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

Periostin Circulating Levels and Genetic Variants in Patients with Non-Alcoholic Fatty Liver Disease

Circulating periostin has been suggested as a possible biomarker in non-alcoholic fatty liver disease (NAFLD) in Asian studies. In the present study, we aimed to test its still controversial relevance in a Caucasian population. In patients with histologically-proven NAFLD (N. = 74; 10 with hepatocellular carcinoma, HCC) plasma periostin concentrations were analyzed. POSTN haplotype analysis was based on rs9603226, rs3829365, and rs1029728. Hepatitis C patients (N. = 81, 7 HCC) and healthy subjects (N. = 27) were used as controls. The median plasma periostin concentration was 11.6 ng/mL without differences amongst groups; it was not influenced by age, liver fibrosis or steatosis. However, possession of haplotype two (rs9603226 = G, rs3829365 = C, rs1028728 = A) was associated with lower circulating periostin compared to other haplotypes. Moreover, periostin was higher in HCC patients. At multivariate analysis, HCC remained the only predictor of high periostin. In conclusion, plasma periostin concentrations in Caucasians NAFLD patients are not influenced by the degree of liver disease, but are significantly higher in HCC. Genetically-determined differences may account for some of the variability. These data suggest extreme caution in predicting a possible future role of periostin antagonists as a rational therapeutic alternative for NAFLD, but show a potential periostin role in the management of NAFLD-associated HCC

Improvement of insulin sensitivity in diabetic and non diabetic patients with chronic hepatitis C treated with direct antiviral agents

The increased incidence of type 2 diabetes mellitus among hepatitis C virus (HCV) infected patients is likely due to viral-induced insulin resistance (IR). Indeed, control of diabetes in these patients benefits of successful antiviral treatment; whether the same applies to subtler alterations of glucose metabolism is unknown. We aimed to fill this gap

Recent advances in HCV entry

ABSTRACT:  The elucidation of the mechanisms by which HCV infects hepatocytes and replicates has been paramount for identifying therapeutic targets and developing the highly efficacious antiviral drugs from which we benefit today. The earliest stage of HCV infection is viral entry, a process in which a complex interplay is thought to occur between host molecules (including glycosaminoglycans, low-density lipoprotein receptor, CD81, SR-B1, CLDN1, OCLN, EGF receptor, ephrin type A receptor 2 and transferrin receptor 1) and envelope viral glycoproteins E1 and E2. The wealth of experimental data produced in the field of HCV entry is summarized in a proposed mechanism, updated to include the most recently published data on the topic. Compounds with putative entry-blocking and/or entry-inhibiting activity in vitro and in vivo are also briefly reviewed. </jats:p

17&beta;-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon

Background and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17&beta;-oestradiol controls HCV&rsquo;s life cycle. We investigated the mechanism(s) behind oestrogen&rsquo;s antiviral effect. Methods: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17&beta;-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. Results: Stimulation of 17&beta;-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. Conclusion: Resulting in viral control and suppression, 17&beta;-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling

Occult hepatitis B virus infection of peripheral blood mononuclear cells among treatment-naïve patients with chronic lymphocytic leukemia

Recent guidelines emphasise the risk of hepatitis B virus (HBV) reactivation among patients with hematologic malignancies of B lineage, in which HBV has been recently hypothesised to play a pathogenetic role. We aimed to determine the prevalence of occult HBV infection (OBI) of peripheral blood mononuclear cells, defined as detection of sequences from >or=2 HBV genes in subjects lacking hepatitis B surface antigen, among patients with treatment-naive chronic lymphocytic leukemia (CLL). HBV DNA sequences from four HBV genes (S, X, core and pol) were searched for in archival material obtained at diagnosis (N = 173), and from age and sex-matched controls. OBI was observed in 17/173 (10%) patients and 5/173 (3%) controls (OR = 3.6, 95% CI 1.37-9.79, p = 0.014). OBI was not associated with differences on 5-year survival and biological predictors, but patients with CLL with OBI had significantly lower peripheral blood lymphocyte count. After 8 years of observation without treatment, one OBI positive patient with CLL converted into positive HBsAg serology and developed active hepatitis. In conclusion, OBI is significantly more prevalent among patients with CLL than in age and sex-matched controls, and may contribute to the susceptibility of patients with CLL to HBV reactivation, whether exposed or not to biological agents

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 &lt; 0.001) and had less commonly achieved an SVR (68% vs. 98%, P &lt; 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 &lt; 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