survey rounds for incident HBV. Poisson incidence methods were used to estimate incidence of HBV with 95% confidence intervals (CIs), whereas Cox proportional regression methods were used to estimate hazard ratios (HRs).Thirty-nine HBV infections occurred over 3342 person-years, incidence 1.17/100 person-years. HBV incidence was significantly lower with ART use: 0.49/100 person-years with ART and 2.3/100 person-years without ART [adjusted HR (aHR) 0.25, 95% CI 0.1-0.5, P 0.001], and with lamivudine (3TC) use: 0.58/100 person-years) with 3TC and 2.25/100 person-years without 3TC (aHR 0.32, 95% CI 0.1-0.7, P = 0.007). No new HBV infections occurred among those on tenofovir-based ART. HBV incidence also decreased with HIV RNA suppression: 0.6/100 person-years with 400 copies/ml or less and 4.0/100 person-years with more than 400 copies/ml (aHR, 6.4, 95% CI 2.2-19.0, P 0.001); and with age: 15-29 years versus 40-50 years (aHR 3.2, 95% CI 1.2-9.0); 30-39 years versus 40-50 years (aHR 2.1, 95% CI 0.9-5.3).HBV continues to be acquired in adulthood among HIV-positive Ugandans and HBV incidence is dramatically reduced with HBV-active ART. In addition to widespread vaccination, initiation of ART may prevent HBV acquisition among HIV-positive adults in sub-Saharan Africa.

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

Patients with acute liver failure (ALF) frequently develop renal dysfunction, yet its overall incidence and outcomes have not been fully assessed. We investigated the incidence of acute kidney injury (AKI) among patients with ALF, using defined criteria to identify risk factors and to evaluate its effect on overall outcomes.We performed a retrospective review of data from 1604 patients enrolled in the Acute Liver Failure Study Group, from 1998 through 2010. Patients were classified by the Acute Kidney Injury Network criteria, as well as for etiology of liver failure (acetaminophen-based, ischemic, and all others).Seventy percent of patients with ALF developed AKI, and 30% received renal replacement therapy (RRT). Patients with severe AKI had higher international normalized ratio values than those without renal dysfunction (P.001), and a higher proportion had advanced-grade coma (coma grades 3 or 4; P.001) or presented with hypotension requiring vasopressor therapy (P .001). A greater proportion of patients with acetaminophen-induced ALF had severe kidney injury than of patients with other etiologies of ALF; 34% required RRT, compared with 25% of patients with ALF not associated with acetaminophen or ischemia (P.002). Of the patients with ALF who were alive at 3 weeks after study entry, significantly fewer with AKI survived for 1 year. Although AKI reduced the overall survival time, more than 50% of patients with acetaminophen-associated or ischemic ALF survived without liver transplantation (even with RRT), compared with 19% of patients with ALF attribute to other causes (P.001). Only 4% of patients requiring RRT became dependent on dialysis.Based on a retrospective analysis of data from more than 1600 patients, AKI is common in patients with ALF and affects short- and long-term outcomes, but rarely results in chronic kidney disease. Acetaminophen-induced kidney injury is frequent, but patients have better outcomes than those with other forms of ALF.

Background: Co-infection with hepatitis B (HBV) and hepatitis D (HDV) is common among human immunodeficiency virus (HIV) infected individuals in developing countries and it aggressively accelerates progression of liver disease to cirrhosis and other complications. There is scarcity of data on HDV in sub-Saharan Africa .We investigated the sero-prevalence and factors associated with HDV antibody among HIV/HBV co-infected patients attending a large urban HIV clinic in Uganda. Methods: We screened 189 HIV/HBV co-infected individuals for anti-HDV immunoglobulin G (IgG) and performed logistic regression to determine the associated factors. Socio-demographic, clinical data, immunological status, and liver fibrosis (as determined by the Aspartate transaminase to platelet ratio index and transient elastography) were included. Results: Participants were predominately young and of sound immunologic status (median age 40 years, median CD4 440 cells/μl). 98% were on ART regimens containing anti-HBV active medications (95.2% were on TDF/3TC while 4.8% on 3TC containing regimen). Median duration on ART was 36 months (IQR 22-72). Anti-HDV was detected in 6/198, 3.2% (95% CI 1.14-6.92%), associated with male gender and a duration of more than 5 years since HIV diagnosis. Conclusions: The sero-prevalence of HDV antibodies among the HIV/HBV co-infected patients is low in a Ugandan urban cohort. Keywords: Co-infection in Uganda, hepatitis delta antibodies, hepatitis B virus, HIV

Background Very little has been published about acute transfusion reactions (ATRs) in developing countries. This study was undertaken to determine the incidence, type, imputability, severity, and possible associated factors of ATRs observed in a university-affiliated hospital in Uganda. Study Design and Methods We prospectively followed the transfusion of blood units issued over a 7-week period from the hospital blood bank during regular working hours to nonbleeding patients. For each transfusion, we recorded the patient's status before, during, at the end of, and 4 hours after transfusion. Three physicians independently reviewed all reports of suspected ATRs and related hospital charts. Using predefined criteria, the presence, type, imputability, and severity of ATRs were adjudicated by consensus of two of three physicians. Factors potentially associated with ATRs were analyzed for statistical significance. Results A total of 507 transfusions were analyzed. Fifty-three acute transfusion events were recorded and 49 of 53 or 9.6% of the 507 transfusions were confirmed to be ATRs by physician consensus: 24 febrile, seven allergic, five hypertensive, three hypotensive, three transfusion-associated circulatory overload, two acute hemolytic, and five others. Imputability of ATRs was definite, probable, or possible in 45 of 49 ATRs (92% of ATRs or 8.9% of transfusions) and judged to be severe in nine of 45. No significant associated factors were identified. Conclusions Our findings suggest that ATRs may occur more commonly in resource-limited settings than in high-income countries. Although some reactions are unavoidable, improved surveillance of transfusions and implementation of transfusion guidelines could improve the safety of transfusions in these settings.

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.

Background: Hepatitis B (HBV) in sub-Saharan Africa is believed to be horizontally acquired. However, because of the high HBV prevalence in northern Uganda, no hepatitis B vaccination at birth and no access to HBV immunoglobulin, we hypothesize that vertical transmission also could also play an important role. We therefore investigated the incidence of HBV among babies presenting for their first HBV vaccine dose in Gulu, Uganda. Methods: We recruited mothers and their babies (at least 6-week old) presenting for their postnatal care and first HBV vaccine dose respectively. Socio-demographic and risk factors for HBV transmission were recorded. Mothers were tested for Hepatitis B core antibody (anti-HBc-IgG) and hepatitis B surface antigen (HBsAg). HBsAg-positive sera were tested for hepatitis B e antigen (HBeAg) and HBV viral load (HBVDNA). Babies were tested for HBsAg at presentation and at the last immunization visit. A sample of HBsAg-negative babies were tested for HBVDNA. Incident HBV infection was defined by either a positive HBsAg or HBVDNA test. Chi-square or fisher's exact tests were utilized to investigate associations and t-tests or Wilcoxon rank-sum test for continuous differences. Results: We recruited 612 mothers, median age 23 years (IQR 20-28). 53 (8.7%) were HBsAg-positive and 339 (61.5%) were anti-HBc-IgG-positive. Ten (18.9%) of the HBsAg-positive mothers were HBeAg-positive. Median HBVDNA levels of HBV-infected mothers was 5.7log (IQR 4.6-7.0) IU/mL with 9 (17.6%) having levels >= 10(5) IU/mL. Eighty (13.3%) mothers were HIV-infected of whom 9 (11.5%) were co-infected with HBV. No baby tested HBsAg or HBVDNA positive. Conclusion: Vertical transmission does not seem to contribute substantially to the high HBV endemicity in northern Uganda. The current practice of administering the first HBV vaccine to babies in Uganda at six weeks of age may be adequate in control of HBV transmission. (C) 2017 Elsevier Ltd. All rights reserved.

Noninvasive markers of liver fibrosis, measured at baseline, have been shown to predict liver-related mortality. It remains unknown if a change in the value of the scores over time predicts mortality in patients with HIV and viral hepatitis. In this retrospective study, survival in HIV/hepatitis B virus (HBV; n = 67), HIV/hepatitis C virus (HCV; n = 43), and HIV/HBV/HCV (n = 41) patients was examined using Kaplan-Meier life table analysis. Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and FIB-4 scores, two noninvasive markers of liver fibrosis, were calculated at baseline and at last available clinical follow-up to determine the change in fibrosis score. Factors associated with mortality were assessed by Cox proportional hazards, including the change in the noninvasive marker score between the two time points. All-cause mortality was determined by Social Security Death Index and chart review. Sixty-seven were coinfected with HIV/HBV, 43 with HIV/HCV, and 41 were triply infected (HIV/HBV/HCV). Kaplan-Meier analysis showed similar survival for the three groups at 7 years of follow-up (p = 0.10). However, median length of follow-up was lower in HIV/HCV (60.5; range 0-102) compared to HIV/HBV (75.7; 12.3-126.5) and HIV/HBV/HCV (80.0; 2.7-123) months, respectively, p = 0.02. Baseline fibrosis score (p = 0.002), an increase in the value for noninvasive measurements for fibrosis (p0.001), and the presence of HIV/HCV coinfection (p = 0.041) were each associated with higher risk for mortality. Baseline fibrosis score (p = 0.03) and an increase in FIB-4 score (p = 0.05) were independent predictors of all-cause mortality, but liver-related mortality was not evaluated. In this study, baseline fibrosis score was predictive of 7-year all-cause mortality. Further studies are needed in a prospective cohort to evaluate the predictive value of monitoring changes in fibrosis scores over time to predict mortality in patients with viral hepatitis.

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.

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 NorthernUganda. 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 Key words : HIV, HBV, Co-infection, Treatment

Abstract 30 Background and objective: Co-infection with Hepatitis B (HBV) and HIV is common in sub-Saharan Africa (SSA) and accelerates progression of liver disease to cirrhosis, hepatocellular carcinoma (HCC) and other complications. About 60% of HCC in Africa is attributed to HBV. In Uganda, 80% of HCC patients have HBV and 20% have HIV/HBV coinfection. HCC is the 4th commonest cancer among Ugandan males and the 6th commonest in females. It is almost always a fatal malignancy in SSA. Prevention of HBV is best achieved through vaccination. Vaccination of HIV-infected adults for HBV is standard of care in developed countries but not in SSA where HBV is believed to be acquired in childhood and where there is lack of HBV incidence data. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda. Methods: We screened stored sera from 944 HIV infected adults enrolled in the Rakai Community Cohort Study between September 2003 and March 2015 for evidence of HBV exposure using the anti-HBc marker. Serum from participants who tested anti-HBc negative (497) at the baseline round was tested over 3-7 consecutive survey rounds for either anti-HBc or HBsAg sero-conversion. The time of HBV incidence was defined as the median date between the last anti-Hbc or HBsAg negative sample and the first positive anti-HBc or HBsAg serum sample. Almost all ART treatment regimens contained at least one HBV active medication. Exact poisson incidence methods were used to estimate the incidence of HBV with 95% confidence intervals while the Cox proportional regression methods were used to estimate adjusted hazard ratios of ART use and other confounders. Results: Thirty nine infections occurred (8 positive for both HBsAg and anti-HBc, 3 for HBsAg only, and 28 for anti-HBc only) over 3,342 person-years (pys), incidence 1.17/100 person-years. HBV incidence was significantly lower with ART use: 0.48 /100 person-years with ART use and 2.34/100 person-years without ART (p400copies/mL (p400copies/mL, aHR= 6.4(2.2-19.0) and by age: 40-50 years versus 15-29 years, aHR= 3.66 (1.3-10.2); 40-50 years versus 30-39 years, aHR=2.18(0.9-5.4). No new HBV infections occurred among participants on a tenofovir-based regimen and there was no statistical significant differences by gender, occupation, marital status or number of sex partners, duration on ART or baseline CD4 count. Conclusion: The protective effects of HBV-active ART medications underscores additional benefits of earlier initiation of ART. Ongoing HBV transmission demonstrated by this study represents an opportunity for vaccine preventive strategies which could ultimately significantly reduce the burden of HCC in SSA. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Emmanuel Seremba No relationship to disclose Victor Ssempijja No relationship to disclose Sarah Kalibbala No relationship to disclose Ronald Gray No relationship to disclose Maria Wawer No relationship to disclose Fred Nalugoda No relationship to disclose Corey Casper Consulting or Advisory Role: Temptime Corporation, GlaxoSmithKline Research Funding: Janssen Pharmaceuticals Travel, Accommodations, Expenses: GlaxoSmithKline, TempTime Warren T. Phipps No relationship to disclose Ponsiano Ocama No relationship to disclose David L. Thomas No relationship to disclose Steven J. Reynolds No relationship to disclose

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. Keywords: HIV, S.Mansoni , peri-portal fibrosis

Introduction: Uganda is among the top ten consumers of alcohol worldwide though there is little data on alcohol related liver disease. We describe alcohol use, alcohol misuse, and alcoholic liver disease among adults at the emergency admission service of a large urban hospital in Uganda. Methods: All adults who consented were prospectively evaluated for alcohol use by inquiry and alcohol misuse by the "Cutting down, Annoyance, Guilt and Eye-opener- CAGE" questionnaire. Alcohol related hepatocellular liver injury was assessed using aspartate aminotransferase, and alanine aminotransferase levels. A combination of CAGE score ≥2 and De Ritis ratio ≥2 defined alcoholic liver disease (ALD). Human Immunodeficiency Virus (HIV), and viral hepatitis B and C serologies were evaluated in all the patients. Descriptive and inferential statistics were generated to answer our research questions. Results: Three hundred and eighty individuals consented and participated in the study. Among these, 46.8% acknowledged use of alcohol while 21% and 10% met the study definition of alcoholic misuse and alcoholic liver disease respectively. Both alcohol misuse and alcoholic liver disease was significantly associated (p-value ≤ 0.05) with male gender, region of origin, number of life time sexual partners and serum albumin below 3.5 mg/dl after univariate and multivariate analysis. Conclusion: Alcohol misuse and alcoholic liver disease is frequent in this medical emergency unit. Our study suggests a link between alcohol misuse or alcoholic liver disease and male gender, region of origin, number of sexual partners, and serum albumin below 3.5mg/dl.Key words: Alcohol use, alcohol misuse, alcoholic liver disease, aspartate aminotransferase, alanine aminotransferase, CAGE questionnaire, De Ritisratio

Very little has been published about acute transfusion reactions (ATRs) in developing countries. This study was undertaken to determine the incidence, type, imputability, severity, and possible associated factors of ATRs observed in a university-affiliated hospital in Uganda.We prospectively followed the transfusion of blood units issued over a 7-week period from the hospital blood bank during regular working hours to nonbleeding patients. For each transfusion, we recorded the patient's status before, during, at the end of, and 4 hours after transfusion. Three physicians independently reviewed all reports of suspected ATRs and related hospital charts. Using predefined criteria, the presence, type, imputability, and severity of ATRs were adjudicated by consensus of two of three physicians. Factors potentially associated with ATRs were analyzed for statistical significance.A total of 507 transfusions were analyzed. Fifty-three acute transfusion events were recorded and 49 of 53 or 9.6% of the 507 transfusions were confirmed to be ATRs by physician consensus: 24 febrile, seven allergic, five hypertensive, three hypotensive, three transfusion-associated circulatory overload, two acute hemolytic, and five others. Imputability of ATRs was definite, probable, or possible in 45 of 49 ATRs (92% of ATRs or 8.9% of transfusions) and judged to be severe in nine of 45. No significant associated factors were identified.Our findings suggest that ATRs may occur more commonly in resource-limited settings than in high-income countries. Although some reactions are unavoidable, improved surveillance of transfusions and implementation of transfusion guidelines could improve the safety of transfusions in these settings.

Background: We determined the prevalence and factors associated with hyperlactatemia among HIV patients admitted on the emergency ward of a national hospital in Uganda. Objective: We were specifically interested in knowing whether there was an association between clinically significant hyperlactatemia and concurrent antiretroviral therapy (ART) use. Methods: A cross sectional descriptive study enrolled 303 HIV infected patients at a national referral hospital between March and April 2008. We consecutively recruited all eligible HIV infected patients above 18 years admitted on the emergency ward. Data were collected on socio-demographic, clinical and laboratory characteristics. Lactate levels were measured using the Accutrend (R) portable lactate analyser. Data analysis was performed using Stata 10.0; P-value of = 2.5mmol/L) was 252 (83.2%). Clinically significant hyperlactatemia (lactate >= 4mmol/L) was present in 105/303(34.6%) patients. There was no association between use of ART and clinically significant hyperlactatemia. In the multivariate analysis, body weakness 1.91 (1.09-3.35), skin rash 3.18 (1.11-9.10) and tachypnoea 1.04 (1.01-1.07) were independently associated with clinically significant hyperlactatemia. Conclusion: There was a high prevalence of clinically significant hyperlactatemia among HIV infected patients but it was not associated with concurrent antiretroviral use. African Health Sciences 2012; 12(3): 268 - 275 http://dx.doi.org/10.4314/ahs.v12i3.4

Background: Hepatitis B virus (HBV) is the commonest cause of primary hepatocellular (PHC) carcinoma worldwide. Coinfection with the HIV leads to more rapid progression of liver disease. Objectives: We described prevalence of HBV and HIV among patients with PHC admitted to Mulago Hospital, Kampala, Uganda. Methods: We assessed all patients admitted to the gastrointestinal service of Mulago hospital with a diagnosis of PHC for HBV and HIV infection. Results: From March to June 2008, we recruited 15 patients. Nine (60%) were male; the overall median age was 32 years (IQR 15 -67), with median ages for male and female 33 and 36 years respectively. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and AFP were all elevated with median values of 57.5 IU/L, 222 IU/L, 392 IU/L and 362 ng/ml respectively (IQR 14-145, 49-393, 165-1294 and 7-480). Eight (53%) patients were from North and Northeastern Uganda. The HBsAg was reactive in 13(87%) patients and HIV in 3(20%), all of whom were also co-infected with HBV. Conclusion: There is high prevalence of HBV and HBV/HIV co-infection among patients with PHC in Uganda with high mortality. Reduction in incidence and mortality due to PHC in Uganda will require urgent large scale HBV vaccination. Key Words: Hepatitis B, HIV, Primary Hepatocelular Carcinoma

PURPOSE OF REVIEW To provide an update on the epidemiology and management of HIV and hepatitis C virus (HCV) in resource-limited settings (RLSs). RECENT FINDINGS The global prevalence of HIV is 33.3 million people of whom 22.5 million live in sub-Saharan Africa. Hepatitis C affects 170 million people globally with majority of the infected persons living in sub-Saharan Africa and other RLSs. Transmission of these viruses varies greatly even within the RLSs. In the RLSs in Europe, Asia and Central/South America, most transmissions occur through injection drug use, whereas in Africa use of needles for medical treatment and blood transfusion may be the main modes of transmission. However, generally there is a rise in injection drug use even in RLSs. SUMMARY Hepatitis C and HIV are common infections and are more prevalent in RLSs, but there are regional differences in transmission even in RLSs. Treatment is difficult in some of the RLSs and prevention by screening donor blood as well and use of sterile instruments in treatment of patients will be important in curbing transmission in some of these settings.

The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF. The US Acute Liver Failure Study Group, a 23-site registry, prospectively enrolled 1,413 patients with ALF with different etiologies between 1998 and 2008. Of those, 105 patients were identified as HBV-ALF patients, of whom we excluded those without data on NA use or with co-infection with hepatitis C, leaving 85 patients, 43 of whom had received NA treatment. HBV-DNA on admission was quantified by real time polymerase chain reaction. The treated and untreated groups were similar in most respects but differed significantly in regard to higher aminotransferase and bilirubin levels and hepatic coma grades, all being observed in the untreated group. Median duration of NA treatment was 6 days (range, 1–21 days). Overall survival in the NA treated and untreated groups were 61 and 64%, respectively (P = 0.72). Rates of transplant-free survival were 21 and 36% in the treated and untreated groups, respectively (P = 0.42). Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1–18.1, P = 0.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3–62.8, P

Most hepatitis C testing in Uganda is performed using commercial rapid strip assays (RSA) to detect antibodies to hepatitis C virus (anti-HCV), rather than enzyme immunoassays (EIA). The prevalence of hepatitis C antibodies in a Ugandan hospital population was determined using both methods to test their accuracy using nucleic acid testing (NAT) as a reference. Sera from 380 consecutive hospitalized Ugandan patients were tested for anti-HCV using an RSA in Uganda, with subsequent automated third-generation EIA testing in the United States, followed by NAT. Recombinant immunoblot assays (RIBA) were used as a supplementary test to detect anti-HCV epitopes. Overall, anti-HCV was detected in 48/380 (13%) by one or both antibody tests. Anti-HCV was detected in 19 (5.0%) patients by RSA and in 33 (8.7%) patients by EIA; only four patients were anti-HCV positive by both methods. Fourteen of the 48 anti-HCV positive patients had detectable serum HCV RNA, 7 each by bDNA assay or by PCR. RSA detected only 7 of 14 HCV RNA positive sera. Of 29 RNA negative but anti-HCV positive patients tested by RIBA, only two were anti-HCV positive; 27 were anti-HCV negative or indeterminate. Anti-HCV testing by RSA and/or EIA was neither sensitive nor specific for detection of ongoing HCV infection in hospitalized Ugandan patients. Our findings underscore the importance of confirmatory nucleic acid testing, which, despite its increased cost, appears essential to manage African patients with HCV.

Commercially available rapid strip assays (RSAs) for hepatitis B surface antigen (HBsAg) are used for most routine clinical testing in sub-Saharan Africa. This study evaluated the validity of RSA and a more sophisticated enzyme immunoassay (EIA) with confirmation by nucleic acid testing (NAT) in hospitalized patients in Uganda. Sera from 380 consecutive patients collected and tested for HBsAg and anti-HIV in Kampala, Uganda by RSA were sent frozen to Dallas for EIA including HBsAg, total anti-hepatitis B core, hepatitis B e antigen, and anti-HIV. NAT was performed on all HBsAg-positives and on a random sample of 102 patients that were HBsAg-negative by both assays. Overall, 31 (8%) were HBsAg positive by RSA while 50 (13%) were HBsAg-positive by EIA; 26 were concordant between the two assays. Of 55 HBsAg-positive patients, nearly all showed detectable serum hepatitis B virus (HBV) DNA by bDNA (46) or PCR (4) assay. The 26 patients who were HBsAg positive by both EIA and RSA had significantly higher median serum HBV DNA levels than the 24 patients who were HBsAg positive by EIA alone. An additional 12/102 (12%) HBsAg negative patients had very low serum HBV DNA levels by NAT. Several differences in expected results of serologic testing were observed in this large series of African patients. RSA HBsAg testing is less sensitive than EIA; even EIA failed to detect all HBV DNA positive sera. A more complex testing protocol than RSA alone will be needed in Africa to improve patient care.

Anaemia increases morbidity and mortality in patients with congestive cardiac failure (CCF). Few studies have examined the prevalence of anaemia and its impact among patients with CCF in sub-Saharan Africa. We assessed the prevalence of anaemia and its influence on treatment outcome in patients with CCF attending a large referral hospital in Kampala, Uganda.Echocardiography was done and haemoglobin levels were determined in 157 patients with CCF admitted to Mulago Hospital. The patients were followed up for 2 weeks and their treatment outcome was recorded.Of the 157 patients, 101 (64.3%) had anaemia (mean haemoglobin concentration/=11.9 g/dl for women and/=12.9 g/dl for men) at admission. Increasing age and hypertensive heart disease were significantly associated with anaemia (odds ratio (OR) 2.92, confidence interval (CI) 1.41 - 6.05, p0.01 and OR 0.31, CI 0.13 - 0.74, p0.01, respectively). In-hospital mortality at the end of the 2 weeks of treatment was 10.2% and was significantly higher among the anaemic patients than their non-anaemic counterparts (OR 4.9, CI 1.07 - 22.35, p0.03). The mean duration of in-hospital stay was 7.5 (significant deviation 3.4) days. This did not differ significantly between anaemic and non-anaemic patients.The prevalence of anaemia among patients with CCF attending Mulago Hospital was high. Anaemia in these patients was significantly associated with mortality by the end of 2 weeks of treatment.

Acute liver failure remains a unique syndrome that results from massive loss of hepatocytes or hepatocyte function due to a variety of etiologies: viruses, drugs, toxins and other genetic and autoimmune conditions. The resulting clinical picture is remarkably similar across the different etiologies, reflecting common patterns of response of the innate immune system and the resulting inflammatory response. This review highlights developments in the delineation of etiologies of this relatively rare condition.The contribution of different etiologies to the overall picture varies by country. Europe and North America demonstrate a large proportion of cases due to acetaminophen and to idiosyncratic drug reactions, whereas reports from emerging countries in Asia and Africa are more likely to feature viral illnesses, particularly hepatitis B and E. Recent studies have suggested ever more exotic etiologies, new drugs and viruses.A careful search for the cause of acute liver failure in each case is of value in determining whether there are specific antidotes available and what the prognosis might be.

Sub-Saharan Africa is probably the region with the worst health indices in the region. Although health problems in this region are largely preventable through a good primary health care system, efforts to implement such a system have not been so successful and neither have reforms suggested by the World Bank. However, there are new efforts to improve delivery of health care by introducing family medicine in the region through decentralized health care systems. Uganda is at the forefront of these efforts, and ways to integrate family physicians into the health system are still being debated. This paper reviews the potential role of family medicine/general practice in the health care systems of sub-Saharan Africa and in Uganda in particular and offers suggestions based on successes made in other countries.

Introduction : Splanchnic venous thrombosis (SVT) has varied etiology with Philadelphia-negative myeloproliferative neoplasms (MPNs) being the most frequent underlying prothrombotic factor. Hematological indices often remain within normal range because of portal hypertension and its sequelae, causing diagnostic challenges. The high frequency of JAK2 mutation among patients with SVT reinforces the diagnostic utility of JAK2 V617F testing. Case report : We report a case of a 62-year-old black man with progressive abdominal swelling and features of decompensated chronic liver disease found to have SVT-portal vein thrombosis and how JAK2 V617F was useful in unmasking an underlying myeloproliferative neoplasm. Conclusion : A high index of suspicion for an underlying prothrombotic factor is critical for patients presenting with thrombosis in unusual sites. This is useful in prognostic stratification and patient outcomes. JAK2 mutation screening is now part of the standard diagnostic workup in SVT. Keywords : venous thrombosis, myeloproliferative neoplasm.