Shahab Abid

Epidemiology and clinical pattern of hepatitis delta virus infection in Pakistan

Background and Aims:  The global epidemiology of hepatitis delta virus (HDV) infection is changing. This study was performed to determine the epidemiology and clinical impact of hepatitis delta in Pakistan.

Terlipressin vs. Octreotide in Bleeding Esophageal Varices as an Adjuvant Therapy With Endoscopic Band Ligation: A Randomized Double-Blind Placebo-Controlled Trial

OBJECTIVES:Data are scarce on the head-to-head efficacy of terlipressin and octreotide as an adjuvant therapy to endoscopic management of variceal bleed. The aim of this study was to compare the efficacy and safety of terlipressin with octreotide as an adjuvant therapy to endoscopic variceal band ligation in patients with esophageal variceal bleeding.METHODS:Cirrhotic patients with esophageal variceal bleed were randomized on admission to receive terlipressin (group A) or octreotide (group B) along with the placebo in the other arm in a double-blind fashion. The two groups were compared for efficacy, safety, overall survival, and length of hospital stay. “Control of variceal bleed” was the measure of efficacy of terlipressin and octreotide. Factors predicting length of stay were also assessed.RESULTS:A total of 324 patients were enrolled; 163 in the terlipressin group (group A) and 161 in the octreotide group (group B). The baseline characteristics of the two groups were comparable for age, gender, etiology of cirrhosis, hemoglobin at presentation, and Child–Pugh class, except that active bleed was seen during upper gastrointestinal endoscopy at the time of enrollment in 26 (16%) and 41 (25.5%) patients in groups A and B, respectively (P=0.034). Overall sixteen patients died (three failure to control bleed and thirteen from causes other than variceal bleed); nine in group A (5.5%) and seven (4.3%) in group B (P=0.626). In the intention to treat analysis, “control of variceal bleed” was noted in 305 patients (94.13%); 151 (92.63%) patients in group A and 154 (95.6%) patients in group B (confidence interval: 0.219–1.492). Packed cell transfusions in group A were 3.7±2.3 units, whereas in group B there were 3.9±2.5 units (P=0.273). Length of hospital stay in groups A and B was 108.40±34.81 and 126.39±47.45 h, respectively (P≤0.001). No cardiovascular side effects were observed in either group. High pulse, low hemoglobin, prothrombin time, blood in nasogastric aspirate, and portosystemic encephalopathy (PSE) were predictors of prolonged hospital stay.CONCLUSIONS:The efficacy of terlipressin was not inferior to octreotide as an adjuvant therapy for the control of esophageal variceal bleed and in-hospital survival. The length of hospital stay in the terlipressin group was significantly shorter but not of any clinical importance. The predictors of prolonged hospital stay were low hemoglobin, high pulse, prolonged prothrombin time, blood at nasogastric aspirate, and PSE.

Helicobacter pylori infection in children: population-based age-specific prevalence and risk factors in a developing country.

Aim:  We estimated the prevalence, age of acquisition and risk factors for Helicobacter pylori (H. pylori) seroprevalence in children aged 1–15 years.

Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trial.

BACKGROUND & AIMS Esophageal variceal bleed is a major problem in patients with cirrhosis. Endoscopic variceal ligation (EVL) has been shown to be equal to or better than propranolol in preventing first bleed. Carvedilol is a non-selective β blocker with alpha-1 adrenergic blocker activity. Hemodynamic studies have shown carvedilol to be more effective than propranolol at reducing portal pressure. We compared efficacy of carvedilol with EVL for primary prophylaxis of esophageal variceal bleed. METHODS Cirrhotic patients with esophageal varices were randomized to carvedilol 12.5mg daily or EVL at three university hospitals of Pakistan. End points were esophageal variceal bleeding, death or liver transplant. RESULTS Two hundred and nine patients were evaluated. Eighty two and eighty six patients were randomized in carvedilol and EVL arms respectively. Mean age was 48 ± 12.2 years; 122 (72.7%) were males; 89.9% had viral cirrhosis; mean Child-Pugh score was 7.3 ± 1.6 and mean follow up was 13.3 ± 12.1 months (range 1-50 months). Both EVL and carvedilol groups had comparable variceal bleeding rates (8.5% vs. 6.9%), bleed related mortality (4.6% vs. 4.9%) and overall mortality (12.8% vs. 19.5%) respectively. Adverse events in carvedilol group were hypotension (n=2), requiring cessation of therapy, while transient nausea (n=18) and dyspnea (n=30) resolved spontaneously. In the EVL arm, post banding ulcer bleed (n=1) and chest pain (n=17), were termed as serious adverse events while transient dysphagia (n=58) resolved without treatment. CONCLUSIONS Although our study is underpowered, the findings suggest that carvedilol is probably not superior to EVL in preventing first variceal bleed in patients with viral cirrhosis.

Severe hemolysis and renal failure in glucose-6-phosphate dehydrogenase deficient patients with hepatitis E

Hemolytic anemia as a complication of acute hepatitis is not uncommon in patients with glucose-6-phosphate dehydrogenase deficiency. However, severe hemolysis in these patients is rare. We report a cohort of five patients with acute viral hepatitis E who developed severe intravascular hemolysis and unusually high levels of bilirubin. All five patients had severe, complicated, protracted courses of illness. Four patients developed acute renal failure, and two of these required hemodialysis. To the best of our knowledge this is the first report of a cohort of patients with glucose-6-phosphate dehydrogenase deficiency and acute viral hepatitis E with severe intravascular hemolysis. We emphasize the fact that intravascular hemolysis should be suspected in patients with acute viral hepatitis E with marked bilirubinemia and anemia. Measures to prevent renal failure should be taken in such cases.

Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in Pakistan

BackgroundHelicobacter pylori (H. pylori) infection is known to be associated with a spectrum of gastroduodenal diseases. We studied the association of H. pylori virulence markers cytotoxin-associated gene (cagA) and vacuolating associated cytotoxin gene (vacA) alleles in patients with non ulcer dyspepsia (NUD), gastric ulcer (GU), gastric carcinoma (GC) and duodenal ulcer (DU).MethodsH. pylori infection established by both rapid urease test and histology were studied. The cagA and vacA allelic status was determined by polymerase chain reaction (PCR). Sequencing of vacA i1 and i2 PCR product was carried out.ResultsTwo hundred and twenty-four patients were included, 141 (63%) were males with a mean age of 45 ± 16, range 16-83 years. The virulence marker cagA was associated with GU in 20(63%) (p = 0.04), DU in 23(72%) (p = 0.003) and GC in 29(73%) (p = 0.001) compared to NUD in 51(42%). VacA s1am1 was associated with GU in 23(72%) (p = 0.001), DU in 17(53%) (p < 0.001) and GC in 23(58%) (p = 0.003) compared to NUD in 38(32%) while vacA s1bm1 was also associated with GU in 9(28%) (p = 0.001), DU in 12(37%) (p < 0.001) and GC 11(28%) (p < 0.001) compared to NUD in 13(11%), respectively. The diagnoses of GU in 21(66%), DU in 16(50%), GC in 20(50%) and NUD in 50(42%) were associated with moderately active chronic inflammation. CagA in 55(45%) (p = 0.037), vacA s1am1 in 51(51%) (P < 0.001), s1bm1 in 25(56%) (p = 0.002), s1am2 32(30%) (p < 0.001) and s1bm2 29(69%) (p = 0.004) were also associated with moderately active chronic inflammation.ConclusionCagA was negative in majority of NUD patients with H. pylori infection. However, cagA was associated with peptic ulcer and GC. VacA alleles s1am1 and s1bm1 were associated with H. pylori associated diseases and inflammation.

Role of rapid urease test and histopathology in the diagnosis of Helicobacter pylori infection in a developing country

BackgroundThe aim of this study was to determine the effect of commonly self-prescribed proton pump inhibitors (PPI) on the results of rapid urease test and histology for the diagnosis of H. pylori infection.MethodsOne hundred-nine consecutive patients with dyspeptic symptoms attending the endoscopy suite were enrolled in this study. Antrum biopsy specimens were collected at endoscopy for the rapid urease test (Pronto Dry, Medical Instrument Corp, France) and histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and like-hood ratio of a positive and negative of Pronto Dry test were compared against histology. The gold standard test for the diagnosis of H. pylori infection was histopathology.ResultsSixty-one percent (66/109) patients were males with mean age of 43 ± 14.1 years and age range 17–80 years. Fifty-two percent (57/109) were not on any medications while 48% (52/109) used PPI before presentation to the outpatients. Pronto Dry was positive in 40% (44/109) and negative in 60% (65/109). Histopathology was positive for H. pylori in 57% (62/109) and negative in 43% (47/109). The sensitivity, specificity, PPV, NPV and like-hood ratio of a positive and negative Pronto Dry test with and without PPI were 43.3%, 86.4%, 81.3%, 3.18, 0.656 and 52.8% vs 71.9%, 80%, 82.1%, 69%, 3.59 and 0.35.ConclusionThis study shows that the sensitivity, specificity, NPV and PPV of rapid urease test was reduced in patients who are on PPI. The exclusive use of the rapid urease test for the diagnosis of Helicobacter pylori cannot be recommended in patients with prior PPI use.

The clinical, endoscopic and histological spectrum of the solitary rectal ulcer syndrome: a single-center experience of 116 cases

BackgroundSolitary rectal ulcer syndrome (SRUS) is an uncommon although benign defecation disorder. The aim of this study was to evaluate the variable endoscopic manifestations of SRUS and its association with other diseases.MethodsAll the patients diagnosed with SRUS histologically from January 1990 to February 2011 at The Aga Khan University, Karachi were included in the study. The medical records were reviewed retrospectively to evaluate the clinical spectrum of the patients along with the endoscopic and histological findings.ResultsA total of 116 patients were evaluated. The mean age was 37.4 ± 16.6 (range: 13–80) years, 61 (53%) of the patients were male. Bleeding per rectum was present in 82%, abdominal pain in 49%, constipation in 23% and diarrhea in 22%. Endoscopically, solitary and multiple lesions were present in 79 (68%) and 33 (28%) patients respectively; ulcerative lesions in 90 (78%), polypoidal in 29 (25%), erythematous patches in 3 (2.5%) and petechial spots in one patient. Associated underlying conditions were hemorrhoids in 7 (6%), hyperplastic polyps in 4 (3.5%), adenomatous polyps in 2(2%), history of ulcerative colitis in 3 (2.5%) while adenocarcinoma of colon was observed in two patients. One patient had previous surgery for colonic carcinoma.ConclusionSRUS may manifest on endoscopy as multiple ulcers, polypoidal growth and erythematous patches and has shown to share clinicopathological features with rectal prolapse, proctitis cystica profunda (PCP) and inflammatory cloacogenic polyp; therefore collectively grouped as mucosal prolapse syndrome. This may be associated with underlying conditions such as polyps, ulcerative colitis, hemorrhoids and malignancy. High index of suspicion is required to diagnose potentially serious disease by repeated endoscopies with biopsies to look for potentially serious underlying conditions associated with SRUS.

Short course adjuvant terlipressin in acute variceal bleeding: A randomized double blind dummy controlled trial

BACKGROUND & AIMS Terlipressin is recommended for 3-5 days as adjuvant to endoscopic variceal band ligation (EVBL) in esophageal variceal bleeding (EVB). We assessed whether terlipressin can be administered for a shorter period of time to patients with EVB. METHODS All eligible EVB patients received 24h of open label terlipressin at presentation. After successful EVBL, patients were randomized to receive active or dummy terlipressin for the next 48 h. We excluded patients with failure to achieve initial hemostasis, bleeding gastric varices, known hepatoma, and/or portal vein thrombosis, advanced cirrhosis (Child-Pugh score ≥12), and patients on a ventilator. The primary outcome was failure to control EVB. The secondary outcomes were 30-day mortality; re-bleeding and composite outcome of failure to control EVB. RESULTS A total of 130 eligible patients were randomized to receive terlipressin for a total of 24 (short course or SC) or 72 h (usual course or UC). Baseline patient characteristics were comparable; the majority of patients were HCV-infected and male. There was one failure to control EVB (1.5%) in UC and none in SC terlipressin (p=0.50). The 30-day re-bleeding rate was 1.5% and 3.1% in UC, and SC terlipressin, respectively (p=0.50). The 30-day mortality was 12, 6 (9.2%) patients in each group (p=0.50). The 30-day failure to control bleeding was observed in 14 patients; seven in each group (p=0.494). CONCLUSIONS In patients with esophageal variceal bleeding, a 24-h course of terlipressin is as effective as a 72-h course when used as an adjunctive therapy to successful EVBL.

Discriminant value of Rome III questionnaire in dyspeptic patients.

Background/Aim: Rome III criteria has modified the description of functional dyspepsia (FD) and divided this into subgroups. However, the discriminative value of Rome III questionnaire-based diagnosis of FD is yet to be determined. Objectives: To evaluate the Rome III questionnaire for the diagnosis of FD and whether it can discriminate between postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) in patients with dyspeptic symptoms. Patients and Methods: Consecutive patients, who were not on proton pump inhibitors (PPI), were asked to participate. Patients who have previously established acid peptic disease or predominantly reflux symptoms or having alarm symptoms such as weight loss and hematemesis were excluded. Rome III questionnaire for FD was used to identify the patients as having FD and divide into its subgroups; PDS or EPS. Gastro-duodenal biopsies, liver function tests and ultrasound were done to establish the diagnosis of FD. Results: Out of 272 patients with upper gastrointestinal (GI) symptoms without alarm features, who were enrolled in the study, a total of 191 (70%) fulfilled the criteria of FD based upon Rome III questionnaire. EPS subgroup was found in 109 (57%), PDS in 17 (9%) patients, overlap between EPS and PDS was present in 56 (29%) patients. Nine (5%) patients remained indeterminate. Diagnosis of FD was established in 136/191 (71%) patients only. Gastritis was present in 116 patients (85%), Duodenitis in 44 (32%) and Helicobacter pylori infection in 70 (51%) patients. Among 55 patients (29%) who had organic diseases, EPS was seen in 35 (64%), PDS in 5 (9%) and overlap in 15 (27%) patients. Underlying organic causes were gastric or duodenal ulcers in 14 patients, Barrett esophagus in five, chronic liver disease in seven, gall stones in five, Giardiasis and celiac disease in three each. Gastric carcinoma, Crohns disease and gastric polyps were seen in one patient each. Conclusion: This study indicates that 30% of patients who fulfilled the Rome III criteria for FD actually had organic disease. Almost one-third of patients with functioanl dyspepsia did not qualify for one of the two subgroups of FD of Rome III. There is also a need to further define the Rome III-based subgroups of FD for research purpose.