Rohit Sinha

Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites

BACKGROUND & AIMSnCarvedilol, a non-selective beta-blocker (NSBB) with additional anti-alpha 1 receptor activity, is a potent portal hypotensive agent and has been used as prophylaxis against variceal bleeding. However, its safety in patients with decompensated liver cirrhosis and ascites is still disputed. In this study, we examined whether long-term use of carvedilol in patients with ascites is a risk factor for mortality.nnnMETHODSnA single-centre retrospective analysis of 325 consecutive patients with liver cirrhosis and ascites presenting to our Liver Unit between 1st of January 2009 to 31st August 2012 was carried out. The primary outcome was all-cause and liver-specific mortality in patients receiving or not receiving carvedilol as prophylaxis against variceal bleeding.nnnRESULTSnThe final cohort after propensity score matching comprised 264 patients. Baseline ascites severity and UK end-stage liver disease (UKELD) score between carvedilol (n=132) and non-carvedilol (n=132) treated patient groups were comparable. Median follow-up time was 2.3years. Survival at the end of the follow-up was 24% and 2% for the carvedilol and the non-carvedilol groups respectively (log-rank p<0.0001). The long-term survival was significantly better in carvedilol than non-carvedilol group (log-rank p<0.001). The survival difference remained significant after adjusting for age, gender, ascites severity, aetiology of cirrhosis, previous variceal bleed, spontaneous bacterial peritonitis prophylaxis, serum albumin and UKELD with hazard ratio of 0.59 (95% confidence interval [CI]: 0.44, 0.80; p=0.001), suggesting a 41% reduction in mortality risk. When stratified by the severity of ascites, carvedilol therapy resulted in hazard ratio of 0.47 (95% CI: 0.29, 0.77; p=0.003) in those with mild ascites. Even with moderate or severe ascites, carvedilol use was not associated with increased mortality risk.nnnCONCLUSIONnLong-term carvedilol therapy is not harmful in patients with decompensated cirrhosis and ascites.nnnLAY SUMMARYnThe safety of carvedilol and other non-selective beta-blocker drugs in patients with liver cirrhosis and ascites is still debated. In this study, we have shown that carvedilol therapy in these patients was associated with reduced risk of mortality, particularly in those with mild ascites. We concluded that low dose, chronic treatment with carvedilol in patients with liver cirrhosis and ascites is not detrimental.

The use of hemostatic spray as an adjunct to conventional hemostatic measures in high-risk nonvariceal upper GI bleeding (with video)

BACKGROUNDnEndoscopic management of nonvariceal upper GI bleed (NVUGIB) can be challenging. Hemospray is a novel endoscopic hemostatic agent for NVUGIB. Its efficacy in attaining hemostasis in NVUGIB is promising, particularly with respect to technically difficult lesions. However, most of the currently available data are focused on its application as monotherapy. The aim of this study was to evaluate its efficacy as a second agent to adrenaline, or as an addition to the combination of adrenaline with either clips or a thermal device in NVUGIB.nnnMETHODSnConsecutive patients with Forrest 1a and 1b ulcer treated with hemostatic spray as an adjunct to conventional endoscopic hemostatic measures between July 2013 and June 2015 were included in this retrospective analysis. The endpoints were initial hemostasis, 7-day rebleeding, 30-day rebleeding, all-cause, and GI-related 30-day mortality.nnnRESULTSnA total of 20 patients (median age, 75 years, 50% men, 60% Forrest 1a ulcer) were treated with hemostatic spray as a second agent to adrenaline, or as an adjunct to the combination of adrenaline with either clips orxa0a thermal device. Hemostatic spray was used as a second agent to adrenaline in 40% and as a third agent to combined dual therapy in 60%. Initial hemostasis was attained in 95% with an overall rebleeding rate at 7 days of 16%. There was no difference between the 7-day and 30-day rebleeding rates. The combination of hemostatic spray and adrenaline resulted in 100% initial hemostasis and 25% 7-day rebleeding. Similarly, initial hemostasis was achieved in 92% with a 9% rebleeding rate when hemostatic spray was used as the third agent to 2 of the conventional measures. All-cause mortality was 15% with 1 GI-related death (3%).nnnCONCLUSIONSnIn our single-center retrospective analysis, hemostatic spray appears promising as an adjunct to conventional methods for NVUGIB, although prospective controlled trials are needed to confirm this.

Proteomic profiling of cellular steatosis with concomitant oxidative stress in vitro.

BackgroundNutrient excess underpins the development of nonalcoholic fatty liver disease (NAFLD). The ensuing metabolic derangement is characterised by increased cellular respiration, oxidative stress and mitochondrial impairment. We have previously recapitulated these events in an in vitro cellular steatosis model. Here, we examined the distinct patterns of protein expression involved using a proteomics approach.MethodsHuman hepatoblastoma C3A cells were treated with a combination of energy substrates; lactate (L), pyruvate (P), octanoate (O) and ammonia (N). Proteins extracts were trypsinized and analyzed on a capillary HPLC OrbitrapXL mass spectrometer. Proteins were quantified using a label-free intensity based approach. Functional enrichment analysis was performed using ToppCluster via Gene Ontology (GO) database.ResultsOf the 1327 proteins identified, 104 were differentially expressed between LPON and untreated cells (defined as: ≥2 peptides; fold change ≥1.5; p-value <0.05). Seventy of these were upregulated with LPON. Functional enrichment analysis revealed enhanced protein biosynthesis accompanied by downregulation of histones H2A type 1-A, H1.2, H1.5 and H1.0I in LPON cells. Lipid binding annotations were also enriched as well as proteins involved in cholesterol synthesis, uptake and efflux. Increased expression of aldo-keto reductase family 1, member C1 and C3 suggests enhanced sterol metabolism and increased ROS-mediated lipid peroxidation.ConclusionsThe surge of energy substrates diverts free fatty acid metabolism towards pathways that can mitigate lipotoxicity. The histones depletion may represent an adaptation to increased protein synthesis. However, this can also expose DNA to oxidative stress thus should be explored further in the context of NAFLD progression.

Fulminant hepatic failure in autoimmune polyendocrine syndrome type-1

Fulminant hepatic failure is liver disease that causes encephalopathy within 8 weeks of onset of symptoms or within 2 weeks of onset of jaundice in a patient without prior evidence of liver disease. Autoimmune polyendocrine syndrome type-1 is an autoimmune autosomal-recessive condition causing parathyroid and adrenal insufficiency, alopecia, chronic mucocutaneous candidiasis, ectodermal dystrophy and, rarely, hepatitis. Although the liver can be affected as a consequence of the autoimmune process, the spectrum of disease activity is varied. Autoimmune hepatitis develops in 10-20% of patients and successful liver transplantation has been reported in pediatric patients who failed immunosuppressive treatment. We report fulminant hepatic failure in an adult patient with autoimmune polyendocrine syndrome type-1 who responded to medical treatment and did not require liver transplantation. We highlight the diagnostic scoring system for autoimmune hepatitis and the referral criteria for liver transplantation in fulminant hepatic failure.

Electronic-nose breath print distinguishes non-alcoholic fatty liver disease from healthy lean control: A pilot study

Sensor 1, Sensor 2, Sensor 3 and Sensor 4 identified NAFLD cirrhosis patients with AUC 0.96 (standard error=0.043; p<0.001), 0.89 (standard error=0.046; p<0.001), 0.98 (standard error =0.016; p<0.001) and 0.96 (standard error=0.022; p<0.001) respectively eNose was able to differentiate between healthy from; non-cirrhotic NAFLD (p<0.001, CVV 96.8%) and NAFLD cirrhotic (p<0.001, CVV 95.1%). This method, designed to reflect the generalization property of the k-nearest neighbour’s (k-NN) classifier, scored a classification rate of 96%. METHODS