Combined PEG3350 Plus Lactulose Results in Early Resolution of Hepatic Encephalopathy and Improved 28-Day Survival in Acute-on-Chronic Liver Failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality in those with hepatic encephalopathy (HE). Polyethylene glycol (PEG) 3350 electrolyte solution can ensure rapid gut catharsis, which may resolve HE more effectively than lactulose. In this open-label-randomized trial, we compared PEG+lactulose versus lactulose alone in ACLF with HE grade ≥2 for efficacy and outcome. PATIENTS AND METHODS: Patients were randomized to receive PEG (2 L q12 h) followed by lactulose (30 mL q8 h) or standard medical treatment [SMT, lactulose (titrated 30 mL q8 h)]. Endpoints were HE grade improvement at 24 hours, 48 hours, and 7 days using hepatic encephalopathy scoring algorithm (HESA), ammonia reduction, HE resolution, and survival benefit. RESULTS: Of 60 patients, 29 were randomized to PEG+lactulose arm and 31 to SMT. In the PEG arm, early reduction in HESA score was noted in more persons [18 (62.1%) vs. 10 (32.2%); P=0.021] with a shorter median time to HE resolution [4.5 (3 to 9) d vs. 9 (8 to 11) d; P=0.023]. On multivariate analysis, age [hazard ratio (HR),1.06 (1.00 to 1.13); P=0.03], HESA score [HR, 6.01 (1.27 to 28.5); P=0.024], and model for end-stage liver disease [HR, 1.26 (1.01 to 1.53); P=0.022] were predictors of mortality at 28 days. Ammonia level or reduction did not correlate with HE grades. Adverse events included excessive diarrhea (20.6% vs. 9.6%) in the PEG and SMT arms, albeit without dyselectrolytemia or worsened renal function. In the PEG versus SMT arm, survival at 28 days were 93.1% versus 67.7% (P=0.010) and at 90 days was 68.9% versus 48.3% (P=0.940), respectively, with fewer persons relapsing with HE in the PEG arm. CONCLUSIONS: PEG resulted in early and sustained HE resolution with improved short-term survival making, it a suitable and safe drug in patients with acute HE in ACLF.

Dual treatment with sofosbuvir plus ribavirin is as effective as triple therapy with pegylated interferon plus sofosbuvir plus ribavirin in predominant genotype 3 patients with chronic hepatitis C.

BACKGROUND AND AIM: Sofosbuvir (SOF) was the first directly acting antiviral made available for chronic hepatitis C (CHC) in India. We describe our "real life" experience of using SOF with ribavirin (RBV) with or without pegylated interferon (Peg-IFN) in predominant genotype 3 patients with CHC. METHODS: A total of 158 patients (men 99 [62.6%], mean age 40.3 ± 12.8 years) with CHC treated with dual therapy (SOF + RBV) for 24 weeks or triple therapy (Peg-IFN + SOF + RBV) for 12 weeks were included prospectively. Patients with co-infection, decompensated liver disease, and post-organ transplantation were excluded. Data were analysed for the preference of treatment regimen, end of treatment response (ETR), sustained virological response at 12 weeks, and side effects. RESULTS: Genotype 3 was the predominant genotype (105 [66.4%]) followed by genotype 1 (40 [25.3%]) and genotype 4 (13[8.2%]). Forty-eight (30.37%) patients had cirrhosis (LSM ≥ 13 kPa), and 30 (19%) were treatment experienced with Peg-IFN + RBV. A total of 103 (65.18%) patients received dual therapy, and 55 (34.81%) received triple therapy. Resentment to receive injections, inaccessibility to a facility, fear of injection or its side effects, and financial constraints were the reasons to refuse triple therapy. All patients in triple therapy group and all but two patients (98%) in the dual therapy group attained ETR. All those who achieved ETR achieved sustained virological response at 12 weeks in both groups. But for anemia in three patients (two in triple, one in dual therapy), there were no major side effects. CONCLUSIONS: Most patients with CHC prefer an oral treatment with directly acting antivirals. Both oral and interferon-based regimens achieve high response rate.

Treatment of chronic hepatitis C in end stage renal disease: experience at a tertiary care centre.

INTRODUCTION: Treatment of patients with chronic hepatitis C (CHC) is difficult in the setting of end stage renal disease (ESRD). The present study aimed to analyze the treatment outcome in patients with CHC and ESRD, being evaluated for kidney transplantation. METHODS: Data of 65 patients of ESRD with CHC (males: 53, mean age: 39.2 +/- 14.4 years) was analysed retrospectively. Patients were treated with either pegylated or conventional interferon (IFN) without ribavirin. Treatment response was assessed for rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR) and sustained virological response (SVR). RESULTS: All patients were receiving hemodialysis (duration 1-60 months). Sixteen patients (25%) (genotype 1: 11, genotype 3: 4, genotype 2: 1) agreed for treatment (13 pegylated IFN and 3 conventional IFN). RVR was achieved in 7 patients (44%) and out of 11 patients (69%) who achieved EVR, ETR was achieved in 7 (44%) patients. Seven patients (44%) dropped out during treatment (2 because of side effects). SVR could be demonstrated in one of 7 patients who achieved ETR (6 patients were lost to follow up after ETR). CONCLUSIONS: In our experience, dropouts before, during and after treatment are a major problem in patients with CHC and ESRD. Of those who complete treatment, around half of them are able to achieve the end of treatment response.

Tackling the Hepatitis C Disease Burden in Punjab, India.

Hepatitis C virus (HCV) is a globally prevalent pathogen and is a major cause of healthcare burden in India. HCV poses a significant problem in the state of Punjab, India owing to the higher prevalence of risk factors like unsafe medical practices (including unsafe injections and dental procedures) and intravenous drug use. The reported prevalence of HCV in this part of the country was 5.2% in 2012, while a recent study has shown the prevalence to be 3.2% in 2016. Similar to the other geographic belts in India, genotype 3 predominates in the state of Punjab. Control of HCV infection in Punjab requires focusing on several strategies. There is a need to formulate a health educational curriculum targeting not only the high-risk population but also the general population regarding the transmission of HCV. Training of family physicians who form the first link to patients in the community is imperative in the success of healthcare programmes. Adopting the dual approach of treating the old cases (decreasing the reservoir pool of HCV) and decreasing the incidence of new ones would help curtail the disease and decrease liver related mortality. A commendable initiative has been launched by the Punjab state government to eliminate HCV from Punjab. However, besides the initiative by the government, a concerted effort by all other stakeholders in managing the HCV burden in India, namely the doctors, the drug companies and the non-government organizations is required for control of HCV.

Endoscopic sclerotherapy of gastric variceal bleeding with N-butyl-2-cyanoacrylate.

BACKGROUND: bleeding from gastric varices is a life-threatening complication of portal hypertension. Fundal and isolated gastric varices are at high risk for variceal bleeding. In this study, we report our experience with n-butyl-2-cyanoacrylate (BC) in patients with large gastric varices. STUDY: twenty-nine patients (15 male, 14 female) with large fundal varices (active bleed, 5; passive bleed after eradication of esophageal varices, 13; unbled fundal varices with red color sign, 11) underwent endoscopic sclerotherapy with BC. Cirrhosis was present in 13 patients; extrahepatic portal venous obstruction, in 13; and noncirrhotic portal fibrosis, in 3. N-Butyl-2-cyanoacrylate after mixing with lipiodol (1:1) was given to the initial 10 patients and was given in undiluted form to the remaining patients, followed by injection of 0.7 mL of distilled water to rinse the injection catheter. One to three injections (0.5-1 mL) were given until all gastric varices became hard. All patients were on long-term endoscopic sclerotherapy or variceal ligation programs for eradication of esophageal varices. RESULTS: acute variceal bleeding was controlled in all five patients with BC injections. Eradication of gastric varices was achieved in 27 (93.1%) patients (20 patients in 1 session, 4 patients in 2, and 3 patients in 3-6). Rebleeding occurred in three (10.3%) patients who responded to repeat BC injections. Complications related to the procedure occurred in two (6.9%) patients. In one patient, the needle became impacted into the tissue adhesive. This patient died 5 days later because of massive upper gastrointestinal bleeding. In the other patient, there was distal embolization. CONCLUSIONS: sclerotherapy of gastric varices with BC is a safe and an effective treatment for control of bleeding and eradication. The needle should be withdrawn immediately after the BC injection to prevent its impaction into the tissue adhesive.