The safety and efficacy of Houtou Jianweiling tablet in patients with chronic non-atrophic gastritis: a double-blind, non-inferiority, randomized controlled trial.

Background: Common symptoms of Chronic Non-atrophic Gastritis (CNAG) include nausea, stomach distension, and abdominal pain. The Houtou Jianweiling Tablet (HTJWT) is a chinese patent medicine (CN1368229A) and it has been used clinically for more than 20 years with proven clinical efficacy in treating CNAG, prompted us to establish the clinical efficacy and safety of HTJWT on patients with mild to moderate CNAG symptoms in Pakistani population. Methods: This phase II, double-blind, randomized, parallel-controlled trial was conducted in a single center between November 2022 and February 2023 in Pakistan. In a ratio of 1:1, total 240 CNAG patients with erosion identified by pathological biopsy and gastroscopy were randomly assigned to control (Omeprazole) group (n = 120) and the treatment (HTJWT) group (n = 120). Patients in the treatment group received orally four HTJWT (0.38g/tablet), three times a day and one placebo of Omeprazole enteric-coated tablet prior to breakfast, daily. On the other hand, patients in the control group received one Omeprazole enteric-coated tablet (20 mg/tablet) prior to breakfast and four placebo of HTJWT, thrice a day. The patients consumed the investigated drugs (i.e., treatment and control) treatment regimen was followed for a duration of 28 days. The safety of the patients were evaluated through adverse events, serious adverse events and laboratory tests such as blood biochemistry, urine analysis, liver and renal function tests. Vital signs like; blood pressure, pulse rate, body temperature, respiratory rate for all the patients were recorded. The cardiac status of the patients were assessed through electrocardiogram (ECG). The primary efficacy indicators were the improvement rate of gastric distention and gastralgia as the main clinical symptoms. Secondary indicators were visual analogue score (VAS); improvement rate of secondary clinical symptoms and signs; improvement rate of total clinical signs and symptoms; the disappearance/remission rate of Gastric pain and, remission/disappearance time of gastric distension; and the negative conversion rate of Helicobacter pylori (H. pylori). The outcomes among each group were compared using the chi-square test. Results: Patients in both groups had good drug compliance (80%-120%), and there was no statistically significant difference in the patients' baseline characteristics. The clinical improvement rate was found to be 91.1% in the treatment group and 91.0% in the control group with negligible variation among the two groups (p = 0.9824; 95% confidence interval: -0.0781-0.0798). Similarly, hardly no difference was found in the negative conversion rate of H. pylori between the treatment group and the control group (i.e., 70.1% and 71.8% respectively, p = 0.8125). There were no significant differences in respiratory rate, vital signs, blood pressure, laboratory results for blood biochemistry, urine analysis, liver and renal function tests between the two groups. The ECG assessment carried out for the treatment and control group revealed no considerable difference. Margin variation in the disappearance time of gastric pain (p = 0.1860) and remission rate (p = 0.5784) between the two groups were observed. The control group exhibited a faster remission period for gastrointestinal discomfort indications as compared to treatment group (p = 0.0430). Only one patient in the control group experienced mild to moderate adverse events, namely,; epigastric pain and dyspepsia. The results were consistent with the intention-to-treat and per-protocol analysis that included patients who were 100% compliant to the assigned therapy. Conclusion: The lower limit of confidence interval (CI, 95%) for the differences in the effective rate between the treatment and the control groups was found to be -0.0781 which is greater than -0.15, hence the treatment group is non-inferior to the control group. The therapeutic dosage used in the trial and treatment period did not cause any significant adverse event, and there were no obvious changes in the ECG profile, vital signs and biochemistry of the patients. Based on the clinical efficacy evaluation and reported adverse events, it can be concluded that the HTJWT is a safe and effective traditional chinese medicine for the treatment of patients suffering from chronic non-atrophic gastritis with mild to moderate symptoms. Clinical Trial Registration: [www.clinicaltrials.gov], identifier [NCT04672018].

Metabolic puzzle: Exploring liver fibrosis differences in Asian metabolic-associated fatty liver disease subtypes.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a liver condition marked by excessive fat buildup in the absence of heavy alcohol use. It is primarily linked with metabolic issues like insulin resistance, obesity, and abnormal lipid levels, and is often observed with other conditions such as type 2 diabetes and cardiovascular disease. However, whether the subtypes of MAFLD based on the metabolic disorder differentially impact liver fibrosis is not well explicated, especially in the Asian population. AIM: To compare the severity of liver fibrosis among different MAFLD subtypes. METHODS: A total of 322 adult patients of either gender with fatty liver on ultrasound were enrolled between January to December 2021. MAFLD was defined as per the Asian Pacific Association for the Study of the Liver guidelines. Fibrosis-4 index (Fib-4) and nonalcoholic fatty liver disease fibrosis score (NFS) were employed to evaluate liver fibrosis. RESULTS: The mean age was 44.84 ± 11 years. Seventy-two percent of the patients were female. Two hundred and seventy-three patients were classified as having MAFLD, of which 110 (40.3%) carried a single, 129 (47.3%) had two, and 34 (12.5%) had all three metabolic conditions. The cumulative number of metabolic conditions was related to elevated body mass index, triglyceride (TG) levels, and glycated hemoglobin, lower high-density lipoprotein (HDL) levels, higher liver inflammation (by aspartate aminotransferase and γ-glutamyl transferase), and higher likelihood of fibrosis (by NFS and Fib-4 scores) (P < 0.05 for all). The proportion of advanced fibrosis also increased with an increase in the number of metabolic conditions (4.1%, 25.5%, 35.6%, and 44.1% by NFS and 6.1%, 10.9%, 17%, and 26.5% by Fib-4 for no MAFLD and MAFLD with 1, 2, and 3 conditions, respectively). Among MAFLD patients, those with diabetes alone were the eldest and had the highest mean value of NFS score and Fib-4 score (P < 0.05), while MAFLD patients diagnosed with lean metabolic dysfunction exhibited the highest levels of TG and alanine aminotransferase but the lowest HDL levels (P < 0.05). CONCLUSION: The study suggests that the severity of liver fibrosis in MAFLD patients is influenced by the number and type of metabolic conditions present. Early identification and management of MAFLD, particularly in patients with multiple metabolic conditions, are crucial to prevent liver-related complications.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis.

BACKGROUND & AIMS: Whether non-selective ß-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH). METHODS: By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach. RESULTS: Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I2 = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I2 = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I2 = 0.0%, Q-statistic-p = 0.989). CONCLUSIONS: Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42019144786. LAY SUMMARY: The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective ß-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective ß-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.

Double blind, randomised trial to compare efficacy of escitalopram versus citalopram for interferon induced depression in hepatitis C patients.

OBJECTIVES: The objective of the study was to compare the two antidepressant drugs citalopram and escitalopram on the basis of efficacy in depressed patients of Hepatitis C patients receiving interferons. METHODS: In this double blind randomized trial, the hepatitis C patients visited National institute of liver and Gastro intestinal diseases (NILGID), Dow University Hospital, were screened for depression before starting treatment with interferons. The Institutional review board approval was obtained and its letter reference no.is: IRB-682/DUHS/Approval/2016/169. Patients with previous history of depression were excluded from the study. The patients who started with Interferon therapy were assessed for depression on baseline and then on each visit. Those who developed depression were randomly assigned to receive either citalopram or escitalopram. Treatment groups were assessed with depression scale each time they visit the clinic. Two antidepressants were compared for their efficacy at an interval of 4 weeks, 8weeks and then 12 weeks. RESULTS: In the current study 80 patients were randomized to receive either citalopram or escitalopram. The study outcome was better in patients treated with escitalopram. The mean change in depression score from baseline to the end of the study was greater in escitalopram group i.e. 10.41 as compared to citalopram group i.e. 14.17. The difference in depression score was also calculated as 4.28 and.3.76 (p < 0.001) for both the drugs at week 8 and week 12 respectively, which was statistically significant. Difference in depression score were also calculated for gender 0.576 (p = 0.497) and age 0.950 (p = 0.265), which were found to be non-significant, statistically. CONCLUSION: The results demonstrated superiority of escitalopram over citalopram, the drug is twice as potent as the racemic mixture. Additionally the drug is well tolerated and exhibited better effects. Escitalopram proved to be a safer alternative to citalopram.

HEP-Net opinion on the management of ascites and its complications in the setting of decompensated cirrhosis in the resource constrained environment of Pakistan.

Approximately one half of patients develop ascites within 10 years of diagnosis of compensated cirrhosis. It is a poor prognostic indicator, with only 50% surviving beyond two years. Mortality worsens significantly to 20% to 50% at one year if the ascites becomes refractory to medical therapy. Pakistan has one of the highest prevalence of viral hepatitis in the world and patients with ascites secondary to liver cirrhosis make a major percentage of both inpatient and outpatient burden. Studies indicate that over 80% of patients admitted with ascites have liver cirrhosis as the cause. This expert opinion suggests proper assessment of patients with ascites in the presence of underlying cirrhosis. This expert opinion includes appropriate diagnosis and management of uncomplicated ascites, refractory ascites and complicated ascites (including spontaneous bacterial peritonitis (SBP) ascites, hepatorenal syndrome (HRS) and hyponatremia. The purpose behind this expert opinion is to help consultants, postgraduate trainees, medical officers and primary care physicians optimally manage their patients with cirrhosis and ascites in a resource constrained setting as is often encountered in a developing country like Pakistan.

Evolution of HBV S-gene in the backdrop of HDV co-infection.

HBV-HDV co-infected people have a higher chance of developing cirrhosis, fulminant hepatitis, and hepatocellular carcinoma (HCC) compared to those infected only with HBV. The present study was conducted to investigate HBV genotypes and phylogeny among HBV mono-infected and HBV-HDV co-infected patients, as well as analyze mutations in the surface gene of HBV in mono-infected and co-infected patients. A total of 100 blood samples (50 co-infected with HBV and HDV, and 50 mono-infected with HBV only) were collected for this study. HBV DNA was extracted from patient sera and partial surface antigen gene was amplified from HBV genome using polymerase chain reaction. HBV S gene was sequenced from 49 mono-infected and 36 co-infected patients and analyzed to identify HBV genotypes and phylogenetic patterns. Subsequently, HBV S amino acid sequences were analyzed for mutational differences between sequences from mono- and co-infected patients. HBV genotype D was predominantly found in both mono-infected as well as co-infected patients. Phylogenetic analysis showed the divergence of HBV sequences, between mono- and co-infected patients, into two distinct clusters. HBV S gene mutation analysis revealed certain mutations in HBV-HDV co-infected subjects to be distinct from those found in mono-infected patients. This might indicate the evolution of HBV S gene under selection pressures generated from HDV coinfection.

Initial results of efficacy and safety of Sofosbuvir among Pakistani Population: A real life trial - Hepatitis Eradication Accuracy Trial of Sofosbuvir (HEATS).

OBJECTIVE: The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus (HCV) NS5B polymerase approved for the treatment of chronic HCV infection with genotypes 1 - 4. The objective of the study was to evaluate the interim results of efficacy and safety of regimens containing Sofosbuvir (Zoval) among Pakistani population with the rapid virologic response (RVR2/4 weeks) with HCV infections. METHODS: This is a multicenter open label prospective observational study. Patients suffering from chronic Hepatitis C infection received Sofosbuvir (Zoval) 400 mg plus ribavirin (with or without peg interferon) for 12/24 weeks. The interim results of this study were rapid virological response on week 4. Data was analyzed using SPSS version 21 for descriptive statistics. RESULTS: A total of 573 patients with HCV infection were included in the study. The mean age of patients was 46.07 ± 11.41 years. Out of 573 patients 535 (93.3%) were treatment naive, 26 (4.5%) were relapser, 7 (1.2%) were non-responders and 5 (1.0%) were partial responders. A rapid virologic response was reported in 563(98.2%) of patients with HCV infection after four weeks of treatment. The treatment was generally well tolerated. CONCLUSION: Sofosbuvir (Zoval) is effective and well tolerated in combination with ribavirin in HCV infected patients.

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-α (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.

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 ß 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.

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.

Factors determining the clinical outcome of acute variceal bleed in cirrhotic patients.

Variceal bleed is a severe complication of portal hypertension. We studied the predictors of failure to control variceal bleed and re-bleed in patients with cirrhosis. We reviewed the case records of 382 consecutive patients admitted with variceal bleed from January 2001 to December 2005. Diagnosis of cirrhosis was made on clinical, laboratory, and radiological parameters. Acute variceal bleeding, failure to control bleed, and re-bleeding were defined according to Baveno III consensus report. Failure to control bleed was observed in 39 (10.2%) patients while in hospital re-bleed occurred in 49 (12.8%) patients. Thirty-four patients died. Diabetes was present in 148 (39%) patients. On multivariate logistic regression analysis, predictors of failure to control bleed were presence of diabetes mellitus and active bleeding at the time of endoscopy; predictors of in-hospital re-bleed were diabetes mellitus and serum bilirubin >3 mg/dL. Diabetes mellitus, active bleeding at endoscopy and bilirubin >3 mg/dL are bad prognostic factors for initial control of variceal bleed, and recurrent bleed in patients with cirrhosis.

Role of N-acetylcysteine in adults with non-acetaminophen-induced acute liver failure in a center without the facility of liver transplantation.

PURPOSE: We aimed to study the role of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). METHODS: A total of 47 adult patients were prospectively enrolled with NAI-ALF (group 1 or NAC group) and oral NAC was given. The primary outcome was reduction in mortality with the use of NAC in NAI-ALF. The secondary outcomes were to evaluate safety of NAC and to assess factors predicting mortality. We compared these results with records of NAI-ALF patients admitted in our hospital from 2000 to 2003 (n = 44) who were not given NAC (group 2 or historical controls). RESULTS: The two groups were comparable for the etiology of ALF, prothrombin time (PT), alanine aminotransferase, creatinine, albumin, etc. The mean age in group 1 was 27.7 ± 11.8 years and in group 2 37.5 ± 18.8 years (P = 0.004). Bilirubin was 20.63 ± 11.03 and 14.36 ± 8.90 mg/dl in groups 1 and 2, respectively (P = 0.004). There were 8 (17%) and 1 (2.3%) pregnant ALF women with acute hepatitis E virus (HEV) infection in groups 1 and 2, respectively (P = 0.031). All patients were given supportive care, including mechanical ventilation. A total of 34 (37.36%) patients survived; 22 (47%) in group 1 (NAC group) and 12 (27%) in group 2 (controls) (P = 0.05). On multivariable regression analysis, patients not given NAC (odds ratio [OR] = 10.3, 95% confidence interval [CI] = 1.6-65.7), along with age older than 40 years (OR = 10.3, 95% CI = 2.0-52.5), PT more than 50 s (OR = 15.4, 95% CI = 3.8-62.2), patients requiring mechanical ventilation (OR = 20.1, 95% CI = 3.1-130.2), and interval between jaundice and hepatic encephalopathy (OR = 5.0, 95% CI = 1.3-19.1) were independent predictors of mortality. CONCLUSIONS: The use of NAC causes reduction in NAI-ALF mortality and its use was safe.

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.

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.

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< or =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.

Furazolidone, co-amoxiclav, colloidal bismuth subcitrate, and esomeprazole for patients who failed to eradicate Helicobacter pylori with triple therapy.

There is increasing evidence of Helicobacter pylori (H. pylori) resistance to the classical triple therapy consisting of a proton-pump inhibitor and clarithromycin with either amoxicillin or metronidazole. This study is aimed at establishing the efficacy and safety of a 14-day regimen to eradicate H. pylori in patients who have failed with the classical triple therapy given for 14 days. One hundred seventy-six patients diagnosed to have H. pylori infection were given triple therapy for 14 days. Fifty-two patients who failed to respond as evident from positive 14C-urea breath test (UBT) done 4-6 weeks after the completion of triple therapy were offered a combination regimen comprised of furazolidone 200 mg b.i.d, co-amoxiclav 1 g b.i.d., colloidal bismuth subcitrate 240 mg b.i.d., and esomeprazole 40 mg b.i.d. for 14 days. The mean age of these patients was 41 +/- 13 years (range 20-67). Thirty-four were males. To document eradication of H. pylori, UBT was repeated 4 weeks after the completion of treatment. On an intention-to-treat analysis, the eradication rate was 81% (42 out of 52) whereas on per-protocol basis, the eradication rate was 82.4% (42 out of 51). In conclusion, this new regimen represents a suitable second-line therapy.

Acute sarcoid arthropathy.

A case of middle aged female with acute arthritis, mediastinal lymphadenopathy and diabetes mellitus is described. The patient underwent mediastinal lymph node biopsy and was diagnosed as having acute sarcoidosis (Lofgrens syndrome). She was treated with systemic steroids and responded well.