Emmanuel Seremba

Risk Factors and Outcomes of Acute Kidney Injury in Patients With Acute Liver Failure

BACKGROUND & AIMSnPatients 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.nnnMETHODSnWe 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).nnnRESULTSnSeventy 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 (Pxa0< .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 1xa0year. 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.nnnCONCLUSIONSnBased 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.

Poor performance of hepatitis C antibody tests in hospital patients in Uganda

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. J. Med. Virol. 82:1371–1378, 2010.

Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure.

Background and AimsThe 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.MethodsThe 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.ResultsThe 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 (Pxa0=xa00.72). Rates of transplant-free survival were 21 and 36% in the treated and untreated groups, respectively (Pxa0=xa00.42). Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1–18.1, Pxa0=xa00.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3–62.8, Pxa0<xa00.001] and prothrombin time (PT) [OR 0.59, 95% CI 0.39–0.89, Pxa0=xa00.012] were predictors of improved transplant-free survival.ConclusionsPatients who are admitted with established HBV-ALF do not appear to benefit from viral suppression using nucleoside(tide) analogues presumably because of rapid disease evolution and short treatment duration. Despite the lack of benefit, NAs should still be given to transplantation candidates since viral suppression prevents recurrence after grafting.

Risk Factors and Seroprevalence of Hepatitis C among Patients Hospitalized at Mulago Hospital, Uganda

The emergence of hepatitis C virus (HCV) and its associated sequelae in Africa is a cause for significant concern. Human immunodeficiency virus (HIV) positive patients are at an increased risk of contracting HCV infection due to similar risk factors and modes of transmission. We investigated the seroprevalence of hepatitis C in hospitalized HIV-positive and HIV-negative patients in Mulago Hospital, an academic hospital in Uganda. Blood samples were first tested for HCV antibodies, and positive tests were confirmed with HCV RNA PCR. We enrolled five hundred patients, half HIV-positive and half HIV negative. Overall, 13/500 patients (2.6%) tested positive for HCV antibodies. There was no difference in HCV antibody detection among HIV-positive and HIV-negative patients. Out of all risk factors examined, only an age greater than 50 years was associated with HCV infection. Traditional risk factors for concurrent HIV and HCV transmission, such as intravenous drug use, were exceedingly rare in Uganda. Only 3 of 13 patients with detectable HCV antibodies were confirmed by HCV RNA detection. This result concurs with recent studies noting poor performance of HCV antibody testing when using African sera. These tests should be validated in the local population before implementation.

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

BACKGROUNDnHepatitis 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.nnnOBJECTIVESnTo determine burden of co-infection and HBV viral suppression among patients on ART in Northern Uganda.nnnMETHODSnWe 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.nnnRESULTSnThree 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).nnnCONCLUSIONnA 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.

Anaemia among patients with congestive cardiac failure in Uganda - its impact on treatment outcomes.

BACKGROUNDnAnaemia 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.nnnMETHODSnEchocardiography 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.nnnRESULTSnOf 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, p<0.01 and OR 0.31, CI 0.13 - 0.74, p<0.01, 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, p<0.03). 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.nnnCONCLUSIONnThe 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.

Diagnosis of alcohol misuse and alcoholic liver disease among patients in the medical emergency admission service of a large urban hospital in Sub-Saharan Africa; a cross sectional study

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.

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

INTRODUCTIONnBoth 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.nnnMETHODOLOGYnWe 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.nnnRESULTSnWe 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).nnnCONCLUSIONnWe 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.

Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda

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.

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 104u2009IUu2009ml−. Subjects with chronic HBV infection had a higher median VL compared to OBI patients (Pu2009<u20090.001). 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. J. Med. Virol. 88:674–680, 2016.