Successful Recovery from Severe Alcoholic Hepatitis (SAH) for Third Time.

Alcoholic hepatitis is a clinical syndrome with or without pre-existing chronic liver disease (CLD), and the majority of patients present with acute-on-chronic liver failure (ACLF) having a high 28-day mortality. The treatment of alcoholic hepatitis is suboptimal with corticosteroid having one 1month survival benefit but not translated to a survival benefit beyond six months. Survival benefit has been observed in only about 50-60% of treated patients. Long-term survival depends on underlying liver function and abstinence from alcohol. Relapse is reported in nearly half of the patients who recover from alcoholic hepatitis and even up to 17% after liver transplant. The data on repeated episodes of severe alcoholic hepatitis due to relapse and response to therapy are largely unknown. Here, we report a case of alcoholic hepatitis on three occasions in a period of 2 years follow-up and each time treated with steroids and had complete clinical recovery.

Podoplanin-positive dilated lymphatic vessels in duodenum associates with three-month mortality in patients with cirrhosis.

Dilated and dysfunctional gut lymphatic vessels (LVs) have been reported in experimental cirrhosis. Here, we studied LVs in duodenal (D2)-biopsies of liver cirrhosis patients and investigated the prognostic role of a LV marker, podoplanin (PDPN), in predicting the mortality of patients with cirrhosis. A prospective, single-center cohort study was performed in liver cirrhosis patients (n = 31) and matched healthy controls (n = 9). D2-biopsies were obtained during endoscopy procedure, immunostained with PDPN, and scored based on 1) intensity and 2) density of positively-stained LVs per high power field. Gut and systemic inflammation were estimated by quantifying duodenal CD3+ intraepithelial lymphocytes (IELs), CD68+ macrophages, and serum TNF-α and IL-6 levels, respectively. Gut permeability and inflammation as assessed by quantifying gene expression of TJP1, OCLN, TNF-α, and IL-6 in D2-biopsies. Gene expression of LV markers, PDPN (8-fold), and LYVE1 (3-fold) was enhanced in D2-biopsies of cirrhosis patients compared to control (p < 0.0001). The mean PDPN score in decompensated cirrhosis patients (6.91 ± 1.26, p < 0.0001) was significantly increased as compared to those with compensated (3.25 ± 1.60). PDPN score positively and significantly correlated with the number of IELs (r = 0.33), serum TNF-α (r = 0.35), and IL-6 (r = 0.48) levels, while inversely correlated with TJP1 expression (r = -0.46, p < 0.05 each). In Cox regression, the PDPN score was a significant and independent 3-month-mortality predictor in patients (HR: 5.61; 1.08-29.109; p = 0.04). The area under the curve for the PDPN score was 84.2, and cutoff value for predicting mortality was ≥6.5 with 100% sensitivity and 75% specificity. Collectively, dilated LVs with high PDPN expression in D2-biopsies is a characteristic feature of patients with decompensated cirrhosis. PDPN score correlates with enhanced gut and systemic inflammation and also associates with 3-month mortality in cirrhosis.

Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study.

AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.

Endoscopic management of pleural effusion caused by a pancreatic pleural fistula.

Pancreatic-pleural fistula (PPF) is a rare sequela of pancreatitis. High degree of clinical suspicion is required to diagnose a PPF. Confirmation is done by high amylase content in pleural fluid analysis. Here, we present two cases with varied presentation of PPF. A 43-year-old man presented with acute on chronic pancreatitis with bilateral (predominantly right) pleural effusion. Another 57-year-old man, previously diagnosed with chronic calcific pancreatitis, presented with left pleural effusion. Both cases were effectively managed with endoscopic pancreatic duct stenting.

Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis.

BACKGROUND: Severe alcoholic hepatitis patients have high mortality and limited response to corticosteroids. Microvesicles reflect cellular stress and disease conditions. AIMS: To investigate whether microvesicles are associated with severity, response to steroid therapy and inflammation in severe alcoholic hepatitis. METHODS: Microvesicles originating from different cells were studied pre-therapy in 101 patients; (71 responder to corticosteroid therapy and 30 nonresponders) and 20 healthy controls. Microvesicles and cells were determined in peripheral and hepatic vein samples using flow cytometry and correlated with outcomes. Inflammatory signalling pathways and functional alterations of immune cells after stimulation with microvesicles were also investigated. RESULTS: Microvesicles mean levels were higher in nonresponders for T cells (CD3+ CD4+ ; 10.1 MV/µL vs 5.4; P = 0.06), macrophages (CD68+ CD11b+ ; 136.5 vs 121.9 MV/µL; P = 0.01), haematopoietic stem-cells (CD45+ CD34+ ; 116.8 vs 13.4 MV/µL; P = 0.0001) and hepatocytes (ASGPR+ ; 470 vs 361 MV/µL; P = 0.01); the latter two predicting steroid nonresponse in 94% patients at baseline in peripheral plasma. Microvesicle levels correlated with histological and liver disease severity indices. Whereas, in non-responders hepatic vein CD34+ cells were lower (P = 0.02), the CD34+ microvesicles there from were higher (P = 0.04), thus suggesting impaired regeneration. Also, microvesicles of 0.2-0.4 µm size were higher in nonresponders (P < 0.03) at baseline. Microvesicles from patients trigger more (P = 0.04) ROS generation, TNF-α production (P = 0.04) and up-regulate pro-inflammatory cytokine related genes in neutrophils in vitro. CONCLUSIONS: Pre-therapy peripheral plasma levels of CD34+ and ASGPR+ microvesicles are reliable non-invasive markers of steroid nonresponse and mortality in patients with severe alcoholic hepatitis.

Carvedilol delays the progression of small oesophageal varices in patients with cirrhosis: a randomised placebo-controlled trial.

BACKGROUND AND AIMS: Carvedilol is effective in the primary prophylaxis for large oesophageal varices. We investigated its use in preventing progression of small to large oesophageal varices. METHODS: Consecutive cirrhotics with small oesophageal varices were prospectively randomised to either carvedilol (n=70) or placebo (n=70) and followed up for a minimum of 24 months. Endoscopy was done at baseline and six monthly intervals. Hepatic vein pressure gradient (HVPG) was measured at baseline and at 12 months. The primary endpoint was development of large varices. RESULTS: Baseline characteristics in two groups were comparable. The predominant aetiology of cirrhosis was non-alcoholic fatty liver disease in both the groups. The mean dose of carvedilol administered was 12±1.67 mg/day and the target heart rate achieved was 58±3 bpm. A higher proportion of patients in carvedilol group had non-progression to large varices than placebo (79.4% vs 61.4%; p=0.04); the mean time of non-progression to large varices was 20.8 months (95% CI 19.4 to 22.4) in carvedilol group and 18.7 months (95% CI 17.1 to 20.4) in placebo group (p=0.04). There was a modest reduction of HVPG at 1 year in carvedilol group (-8.64%) compared with placebo (+0.33%) (p=0.22). None of the patients in either group died of variceal bleeding or liver-related causes. No major adverse events were observed in either group. CONCLUSIONS: Carvedilol is safe and effective in delaying the progression of small to large oesophageal varices in patients with cirrhosis. TRIAL REGISTRATION NUMBER: NCT01196507; post-results.