Hatim Mudawi

Molecular characterization of hepatitis B virus in liver disease patients and asymptomatic carriers of the virus in Sudan

BackgroundHepatitis B virus is hyperendemic in Sudan. Our aim was to molecularly characterize hepatitis B virus from Sudanese individuals, with and without liver disease, because genotypes play an important role in clinical manifestation and treatment management.MethodsNinety-nine patients - 30 asymptomatic, 42 cirrhotic, 15 with hepatocellular carcinoma, 7 with acute hepatitis and 5 with chronic hepatitis- were enrolled. Sequencing of surface and basic core promoter/precore regions and complete genome were performed.ResultsThe mean ± standard deviation, age was 45.7±14.8 years and the male to female ratio 77:22. The median (interquartile range) of hepatitis B virus DNA and alanine aminotransferase levels were 2.8 (2.2-4.2) log IU/ml and 30 (19–49) IU/L, respectively. Using three genotyping methods, 81/99 (82%) could be genotyped. Forty eight percent of the 99 patients were infected with genotype D and 24% with genotype E, 2% with putative D/E recombinants and 7% with genotype A. Patients infected with genotype E had higher frequency of hepatitis B e antigen-positivity and higher viral loads compared to patients infected with genotype D. Basic core promoter/precore region mutations, including the G1896A in 37% of HBeAg-negative individuals, could account for hepatitis B e antigen-negativity. Pre-S deletion mutants were found in genotypes D and E. Three isolates had the vaccine escape mutant sM133T.ConclusionSudanese hepatitis B virus carriers were mainly infected with genotypes D or E, with patients infected with genotype E having higher HBeAg-positivity and higher viral loads. This is the first study to molecularly characterize hepatitis B virus from liver disease patients in Sudan.

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.

Prevalence of hepatitis B virus infection in the Gezira state of central Sudan.

AIM This is a cross-sectional study to determine the prevalence and risk factors for transmission of hepatitis B virus (HBV) infection in the Gezira state of central Sudan prior to the introduction of blood screening and vaccination against HBV. MATERIALS AND METHODS The study was carried out on the population of Um Zukra village in Gezira state of Central Sudan. The village was surveyed on five consecutive days in Dec 2000. Epidemiological characteristics were recorded and participants were interviewed for risk factors of viral hepatitis. Blood samples were then collected and tested for HBsAg and HBcAb. RESULTS A total of 404 subjects were screened with a mean age of 35 years; 54.9% were females, HBsAg and HBcAb were reactive in 6.9% and 47.5% of the studied population, respectively. Exposure to HBV increased with increasing age. The only significant risk factor for transmission of infection was a history of parenteral antischistosomal therapy. CONCLUSION This study shows that prevalence of HBV infection is high in the studied population and it is hoped that introduction of blood screening and vaccination against HBV would decrease the carrier pool in the next few years.

Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan

OBJECTIVES Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common routes of blood-borne transmission. In HBV mono-infected Sudanese individuals, genotypes D, E, and A circulate. The objective of this study was to molecularly characterize HBV from HBV/HIV co-infected individuals. METHODS The polymerase overlapping the S region and the basic core promoter (BCP/PC) of HBV from 32 hepatitis B surface antigen (HBsAg)-positive and 18 HBsAg-negative serum samples were amplified and sequenced. RESULTS HBV from 37 samples was successfully genotyped and the genotype distribution was 46.0% D, 21.6% E, 18.9% A, and 13.5% D/E recombinant. Compared to mono-infected individuals, the frequencies of the D/E recombinant and genotype A were higher in HBV/HIV co-infected patients, as was the intra-group divergence of genotype E. BCP/PC mutations affecting hepatitis B e antigen (HBeAg) expression at the transcriptional and translational levels were detected. Two HBsAg-positive individuals had pre-S deletion mutants. The following mutations in the S region could account for the HBsAg negativity: sM133T, sE164G, sV168G, and sS174N. No primary drug resistance mutations were found. CONCLUSIONS In HBV/HIV co-infected Sudanese patients, the ratio of genotype A to non-A was higher than that in mono-infected patients. The genotype E intra-group divergence in HBV/HIV co-infected individuals was significantly higher than that in HBV mono-infected patients.

Paediatric gastrointestinal endoscopy: experience in a Sudanese university hospital.

We investigated the indications for and findings of gastrointestinal (GI) endoscopy in all children < or = 16 years old referred for the procedure to the endoscopy unit at Soba University Hospital, Khartoum from January 2004 to January 2006. Thus 113 children were enrolled; 73% underwent upper GI endoscopy, 27% lower GI endoscopy (15% colonoscopy, 12% flexible sigmoidoscopy). Indications for upper GI endoscopy included haematemesis (24%), portal hypertension (21%), abdominal pain (16%) and vomiting (15%). Diagnoses included oesophageal varices (16%), gastritis (7%) and hiatus hernia (6%). Indications for lower GI endoscopy included rectal bleeding (87%), diarrhoea (19%) and anaemia (10%).

Overt and occult hepatitis B virus infection in adult Sudanese HIV patients

OBJECTIVES Human immunodeficiency virus (HIV) infection in Sub-Saharan Africa is complicated by co-infection with hepatitis B and C viruses (HBV and HCV), which share similar transmission routes. The aims of this study were to determine the prevalence of hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative HBV infection and of HCV infection among HIV-infected patients. METHODS A cross-sectional study was conducted among treatment-naïve HIV-positive adults in Khartoum State. HBV, HCV, and HIV infections were detected using immunoassays for HBsAg, hepatitis B core antibodies (anti-HBc), hepatitis C antibodies (anti-HCV), and HIV antibodies (anti-HIV), while real-time PCR was used to measure HBV DNA. RESULTS The mean age of the 358 patients was 35.2±9.3 years and the male to female ratio was 1.3:1.0. The mean alanine aminotransferase (ALT) level was 10.9±18.0 U/l. Evidence of 23, current or past HBV infection was detected in 62.8% of the patients. HBV DNA was detected in 96 patients (26.8%), 42 HBsAg-positive (11.7%) and 54 (15.1%) HBsAg-negative, indicating occult hepatitis B infection. Anti-HCV was detected in 1.7%. CONCLUSIONS Evidence of HBV infection was detected in 26.8% of HIV patients with HBsAg-negative infection, with viraemia detected in 15.1% of the patients. All HIV-infected patients should be screened carefully for HBV infection with HBsAg and anti-HBc IgG antibodies prior to starting antiretroviral therapy.

Malignant gastric tumors in Sudan

Hematol Oncol Stem Cell Ther 1(2) April 2008 hemoncstem.edmgr.com 130 Gastric cancer is the second leading cause of death due to cancer worldwide.1 Its incidence varies widely in the world with Costa Rica and Japan having the first and the second highest incidence rates in the world.1,2 The risk for developing gastric cant cer in North Africa and the Middle East is less than in the developed countries.3 There is little information on the frequency of gastric malignancies in the rest of Africa. Previous reports from Sudan showed that these tumors were uncommon.4 Most of the cases were ret ported before endoscopy was introduced in the country in the last twenty years. The purpose of this paper is to report on the frequency of gastric malignancies seen in one pathology center over a period of 5 years in Sudan.

Prevalence of gastric varices and portal hypertensive gastropathy in patients with Symmers periportal fibrosis.

BACKGROUND AND OBJECTIVE Symmers’ periportal fibrosis secondary to schistosomiasis is a common cause of portal hypertension worldwide. Data on the prevalence of gastric varices and portal hypertensive gastropathy in this group of patients with portal hypertension is relatively scarce. The aim of this study was to determine the prevalence of gastric varices and portal hypertensive gastropathy in patients presenting with portal hypertension secondary to Symmers’ periportal fibrosis. PATIENTS AND METHODS In a prospective study, upper gastrointestinal endoscopy was carried out to determine the prevalence of gastric varices and portal hypertensive gastropathy in patients with portal hypertension secondary to Symmers’ periportal fibrosis. RESULTS Of 143 patients studied, 24 patients (16.8%) had gastric varices (grade I in 10.5%, grade II in 6.3%) and 31 patients (21.7%) had portal hypertensive gastropathy (mild in 11.2%, severe in 10.5%). Gastric varices were more prevalent in patients with grade I and II esophageal varices and portal hypertensive gastropathy was more prevalent in those with grade III and IV esophageal varices, but the differences were not statiscally signifant. CONCLUSION We concluded that both gastric varices and portal hypertensive gastropathy seem to have a lower prevalence in patients with portal hypertension secondary to Symmers’ periportal fibrosis when compared to reported data in patients with portal hypertension secondary to liver cirrhosis and non-cirrhotic portal fibrosis.

Schistosomal colitis without granuloma formation in a kidney transplant recipient

Background A 40-year-old male from the White Nile region in Sudan, who had received a kidney transplant 6 years previously, presented with fever, lower abdominal pain and diarrhea stained with blood of 5 months duration. He was on immunosuppressive maintenance therapy, consisting of ciclosporin 75 mg twice daily, prednisolone 10 mg once daily, and azathioprine 75 mg once daily.Investigations Laboratory investigations, liver function tests, renal function tests, stool microscopy, stool culture, abdominal ultrasound, and colonoscopy.Diagnosis Severe, left-sided colitis due to Schistosoma mansoni infection, without granuloma formation.Management Oral antischistosomal therapy with praziquantel at a dose of 40 mg/kg body weight.

Use of endoscopy in diagnosis and management of patients with dysphagia in an African setting.

The objectives of this study were to define the utility of esophagogastroduodenoscopy in the diagnosis and management of patients presenting with dysphagia and to determine the relative incidence of the various causes of dysphagia in Sudan. This is a prospective, cross-sectional, descriptive, hospital-based study carried out at the endoscopy unit of Soba University Hospital, Khartoum, Sudan. All patients complaining of dysphagia underwent upper gastrointestinal endoscopy with therapeutic intervention when necessary. A total of 114 patients were enrolled in the study, with a mean age of 47 years SD +/- 19 and a male to female ratio of 1 : 1.04. A benign condition was diagnosed in 56% of the cases; this included esophageal strictures in 21% of the cases and achalasia in 14%. Malignant causes were mainly due to esophageal cancer (40.4%) and cancer of the stomach cardia (3.5%). Therapeutic intervention was attempted in 83% of the cases. Risk factors predictive of a malignant etiology were age over 40 years (P < 0.000), dysphagia lasting between 1 month and 1 year (P < 0.000), and weight loss (P < 0.000). A barium study was performed in 35 cases (31%) prior to endoscopic examination and proved to be inaccurate in three cases (8.6%). Upper gastrointestinal endoscopy in our African setting is an accurate and useful investigation in the diagnosis and management of patients presenting with dysphagia. Patients over the age of 40 years presenting with dysphagia and weight loss are more likely to have a neoplastic disease and should be referred for urgent endoscopy.