Helicobacter pylori Diagnosis and Treatment in Africa: The First Lagos Consensus Statement of the African Helicobacter and Microbiota Study Group.

BACKGROUND: Helicobacter pylori (H. pylori) infection is the most prevalent type of bacterial infection. Current guidelines from different regions of the world neglect specific African conditions and requirements. The African Helicobacter and Microbiota Study Group (AHMSG), founded in 2022, aimed to create an Africa-specific consensus report reflecting Africa-specific issues. SUMMARY: Eighteen experts from nine African countries and two European delegates supported by nine African collaborators from eight other countries prepared statements on the most important African issues in four working groups: (1) epidemiology, (2) diagnosis, (3) indications and prevention, and (4) treatment. Limited resources, restricted access to medical systems, and underdeveloped diagnostic facilities differ from those of other regions. The results of the individual working groups were presented for the final consensus voting, which included all board members. KEY MESSAGES: There is a need for further studies on H. pylori prevalence in Africa, with diagnosis hinged on specific African situation. Treatment of H. pylori in the African setting should be based on accessibility and reimbursement, while indication and prevention should be defined in specific African countries.

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.

Helicobacter pylori Infection in Africa: Update of the Current Situation and Challenges.

BACKGROUND: The burden of Helicobacter pylori infection (HPI) in Africa remains high with varying levels of prevalence among children and adults reported in different regions of the continent. Persistent and uneradicated HPI could result in gastric cancer, although less severe pathological outcomes have been reported among Africans - the so-called "African enigma." SUMMARY: Analysis of endoscopic findings of the upper gastrointestinal tract demonstrates similarities with that of patients from the West. Thus, it could be asserted that the true picture of HPI in Africa is yet to be unveiled due to several challenges including inadequate health-care system, lack of treatment guidelines and standardized protocol for diagnosis, and lack of data. This review explores the prevalence, diagnosis, treatment, and health-care system in Africa as it relates to HPI, thus providing an update and highlighting the need for an African HPI guideline. KEY MESSAGES: There is high prevalence of Helicobacter pylori infection (HPI) in Africa with an increasing burden of antibiotic resistance. Various methods including invasive and noninvasive methods are deployed in the diagnosis of HPI in Africa. There is a need for consensus on diagnosis and treatment of HPI in Africa.

A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa.

BACKGROUND: While some evidence has been demonstrated the cost-effectiveness of routine hepatitis A vaccination in middle-income countries, the evidence is still limited in other settings including in South Africa. Given this, the evidence base around the cost of care for hepatitis A needs to be developed towards considerations of introducing hepatitis A vaccines in the national immunisation schedule and guidelines. OBJECTIVES: To describe the severity, clinical outcomes, and cost of hepatitis A cases presenting to two tertiary healthcare centers in Cape Town, South Africa. METHODS: We conducted a retrospective folder review of patients presenting with hepatitis A at two tertiary level hospitals providing care for urban communities of metropolitan Cape Town, South Africa. Patients included in this folder review tested positive for hepatitis A immunoglobulin M between 1 January 2008 and 1 March 2018. RESULTS: In total, 239 folders of hepatitis A paediatric patients < 15 years old and 212 folders of hepatitis A adult patients [Formula: see text] 15 years old were included in the study. Before presenting for tertiary level care, more than half of patients presented for an initial consultation at either a community clinic or general physician. The mean length of hospital stay was 7.45 days for adult patients and 3.11 days for paediatric patients. Three adult patients in the study population died as a result of hepatitis A infection and 29 developed complicated hepatitis A. One paediatric patient in the study population died as a result of hepatitis A infection and 27 developed complicated hepatitis A, including 4 paediatric patients diagnosed with acute liver failure. The total cost per hepatitis A hospitalisation was $1935.41 for adult patients and $563.06 for paediatric patients, with overhead costs dictated by the length of stay being the largest cost driver. CONCLUSION: More than 1 in every 10 hepatitis A cases (13.3%) included in this study developed complicated hepatitis A or resulted in death. Given the severity of clinical outcomes and high costs associated with hepatitis A hospitalisation, it is important to consider the introduction of hepatitis A immunisation in the public sector in South Africa to potentially avert future morbidity, mortality, and healthcare spending.

A Randomized Controlled Trial of Intravenous N-Acetylcysteine in the Management of Anti-tuberculosis Drug-Induced Liver Injury.

BACKGROUND: Liver injury is a common complication of anti-tuberculosis therapy. N-acetylcysteine (NAC) used in patients with paracetamol toxicity with limited evidence of benefit in liver injury due to other causes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to assess the efficacy of intravenous NAC in hospitalized adult patients with anti-tuberculosis drug-induced liver injury (AT-DILI). The primary endpoint was time for serum alanine aminotransferase (ALT) to fall below 100 U/L. Secondary endpoints included length of hospital stay, in-hospital mortality, and adverse events. RESULTS: Fifty-three participants were randomized to NAC and 49 to placebo. Mean age was 38 (SD±10) years, 58 (57%) were female, 89 (87%) were HIV positive. Median (IQR) serum ALT and bilirubin at presentation were 462 (266-790) U/L and 56 (25-100) µmol/L, respectively. Median time to ALT <100 U/L was 7.5 (6-11) days in the NAC arm and 8 (5-13) days in the placebo arm. Median time to hospital discharge was shorter in the NAC arm (9 [6-15] days) than in the placebo arm (18 [10-25] days) (HR, 1.73; 95% CI, 1.13-2.65). Mortality was 14% overall and did not differ by study arm. The study infusion was stopped early due to an adverse reaction in 5 participants receiving NAC (nausea and vomiting [3], anaphylaxis [1], pain at drip site [1]). CONCLUSIONS: NAC did not shorten time to ALT <100 U/L in participants with AT-DILI, but significantly reduced length of hospital stay. NAC should be considered in management of AT-DILI. CLINICAL TRIALS REGISTRATION: South African National Clinical Trials Registry (SANCTR: DOH-27-0414-4719).

Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.

RATIONALE: The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. METHODS: South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (∼10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. RESULTS: 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18-41) to 0 (0-0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1-49) versus 7 (0-21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. CONCLUSIONS: MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment.

Helicobacter pylori Infection: Antibiotic Resistance and Solutions for Effective Management in Africa.

Helicobacter pylori (H. pylori) infection is ubiquitous worldwide, with prevalence rates of greater than 70% in Africa. Symptomatic patients present with foregut gastrointestinal symptoms which can be readily diagnosed with standardized non-invasive or invasive tests. The biggest challenge, however, is in the management of this condition with rising antimicrobial resistance rates to most of the antibiotics recommended for therapy. This is a problem worldwide, but more specifically in Africa, where the socio-economic and political climate is such that eradication of this organism seems impossible. Furthermore, the recommended antimicrobial susceptibility testing for drug resistance is not widely available in Africa due to the lack of infrastructural as well as human resources. With the widespread unregulated use of antibiotics in some parts of Africa, the figures of antimicrobial resistance are likely to soar. In the face of these significant challenges, this 'perspectives' article aims to address the issue of antimicrobial resistance in Africa, by providing achievable and targeted goals to curb the spread of infection and rising antimicrobial resistance.

Face-to-face interviews versus Internet surveys: Comparison of two data collection methods in the Rome foundation global epidemiology study: Implications for population-based research.

BACKGROUND AND AIMS: The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. METHODS: The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. RESULTS: Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. CONCLUSIONS: The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly.

Use of thiopurines in the treatment of inflammatory bowel disease is associated with an increased risk of non-melanoma skin cancer in an at-risk population: a cohort study.

BACKGROUND AND AIM: The thiopurines azathioprine and 6-mercaptopurine are effective in the management of patients with inflammatory bowel disease (IBD) in whom aminosalicylates, antibiotics and corticosteroids have failed to induce or maintain remission. Long-term use of these agents has been linked to a greatly increased risk of non-melanoma skin cancer and lymphatic cancer in organ transplant recipients. There is some evidence to suggest that IBD patients receiving thiopurines might be at increased risk of cancer. Our aim was to determine the incidence of cancer in a cohort of patients with IBD managed in our clinic, and to relate this to thiopurine exposure. METHODS: We conducted a retrospective study based on the clinical and pathology records of patients attending a specialist IBD clinic at Groote Schuur Hospital, Cape Town, South Africa between 1960 and 2007. RESULTS: We analyzed the records of 1084 patients. A total of 123 subjects (11.5%) had received thiopurine therapy. Cancer was identified in 51 patients (4.7%), including colorectal cancer (15 patients), melanoma (two patients), non-melanoma skin cancer (seven patients) and non-Hodgkin's lymphoma (five patients). A diagnosis of non-melanoma skin cancer was significantly associated with thiopurine exposure (odds ratio 5.0, 95% confidence interval 1.1-22.8). Six of seven non-melanoma skin cancers occurred in Caucasian patients, with a highly significant association with thiopurine use (odds ratio 12.4, 95% confidence interval 2.3-67.4). CONCLUSIONS: Patients with IBD who receive thiopurines are at increased risk of non-melanoma skin cancer. The risk is highest in Caucasian patients, and is negligible in other groups.

The impact of Helicobacter pylori and intestinal helminth infections on gastric adenocarcinoma and inflammatory bowel disease in Sub-Saharan Africa.

Gastric adenocarcinoma (GCA) is the 5th leading cancer globally with an estimated 1.1 million cases reported in 2020. Ninety percent of non-cardia GCAs are attributable to Helicobacter pylori (H. pylori), the most prevalent bacterial infection globally. Rates of H. pylori infection are highest in Sub-Saharan Africa (SSA), yet surprisingly low numbers of GCAs are reported in the region. A similar phenomenon is seen with the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. These disorders have risen dramatically over the past century in high income countries across the globe, with sharp increases noted more recently in newly industrialized regions. In contrast IBD is rare in most regions in SSA. For both diseases this may reflect under-reporting or limited access to diagnostic modalities, but an alternative explanation is the high burden of infection with gastrointestinal parasites endemic to SSA which may attenuate the risk of developing GCA and IBD. In this mini review we discuss the complex interplay between these microorganisms, GCA, and IBD, as well as a possible protective role of H. pylori and the development of IBD.

Inflammatory bowel disease in sub-Saharan Africa: epidemiology, risk factors, and challenges in diagnosis.

Over the past century, the incidence of inflammatory bowel disease (IBD) in high-income countries has shown a sharp rise that then plateaued, and a similar trend has been observed in newly industrialised countries. IBD has long been considered uncommon in sub-Saharan Africa, possibly reflecting low exposure to environmental risk factors described in high-income populations. Alternatively, individuals living in sub-Saharan Africa might have a different genetic disposition. However, some cases of IBD might remain undetected in sub-Saharan Africa because of a lack of awareness, deficiencies in diagnostic and clinical capacity, and a substantial rate of misdiagnosis due to the high burden of infectious diseases. There are few published data describing the natural history of IBD in sub-Saharan Africa, and the true burden of the disease remains largely unknown, although there is some evidence that the incidence of IBD is rising in this region. This Series paper summarises the present understanding of IBD and challenges facing clinicians when diagnosing this disease in sub-Saharan Africa.

Challenges in the management of inflammatory bowel disease in sub-Saharan Africa.

Inflammatory bowel disease (IBD) is generally considered a disease of high-income countries and is regarded as rare in sub-Saharan Africa. However, this assumption is almost certainly an underestimate, and the high burden of communicable diseases makes IBD in sub-Saharan Africa difficult to detect. Furthermore, some gastrointestinal infections can closely mimic IBD, contributing to delays in diagnosis and complicating therapeutic decision making. Constraints in endoscopic capacity alongside a scarcity of qualified diagnostic pathologists add to the difficulties. Implementing evidence-based guidelines recommended by international societies is challenging, mostly due to high costs and unavailability of medication. However, cost-effective approaches can still be implemented to manage IBD in sub-Saharan Africa as the predominant disease phenotype is mild-to-moderate ulcerative colitis, which often responds to treatment with basic medication. In this Series paper, we summarise the current management of IBD in sub-Saharan Africa and propose how it can be tailored to suit the epidemiological and socioeconomic specificities of the region. We also discuss measures required to address existing challenges, such as educating health-care workers about the diagnosis and management of IBD or improving endoscopic capacity.

Rechallenge after anti-tuberculosis drug-induced liver injury in a high HIV prevalence cohort.

Background: There are limited data on the outcomes of rechallenge with anti-tuberculosis therapy (ATT) following anti-tuberculosis drug-induced liver injury (AT-DILI) in a high HIV prevalence setting. Objectives: To describe the outcomes of rechallenge with first-line ATT. Method: Hospitalised participants with AT-DILI who were enrolled into a randomised controlled trial of N-acetylcysteine in Cape Town, South Africa, were followed up until completion of ATT rechallenge. We described rechallenge outcomes, and identified associations with recurrence of liver injury on rechallenge (positive rechallenge). Results: Seventy-nine participants were rechallenged of whom 41 (52%) were female. Mean age was 37 years (standard deviation [s.d.] ±10). Sixty-eight (86%) were HIV-positive, of whom 34 (50%) were on antiretroviral therapy (ART) at time of AT-DILI presentation. Five participants had serious adverse reactions to an aminoglycoside included in the alternate ATT regimen given after first-line ATT interruption: acute kidney injury in three and hearing loss in two. The median time from first-line ATT interruption to start of first-line ATT rechallenge was 13 days (interquartile range [IQR]: 8-18 days). Antiretroviral therapy was interrupted for a median of 32 days (IQR: 17-58) among HIV-positive participants on ART before AT-DILI. Fourteen participants had positive rechallenge (18%). Positive rechallenge was associated with pyrazinamide rechallenge (P = 0.005), female sex (P = 0.039) and first episode of tuberculosis (TB) (P = 0.032). Conclusion: Rechallenge was successful in most of our cohort. Pyrazinamide rechallenge should be carefully considered.

Limited therapeutic effect of N-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis.

BACKGROUND: Alcohol-related steatohepatitis is associated with increased oxidative stress, DNA damage, lipotoxicity, and insulin resistance in liver. As inflammation and oxidative stress can promote insulin resistance, effective treatment with antioxidants, for example, N-acetylcysteine (NAC), may restore ethanol-impaired insulin signaling in the liver. METHODS: Adult male Sprague-Dawley rats were fed for 130 days with liquid diets containing 0 or 37% ethanol by caloric content, and simultaneously treated with vehicle or NAC. Chow-fed controls were studied in parallel. Liver tissues were used for histopathology, cytokine activation, and insulin/IGF-1 signaling assays. RESULTS: We observed significant positive trends of increasing severity of steatohepatitis (p = 0.016) with accumulation of neutral lipid (p = 0.0002) and triglycerides (p = 0.0004) from chow to control, to the ethanol diet, irrespective of NAC treatment. In ethanol-fed rats, NAC reduced inflammation, converted the steatosis from a predominantly microvesicular to a mainly macrovesicular histological pattern, reduced pro-inflammatory cytokine gene expression, ceramide load, and acid sphingomyelinase activity, and increased expression of IGF-1 receptor and IGF-2 in liver. However, NAC did not abrogate ethanol-mediated impairments in signaling through insulin/IGF-1 receptors, IRS-1, Akt, GSK-3ß, or p70S6K, nor did it significantly reduce pro-ceramide or GM3 ganglioside gene expression in liver. CONCLUSIONS: Antioxidant treatments reduce the severity of chronic alcohol-related steatohepatitis, possibly because of the decreased expression of inflammatory mediators and ceramide accumulation, but they do not restore insulin/IGF-1 signaling in liver, most likely due to persistent elevation of GM3 synthase expression. Effective treatment of alcohol-related steatohepatitis most likely requires dual targeting of oxidative stress and insulin/IGF resistance.

Managing acute abdominal pain in the emergency centre: Lessons from a patient's experience.

Pain is one of the most common reasons people present to the emergency centre with 7-10% of presentations being due to acute abdominal pain. However, pain is also often neglected by clinicians in emergency centres. The well validated South African Triage Score (SATS) incorporates pain assessment in the prioritising of patients with the aim of guiding clinicians. Based on the SATS, severe pain (a score of ≥8 out of 10) should prompt the clinician to initiate treatment within 10 min of presentation, as unmanaged pain has multiple negative consequences, including poor outcomes of the acute incident with delayed healing and increased risk of developing chronic pain. In this commentary, we present a patient's experience when attending an emergency centre for acute abdominal pain, describe relevant pain mechanisms and highlight the stages where clinical management could have been optimised.

Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation.

Depleting the microenvironment of important nutrients such as arginine is a key strategy for immune evasion by cancer cells. Many tumors overexpress arginase, but it is unclear how these cancers, but not T cells, tolerate arginine depletion. In this study, we show that tumor cells synthesize arginine from citrulline by upregulating argininosuccinate synthetase 1 (ASS1). Under arginine starvation, ASS1 transcription is induced by ATF4 and CEBPß binding to an enhancer within ASS1. T cells cannot induce ASS1, despite the presence of active ATF4 and CEBPß, as the gene is repressed. Arginine starvation drives global chromatin compaction and repressive histone methylation, which disrupts ATF4/CEBPß binding and target gene transcription. We find that T cell activation is impaired in arginine-depleted conditions, with significant metabolic perturbation linked to incomplete chromatin remodeling and misregulation of key genes. Our results highlight a T cell behavior mediated by nutritional stress, exploited by cancer cells to enable pathological immune evasion.

Systematic review of the global epidemiology of viral-induced acute liver failure.

OBJECTIVES: The aetiology and burden of viral-induced acute liver failure remains unclear globally. It is important to understand the epidemiology of viral-induced ALF to plan for clinical case management and case prevention. PARTICIPANTS: This systematic review was conducted to synthesize data on the relative contribution of different viruses to the aetiology of viral-induced acute liver failure in an attempt to compile evidence that is currently missing in the field. EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science were searched for relevant literature published from 2009 to 2019. The initial search was run on 9 April 2019 and updated via PubMed on 30 September 2019 with no new eligible studies to include. Twenty-five eligible studies were included in the results of this review. RESULTS: This systematic review estimated the burden of acute liver failure after infection with hepatitis B virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, herpes simplex virus/human herpesvirus, cytomegalovirus, Epstein-Barr virus and parvovirus B19. Data were largely missing for acute liver failure after infection with varicella-zostervirus, human parainfluenza viruses, yellow fever virus, coxsackievirus and/or adenovirus. The prevalence of hepatitis A-induced acute liver failur was markedly lower in countries with routine hepatitis A immunisation versus no routine hepatitis A immunisation. Hepatitis E virus was the most common aetiological cause of viral-induced acute liver failure reported in this review. In addition, viral-induced acute liver failure had poor outcomes as indicated by high fatality rates, which appear to increase with poor economic status of the studied countries. CONCLUSIONS: Immunisation against hepatitis A and hepatitis B should be prioritised in low-income and middle-income countries to prevent high viral-induced acute liver failure mortality rates, especially in settings where resources for managing acute liver failure are lacking. The expanded use of hepatitis E immunisation should be explored as hepatitis E virus was the most common cause of acute liver failure. REGISTRATION: PROSPERO registration number: CRD42017079730.

Defining the advantages and exposing the limitations of endoscopic variceal ligation in controlling acute bleeding and achieving complete variceal eradication.

BACKGROUND: Bleeding esophageal varices (BEV) is a potentially life-threatening complication in patients with portal hypertension with mortality rates as high as 25% within six weeks of the index variceal bleed. After control of the initial bleeding episode patients should enter a long-term surveillance program with endoscopic intervention combined with non-selective ß-blockers to prevent further bleeding and eradicate EV. AIM: To assess the efficacy of endoscopic variceal ligation (EVL) in controlling acute variceal bleeding, preventing variceal recurrence and rebleeding and achieving complete eradication of esophageal varices (EV) in patients who present with BEV. METHODS: A prospectively documented single-center database was used to retrospectively identify all patients with BEV who were treated with EVL between 2000 and 2018. Control of acute bleeding, variceal recurrence, rebleeding, eradication and survival were analyzed using Baveno assessment criteria. RESULTS: One hundred and forty patients (100 men, 40 women; mean age 50 years; range, 21-84 years; Child-Pugh grade A = 32; B = 48; C = 60) underwent 160 emergency and 298 elective EVL interventions during a total of 928 endoscopy sessions. One hundred and fourteen (81%) of the 140 patients had variceal bleeding that was effectively controlled during the index banding procedure and never bled again from EV, while 26 (19%) patients had complicated and refractory variceal bleeding. EVL controlled the acute sentinel variceal bleed during the first endoscopic intervention in 134 of 140 patients (95.7%). Six patients required balloon tamponade for control and 4 other patients rebled in hospital. Overall 5-d endoscopic failure to control variceal bleeding was 7.1% (n = 10) and four patients required a salvage transjugular intrahepatic portosystemic shunt. Index admission mortality was 14.2% (n = 20). EV were completely eradicated in 50 of 111 patients (45%) who survived > 3 mo of whom 31 recurred and 3 rebled. Sixteen (13.3%) of 120 surviving patients subsequently had 21 EV rebleeding episodes and 10 patients bled from other sources after discharge from hospital. Overall rebleeding from all sources after 2 years was 21.7% (n = 26). Sixty-nine (49.3%) of the 140 patients died, mainly due to liver failure (n = 46) during follow-up. Cumulative survival for the 140 patients was 71.4% at 1 year, 65% at 3 years, 60% at 5 years and 52.1% at 10 years. CONCLUSION: EVL was highly effective in controlling the sentinel variceal bleed with an overall 5-day failure to control bleeding of 7.1%. Although repeated EVL achieved complete variceal eradication in less than half of patients with BEV, of whom 62% recurred, there was a significant reduction in subsequent rebleeding.

The global epidemiology of viral-induced acute liver failure: a systematic review protocol.

INTRODUCTION: The burden of viral-induced acute liver failure (ALF) around the world still remains unclear, with little to no data collected regarding the disease incidence in general and synthesised data on the relative contribution of different viruses to the aetiology of ALF is missing in the field. The aim of this review is to estimate the burden (prevalence, incidence, mortality, hospitalisation) of ALF following infection HAV, HBV, HCV, HDV, HEV, EBV), HSV1, HSV2, VZV, parvo-virus B19, HPIVs, YFV, HVV-6, CMV, CA16 and/or HAdVs. Establishing the common aetiologies of viral-induced ALF, which vary geographically, is important so that: (1) treatment can be initiated quickly, (2) contraindications to liver transplant can be identified, (3) prognoses can be deterined more accurately, and most importantly, (4) vaccination against viral ALF aetiologies can be prioritised especially in under-resourced regions with public health risks associated with the relevant attributable diseases. METHODS AND ANALYSIS: EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science databases will be searched for relevant literature published and grey literature from 2009 up to 2019. Published cross-sectional and cohort studies will be eligible for inclusion in this review. Qualifying studies will be formally assessed for quality and risk of bias using a standardised scoring tool. Following standardised data extraction, meta-analyses will be carried out using STATA. Depending on characteristics of included studies, subgroup analyses and meta-regression analyses will be performed. This review will be reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. ETHICS AND DISSEMINATION: No ethics approval is required as the systematic review will use only published data already in the public domain. Findings will be disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018110309.