Charles A. Onyekwere

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

Problem of hepatocellular carcinoma in West Africa

The incidence of hepatocellular carcinoma (HCC) is known to be high in West Africa with an approximate yearly mortality rate of 200000. Several factors are responsible for this. Early acquisition of risk factors; with vertical or horizontal transmission of hepatitis B (HBV), environmental food contaminants (aflatoxins), poor management of predisposing risk factors and poorly-managed strategies for health delivery. There has been a low uptake of childhood immunisation for hepatitis B in many West African countries. Owing to late presentations, most sufferers of HCC die within weeks of their diagnosis. Highlighted reasons for the specific disease pattern of HCC in West Africa include: (1) high rate of risk factors; (2) failure to identify at risk populations; (3) lack of effective treatment; and (4) scarce resources for timely diagnosis. This is contrasted to the developed world, which generally has sufficient resources to detect cases early for curative treatment. Provision of palliative care for HCC patients is limited by availability and affordability of potent analgesics. Regional efforts, as well as collaborative networking activities hold promise that could change the epidemiology of HCC in West Africa.

Application of stool-PCR for the diagnosis of Helicobacter pylori from stool in Nigeria- a pilot study

There are various methods for detection of Helicobacter pylori and the gold standard for non-invasive detection is the urea breath test (UBT). The aim of the study is therefore to detect H. pylori from the stool of patients with dyspepsia by PCR and compare results obtained with UBT. A total of 97 stool samples from patients presenting with dyspeptic symptoms in Lagos University Teaching Hospital (LUTH) were screened for urea breath test (UBT) and the presence of H. pylori DNA using stool-PCR. Out of 97 stool samples analysed, 38 (39.2%) were positive for Helicobacter spp. and 20 (20.6%) positive for H. pylori by PCR, through amplification of 16S rRNA and glmM genes respectively. Of the 20 positive by glm M gene, the cagA gene was detected in 8 (40%) samples, while 47 (48.5%) out of 97 stool samples were positive for H. pylori by UBT. The sensitivity and specificity of the glmM gene compared with UBT as the gold standard is 42.6% and 100% respectively. The positive predictive value (PPV) was 100% while the negative predictive value (NPV) was 60%.The method may be useful for detecting H. pylori from stool amongst children especially where most hospitals lack endoscope for children although the method is expensive.

Hepatitis B and C virus prevalence and association with demographics: report of population screening in Nigeria

Hepatitis B and C remain a major cause of chronic liver disease worldwide with its attendant consequences. The burden of these viral infections in sub-Saharan Africa including Nigeria rely on estimates based on small population studies in some select populations. We present the report of a population survey in Nigeria during the period 2010–2012. A total of 5,558 adults participated in the screening exercise. The minimum age recorded was 18 years, while the maximum age was 75 years. The mean ± S.D. was 36.07 ± 8.76 years. The prevalence of hepatitis B (HBsAg) among the adults screened was determined to be 6.7% while that of hepatitis C (HCV) was 0.9%. The peak prevalence for HBsAg carriage was in the third to fourth decade in keeping with childhood acquisition while of HCV antibody was in the sixth to seventh decade. Male gender was significantly associated with HBsAg carriage while we noted a higher prevalence in those within the lower socioeconomic status. Overall our findings suggest that hepatitis B is endemic in Nigeria, much less than previously reported, while the prevalence for HCV is low although reports of pockets of high prevalence exist in select populations (hospital patients including those living with HIV).

Chronic liver disease and hepatic encephalopathy: Clinical profile and outcomes

BACKGROUND Hepatic encephalopathy (HE) is an important neuropsychiatry complication of liver disease causing significant morbidity and mortality worldwide. Efforts at improving the outcome have resulted in development of new strategies in the management given the background of new insights in the pathogenesis of this disease entity. Understanding the disease profile including precipitants as well as prognostic factors will contribute in this regard as new strategies are yet to be widely applied. The aim of this report is to document the profile of patients with HE, the precipitants, prognostic factors as well as the scope of the burden associated with it. MATERIALS AND METHODS In this prospective study, all patients managed for HE from January to December 2008 were recruited. A questionnaire was used to extract their basic demographics, clinical features noting any possible precipitants, complications, management protocol as well as outcome. RESULTS A total of 21 subjects (11 females and 10 males) within the age range of 16-83 years were seen during the period under review. (mean age 57.9 ± 13). There was no significant difference in the mean ages of males and females. Two patients had acute encephalopathy, while others had acute-on chronic encephalopathy. The risk factors for liver disease included significant alcohol ingestion, hepatitis B virus infection, and previous jaundice, while other complications of liver disease noted were deepening jaundice, ascites, bleeding tendencies, and renal failure. The identified precipitants for HE were sepsis 6 (29%), electrolyte inbalance 3 (14%), gastrointestinal bleed 5 (24%), drugs (5%), and possible malignant transformation 6 (29%). Focus of sepsis was bacterial peritonitis in two cases. Majority of our patients (61%) came during advanced stage of liver disease (Child-Pugh class C). Length of hospital stay ranged from 1 to 7 weeks and a mortality of 48% was observed. Predictors of mortality were a history of significant alcohol ingestion, previous blood transfusion, Hepatitis B and C infections, and severe liver dysfunction on presentation (Child-Pugh class C). CONCLUSIONS HE is associated with a high mortality rate and this scenario is associated with a history of previous blood transfusion, Hepatitis B and C infections, and severe liver dysfunction on presentation. Measures to reduce the burden of viral Hepatitis B and C, safe blood transfusion, and responsible use of alcohol should be promoted. Screening of those at risk of encephalopathy (liver disease patients) with a psychometric test of good predictability should be part of their routine evaluation in daily practice so as to detect cases of latent encephalopathy. Intensive care facilities and necessary personnel should be provided.

Ulcerative colitis in a Nigerian girl: A case report

BackgroundUlcerative colitis (UC) is uncommon in the tropics and sub-tropics. We report a case of UC in a 7 year old girl whose parents were both Nigerians. This report is to alert healthcare professionals in sub-Saharan Africa that UC is not a rare health problem, especially in children.Case presentationThe patient presented with frequent passage of blood stained stool, abdominal pain and significant weight loss. The diagnosis was entertained after she was investigated for common causes of chronic diarrhea in our setting and the findings were negative. The patient symptoms abated after she was commenced on steroid therapy.ConclusionUnder-diagnosis and misdiagnosis may account for a dearth of information on UC in African children.

Helicobacter pylori strains from a Nigerian cohort show divergent antibiotic resistance rates and a uniform pathogenicity profile

Antibiotic resistance in Helicobacter pylori is a factor preventing its successful eradication. Particularly in developing countries, resistance against commonly used antibiotics is widespread. Here, we present an epidemiological study from Nigeria with 111 isolates. We analyzed the associated disease outcome, and performed a detailed characterization of these isolated strains with respect to their antibiotic susceptibility and their virulence characteristics. Furthermore, statistical analysis was performed on microbiological data as well as patient information and the results of the gastroenterological examination. We found that the variability concerning the production of virulence factors between strains was minimal, with 96.4% of isolates being CagA-positive and 92.8% producing detectable VacA levels. In addition, high frequency of bacterial resistance was observed for metronidazole (99.1%), followed by amoxicillin (33.3%), clarithromycin (14.4%) and tetracycline (4.5%). In conclusion, this study indicated that the infection rate of H. pylori infection within the cohort in the present study was surprisingly low (36.6%). Furthermore, an average gastric pathology was observed by histological grading and bacterial isolates showed a uniform pathogenicity profile while indicating divergent antibiotic resistance rates.

Nonalcoholic fatty liver disease: Synopsis of current developments.

Non-alcoholic fatty liver disease (NAFLD) which is defined as the accumulation of fat>5% of liver weight is increasingly becoming an important cause of chronic liver disease. This article tries to chronicle advances that have occurred in the understanding of the pathogenesis, pathology as well as the management of this disease. We have done a Medline search on published work on the subject and reviewed major conference proceedings in the preceding years. The Pathogenesis involves a multi-hit process in which increased accumulation of triglycerides in face of insulin resistance results in increased susceptibility to inflammatory damage mediated by increased expression of inflammatory cytokines and adipokines, oxidative stress and mitochondrial dysfunction, endoplasmic reticulum stress and gut derived endotoxemia. An interplay of multiple metabolic genetic expression and environmental factors however determine which patient with NAFLD will progress from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. The minimum criteria for diagnosis of NASH are steatosis, ballooning and lobular inflammation; fibrosis is not required. The NASH Clinical Research Network (CRN), histological scoring system is used to grade and stage the disease for standardization. The management of NAFLD consists of treating liver disease as well as associated metabolic co-morbidities such as obesity, hyperlipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM). Patient education is important as their insight and commitment is pivotal, and lifestyle modification is the first line of treatment. Improvement in liver histology in non-diabetic NASH patients has been reported with use of Vitamin E. Other liver-related therapies under investigations include pentoxyfiylins, Caspar inhibitors, Resveratrol as well as probiotics. The prognosis (both overall and liver-related mortality) for simple steatosis is not different from that of the general population however.

Hepatitis C Virus (HCV) Prevalence in Special Populations and Associated Risk Factors: A Report From a Tertiary Hospital.

Background With the advent of highly effective anti-hepatitis C virus (HCV) drugs, efforts to identify infected cases, high-risk groups, and associated risk factors have become the focus of current control measures. Objectives To determine the prevalence of the HCV antibody among diabetics and patients with lymphoproliferative disorders (LPD) who presented to the outpatient clinics of a university hospital and its associated risk factors Patients and Methods Consecutively consenting patients who had been previously diagnosed with diabetes mellitus and LPD at the outpatient department of the Lagos State University teaching hospital were recruited. A case record form was used to extract their demographics and physical examination findings as well as any risk factors for HCV infection; blood was also drawn to run a serological assay for the HCV antibody. All data were collated and analyzed using the Statistical Package for the Social Sciences version 20. Student T-test, Chi square, and logistic regression were some of the inferential statistics used in addition to descriptive statistics. Results In all, 438 patients (405 diabetics and 33 patients with LPD) were recruited. Their ages ranged from 17 - 87 years with a mean + Standard deviation of 59.61 + 11.859 years. The prevalence of hepatitis C among the diabetic subgroup was 0.7%, while the antibody was present in 9.1% of the LPD patients. The occurrence of the HCV antibody was, however, not significantly associated with age, sex, educational level, or marital status (P > 0.05). Having multiple sexual partners was identified as the only significant risk factor for hepatitis C (OR = 9.148; P = 0.017). Conclusions This survey suggested that a higher HCV prevalence exists in this population than is currently reported in the general population, and having sex with multiple partners was a risk factor for HCV infection.