Abraham O. Malu

Characterization of urinary biomarkers of hepatocellular carcinoma using magnetic resonance spectroscopy in a Nigerian population.

Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy worldwide. Current serum diagnostic biomarkers, such as alpha-fetoprotein, are expensive and insensitive in early tumor diagnosis. Urinary biomarkers differentiating HCC from chronic liver disease would be practical and widely applicable. Using an 11.7T nuclear magnetic resonance system, urine was analyzed from three well-matched subject groups, collected at Jos University Teaching Hospital (JUTH), Nigeria. Multivariate factor analyses were performed using principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). All patients were of Nigerian descent: 18 hepatitis B surface antigen (HBsAg)-positive patients with HCC, 10 HBsAg positive patients with cirrhosis, and 15 HBsAg negative healthy Nigerian controls. HCC patients were distinguished from healthy controls, and from the cirrhosis cohort, with sensitivity/specificity of 100%/93% and 89.5%/88.9%, respectively. Metabolites that most strongly contributed to the multivariate models were creatinine, carnitine, creatine and acetone. Urinary (1)H MRS with multivariate statistical analysis was able to differentiate patients with HCC from normal subjects and patients with cirrhosis. Creatinine, carnitine, creatine and acetone were identified as the most influential metabolites. These findings have identified candidate urinary HCC biomarkers which have potential to be developed as simple urinary screening tests for the clinic.

Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium

BACKGROUND Hepatocellular carcinoma is a leading cause of cancer-related death in Africa, but there is still no comprehensive description of the current status of its epidemiology in Africa. We therefore initiated an African hepatocellular carcinoma consortium aiming to describe the clinical presentation, management, and outcomes of patients with hepatocellular carcinoma in Africa. METHODS We did a multicentre, multicountry, retrospective observational cohort study, inviting investigators from the African Network for Gastrointestinal and Liver Diseases to participate in the consortium to develop hepatocellular carcinoma research databases and biospecimen repositories. Participating institutions were from Cameroon, Egypt, Ethiopia, Ghana, Ivory Coast, Nigeria, Sudan, Tanzania, and Uganda. Clinical information-demographic characteristics, cause of disease, liver-related blood tests, tumour characteristics, treatments, last follow-up date, and survival status-for patients diagnosed with hepatocellular carcinoma between Aug 1, 2006, and April 1, 2016, were extracted from medical records by participating investigators. Because patients from Egypt showed differences in characteristics compared with patients from the other countries, we divided patients into two groups for analysis; Egypt versus other African countries. We undertook a multifactorial analysis using the Cox proportional hazards model to identify factors affecting survival (assessed from the time of diagnosis to last known follow-up or death). FINDINGS We obtained information for 2566 patients at 21 tertiary referral centres (two in Egypt, nine in Nigeria, four in Ghana, and one each in the Ivory Coast, Cameroon, Sudan, Ethiopia, Tanzania, and Uganda). 1251 patients were from Egypt and 1315 were from the other African countries (491 from Ghana, 363 from Nigeria, 277 from Ivory Coast, 59 from Cameroon, 51 from Sudan, 33 from Ethiopia, 21 from Tanzania, and 20 from Uganda). The median age at which hepatocellular carcinoma was diagnosed significantly later in Egypt than the other African countries (58 years [IQR 53-63] vs 46 years [36-58]; p<0·0001). Hepatitis C virus was the leading cause of hepatocellular carcinoma in Egypt (1054 [84%] of 1251 patients), and hepatitis B virus was the leading cause in the other African countries (597 [55%] of 1082 patients). Substantially fewer patients received treatment specifically for hepatocellular carcinoma in the other African countries than in Egypt (43 [3%] of 1315 vs 956 [76%] of 1251; p<0·0001). Among patients with survival information (605 [48%] of 1251 in Egypt and 583 [44%] of 1315 in other African countries), median survival was shorter in the other African countries than in Egypt (2·5 months [95% CI 2·0-3·1] vs 10·9 months [9·6-12·0]; p<0·0001). Factors independently associated with poor survival were: being from an African countries other than Egypt (hazard ratio [HR] 1·59 [95% CI 1·13-2·20]; p=0·01), hepatic encephalopathy (2·81 [1·72-4·42]; p=0·0004), diameter of the largest tumour (1·07 per cm increase [1·04-1·11]; p<0·0001), log α-fetoprotein (1·10 per unit increase [1·02-1·20]; p=0·0188), Eastern Cooperative Oncology Group performance status 3-4 (2·92 [2·13-3·93]; p<0·0001) and no treatment (1·79 [1·44-2·22]; p<0·0001). INTERPRETATION Characteristics of hepatocellular carcinoma differ between Egypt and other African countries. The proportion of patients receiving specific treatment in other African countries was low and their outcomes were extremely poor. Urgent efforts are needed to develop health policy strategies to decrease the burden of hepatocellular carcinoma in Africa. FUNDING None.

Hepatocellular carcinoma occurs at an earlier age in Africans, particularly in association with chronic Hepatitis B

Hepatocellular Carcinoma Occurs at an Earlier Age in Africans, Particularly in Association With Chronic Hepatitis B

Irritable bowel syndrome among patients attending General Outpatients' clinics in Jos, Nigeria

Irritable bowel syndrome (IBS) is a common disorder in the Western world. Its prevalence is yet to be fully determined in the African setting. This was a cross-sectional study of patients attending three General Outpatient clinics in Jos, Nigeria. Four hundred and eighteen randomly selected patients were interviewed using a structured questionnaire based on the Rome II diagnostic criteria for IBS. Excluded from the study were patients with established organic disease, memory problems, and pregnant women. Eighteen patients were excluded based on these criteria and 400 were analysed using Epi Info 2000 (Atlanta, Georgia, USA) statistical computer software. One hundred and thirty-two (33%) out of the 400 patients fulfilled the criteria for the diagnosis of IBS, the female to male ratio being 1.13 : 1. IBS was significantly associated with increasing age (P=0.03) and depression (P<0.001). The prevalence of IBS is high among patients attending primary care in the African setting with depression being the likely reason for seeking care.

A plausible causal link between antiretroviral therapy and increased blood pressure in a sub-Saharan African setting: A propensity score-matched analysis.

BACKGROUND The transition from association to causation could represent a fundamental step for taking preventive action against hypertension and its complications, especially among HIV-infected persons on antiretroviral therapy in sub-Saharan African countries. METHODS 406 consecutive HIV-infected adults attending a tertiary HIV clinic in semi-urban Nigeria were prospectively recruited between August and November 2014. These participants were stratified by antiretroviral treatment status. A propensity score matching model was fitted to examine the causal average treatment effects on the treated (ATT) of antiretroviral therapy on blood pressure. Propensity score matching entailed using nearest neighbour matching with a calliper width of 0.2 to achieve similarity in the baseline characteristics between participants naïve and exposed to antiretroviral therapy. RESULTS Matching HIV-infected patients naïve and exposed to antiretroviral therapy on the propensity score yielded a total of 303 participants - 229 antiretroviral-exposed and 74 antiretroviral-naïve - matched without any residual differences in the baseline characteristics between both groups of patients. In this propensity score-matched sample, the estimated ATT for the effects of antiretroviral therapy on systolic (7.85mmHg, 95% CI 3.72 to 15.68) and diastolic blood pressure (7.45mmHg, 95% CI 4.99 to 13.61) were statistically significant (P<0.001 for each). CONCLUSIONS There is a high probability that the epidemiological association between antiretroviral therapy and increased blood pressure be causal in nature among people living with HIV in sub-Saharan African settings. HIV-infected patients commencing antiretroviral treatment in these settings may require regular hypertension screening and other cardiovascular risk assessments.

Anti-CagA antibodies in Helicobacter pylori-positive patients and blood donors from Nigeria.

The prevalence of antibodies to CagA protein was evaluated in 174 Helicobacter pylori-positive subjects: 110 patients submitted to upper gastrointestinal endoscopy and 64 male blood donors. The patients were from different regions of Nigeria: Jos, North, Benue, West and East and the blood donors were from Jos. Sera were assayed for anti-CagA antibodies using Helicobacter p120, CagA ELISA (Viva Diagnostika, Hürth, Germany). Anti-CagA antibodies were detected in 104 (94.5%) patients and in 61 (95.3%) blood donors (P=1.0). Patients from the Benue region presented a lower frequency of anti-CagA antibodies than patients from the other regions (P=0.0004). When the subjects were stratified by age, a significant increase in IgG concentration was observed among the men (P=0.03) but not among the women (P=0.57) or among the blood donors (P=0.83). In conclusion, similarly to Asian countries, CagA-positive H. pylori infection is highly frequent in Nigeria.

Comparison of Simple Non-Invasive Tests for Liver Fibrosis with Histology of Chronic Hepatitis B Patients of African Descent

Background: We compared the diagnostic validity of three non-invasive tests of fibrosis: age to platelet index, aspartate transaminase to platelet ratio index and aspartate transaminase to alanine transaminase ratio to histology fibrosis stage among Africans chronically infected with the hepatitis B virus. Methods: Ninety treatment-naive chronic hepatitis B patients were subjected to liver biopsy. Excluded from the study were patients with HCV and HIV co-infection, and significant alcohol consumption. Staging was performed using the Metavir system, whereas AST, ALT, and platelet count were determined using manual methods, within 4 weeks of liver biopsy. Results of fibrosis score and markers of fibrosis were compared using EPI Info 2005 version 3.3.2. Results: The mean age of the study population was 31.8 ± 8.9 years. Fibrosis stages and AAR, API and APRI scores were positively correlated, respective correlation coefficients being 0.48, 0.48 and 0.22 ( p %lt; 0.0001). Their positive predictive values were ...