Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial.

INTRODUCTION: Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. METHODS: This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. RESULTS: A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. DISCUSSION: In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

Low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet versus traditional dietary advice for functional dyspepsia: a randomized controlled trial.

BACKGROUND AND AIM: Prospective trials evaluating efficacy of specific diet restriction in functional dyspepsia (FD) are scarce. We aimed to assess efficacy of low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet in FD, compared with traditional dietary advice (TDA). METHODS: In this prospective, single-blind trial, patients with FD (Rome IV) were randomized into low FODMAP diet (LFD) and TDA groups, for 4 weeks (phase I). In phase II (4-12 weeks), LFD group was advised systematic re-introduction of FODMAPs. Symptom severity and quality of life were assessed using "Short-Form Nepean Dyspepsia Index (SF-NDI)." Primary outcome was symptomatic response (symptom score reduction of ≥ 50%), at 4 weeks. Study was registered with CTRI (2019/06/019852). RESULTS: Of 184 patients screened, 105 were randomized to LFD (n = 54) and TDA (n = 51) groups. At 4 weeks, both groups showed significant reduction in SF-NDI symptom scores compared with baseline, with no significant difference in inter-group response rates [LFD: 66.7% (36/54); TDA: 56.9% (29/51); P = 0.32]. On sub-group analysis, patients with postprandial distress syndrome or bloating had significantly better symptomatic response with LFD (P = 0.04). SF-NDI quality of life scores improved significantly in both groups. On multivariate analysis, factors predicting response to LFD were bloating and male gender. Incidences of adverse events (minor) were similar in both groups. CONCLUSIONS: In patients with FD, LFD and TDA lead to significant symptomatic and quality of life improvement. Patients with postprandial distress syndrome or bloating respond significantly better to LFD. Therefore, dietary advice for FD should be individualized according to FD subtype.

Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores. CONCLUSION: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.

Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet in patients with diarrhea-predominant irritable bowel syndrome: A prospective, randomized trial.

BACKGROUND AND AIM: Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet improves irritable bowel syndrome (IBS) symptoms. Data on long-term "modified" FODMAP diet are emerging. We aimed to assess efficacy and acceptability of short-term "strict" low FODMAP diet (LFD) and long-term "modified" FODMAP diet in patients with diarrhea-predominant IBS (IBS-D). METHODS: This prospective randomized trial included patients with IBS-D (Rome IV) and IBS severity scoring system (IBS-SSS) ≥ 175. In phase I (4 weeks), patients were randomized to strict LFD and traditional dietary advice (TDA) groups. From 4 to 16 weeks, LFD group was advised systematic reintroduction of FODMAPs ("modified" FODMAP diet). Response was defined as > 50-point reduction in IBS-SSS. RESULTS: Of the total 166 patients with IBS-D screened, 101 (mean age 41.9 ± 17.1 years, 58% male) were randomized to LFD (n = 52) and TDA (n = 49) groups. Both at 4 and 16 weeks, total IBS-SSS and IBS quality of life score reduced significantly in both groups, but there was significantly greater reduction in LFD group. By intention-to-treat analysis, responders in LFD group were significantly higher than TDA group (4 weeks-62.7% [32/51] vs 40.8% [20/49], respectively, P = 0.0448; 16 weeks-52.9% [27/51] vs 30.6% [15/49], respectively; P = 0.0274). Compliance to LFD was 93% at 4 weeks and 64% at 16 weeks. Energy, carbohydrate, fat, and fiber intake showed reduction in LFD group at 4 weeks, which improved till 16 weeks. CONCLUSIONS: Strict LFD for short-term and "modified" LFD for long term in IBS-D patients is acceptable and leads to significant improvement in symptoms and quality of life.

L-ornithine L-aspartate in bouts of overt hepatic encephalopathy.

High-quality data on the efficacy of L-ornithine L-aspartate (LOLA) in patients with cirrhosis and bouts of overt hepatic encephalopathy (OHE) are missing. We evaluated the efficacy of intravenous LOLA in the reversal of bouts of OHE in patients with cirrhosis. In this prospective, double-blind, randomized, placebo-controlled trial conducted at two tertiary care institutes in India, 370 patients with cirrhosis and bouts of OHE were screened. After exclusion, 193 (52.16%) patients were randomized to receive either intravenous infusions of LOLA (n = 98), 30 g daily, or placebo (n = 95) for 5 days. Standard of care treatment (including lactulose and ceftriaxone) was given in both groups. Randomization was done centrally (http://www.sealedenvelope.com/). All study personnel were blinded to the treatment assignment. Fasting venous ammonia levels were estimated daily from 0 to 5 days. Serum tumor necrosis factor-alpha, interleukins, hemogram, and liver and renal function tests were performed at days 0 and 5. Primary outcome was mental state grade at day 5 of treatment. The grade of OHE was significantly lower in the LOLA group (compared to placebo) on days 1-4 but not on day 5. The mean time taken for recovery was lower in the LOLA group compared to the placebo group (1.92 ± 0.93 versus 2.50 ± 1.03 days, P = 0.002; 95% confidence interval -0.852 to -0.202). Venous ammonia at day 5 and length of hospital stay were significantly lower in the LOLA group. No significant difference in interleukins was seen between the groups. Conclusion: In patients with bouts of OHE, intravenous LOLA (as an add-on therapy to lactulose and ceftriaxone) significantly improves the grade of OHE over days 1-4, but not on day 5, and decreases venous ammonia, time of recovery, and length of hospital stay. (Hepatology 2018;67:700-710).

Early feeding after esophageal variceal band ligation in cirrhotics is safe: Randomized controlled trial.

BACKGROUND AND AIM: Oral feeding following variceal ligation in cirrhotics is usually delayed due to fear of rebleeding. Solid diet is usually further delayed (until 72 h) despite lack of evidence. We aimed to compare the impact of early versus delayed feeding on rebleeding following variceal ligation. METHODS: This was a prospective randomized controlled trial including patients undergoing variceal ligation for active esophageal variceal bleeding. Patients were randomized into two groups. In the early-feeding group, liquid diet was given after 1 h following variceal ligation and a regular solid diet was resumed after 4 h. In the delayed-feeding group, patients fasted for the first 4 h after variceal ligation, liquid diet was given until 24 h, soft diet for the next 48 h and a regular solid diet after 72 h. RESULTS: There were 52 and 49 patients in the early and delayed feeding groups, respectively. Very early rebleeding rates [2 (3.84%) vs 1 (2.04%); P ≥ 0.99] and delayed rebleeding rates [2 (3.84%) vs 4 (8.16%); P = 0.75] were similar in both groups. Protein and calorie intake in the early-feeding group was significantly better and early infections in active bleeders were significantly lower compared to the delayed-feeding group. One-month mortality was similar in both groups [3 (5.76%) vs 4 (8.16%); P = 0.75]. CONCLUSION: Early feeding with a regular solid diet in conscious patients after successful variceal ligation for esophageal varices is safe, provides better nutrition and results in lower incidence of infections in bleeders compared to delayed feeding.

Clinical profile of hepatitis C virus infection in a developing country: India.

BACKGROUND AND AIM: The epidemiology and clinical profile of hepatitis C virus (HCV) varies worldwide, and data from developing countries are sparse. The aim of the present study was to assess the clinical profile of HCV infection in a developing country in South-East Asia (India). METHODS: This observational study assessed patient demographics, viral characteristics, risk factors for virus acquisition, and disease characteristics in HCV patients diagnosed between January 2004 and December 2015. RESULTS: Of 8035 patients who were diagnosed with HCV infection, a majority were men (68.3%), middle aged (52.2%), and from low (34%) to middle (46%) socioeconomic status and rural population (69.8%). Eighty-two percent had identifiable risk factors, the most common being history of dental treatment (52%) and therapeutic injections with reusable syringes/needles (45%). Household contacts of index patients had high prevalence of HCV (15.3%). Common genotypes were genotype 3 (70.4%) and genotype 1 (19.3%). Although a majority of patients were either asymptomatic (54.8%) or had non-specific symptoms (6.7%) at presentation, a significant proportion (9.3%) had advanced liver disease. Presentation with cirrhosis (38.8%) was associated with male gender, higher age at time of virus detection, rural residence, alcohol or opium intake, and coinfections with hepatitis B virus or human immunodeficiency virus. CONCLUSIONS: Hepatitis C virus infection in northern India is seen more commonly in men, the middle aged and people from rural background and low to middle socioeconomic status. The common possible risk factors are dental treatment and exposure to reused syringes and needles. Although the most common presentation is incidental detection, a large number of patients present with advanced liver disease.

Minimal hepatic encephalopathy in cirrhosis- how long to treat?

INTRODUCTION: Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. MATERIAL AND METHODS: In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. RESULTS: Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn't. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. CONCLUSION: Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

Emphysematous Gastritis with Air in Portal Venous System.

Emphysematous gastritis is a rare but severe form of phlegmonous gastritis caused by gastric mucosal disruption and infection of stomach wall by gas-forming bacteria. Ingestion of corrosive substances is the most common predisposing factor, followed by alcohol abuse, abdominal surgery, diabetes and immunosuppression. Patients usually present with abdominal pain, vomiting, diarrhea, constipation and/or gastro-intestinal hemorrhage. Characteristic radiological findings include presence of gas in the gastric wall. Management of this condition includes broad-spectrum antibiotics and supportive therapy. Outcome of emphysematous gastritis is frequently fatal due to septic shock and multi-organ failure. We report a case of a 65 years old male who presented with fever and upper abdominal tenderness. He had history of uncontrolled diabetes and chronic alcohol intake. Radiological investigations revealed air within the gastric wall, portal vein, liver and spleen. Despite initial improvement with conservative management, patient succumbed due to sepsis and shock.

Rifaximin vs. lactulose in treatment of minimal hepatic encephalopathy.

BACKGROUND & AIMS: Lactulose and rifaximin have already been shown to improve both cognitive functions and health related quality of life (HRQOL) in MHE patients. We aimed to compare the efficacy of rifaximin with lactulose in reversal of MHE and improvement in HRQOL in cirrhotic patients with MHE. METHOD: This prospective, randomized, open label, non-inferiority trial, was conducted at the Gastroenterology department of a tertiary care institute in Northern India. MHE was diagnosed if any two of the five neuro-psychometric (NP) tests were positive. HRQOL was assessed using the sickness impact profile (SIP) questionnaire (John Hopkins University, USA). RESULTS: Of 527 cirrhotics screened, 351 were found eligible and tested for MHE. A total of 112 (31.9%) patients were found to have MHE and then randomized into two groups group A (lactulose; 30-120 ml/day) and B (Tablet. rifaximin; 400 mg thrice a day). Based on the intention-to-treat population, the proportion of patients with MHE reversal at 3 months was 73.7% (42/57) in the rifaximin arm and 69.1% (38/55) in the lactulose arm [4.6% difference (90% CI -9.3% to 18.4%)]. However, non-inferiority of rifaximin over lactulose could not be established as the pre-specified non-inferiority margin (-5%) lies within the two-sided 90% confidence interval of the difference. HRQOL was significantly improved in both groups (P = 0.20). However, the proportion of patients with flatulence (P = 0.004) and diarrhoea (P = 0.0002) was significantly higher in patients who took lactulose. CONCLUSION: Non-inferiority of rifaximin over lactulose for MHE reversal was not established.

Noradrenaline is as Effective as Terlipressin in Hepatorenal Syndrome Type 1: A Prospective, Randomized Trial.

OBJECTIVES: Hepatorenal syndrome (HRS) is a functional renal failure occurring in end stage liver disease, which is associated with poor prognosis. Terlipressin has been shown to be effective in treatment of HRS. More recently, it was suggested that noradrenaline, an alpha-adrenergic drug may be also effective in HRS. We aimed to compare the efficacy of noradrenaline versus terlipressin in treatment of HRS type 1. METHODS: Consecutive patients with cirrhosis and HRS type 1 were enrolled and randomised into 2 groups- Group A received intravenous noradrenaline infusion (0.5-3 mg/h) and group B received intravenous terlipressin (0.5-2 mg/6h) for 2 weeks. Intravenous albumin (20 g/day) was given to both groups. RESULTS: Out of 55 cirrhotics screened, 41 were randomised into group A (n=21) or group B (n=20). Baseline characteristics of the two groups were similar. HRS reversal was seen in 47.6%(10/21) patients in group A, and 45% (9/20) patients in group B (p=1.00). In both groups, there was a significant decrease in serum creatinine from baseline (group A- 3.1±1.4 mg/dl to 2.2±1.3 mg/dl, p=0.028; group B- 3.4±1.6 mg/dl to 2.3±1.3 mg/dl, p=0.035). Both the groups showed a significant increase in mean arterial pressure (group A- 77.3±8.6 mmHg to 103.4±8.3 mmHg, p=0.0001; group B- 76.8±11.6 mmHg to 100±9.4 mmHg, p=0.0001). Noradrenaline was associated with fewer adverse events and was significantly cheaper than terlipressin. Lower baseline MELD score was an independent predictor of response to treatment. CONCLUSIONS: Noradrenaline is as effective and safe as terlipressin in the treatment of HRS type 1.

Treatment of chronic hepatitis C genotype 1 early responders with 36 week pegylated interferon and ribavirin therapy.

INTRODUCTION: Standard treatment for patients with chronic hepatitis C genotype 1 (CHC G-1) infection includes pegylated interferon plus ribavirin (PEG-RBV) for 48 weeks. Shorter treatment regimen would be more acceptable due to lower cost and fewer side-effects. We aimed to compare the efficacy of 36 week PEG-RBV therapy with standard 48 week therapy in CHC G-1 patients who achieve complete early virological response (cEVR). MATERIAL AND METHODS: Consecutive treatment-naïve patients with CHC G-1 were treated with pegylated interferon a2b (1.5 µg/kg/week) or α2a (180 µg/week) and weight based ribavirin. Patients who achieved cEVR at 12 weeks [undetectable HCV RNA irrespective of RVR (rapid virological response)] were randomized into- group A (48 weeks therapy) and group B (36 weeks therapy). Primary end-point was achievement of sustained virological response (SVR) at 24 weeks of follow up. RESULTS: Out of the total 166 patients started on treatment, 112 (69.3%) achieved cEVR, and were randomized into group A (n = 59) and group B (n = 53). Fifty-five (93.2%) patients in group A and 50 (94.3%) in group B completed therapy. The overall SVR rate in group A was 79.6% (47/59) and group B was 84.9% (45/53) (p = 0.622). SVR rates in the two groups were comparable in all patient sub-groups according to factors like viral load (≤ or > 400,000 IU/mL), RVR (achieved/not achieved), age (≤ or > 40 years), body mass index (≤ or > 27) and cirrhosis (present/absent). CONCLUSION: In CHC G-1 patients who achieve cEVR, 36 weeks PEG-RBV therapy is as effective as standard 48 weeks therapy, irrespective of other host or virological factors.

Normative values of skeletal muscle mass, strength and performance in the Indian population.

BACKGROUND AND OBJECTIVES: Skeletal muscle is characterized by its mass, strength and performance. These normative values are pivotal in defining sarcopenia. Sarcopenia is associated with poor outcome of numerous medical and surgical conditions. This study aimed to establish normative benchmarks for skeletal muscle mass, strength and performance within the context of the Asian (Indian) population. METHODS: Our investigation utilized the computed tomography (CT) skeletal muscle index (SMI), handgrip strength (HGS), gait velocity and chair-stand test to construct reference values for muscle characteristics in the Indian population. RESULTS: The SMI analysis incorporated 1485 cases of acute abdomen (54.7%) males). The calculated SMI (kg/m2) was 38.50 (35.05-42.30) in males and 36.30 (32.20-41.20) in females (p = 0.510). The study also involved 3083 healthy individuals (67.6% males) evaluated for muscle strength and performance between August 2017 and August 2018. Notably, HGS (kg force) was recorded at 34.95 (26.50-43.30) in males and 25.50 (18.60-31.20) in females (p < 0.001). Gait velocity (metres/second) exhibited values of 1.25 (1.04-1.56) in males and 1.24 (1.03-1.56) in females (p = 0.851). Additionally, chair-stand test (seconds) results were 10.00 (9.00-13.00) in males and 12.00 (10.00-14.00) in females (p < 0.001). CONCLUSIONS: The investigation determined that males had greater muscle strength and performance than females. But gender wise, there was no significant difference in muscle mass. Interestingly, our population's muscle parameters were consistently lower compared to western literature benchmarks. These normative values will help to define sarcopenia parameters in our population, which have prognostic value in multiple ailments.

Effect of aerobic exercise on auditory and visual reaction times: a prospective study.

Physical exercise provides multiple benefits to an individual. However, the beneficial effect of exercise on psychomotor performance remains controversial. The present study was undertaken to determine the effect of aerobic exercise on auditory reaction time (ART) and visual reaction time (VRT). Fifty subjects were enrolled consisting of healthy subjects who were not exercising (n = 25; group I) and subjects doing regular aerobic exercisers (n = 25; group II). ART and VRT were recorded using digital display response time apparatus equipped with three lights (red, green and yellow) and three auditory stimuli (low, medium and high pitched sounds). The mean VRT of group II subjects (318.24 +/- 6.709) was significantly lower than that of group I (505.73 +/- 16.961) (P < 0.001). The mean ART of group II subjects (313.33 +/- 8.160) was significantly lower than that of group I (573.09 +/- 17.950) (P < 0.001). Auditory and visual reaction times are better in aerobic exercisers as compared to non-exercisers irrespective of age and gender.

Indian consensus statements on irritable bowel syndrome in adults: A guideline by the Indian Neurogastroenterology and Motility Association and jointly supported by the Indian Society of Gastroenterology.

The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of "completely accepted" and "accepted with minor reservation" voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

AARC score determines outcomes in patients with alcohol-associated hepatitis: a multinational study.

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients. METHODS: Prospectively collected data from the AARC database were analyzed. RESULTS: Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p < 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p < 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores. CONCLUSION: Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

Corticosteroid plus pentoxifylline is not better than corticosteroid alone for improving survival in severe alcoholic hepatitis (COPE trial).

BACKGROUND: Corticosteroids and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis (SAH), but not to the extent desired. Combining both drugs may lead to better survival, but has not yet been studied. AIM: To compare the efficacy of corticosteroids plus pentoxifylline with that of corticosteroids alone in improving survival of SAH patients. METHODS: Of the 111 patients screened, 70 patients with SAH (Maddrey discriminant function (MDF) ≥ 32) were enrolled. Patients with active infection, bleeding, renal failure, or pancreatitis were excluded. Treatment was given for four weeks to group A (n = 36; prednisolone 40 mg/day plus pentoxifylline 400 mg thrice/day) and group B (n = 34; prednisolone 40 mg/day). Patients were followed up for 6 months. Data are expressed as median (range) or percentage. RESULTS: Baseline characteristics of the two groups were similar (MDF group A 78.5 (36.8-140.9), group B 74.9 (45.6-140.2)). Four-week and six-month survival in groups A and B were not significantly different (four-week 72.2 and 73.5%, respectively, p = 1.00; six-month 30.6 and 23.5%, respectively, p = 0.417). At seven days, 55.6% of patients in group A and 64.7% in group B had a Lille score <0.45 (p = 0.473). Six-month survival was significantly higher for patients with a Lille Score <0.45 than for those with a Lille score ≥0.45 (group A 55.5 vs. 0%, p = 0.0006; group B 36 vs. 0%, p = 0.0304). Biological improvement at 28 days was significant for both groups; however, the difference between the groups was not significant. CONCLUSIONS: For patients with severe alcoholic hepatitis, a combination of corticosteroids and pentoxifylline has no additional survival advantage compared with corticosteroids alone.

Pentoxifylline in severe alcoholic hepatitis: a prospective, randomised trial.

BACKGROUND: Role of corticosteroids in treatment of severe alcoholic hepatitis (SAH) is controversial. Pentoxifylline (PTX), an inhibitor of TNF, has also been shown to decrease short term mortality in SAH. Aim of this study was to evaluate the effect of PTX on short term mortality, renal and hepatic functions in patients with SAH. METHODS: Fifty patients with SAH {Maddrey's Discriminant Function (DF) > or = 32} were prospectively enrolled. Twenty five patients received PTX (400 mg orally, three times a day), and 25 received placebo for 4 weeks. Serum tumor necrosis factor (TNF) was measured in both groups. RESULTS: Baseline characteristics of the two groups were similar. At 4 weeks, mortality in PTX group was lower than that in controls {20% (5/25) versus 40% (10/25) respectively; p = 0.216; RR 0.5; 95% CI 0.19-1.25}. Renal failure was the cause of mortality in 20% (1/5) patients in PTX group, and 70% (7/10) in controls (p = 0.11). Significant reduction in urea, creatinine, DF and TNF was noted in PTX group. Reduction in TNF did not correlate with reduction in creatinine or DF. CONCLUSIONS: In patients with SAH, PTX leads to a significant improvement in renal and hepatic functions, and a trend towards decreased short term mortality.