Diagnostikk og behandling av autoimmun hepatitt

Autoimmun hepatitt er en kronisk leversykdom som ubehandlet kan føre til levercirrhose og leversvikt. Majoriteten av pasientene responderer godt på standard immunsuppressiv behandling, men noen opplever bivirkninger eller manglende behandlingseffekt. Diagnostikk, evaluering av behandlingsrespons og valg av annenlinjebehandling kan være utfordrende. Vi sammenfatter her oppdatert kunnskap om diagnostikk og behandling av pasienter med komplisert autoimmun hepatitt.publishedVersio

Hepatitis C Treatment Uptake among Patients Who Have Received Opioid Substitution Treatment: A Population-Based Study

Background and Aims There is limited data on hepatitis C (HCV) treatment uptake among people who inject drugs including individuals receiving opioid substitution treatment (OST). We aimed to calculate cumulative HCV treatment uptake, estimate annual treatment rates, and identify factors associated with HCV treatment among individuals who have received OST in Norway. Methods This observational study was based on linked data from The Norwegian Prescription Database and The Norwegian Surveillance System for Communicable Diseases between 2004 and 2013. Both registries have national coverage. From a total of 9919 individuals who had been dispensed OST (methadone, buprenorphine or buprenorphine-naloxone), we included 3755 individuals who had been notified with HCV infection. In this population, dispensions of HCV treatment (pegylated interferon and ribavirin), benzodiazepines, selective serotonin reuptake inhibitors and antipsychotics were studied. Results Among 3755 OST patients notified with HCV infection, 539 (14%) had received HCV treatment during the study period. Annual HCV treatment rates during OST ranged between 1.3% (95% confidence interval [CI] 0.7-2.2) in 2005 and 2.6% (95% CI 1.9-3.5) in 2008 with no significant changes over time. HCV treatment uptake was not associated with age or gender, but associated with duration of active OST (adjusted odds ratio [aOR] 1.11 per year; 95% CI 1.07-1.15), high (> 80%) OST continuity (aOR 1.62; 95% CI 1.17-2.25), and heavy benzodiazepine use (aOR 0.65; 95% CI 0.49-0.87). Conclusions Cumulative HCV treatment uptake among OST patients notified with HCV infection in Norway between 2004 and 2013 was 14%. Annual treatment rates during OST remained unchanged below 3% per year. High continuity of OST over time and absence of heavy benzodiazepine use predicted HCV treatment uptake. Increased awareness for HCV among OST patients is needed as tolerable and efficient directly acting antiviral treatment is being introduced

Diagnostikk og behandling av autoimmun hepatitt

Autoimmun hepatitt er en kronisk leversykdom som ubehandlet kan føre til levercirrhose og leversvikt. Majoriteten av pasientene responderer godt på standard immunsuppressiv behandling, men noen opplever bivirkninger eller manglende behandlingseffekt. Diagnostikk, evaluering av behandlingsrespons og valg av annenlinjebehandling kan være utfordrende. Vi sammenfatter her oppdatert kunnskap om diagnostikk og behandling av pasienter med komplisert autoimmun hepatitt

Effect of gender on mortality and causes of death in cirrhotic patients with gastroesophageal varices. A retrospective study in Norway

Background & aims The prognostic role of gender in patients with liver cirrhosis is not fully understood. Our primary aim was to assess how gender affects cumulative incidence and risk of death without liver transplantation (LT) in cirrhotic patients with gastroesophageal varices. Secondary aims were to assess the relationship between gender and cause specific death, risk of variceal bleeding and incidence rates of gastroesophageal varices in patients with cirrhosis. Methods All new patients with gastroesophageal varices due to liver cirrhosis at Oslo University Hospital between 2006 and May 2016 were identified. Clinical data were retrieved retrospectively from hospital files. Causes of death were classified according to a specified protocol in cases of in-hospital-death, otherwise by data from the Norwegian Death Registry. Competing risk analyses were used to calculate cumulative incidences and risks of i) all-cause death, ii) cause-specific death and iii) variceal bleeding or re-bleeding. Results Cumulative one- and five years incidence of death without LT in 266 included patients were 28% and 51%, respectively. In univariate analysis, risk of death was positively associated with age, Child Pugh class, alcoholic liver disease and presentation with variceal bleeding, and negatively associated with female sex. In a multivariate model, risk of death without LT was associated with female sex (SHR 0.59 [0.40–0.86]), age (SHR 1.05 [1.04–1.07] per year), Child Pugh class B (SHR 1.54 [1.03–2.32]) and Child Pugh class C (SHR 4.29 [2.57–7.17]). Variceal bleeding caused 27% of deaths. Adjusting for age and Child Pugh score, a trend towards reduced risk of death due to variceal bleeding was seen in women (SHR 0.53; [0.26–1.06]). High alcohol consumption was associated with increased risk of first variceal bleeding, both at univariate analysis (SHR 7.73 [1.71–34.9]) and multivariate analysis (SHR 13.9 [2.51–77.0]). Conclusions Reduced mortality due to variceal bleeding may contribute to improved survival without LT in cirrhotic women with gastroesophageal varices

Increased serum levels of LIGHT/TNFSF14 in nonalcoholic fatty liver disease: Possible role in hepatic inflammation

Objectives: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD). Methods: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. Results: (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes. Conclusion: We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression