Pancreatobiliary Reflux Resulting in Pancreatic Ascites and Choleperitoneum after Gallbladder Perforation

A 65-year-old man with chronic hepatitis C and no history of alcohol abuse was admitted to our liver unit for the recent development of massive ascites and presumed hepatorenal syndrome. In the preceding two weeks, he had received medical treatment for acute pancreatitis and cholecystitis. Abdominal paracentesis demonstrated a cloudy, orange peritoneal fluid, with total protein concentration 3.6 g/dl, serum-ascites albumin gradient 1.0 g/dl, and ratios of ascites-serum bilirubin and amylase approximately 8:1. Diagnostic imaging demonstrated no pancreatic pseudocysts. Ten days later, at laparotomy, acalculous perforation of the gallbladder was identified. After cholecystectomy, amylase concentration in the ascitic fluid dropped within a few days to 40% of serum values; ascites disappeared within a few weeks. We conclude that in the presence of a perforated gallbladder, pancreatobiliary reflux was responsible for this unusual combination of choleperitoneum and pancreatic ascites, which we propose to call pancreatobiliary ascites

Response rates to direct antiviral agents among hepatitis C virus infected patients who develop hepatocellular carcinoma following direct antiviral agents treatment

Aim: Patients with chronic hepatitis C virus (HCV) infection who develop hepatocellular carcinoma (HCC) soon after treatment with direct antiviral agents (DAA) may have been harboring hitherto hidden tumors. If this were true, they should have a lower sustained viral response (SVR) rate, since active HCC hampers DAA efficacy. We aimed to verify this hypothesis.Methods: We included all patients who attended an HCV clinic, provided that they: (1) had no previous history of HCC; (2) had received at least one DAA dose; and (3) had been followed-up clinically and ultrasonographically for at least six months after concluding DAA.Results: The study population included n = 789 patients (55% males, median age 62 years). A median of 9.3 months (8.8-11.9) after concluding DAA, n = 19 (2.4%) patients were discovered to harbor HCC. In comparison to all others, patients with HCC were more commonly male (84% vs. 54%, P = 0.009), obese (47% vs. 17%, P = 0.002), and cirrhotic (95% vs. 35%, P < 0.001) and had less commonly achieved an SVR (68% vs. 98%, P < 0.001). Moreover, they had a trend for being less commonly treatment naïve (58% vs. 67%, P = 0.051). Based on multivariate analysis, the independent predictors of HCC were male sex (P = 0.031), cirrhosis (P = 0.004), obesity (P = 0.006), and failure to achieve an SVR (P < 0.001).Conclusion: Lack of achieving SVR is a strong independent predictor of development of HCC early after treatment of hepatitis C with DAA. Treatment failure should further alert clinicians to the possibility of this dreadful complication

Interplay of PNPLA3 and HSD17B13 Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients

A single-nucleotide polymorphism causing a C to G change in the PNPLA3 gene (rs738409) is associated with disease severity and development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease; the insertion variant rs72613567:TA of the 17β-hydroxysteroid dehydrogenase type 13 (HSD17B13) mitigates this detrimental effect. Our aim was to evaluate if the same holds true in chronic hepatitis C virus infection (HCV). With a case control retrospective study design, we selected 110 patients who developed HCC on a background of HCV infection, matching each patient for sex and age (±30 months) to three HCV-infected, non-HCC patients. All participants underwent genotyping for PNPLA3 and HSD17B13 gene variants. Both univariate and multivariate analyses of risk factors for advanced disease and HCC were performed. Carriage of PNPLA3 G∗ allele was associated with a trend of progressively more severe liver disease, from mild fibrosis to significant fibrosis, cirrhosis, and HCC (p=0.007). When the HSD17B13:TA status of these patients was taken into account, the abovementioned trend was strengthened among HSD17B13 major allele homozygotes and completely blunted among carriers of the minor allele (p=0.0003 and 0.953, respectively). In a conditional logistic regression model including diabetes and AST to platelet ratio index among predictor variables, the unfavourable genetic profile characterized by the coexistence of the PNPLA3 minor allele and HSD17B13 major allele (vs. all other possible combinations) was an independent risk factor for HCC (OR=2.00, 95% CI: 1.23-3.26) together with a history of alcohol abuse. In conclusion, carriage of the combination PNPLA3 minor allele and HSD17B13 major allele may represent a risk factor for HCC among HCV-infected patients. The interplay between the two genes may explain some of the controversy on this topic and may be exploited to stratify HCC risk in hepatitis C

Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma

none25Splenic marginal zone lymphoma (SMZL) is one of the few B-cell lymphoma types that remain orphan of molecular lesions in cancer-related genes. Detection of active NF-kappa B signaling in 14 (58%) of 24 SMZLs prompted the investigation of NF-kappa B molecular alterations in 101 SMZLs. Mutations and copy number abnormalities of NF-kappa B genes occurred in 36 (36%) of 101 SMZLs and targeted both canonical (TNFAIP3 and IKBKB) and noncanonical (BIRC3, TRAF3, MAP3K14) NF-kappa B pathways. Most alterations were mutually exclusive, documenting the existence of multiple independent mechanisms affecting NF-kappa B in SMZL. BIRC3 inactivation in SMZL recurred because of somatic mutations that disrupted the same RING domain that in extranodal marginal zone lymphoma is removed by the t(11;18) translocation, which points to BIRC3 disruption as a common mechanism across marginal zone B-cell lymphomagenesis. Genetic lesions of NF-kappa B provide a molecular basis for the pathogenesis of more than 30% of SMZLs and offer a suitable target for NF-kappa B therapeutic approaches in this lymphoma.noneD. Rossi; S. Deraglio; D. Dominguez-Sola; S. Rasi; T. Vaisitti; C. Agostinelli; V. Spina; A. Bruscaggin; S. Cresta; S. Monti; M. Cerri; M. Fangazio; L. Arcaini; M. Paulli; R. Marasca; C. Thieblemont; D. Capello; F Facchetti; I. Kwee; S. Pileri; R. Foà; F. Bertini; R. Dalla-Favera; L. Pasqualucci; G. Gaidano.D. Rossi; S. Deraglio; D. Dominguez-Sola; S. Rasi; T. Vaisitti; C. Agostinelli; V. Spina; A. Bruscaggin; S. Cresta; S. Monti; M. Cerri; M. Fangazio; L. Arcaini; M. Paulli; R. Marasca; C. Thieblemont; D. Capello; F Facchetti; I. Kwee; S. Pileri; R. Foà; F. Bertini; R. Dalla-Favera; L. Pasqualucci; G. Gaidano