Hepatitis delta virus infection prevalence, diagnosis and treatment in the Middle East: A scoping review.

Hepatitis D virus (HDV) infection is a global public health concern, especially because of its unique existence in the presence of hepatitis B virus infection. HDV infection is estimated to affect 12 million people globally. Having a clearer understanding of its prevalence in all regions of the world is essential for helping direct preventive and early interventional treatment. This mini-review assessed the literature over the last 10 years to determine the prevalence, diagnostic means and treatment guidelines available for HDV in the Middle East. The search found limited data available in 21 articles, of which 18 were studies focused on Iran. Prevalence rates ranged dramatically among the countries, and none of the 12 countries included in the search had specific HDV guidelines. This review highlights the urgent need for more precise data for the Middle East region to help establish early diagnosis and treatment options for HDV.

Development and Validation of a Novel 1-year Mortality Risk Score That Includes the Use of Antithrombotic in Patients With Overt Gastrointestinal Bleeding.

GOALS AND BACKGROUND: We aimed to develop a novel 1-year mortality risk-scoring system that includes use of antithrombotic (AT) drugs and to validate it against other scoring systems in patients with acute gastrointestinal bleeding (GIB). STUDY: We developed a risk-scoring system from prospectively collected data on patients admitted with GIB between January 2013 and August 2020, who had at least 1- year of follow-up. Independent predictors of 1-year mortality were determined after adjusting for the following confounders: the age-adjusted Charlson Comorbidity Index (CCI) (divided into 4 groups: CCI-0=0, CCI-1=1 to 3, CCI-2=4 to 6, CCI-3 ≥7), need for blood transfusion, GIB severity, need for endoscopic therapy, and type of AT. The risk score was based on independent predictors. RESULTS: Five hundred seventy-six patients were included and 123 (21%) died at 1-year follow-up. Our risk -score was based on the following: CCI-2 (2 points), CCI-3 (4 points), need for blood transfusion (1 point), and no use of aspirin (1 point), as aspirin use was protective (maximum score=6). Patients with higher risk scores had higher mortality. The model had a better predictive accuracy [AUC=0.82, 95% confidence interval (0.78-0.86), P <0.0001] than the Rockall score for upper GIB (Area Under the Curve (AUC)=0.68, P <<0.0001), the Oakland score for lower GIB (AUC=0.69, p =0.004), or the Shock Index for all (AUC=0.54, P <0.0001). CONCLUSION: A simple and novel score that includes use of AT upon admission accurately predicts 1-year mortality in patients with GIB. This scoring system may help guide follow-up decisions and inform the prognosis of patients with GIB.

Efficacy and Safety of Tofacitinib in Ulcerative Colitis Based on Prior Tumor Necrosis Factor Inhibitor Failure Status.

BACKGROUND & AIMS: Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We summarize the efficacy and safety data of tofacitinib 5 or 10 mg twice daily in the UC clinical program, stratified by prior tumor necrosis factor inhibitor (TNFi) failure status. METHODS: Efficacy was assessed in the pooled phase 3 OCTAVE Induction 1 and 2 studies (N = 1139), the phase 3 OCTAVE Sustain maintenance study (N = 593), and the dose-escalation subpopulation of the open-label, long-term extension OCTAVE Open study (N = 59). Safety was assessed in OCTAVE Sustain, the dose-escalation subpopulation, and the Overall Cohort, which included patients from OCTAVE Induction 1 and 2, OCTAVE Sustain, and OCTAVE Open (N = 1124; no prior TNFi failure N = 541; prior TNFi failure N = 583; phase 2 data were excluded when stratified by prior TNFi failure status). The dose-escalation subpopulation received tofacitinib 10 mg twice daily in OCTAVE Induction 1 and 2, tofacitinib 5 mg twice daily in OCTAVE Sustain, and tofacitinib 10 mg twice daily in OCTAVE Open. RESULTS: Tofacitinib had greater efficacy than placebo, regardless of prior TNFi failure status. In OCTAVE Sustain and the Overall Cohort, herpes zoster [HZ] (nonserious and serious) rates were numerically higher in tofacitinib-treated patients with vs without prior TNFi failure. Dose escalation to tofacitinib 10 mg twice daily generally recaptured clinical response for most patients. HZ (nonserious and serious) rates were numerically higher in the dose-escalation subpopulation vs the Overall Cohort. CONCLUSIONS: Tofacitinib was efficacious in patients with UC regardless of prior TNFi failure status. HZ (nonserious and serious) rates were numerically higher in patients who had previously failed TNFi. ClinicalTrials.gov: A3921063 (NCT00787202); OCTAVE Induction 1 (NCT01465763); OCTAVE Induction 2 (NCT01458951); OCTAVE Sustain (NCT01458574); and OCTAVE Open (NCT01470612).

Development and multicenter validation of FIB-6: A novel, machine learning, simple bedside score to rule out liver cirrhosis and compensated advanced chronic liver disease in patients with chronic hepatitis C.

BACKGROUND: Non-invasive tests (NITs), such as Fibrosis-4 index (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI), developed using classical statistical methods, are increasingly used for determining liver fibrosis stages and recommended in treatment guidelines replacing the liver biopsy. Application of conventional cutoffs of FIB-4 and APRI resulted in high rates of misclassification of fibrosis stages. AIM: There is an unmet need for more accurate NITs that can overcome the limitations of FIB-4 and APRI. PATIENTS AND METHODS: Machine learning with the random forest algorithm was used to develop a non-invasive index using retrospective data of 7238 patients with biopsy-proven chronic hepatitis C from two centers in Egypt; derivation dataset (n = 1821) and validation set in the second center (n = 5417). Receiver operator curve analysis was used to define cutoffs for different stages of fibrosis. Performance of the new score was externally validated in cohorts from two other sites in Egypt (n = 560) and seven different countries (n = 1317). Fibrosis stages were determined using the METAVIR score. Results were also compared with three established tools (FIB-4, APRI, and the aspartate aminotransferase-to-alanine aminotransferase ratio [AAR]). RESULTS: Age in addition to readily available laboratory parameters such as aspartate, and alanine aminotransferases, alkaline phosphatase, albumin (g/dl), and platelet count (/cm3 ) correlated with the biopsy-derived stage of liver fibrosis in the derivation cohort and were used to construct the model for predicting the fibrosis stage by applying the random forest algorithm, resulting in an FIB-6 index, which can be calculated easily at http://fib6.elriah.info. Application of the cutoff values derived from the derivation group on the validation groups yielded very good performance in ruling out cirrhosis (negative predictive value [NPV] = 97.7%), compensated advance liver disease (NPV = 90.2%), and significant fibrosis (NPV = 65.7%). In the external validation groups from different countries, FIB-6 demonstrated higher sensitivity and NPV than FIB-4, APRI, and AAR. CONCLUSION: FIB-6 score is a non-invasive, simple, and accurate test for ruling out liver cirrhosis and compensated advance liver disease in patients with chronic hepatitis C and performs better than APRI, FIB-4, and AAR.

Dexlansoprazole is Effective in Relieving Heartburn during the Fasting Month of Ramadan.

BACKGROUND AND AIMS: Proton pump inhibitors are effective at reducing heartburn. No studies have evaluated their efficacy in Ramadan. Dexlansoprazole has a unique active formulation independent of time-of-day dosing or food. The aim is to investigate the efficacy of dexlansoprazole 60 mg during Ramadan in patients with symptomatic heartburn. METHODS: Subjects recruited using poster, radio, and SMS advertisements completed a diary using a mobile-friendly application and received daily SMS reminders. Dexlansoprazole was started on day 8 for 3 weeks. No placebo arm was used in this trial. Primary endpoint was relief of heartburn expressed as mean 24-h free heartburn percentage (24FH%) per weekly period. RESULTS: A total of 32 patients were enrolled. During week 1, only 1 person (3.1%) was heartburn-free and mean 24FH% was 41.1 ± 24.8%. On dexlansoprazole, mean 24FH% rose to 63.4 ± 23.8 and 81.6 ± 24.5% in weeks 2 and 4, respectively (p < 0.001 for both). Median 24FH% increased from 35.7% in week 1 to 71.4 and 85.7% in weeks 2 and 4, respectively. Mean Gastroesophageal Reflux Disease Questionnaire (GERDQ) scores decreased from 10.0 ± 3.2 in week 1 to 6.53 ± 2.2 in week 2 (p < 0.001) and 5.87 ± 2.1 in week 4 (p < 0.001). Mean heartburn severity score decreased from 2.5 ± 1.0 to 1.7 ± 0.8 (p = 0.001). Early response was higher in patients with GERDQ scores ≥8 (p = 0.012). CONCLUSION: Dexlansoprazole is effective in the treatment of heartburn during Ramadan. Clinicaltrials.gov number: NCT03079050.

Clinical utility and economic burden of routine serum lipase determination in the Emergency Department.

BACKGROUND: Serum lipase is a rapid and reliable laboratory test central to diagnosing acute pancreatitis (AP). Routine use in the emergency department (ED) setting for all cases of abdominal pain or as part of a standard laboratory biochemical profile may lead to unnecessary expenses. AIM: To examine the utility of serum lipase determination at a tertiary care centre ED. METHODS: Retrospective cross-sectional study of ED patients having serum lipase determination over a 12-month period. Electronic medical records were reviewed for indication and interpretation leading to additional diagnostic imaging, specialist consultation, interventions or hospital admission. RESULTS: A total of 24 133 adult patients visited the ED during the study period: 4976 (20.6%) had serum lipase determination, 614 (12.4%) had abnormal lipase, 130 of which (21.1%) were above the diagnostic threshold for acutre pancreatitis (AP) (>3× ULN). A total of 75 patients had confirmed AP (0.3% of all adult ED visits). The positive and negative predictive values of serum lipase (>3× ULN) for AP were 43.6% and 99.6%, respectively. One thousand eight hundred and ninety patients (38.0%) had no abdominal pain on history or physical examination. In this group, the total charge associated with lipase determination was $51 030 with 251 (13.3%) elevated lipase values triggering cross-sectional abdominal imaging in 61 (24.3%) patients and unwarranted gastroenterology consultation in three (1.2%) for an additional charge of $28 975. CONCLUSIONS: Serum lipase is widely overutilised in the emergency setting resulting in unnecessary expenses and investigations. Evidence-based review of clinical guidelines and more restrictive testing can result in substantial cost savings and improved patient care.

Molecular characterization, toxin detection and resistance testing of human clinical Clostridium difficile isolates from Lebanon.

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen's occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing. Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively. The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area.

Low Prevalence of Hypomagnesemia in Long-term Recipients of Proton Pump Inhibitors in a Managed Care Cohort.

BACKGROUND & AIMS: Chronic intake of proton pump inhibitors (PPI) has been associated with hypomagnesemia, but prevalence of PPI-associated hypomagnesemia is not known. METHODS: We examined the prevalence of hypomagnesemia among long-term PPI recipients by using a large health maintenance organization database. We collected data on 10,167 participants eligible for chronic drug prescriptions from 2008 through 2013. Adult subjects receiving continuous PPI therapy for ≥ 6 months between 2008 and 2013 and ≥ 1 serum magnesium determination(s) were identified. Patients with any magnesium levels less than 1.6 mg/dL were selected for analysis; those with recognizable causes of altered magnesium homeostasis were excluded. RESULTS: Five hundred ninety participants received long-term PPIs, and 414 (70.2%) met the inclusion criteria for a total exposure of 2293 PPI-years (average, 5.7 years/subject). Of these patients, 57 (13.8%) had ≥ 1 low serum magnesium; 5 were no longer on PPIs, and 44 had other recognizable causes for hypomagnesemia (25 receiving diuretics, 8 with chronic diarrhea, 8 with chronic kidney disease, and 3 with malignancies). Of the 8 remaining patients (7 female; mean age, 71.2 ± 13.4 years; mean daily medications, 5.4 ± 1.1), mild hypomagnesemia (range, 1.2-1.5 mg/dL) was noted in 13.9% of 289 measurements. All 8 patients had normal serum levels of magnesium at their final measurement. CONCLUSIONS: In the absence of known precipitating factors, chronic PPI use does not appear to be associated with hypomagnesemia.

When to Start Immunomodulators in Inflammatory Bowel Disease?

BACKGROUND: Immunomodulators (IMMs), including thiopurines (TPs) and methotrexate (MTX), are commonly used in the treatment of inflammatory bowel disease (IBD). KEY MESSAGES: In ulcerative colitis (UC), TPs have modest steroid-sparing effects and established efficacy in maintenance of remission. The role of MTX in UC is unclear but current evidence suggests no benefit over placebo. In Crohn's disease (CD), MTX is not effective for induction but has a modest steroid-sparing effect and is superior to placebo in maintenance of remission in responders. The addition of MTX to infliximab reduces immunogenicity and boosts infliximab levels but does not improve outcomes in active CD. TPs are not effective for induction of remission in CD but have proven steroid-sparing effects and modest efficacy in maintenance of remission and prevention of postoperative recurrence. Although effective in pediatric CD, recent evidence has questioned the benefit of early TPs in newly diagnosed adult CD. The addition of TPs to infliximab reduces immunogenicity and inflammatory markers, leads to higher infliximab levels and improves outcomes in patients with early disease. However, the benefit of continued TP therapy in this setting is unclear and should be weighed against possible side effects including an increased risk of opportunistic infections, lymphoma and non-melanoma skin cancer. CONCLUSIONS: IMMs are an important therapeutic option in IBD particularly in non-severe steroid-dependent disease and for maintenance of remission. Combination with anti-TNF agents is an important emerging option as part of a treat-to-target strategy but further research regarding patient selection, long-term use and de-escalation options is needed.

Prediction of celiac disease at endoscopy.

BACKGROUND AND STUDY AIMS: Celiac disease is increasingly recognized worldwide, but guidelines on how to detect the condition and diagnose patients are unclear. In this study the prevalence and predictors of celiac disease were prospectively determined in a cross-sectional sample of Lebanese patients undergoing esophagogastroduodenoscopy (EGD). PATIENTS AND METHODS: Consecutive consenting patients (n = 999) undergoing EGD answered a questionnaire and had blood taken for serologic testing. Endoscopic markers for celiac disease were documented and duodenal biopsies were obtained. The diagnosis of celiac disease was based on abnormal duodenal histology and positive serology. Risk factors were used to classify patients to either high or low risk for celiac disease. Independent predictors of celiac disease were derived via multivariate logistic regression. RESULTS: Villous atrophy (Marsh 3) and celiac disease were present in 1.8 % and 1.5 % of patients, respectively. Most were missed on clinical and endoscopic grounds. The sensitivity of tissue transglutaminase (tTG) testing for the diagnosis of villous atrophy and celiac disease was 72.2 % and 86.7 %, respectively. The positive predictive value of the deamidated gliadin peptide (DGP) test was 34.2 % and that of a strongly positive tTG was 80 %. While the strongest predictor of celiac disease was a positive tTG (odds ratio [OR] 131.7, 95 % confidence interval [CI] 29.0 - 598.6), endoscopic features of villous atrophy (OR 64.8, 95 %CI 10.7 - 391.3), history of eczema (OR 4.6, 95 %CI 0.8 - 28.8), anemia (OR 6.7, 95 %CI 1.2 - 38.4), and being Shiite (OR 5.4, 95 %CI 1.1 - 26.6) significantly predicted celiac disease. A strategy of biopsying the duodenum based on independent predictors had a sensitivity of 93 % - 100 % for the diagnosis of celiac disease, with an acceptable (22 % - 26 %) rate of performing unnecessary biopsies. A strategy that excluded pre-EGD serology produced a sensitivity of 93 % - 94 % and an unnecessary biopsy rate of 52 %. CONCLUSION: An approach based solely on standard clinical suspicion and endoscopic findings is associated with a significant miss rate for celiac disease. A strategy to biopsy based on the derived celiac disease prediction models using easily obtained information prior to or during endoscopy, maximized the diagnosis while minimizing unnecessary biopsies.

Radiation enteritis.

Radiation enteritis continues to be a major health concern in recipients of radiation therapy. The incidence of radiation enteritis is expected to continue to rise during the coming years paralleling the unprecedented use of radiotherapy in pelvic cancers. Radiation enteritis can present as either an acute or chronic syndrome. The acute form presents within hours to days of radiation exposure and typically resolves within few weeks. The chronic form may present as early as 2 months or as long as 30 years after exposure. Risk factors can be divided into patient and treatment-related factors. Chronic radiation enteritis is characterized by progressive obliterative endarteritis with exaggerated submucosal fibrosis and can manifest by stricturing, formation of fistulae, local abscesses, perforation, and bleeding. In the right clinical context, diagnosis can be confirmed by cross-sectional imaging, flexible or video capsule endoscopy. Present treatment strategies are directed primarily towards symptom relief and management of emerging complications. Recently, however, there has been a shift towards rational drug design based on improved understanding of the molecular basis of disease in an effort to limit the fibrotic process and prevent organ damage.

Brunner's gland hamartomas: Not always benign.

Brunner's gland hamartoma (BGH) is a rare, benign tumor of the duodenum. It is mostly asymptomatic and usually found incidentally on routine esophagogastroduodenoscopy (EGD). However, some BGHs present with major complications including anemia, bleeding, obstruction, or dysplasia, requiring management and resection of these lesions. Herein, we present two cases of large BGHs of the duodenum, one presenting as severe gastrointestinal bleeding and the other, noted on EGD for iron deficiency anemia, found to have high grade dysplasia. This literature review discusses the rare serious complications of BGH, including iron deficiency anemia, overt gastrointestinal bleeding, and malignant potential.

Mesenteric Panniculitis.

Background: Mesenteric panniculitis (MP) is an uncommon non-neoplastic idiopathic inflammation of adipose tissue, mainly affecting the mesentery of the small intestine, with its etiology remaining largely speculative. The difference in prevalence of MP among females and males varies across multiple studies. In most cases, MP is asymptomatic; however, patients can present with nonspecific abdominal symptoms or can mimic underlying gastrointestinal and abdominal diseases. The diagnosis is suggested by computed tomography and is usually confirmed by surgical biopsies if necessary. Treatment is generally supportive and based on a few selected drugs, namely, nonsteroidal anti-inflammatory drugs or corticosteroids. Surgery is reserved when the diagnosis is unclear, when malignancy is suspected or in the case of severe presentation such as mass effect, bowel obstruction, or ischemic changes. Summary: MP is a rare inflammatory condition of the mesentery often asymptomatic but can cause nonspecific abdominal symptoms. Diagnosis relies on computed tomography imaging, with treatment mainly supportive, utilizing medications like nonsteroidal anti-inflammatory drugs or corticosteroids, while surgery is reserved for severe cases or diagnostic uncertainty. Key Messages: MP causes abdominal pain, and it is mainly diagnosed with CT scan.

Impact of blood transfusion on mortality and rebleeding in gastrointestinal bleeding: an 8-year cohort from a tertiary care center.

Background: The aim of this study was to investigate the impact of blood transfusion (BT) on mortality and rebleeding in patients with gastrointestinal bleeding (GIB) and whether BT at a threshold of ≤7 g/dL may improve these outcomes. Methods: A prospective study was conducted in patients admitted with GIB between 2013 and 2021. Antithrombotic (AT) use and clinical outcomes were compared between transfused and non-transfused patients, and between those transfused at a threshold of ≤7 vs. >7 g/dL. Multivariate analysis was performed to identify predictors of mortality and rebleeding. Results: A total of 667 patients, including 383 transfused, were followed up for a median of 56 months. Predictors of end-of-follow-up mortality included: age-adjusted Charlson Comorbidity Index, stigmata of recent hemorrhage (SRH), and being on anticoagulants only upon presentation (P=0.026). SRH was a predictor of end-of-follow-up rebleeding, while having been on only antiplatelet therapy (AP) upon presentation was protective (P<0.001). BT was not associated with mortality or rebleeding at 1 month or end of follow up. Among transfused patients, being discharged only on AP protected against mortality (P=0.044). BT at >7 g/dL did not affect the risk of short or long-term rebleeding or mortality compared to BT at ≤7 g/dL. Conclusions: Short- and long-term mortality and rebleeding in GIB were not affected by BT, nor by a transfusion threshold of ≤7 vs. >7 g/dL, but were affected by the use of AT. Further studies that account for AT use are needed to determine the best transfusion strategy in GIB.

Sugar-free menthol candy drops improve the palatability and bowel cleansing effect of polyethylene glycol electrolyte solution.

BACKGROUND: Colon preparations are generally poorly tolerated. OBJECTIVE: To study the efficacy of sugar-free candy drops in improving palatability and tolerability of polyethylene glycol electrolyte solution (PEG-E). DESIGN: Single-blind, randomized, controlled trial. SETTING: University medical center. PATIENTS: Ambulatory patients scheduled for elective colonoscopy. INTERVENTION: Menthol candy drops. Patients were randomly assigned to split-dose, 4-L, PEG-E ± cough drops. Palatability was assessed on a linear scale of 1 to 5 (1 = disgusting; 5 = tasty). Quality of preparation, remaining unconsumed volume, and side effects were secondary outcomes. MAIN OUTCOME MEASUREMENTS: Palatability and tolerability of PEG-E. RESULTS: A total of 99 patients were enrolled (50 control group, 49 candy drops-added group). The mean (± standard deviation) palatability score was significantly better in candy drop users versus controls (3.9 ± 0.7 vs 2.8 ± 1.2, respectively; P < .001) as were the preparations scored as excellent (63.3% vs 34% of controls; P = .004). Side effects were similar except for nausea (24.5% candy drops vs 44% controls; P = .04). The amount of unconsumed PEG-E was not different between candy drop and control groups (128 [± 361 mL] versus 69 [± 194 mL], respectively; P = .32) but was significantly lower in excellent grade preparations versus other grades (31 [± 103 mL] versus 162 [± 384 mL], respectively; P = .024). On multivariate logistic regression, an excellent preparation was associated with candy drops (odds ratio [OR] 3.3, 95% confidence interval [CI], 1.4-7.8; P = .006) and smaller unconsumed volume of same-day PEG-E [OR 0.996, 95% CI, 0.992-1.000; P = .044). LIMITATIONS: Single-center study. CONCLUSION: Sugar-free menthol candy drops are a safe and effective addition to split-dose PEG-E, resulting in improved tolerability and patient compliance, which appears to translate into improved bowel cleansing. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01541683.).