DILI in Asia has a different aetiology as compared with the West, and could be related to presence of adulterants in traditional CAM.

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Purpose Tumor necrosis factor-a (TNF-a) is implicated in non-alcoholic steatohepatitis (NASH). Pentoxifylline inhibits TNF-a. We wanted to evaluate the efficacy of Pentoxifylline on NASH patients. Methods Patients with biopsy proven NASH and persistently elevated alanine aminotransferase (ALT) greater than 1.5 times the upper limit of normal were randomized to 3 months of treatment with a step 1 American Heart Association diet and daily exercise with Pentoxifylline or placebo. Liver function tests, serum lipids and TNF-a, Interleukin 6 (IL-6), and plasma hyaluronic acid were measured at baseline, at weeks 6 and 12. Categorical data were analyzed by Fisher's exact test while independent sample t-test and Mann-Whitney test were used for continuous data. Results Eleven patients were randomized into the Pentoxifylline and nine to the placebo group. After 3 months of treatment body mass index (BMI), ALT and aspartate aminotransferase (AST) decreased significantly in both groups. There was no difference between the two groups in reduction of BMI (P = 0.897). There was significantly greater reduction in AST in the Pentoxifylline group (P = 0.038). There was a trend toward lower ALT level (P = 0.065) in the Pentoxifylline group. TNF-a and IL-6 decreased significantly in both groups after treatment, but there was no significant difference between the two groups. Conclusion Three months of Pentoxifylline treatment in combination with diet and exercise results in significantly greater reduction in AST levels in patients with NASH as compared with controls.

A 48-year-old Indian male with alcoholic liver cirrhosis was admitted after being found unresponsive. He was hypotensive and had hematochezia. Esophagogastroduodenoscopy (EGD) showed small esophageal varices and a clean-based duodenal ulcer. He continued to have hematochezia and anemia despite blood transfusions. Colonoscopy was normal. Repeat EGD did not reveal any source of recent bleed. Twelve days after admission, his hematochezia ceased. He refused further investigation and was discharged two days later. He presented one week after discharge with hematochezia. EGD showed non-bleeding Grade 1 esophageal varices and a clean-based duodenal ulcer. Colonoscopy was normal. Abdominal computed tomography (CT) showed liver cirrhosis with mild ascites, paraumbilical varices, and splenomegaly. He had multiple episodes of hematochezia, requiring repeated blood transfusions. Capsule endoscopy identified the bleeding site in the jejunum. Concurrently, CT angiography showed paraumbilical varices inseparable from a loop of small bowel, which had herniated through an umbilical hernia. The lumen of this loop of small bowel opacified in the delayed phase, which suggested variceal bleeding into the small bowel. Portal vein thrombosis was present. As he had severe coagulopathy and extensive paraumbilical varices, surgery was of high risk. He was not suitable for transjugular intrahepatic porto-systemic shunt as he had portal vein thrombosis. Percutaneous paraumbilical embolization via caput medusa was performed on day 9 of hospitalization. Following the embolization, the hematochezia stopped. However, he defaulted subsequent follow-up.

AIMTo explore the applicability of the Asia-Pacific Association for the Study of the Liver (APASL) and European Association for the Study of the Liver (EASL) guidelines for acute-on-chronic liver failure (ACLF) in profiling patients and determining the outcome.METHODSPatients admitted to a tertiary hospital in Singapore with acute decompensation of liver disease from January 2004 to July 2014 are screened for ACLF according to the APASL and EASL criteria. The patients’ data (including basic demographics, information about existing chronic liver disease, information about the acute decompensation, relevant laboratory values during admission, treatment, and outcome) are retrospectively analyzed to determine the background, precipitating factors and outcome.RESULTSA total of 458 liver patients is analyzed, and 78 patients with ACLF are identified. Sixty-three patients (80.8%) meet the APASL criteria, 64 patients (82.1%) meet the EASL criteria, and 49 patients (62.8%) fulfilled both criteria. The most common causes of acute liver injury are bacterial infections (59.0%), hepatitis B flare (29.5%), and variceal bleeding (24.4%). The common aetiologies of the underlying chronic disease included hepatitis B (43.6%), alcoholic (20.5%) and cryptogenic (11.5%) liver disease. The overall mortality rate is 61.5%. Increased age, the number of organ failures (as per CLIF-SOFA score), peak creatinine, INR, and amylase levels are associated with increased mortality or the need for liver transplantation. 14.3% of patients undergo liver transplantation with a 100% 1-year survival rate.CONCLUSIONBoth APASL and EASL criteria have identified ACLF patients with high three-month mortality, but those who fulfill APASL criteria alone have a better survival.

In this non-randomized study, survival after MARS was related to the availability of transplant, and in patients where living or deceased donor transplant was unavailable, MARS was of little benefit. Randomized-controlled trials on MARS((R)) are urgently needed to clarify its clinical utility.

Septic cirrhotic patients with pneumonia, >1 site of infection, Child's C cirrhosis, and high MELD score had a high mortality risk.

Background: Little information is available about early virologic responses for sofosbuvir (SOF)-based regimens in real-world populations with hepatitis C virus (HCV) infection. Methods: All patients starting a SOF-based regimen by 4/12/14 were identified in the VA HCV Clinical Case Registry. Exclusion criteria included: being on a HCV regimen to which SOF was added (n=41), baseline HCV RNA <1000 (n=25) and a non-standard SOF regimen (n=2). Standard regimens included: SOF+pegin-terferon+ribavirin (SPR), SOF+ribavirin (SR) and SOF+sime-previr±ribavirin (SS/R). We assessed 4 week HCV RNA using available results between 2 and 6 weeks after starting SOF in those who received at least 4 weeks of SOF. Advanced liver disease (ALD) was defined as FIB-4 >3.25. Univariate and multivariate analysis including baseline characteristics were performed for undetectable (UD) week 4 HCV RNA. Results: Of 731 patients starting SOF, 663 were included in the analyses. Baseline characteristics included: 95% male, 19% Black, 9% Hispanic, 70% GT1, 18% GT2, 11% GT3, 1% GT4, 60% ALD, 41% prior treatment, 4.8% HIV+ and3.8% post-transplant. Regimens were SPR 37.9%, SR 42.4% and SS/R 19.8%. Overall 5% of patients discontinued treatment by 4 weeks. Among 592 patients with week 4 data, HCV RNA was UD in 75.0%, <50 IU/mL in 15.0%, 50-99 in 3.5%, 100-999 in 5.1% and ≥1000 in 1.4%. ALD patients were less likely to have UD HCV RNA (68.3% vs 84.5%, p<0.0001; OR 0.47 95%CI 0.30-0.73, p=0.001) as were those on SR (67.5% SR, 73.4% SS/R, 84.0% SPR, p=0.0002; OR 0.32 95%CI 0.18-0.55 compared to SPR, p<0.0001). No association was found between age, sex, race/ethnicity, GT, prior treatment, HIV or transplant status and UD week 4 HCV RNA. In 347 patients with ALD, prior treatment (OR 0.59 95%CI 0.36-0.95, p=0.03), age>65 years (OR 0.38 95%CI 0.15-0.94 compared to <55, p=0.04), and SR regimen (OR 0.37 95%CI 0.19-0.69 compared to SPR, p=0.002) were independent predictors of reduced likelihood of UD week 4 HCV RNA. In 245 patients without ALD, GT1 or 4 (OR 0.22 95%CI 0.05-0.84 compared to GT2, p=0.03) and SR regimen (OR 0.15 95%CI 0.04-0.53 compared to SPR, p=0.003) were independent predictors of reduced likelihood of UD week 4 HCV RNA. Conclusion: In a large real-world cohort of patients treated with SOF-based regimens, 90% had undetectable or very low level HCV RNA at week 4 of treatment. ALD and use of SR was associated with a greater likelihood of detectable week 4 HCV RNA. The impact of low level viremia at week 4 on sustained virologic response is yet to be determined.