Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa.

BACKGROUND: Over 30% of the world's population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products. METHOD: Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group. CONCLUSION: The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

Epidemiology of inflammatory bowel disease in sub-Saharan Africa: A review of the current status.

While inflammatory bowel disease (IBD) has been well characterised in the West and other parts of the world, there are little data from sub-Saharan Africa (SSA). To throw light on the current status of IBD in SSA, we performed a systematic review of the literature, extracting relevant publications. We found only 210 documented IBD cases in SSA (excluding South Africa (SA)), which were reported in 34 publications until August 2019. The majority were cases of ulcerative colitis. Only three reports, all from SA, attempted to determine IBD incidence rates. The rest were mostly case reports or small case series; the largest from Nigeria comprised 32 patients. The paucity of documented cases possibly reflects under-diagnosis and under-reporting. Major deficiencies in diagnostic and clinical capacity were noted, which need to be addressed going forward.

Patient blood management: A solution for South Africa.

For more than 70 years the default therapy for anaemia and blood loss was mostly transfusion. Accumulating evidence demonstrates a significant dose-dependent relationship between transfusion and adverse outcomes. This and other transfusion-related challenges led the way to a new paradigm. Patient blood management (PBM) is the application of evidence-based practices to optimise patient outcomes by managing and preserving the patient's own blood. 'Real-world' studies have shown that PBM improves patient outcomes and saves money. The prevalence of anaemia in adult South Africans is 31% in females and 17% in males. Improving the management of anaemia will firstly improve public health, secondly relieve the pressure on the blood supply, and thirdly improve the productivity of the nation's workforce. While high-income countries are increasingly implementing PBM, many middle- and low-income countries are still trying to upscale their transfusion services. The implementation of PBM will improve South Africa's health status while saving costs.

South African guideline for the management of chronic hepatitis B: 2013.

Hepatitis B remains a significant yet preventable health issue in South Africa. The introduction of the hepatitis B vaccine into the country some 18 years ago has demonstrated benefit, but the exposure to, and prevalence of chronic HBsAg positivity remain unacceptably high. Those with chronic hepatitis B virus infection have an elevated risk of developing cirrhosis with end-stage liver disease and a markedly elevated risk of hepatocellular carcinoma, independent of the presence of cirrhosis. The challenge in South Africa remains prevention through the universal vaccination coverage of all children and the identification of those with chronic hepatitis B virus infection. Over the last decade our understanding of hepatitis B and its behaviour and natural history in those with chronic infection has significantly improved. This understanding is key to identifying those who warrant further evaluation and therapy. A number of global societies have updated their guidelines in recent years. This document draws on these guidelines and serves to contextualise, for South Africa, practice guidelines for the management of chronic hepatitis B.

Unexpected Ebola virus in a tertiary setting: clinical and epidemiologic aspects.

OBJECTIVES: To describe the clinical manifestations of viral hemorrhagic fever, and to increase clinicians' awareness and knowledge of these illnesses. DESIGN: Retrospective study of the clinical and laboratory data and management of two cases of Ebola virus infection with key epidemiologic data provided. SETTING: Two tertiary care hospitals. PATIENTS: Two adult patients, the index case and the source patient, both identified as having Ebola, one of whom originated in Gabon. INTERVENTIONS: One patient was admitted to the intensive care unit. The other was managed in a general ward. MEASUREMENT AND MAIN RESULTS: Clinical and laboratory data are reported. One patient, a healthcare worker who contracted this illness in the course of her work, died of refractory thrombocytopenia and an intracerebral bleed. The source patient survived. Despite a long period during which the diagnosis was obscure, none of the other 300 contacts contracted the illness. CONCLUSIONS: Identification of high-risk patients and use of universal blood and body fluid precautions will considerably decrease the risk of nosocomial spread of viral hemorrhagic fevers.

Octreotide infusion or emergency sclerotherapy for variceal haemorrhage.

To compare octreotide with injection sclerotherapy in the treatment of acute variceal haemorrhage, patients admitted with gastrointestinal bleeding and oesophageal varices confirmed by endoscopy were randomised to receive either emergency sclerotherapy with 3% sodium tetradecyl sulphate or octreotide (50 micrograms intravenous bolus plus 50 micrograms per h intravenous infusion for 48 h). At the end of the study period (48 h), the octreotide group also had sclerotherapy to obliterate the varices. 100 patients were recruited. Demographic features including the aetiology of portal hypertension and the Child-Pugh's grading of the two groups were similar. Bleeding was initially controlled in 90% of patients by emergency sclerotherapy and in 84% by octreotide infusion (95% confidence interval 0-19.5, p = 0.55). There were no significant differences between the two groups in early (within 48 h of randomisation) rebleeding (16% vs 14%), blood transfusion (3 units vs 3.5), hospital stay (5 days vs 6 days), or hospital mortality (27% vs 20%). No notable side-effects were associated with octreotide. We conclude that octreotide infusion and emergency sclerotherapy are equally effective in controlling variceal haemorrhage.

Liver injury from cyclosporine A.

To assess the incidence of cyclosporine A-induced hepatotoxicity, we retrospectively analyzed liver biochemical test results in 59 patients with endogenous uveitis who received cyclosporine A. All patients had normal liver tests before treatment and had at least six determinations during a 6- to 36-month course of therapy with cyclosporine A at a dose of 2-10 mg/kg/day. Thirty-four (58%) patients developed at least one abnormality of liver tests, and 19 (32%) had a prolonged pattern of abnormalities. The usual abnormalities consisted of a mild, transient increase in alkaline phosphatase levels occasionally accompanied by slight elevations in serum bilirubin and aminotransferase activities. Peak alkaline phosphatase levels ranged from 125 to 243 units/liter and persisted for seven days to 48 months. Thus, biochemical evidence of mild cholestatic liver injury was common in patients receiving cyclosporine A. These abnormalities are usually self-limited and asymptomatic but may cause diagnostic difficulty if a preexisting liver disease is present.

Therapy of chronic hepatitis B with recombinant human alpha and gamma interferon.

Eight patients with chronic hepatitis B entered a pilot study of gamma interferon and alpha interferon in combination. Gamma interferon alone had minimal inhibitory effects on serum levels of hepatitis B virus as monitored by serum HBV DNA and DNA-polymerase activity. The drug also gave troublesome side effects. In contrast, alpha interferon had more potent inhibitory effects on serum HBV levels and fewer side effects. When combined, the two interferons showed no additive or synergistic effects in inhibiting serum levels of HBV DNA or DNA polymerase. These findings indicate that the addition of gamma interferon to alpha interferon provides no additional antiviral effects but contributes significantly to side effects.

A randomized, double-blind, placebo-controlled trial of recombinant human alpha-interferon therapy for chronic non-A, non-B (type C) hepatitis.

The effects of alpha-interferon therapy were evaluated in a prospective, randomized, double-blind, controlled trial of recombinant human interferon alfa-2b versus placebo in patients with well-documented chronic non-A, non-B hepatitis (type C). Forty-one patients, of whom 37 (90%) had hepatitis C virus antibodies in their serum, were enrolled in the trial. Twenty-one patients received interferon (2 million units) and 20 received placebo as subcutaneous injections three times weekly for 6 months. Mean serum aminotransferase activities and liver histology improved significantly in interferon-treated patients but not in placebo recipients. Ten interferon-treated patients (48%) had a complete response to therapy as shown by a reduction of mean serum aminotransferase activities into the normal range during therapy; three more patients had a partial response with aminotransferase activities decreasing by more than 50% on average. In follow up, however, serum aminotransferase levels usually returned to pre-treatment levels; at 6 to 12 months after stopping interferon, only two (10%) patients still had normal aminotransferase activity. These results indicate that alpha-interferon therapy is beneficial in reducing the disease activity in chronic hepatitis C. Only a minority of patients, however, appear to have a long-term response. In this study, interferon was generally well tolerated, with only one patient discontinuing therapy because of adverse effects.

Therapy of chronic delta hepatitis with interferon alfa-2b.

In this pilot study, 12 patients with chronic delta hepatitis were studied. The diagnosis was based on the presence of antibodies to the hepatitis delta antigen in the serum and hepatitis delta virus RNA and hepatitis delta antigen in the serum and liver. All patients were also positive for hepatitis B surface antigen. The infection was presumed to have been transmitted by intravenous drug abuse in six of the patients, blood transfusion in one and by sexual contact in four (two had antibodies to human immunodeficiency virus in their serum, but did not show signs of acquired immunodeficiency syndrome). In one further patient, the source of infection was unknown. Interferon alfa-2b (INTRON A, Schering-Plough Corporation) was initiated at 5 million units per day subcutaneously for at least 4 months, being reduced by half if side effects occurred. Serum alanine aminotransferase levels, hepatitis delta virus RNA and hepatitis delta antigen were measured at monthly intervals for up to 12 months in some patients. Interferon therapy resulted in decreased serum levels of these three markers. On cessation of therapy, most patients experienced a relapse over 6 months, but alanine amino transferase levels could be normalized once more by restarting interferon therapy. In conclusion, interferon decreased hepatic inflammation by the inhibition of hepatitis delta virus replication, although relapse occurred when interferon was stopped and long-term therapy is required to achieve permanent control of the disease. Care will be required when treating patients with advanced or decompensated liver disease.

Rapidly progressive non-A, non-B hepatitis in patients with human immunodeficiency virus infection.

No information is available on the role of non-A, non-B hepatitis in the various hepatic abnormalities described in patients with the acquired immune deficiency syndrome. Of 97 patients referred with suspected non-A, non-B hepatitis, 3 were found to have antibody to the human immunodeficiency virus. These latter 3 patients all developed symptomatic cirrhosis within 3 yr of onset of hepatitis. Such a rapid progression of liver disease was rare in patients with non-A, non-B hepatitis who did not have simultaneous human immunodeficiency infection. These findings suggest that human immunodeficiency virus infection may potentiate the liver injury of chronic non-A, non-B hepatitis.

Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial.

Infection with the hepatitis C virus may result in chronic liver disease for which no effective therapy is now available. We studied the effects of recombinant human interferon alfa in a prospective, randomized, double-blind, placebo-controlled trial in patients with well-documented chronic hepatitis C. Forty-one patients were enrolled in the trial, 37 of whom were later found to have antibody to hepatitis C virus. Twenty-one patients received interferon alfa (2 million units) subcutaneously three times weekly for six months, and 20 received placebo. The mean serum aminotransferase levels and the histologic features of the liver improved significantly in the patients treated with interferon but not in the patients given placebo. Ten patients treated with interferon (48 percent) had a complete response, defined as a decline in mean serum aminotransferase levels to the normal range during therapy; three others had a decrease in mean aminotransferase levels of more than 50 percent. After treatment ended, however, serum aminotransferases usually returned to pretreatment levels; 6 to 12 months after the discontinuation of interferon therapy, only two patients (10 percent) still had normal values. We conclude that interferon alfa therapy is beneficial in reducing disease activity in chronic hepatitis C; however, the beneficial responses are often transient.

Inhibition of duck hepatitis B virus replication by 2',3'-dideoxycytidine. A potent inhibitor of reverse transcriptase.

The effect of 2',3'-dideoxycytidine, a potent antiviral agent, which, following anabolic phosphorylation, inhibits the reverse transcriptase of the human immunodeficiency virus in vitro, was assessed in 16 Pekin ducks chronically infected with the duck hepatitis B virus. Nine ducks were given 11 mg/m2 of dideoxycytidine intravenously every 6 h, and 7 ducks received no treatment. Serum duck hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity decreased in every duck treated with dideoxycytidine. The mean inhibition of deoxyribonucleic acid polymerase and duck hepatitis B virus deoxyribonucleic acid on the third day of treatment measured 64% (p less than 0.01) and 73% (p less than 0.01), respectively. The inhibition of deoxyribonucleic acid polymerase persisted after treatment was stopped, and 4 ducks continued to show greater than 50% inhibition 12 days after stopping treatment. Duck hepatitis B virus deoxyribonucleic acid, which was measured in total cellular deoxyribonucleic acid extracted from liver biopsy specimens obtained before and on the last day of treatment with dideoxycytidine, showed an average inhibition of 96% in 3 ducks treated with dideoxycytidine, but showed no decrease in the remaining 5 ducks. Thus, dideoxycytidine has potent antiviral activity against duck hepatitis B virus and warrants further evaluation as an antiviral agent in the treatment of chronic hepatitis B virus infection in humans.

Glomerulonephritis caused by chronic hepatitis B virus infection: treatment with recombinant human alpha-interferon.

STUDY OBJECTIVES: To assess the efficacy of alpha-interferon therapy in patients with hepatitis B virus (HBV)-related glomerulonephritis. DESIGN: Prospective, nonrandomized study. PATIENTS: Five patients with persistence of hepatitis B surface antigen, hepatitis B e antigen (HBeAg) and HBV DNA in serum for at least 6 months and histologic changes of chronic hepatitis on liver biopsy as well as persistent proteinuria of greater than 2 g/d and histologic changes of glomerulonephritis on renal biopsy. INTERVENTIONS: Patients received a 4-month course of recombinant human alpha-interferon (alfa-2b) beginning at a dose of 5 million units administered subcutaneously each day. RESULTS: Serum levels of HBV DNA decreased in all patients and fell to undetectable levels during treatment in four of five patients. In the four responding patients, serum HBeAg disappeared, aminotransferases fell into the normal range, and a follow-up liver biopsy showed an improvement in the hepatocyte necrosis and inflammation. Urine protein excretion also decreased during treatment. In the four responding patients, urine protein excretion gradually fell to less than 1 g/d and serum albumin levels rose into the normal range. Resolution of the biochemical and serologic evidence of chronic hepatitis and glomerulonephritis was accompanied by disappearance of signs and symptoms of liver and kidney disease. CONCLUSIONS: A high proportion of patients with HBV-related glomerulonephritis will respond to a 4-month course of alpha-interferon with a clinical, biochemical, and serologic remission.

A technique for liver biopsy in Pekin ducks.

The duck hepatitis B virus (DHBV), a member of the hepadna-virus group, has become a useful animal model for exploring important aspects in this family of viruses such as viral replication, course of infection, and the response to antiviral therapy. In chronically DHBV infected ducks, repeated analyses of liver tissue are important in defining the degree of viral replication and liver injury. We describe a technique for repeated liver biopsy using a Keyes skin punch biopsy. This technique provided sufficient quantities of liver tissue for serial analyses with minimal hemorrhage in 18 Pekin ducks. This procedure offers a safe and reliable method of obtaining serial liver biopsies.

The clinical manifestations and natural history of hepatocellular carcinoma.

Striking geographical differences occur in the clinical presentation of hepatocellular carcinoma in high and low incidence areas. This tumor is also associated with a number of paraneoplastic phenomena that may antedate the clinical appearance.

Prevalence of chronic hepatitis B virus infection in pregnant black women living in Soweto.

Urban black children have an appreciably lower hepatitis B virus (HBV) carrier rate than rural Black children. The purpose of this study was to determine the carrier rate in the preceding generation of urban-born Blacks, in order to establish how rapidly the reduction in carrier rate following urbanization has occurred. HBV markers were measured by radioimmunoassay in the serum of 616 urban-born and 618 rural-born pregnant Black women living in Soweto. HBV carriage was significantly less frequent in the urban-born (1.3%) than in the rural-born women (4.0%; P less than 0.05). Total HBV exposure was also less common in the urban-born women (35.2% compared with 44.7%; P less than 0.001). HBV carrier rates were the same in women whose mothers were urban-born (1.31%) and those with rural-born mothers (1.68%). Only three rural-born and no urban-born women had replicative HBV infection. These findings suggest that the decrease in the HBV carrier rate with urbanization is abrupt, occurring in the first generation born in the urban environment.

Hepatocellular carcinoma in urban born blacks: frequency and relation to hepatitis B virus infection.

Chronic hepatitis B virus infection is far less common in urban born than in rural born southern African blacks, who also have a high incidence of hepatocellular carcinoma. A case-control study was carried out to determine the relative frequency of hepatocellular carcinoma and its relation to hepatitis B virus infection in urban born blacks. Three hundred and ninety two black patients with hepatocellular carcinoma and matched controls seen at two city hospitals were classified by questioning as urban born or rural born. The ratio of rural born to urban born blacks among the controls was 1.1:1.0 (207/185), whereas in the patients with cancer the ratio was 4.8:1.0 (324/68) (p less than 0.0001). Analysis of the prevalence of hepatitis B markers in 62 urban born and matched rural born blacks with hepatocellular carcinoma showed no differences in the frequency of current or past hepatitis B virus infection. It is concluded that urban born blacks are less likely than rural born blacks to develop hepatocellular carcinoma, but when they do the tumour is equally likely to be related to infection with hepatitis B virus. The findings lend further support to an important role for chronic hepatitis B virus infection in the aetiology of hepatocellular carcinoma.