Zahid Azam

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.

Epidemic Spread of Hepatitis C Virus Genotype 3a and Relation to High Incidence of Hepatocellular Carcinoma in Pakistan

Studies conducted in different populations worldwide revealed an association between HCV genotype 1 and the development of hepatocellular carcinoma (HCC) than in infection with other HCV genotypes. There are reports which reveal the association of HCV genotype 3a (HCV‐3a) with hepatic steatosis and fibrosis but its relation with the development of HCC has not been investigated. In Pakistan, where the incidence of HCC is increasing, 189 patients with chronic liver disease including 82 with HCC were enrolled. HCV genotypes were determined by phylogeny in the NS5B region and the epidemic history of HCV‐3a was examined using coalescent theory based methods. HCV‐3a was the predominant genotype (81.4%) in the cohort studied, followed by 3b (9.3%), 3k (2.3%), 1a (1.5%), 1c (1.5%), 1b (0.8%), and 2a (0.8%) where 76% of HCC and 86% of non‐HCC were infected with HCV‐3a. The significant factors associated with HCC were older age (mean ± SD) 55.8 (±9.9) (P < 0.0001), and male gender (P < 0.001). HCV RNA was significantly higher in patients with HCC and chronic hepatitis than in liver cirrhosis (P < 0.0001). Molecular evolutionary analysis revealed a distinct phylogenetic cluster of HCV‐3a in Pakistan and an estimation of the effective number of HCV infections indicated the appearance of HCV‐3a in this region around 1920s and a rapid exponential growth in the 1950s. This indicates that the epidemic spread of HCV‐3a occurred earlier in Pakistan than in other countries in which this genotype has been reported. HCV‐3a which spread earlier in Pakistan may be associated with an increasing incidence of HCC. J. Med. Virol. 81:1189–1197, 2009.

Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial.

Introduction This preliminary study aimed to investigate the effects of the probiotic Saccharomyces boulardii on proinflammatory and anti-inflammatory cytokines in patients with diarrhea-dominant irritable bowel syndrome (IBS-D). The other objectives were to document any clinical improvement as judged by symptoms, quality of life, and histology. Patients and methods This was a randomized, double blind, placebo-controlled trial in which S. boulardii, 750 mg/day, or placebo was administered for 6 weeks in IBS-D patients, in addition to ispaghula husk standard treatment. Results Thirty-seven patients received S. boulardii and 35 patients received the placebo. As compared with placebo, the S. boulardii group showed a significant decrease in blood and tissue levels of proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-&agr; (P<0.001) and an increase in anti-inflammatory IL-10 levels, as well as an increase in the tissue IL-10/IL-12 ratio (P<0.001). No significant change in the blood and tissue levels of cytokines was found in the placebo group. Bowel-related IBS-D symptoms reported in the patients’ daily diary improved in both groups. However, overall improvement in the quality of life was more marked in the S. boulardii group. Although baseline histological findings were mild, an improvement was observed in the probiotic group in the lymphocyte and neutrophil infiltrates (P=0.017 and 0.018), epithelial mitosis (P=0.003), and intraepithelial lymphocytes (P=0.024). No serious adverse events were found in either group. Conclusion S. boulardii with ispaghula husk was superior to placebo with ispaghula husk in improving the cytokine profile, histology, and quality of life of patients with IBS-D. These preliminary results need to be confirmed in a well-powered trial.

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.

Investigating an outbreak of acute viral hepatitis caused by hepatitis E virus variants in Karachi, South Pakistan

Hepatitis E is a classic water‐borne disease in developing countries. Detection of anti‐HEV IgM and IgG antibodies, in addition to HEV RNA are useful epidemiological markers in diagnosis of hepatitis E. This study was conducted to investigate an outbreak of acute viral hepatitis in South‐Pakistan. Anti‐HEV IgM and IgG were assessed comparatively with serological kits manufactured by Abbott, Cosmic, TGH, and Wantai, selecting HEV RNA as reference assay. Molecular evolutionary analysis was performed by phylogeny and HEV spread time analysis by Bayesian Coalescent Theory approach. Of the 89 patients, 24 (26.9%) did not have acute hepatitis viral marker. Of the remaining 65 cases, 4 (6.1%) were positive for anti‐HAV IgM, one (1.5%) for anti‐HBc IgM, 2 (3%) for HCV, 53 (81.5%) for anti‐HEV IgM, and 5 (7.7%) were hepatitis‐negative. The Wantai test was 100% sensitive and specific followed by Cosmic (98.1% and 100%), TGH (98.1% and 97.2%) and Abbott (79.2% and 83.3%). Two HEV variant strains were detected by phylogeny responsible for this acute hepatitis outbreak. Estimates on demographic history of HEV showed that HEV in Pakistan has remained at a steady nonexpanding phase from around 1970 to the year 2005, in which it expanded explosively with the emergence of new HEV variants. In conclusion, the limited sensitivity of available assay (Abbott anti‐HEV EIA) may be a concern in HEV diagnosis in Pakistan. This study cautions that the dissemination of the variant strains to other areas of Pakistan may lead to explosive HEV outbreaks. J. Med. Virol. 83:622–629, 2011.

Satiety drinking tests: effects of caloric content, drinking rate, gender, age, and body mass index.

Objective. To compare the maximum tolerated volumes (MTVs) of drinking water and a nutrient liquid at different rates of drinking and to assess the best drinking test correlating with the symptom scores. Material and methods. Healthy volunteers were requested to drink water at a rate of 10 ml/min or a nutrient liquid drink at 100 and 20 ml/min on three separate occasions. Symptoms of bloating, nausea, and abdominal pain were assessed 30 min after the cessation of drinking using visual analogue scales. Results. The MTV of water was 1595±405 in males and 1327±308 in females (p<0.05). In rapid nutrient drinking, the MTV was 945±376 ml in males, whereas females tolerated 760±174 ml (p<0.05). In slow nutrient drinking, the MTV was 692±184 ml in males and 594±131 ml in females (p=0.051). Multiple regression analysis showed no influence of body mass index (BMI), age, or gender in slow nutrient drinking. However, drinking capacity was significantly influenced by gender, age, and BMI in rapid water drinking and by gender in rapid nutrient drinking. When the tolerated volumes for satiety drinking tests were compared, only males showed some significant positive correlations. Symptom scores were higher after slow nutrient drinking compared to the other two drinking tests. Conclusions. The rate of drinking and the caloric content affect the MTVs in satiety drinking tests. Slow nutrient drinking appears to be the best choice among the different satiety drink tests, as MTV in this test was not influenced by BMI or age and was associated with higher symptom scores.

1174 A NOVEL METHOD FOR NON-INVASIVE DIAGNOSIS OF HEPATITIS C VIRUS USING ELECTROMAGNETIC SIGNAL DETECTION: A MULTICENTER INTERNATIONAL STUDY

A simple, rapid and non-invasive electromagnetic sensor (C-FAST device) waspatented; for diagnosis of HCV RNA. Aim: To test the validity of the device compared to standard HCV PCR. Subjects and Methods: The first phase was done as pilot in Egypt on 79 participants; the second phase was done in five centers: one center from Egypt, two centers from Pakistan and two centers from India (800, 92 and 113 subjects respectively). The third phase was done nationally as multicenter study on (1600) participants for ensuring its representativeness. Results: When compared to PCR technique, C-FAST device revealed sensitivity 95% to 100%, specificity 95.5% to 100%, PPV 89.5% to 100%, NPV 95% to 100% and positive likelihood ratios 21.8% to 38.5%. Conclusion: It is practical evidence that HCV nucleotides emit electromagnetic signals that can be used for its identification. As compared to PCR, C-FAST is an accurate, valid and non-invasive device. Keywords—C-FASTa valid and reliable device, Distant cellular interaction, Electromagnetic signal detection, Non-invasive diagnosis of HCV.