Austrian consensus on the diagnosis and management of portal hypertension in advanced chronic liver disease (Billroth IV).

The Billroth IV consensus was developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on the 26th of November 2022 in Vienna.Based on international recommendations and considering recent landmark studies, the Billroth IV consensus provides guidance regarding the diagnosis and management of portal hypertension in advanced chronic liver disease.

Transmission of oral microbiota to the biliary tract during endoscopic retrograde cholangiography.

BACKGROUND: Endoscopic retrograde cholangiography (ERC) possesses a translocation risk of microbes to the biliary system. We studied bile contamination during ERC and its impact on patients' outcome in a real-life-situation. METHODS: Ninety-nine ERCs were analyzed and microbial samples were taken from the throat before and from bile during ERC and from irrigation fluid of the duodenoscope before and after ERC. RESULTS: 91.2% of cholangitis patients had detectable microbes in the bile (sensitivity 91%), but the same was true for 86.2% in the non-cholangitis group. Bacteroides fragilis (p=0.015) was significantly associated with cholangitis. In 41.7% of ERCs with contaminated endoscopes these microbes were found in the bile after the procedure. Analysis of duodenoscopes' irrigation liquid after ERC matched the microbial bile analysis of these patients in 78.8%. Identical microbial species were in throat and in bile samples of the same ERC in 33% of all cases and in 45% in the non-cholangitis group. Transmission of microbes to the biliary tract did not result in more frequent cholangitis, longer hospital stays, or worse outcome. CONCLUSIONS: During ERC bile samples are regularly contaminated with microbes of the oral cavity but it did not affect clinical outcome.

The impact of COVID-19 on liver transplantation programs in Austria.

BACKGROUND: Coronavirus disease of 2019 (COVID-19) has affected liver disease management. The impact of the COVID-19 pandemic on the Austrian orthotopic liver transplantation (OLT) programs, however, has not been systematically investigated. METHODS: All patients listed for OLT in Austria during 2020-2021 were studied. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, vaccinations, infections, mortality and the overall number of OLTs (vs. pre-COVID-19: 2015-2019) were analyzed. RESULTS: Overall, 490 patients (median age: 58.0 years, 70.4% men, hepatocellular carcinoma: 27.3%) were listed for OLT in Austria in 2020-2021. Alcohol-related cirrhosis (35.3%), cholestatic (16.7%) and viral liver disease (13.9%) were the main etiologies. Of the patients 61.2% underwent OLT and 8.8% died while on the waiting list. The number of OLTs performed during COVID-19 (2020: n = 150; 2021: n = 150) remained unchanged compared to pre-COVID-19 (median: n = 152). Among waiting list patients, 7.7% (n = 31/401) were diagnosed with COVID-19 and 7 (22.6%) of these patients died. By the end of 2021, 45.1% (n = 176/390; 82.8% mRNA vaccinations) and 28.8% (105/365) of patients received 2 and 3 SARS-CoV­2 vaccinations, respectively. After two SARS-CoV­2 vaccinations, antibodies more often remained undetectable in patients vaccinated post-OLT (25.6% vs. 6.5% in patients vaccinated pre-OLT; p = 0.034). Patients with three vaccinations after OLT had lower antibody titers than patients vaccinated pre-OLT (post-OLT: 513.5, IQR 44.4-2500.0 vs. pre-OLT: 2500.0, IQR 1462.0-2500.0 BAU/mL; p = 0.020). CONCLUSION: The number of OLTs in Austria remained unchanged during COVID-19. SARS-CoV­2 infections were rare but associated with high mortality in patients on the Austrian OLT waiting lists. SARS-CoV­2 vaccination rates at the end of 2021 were suboptimal, while serological response was better in patients vaccinated pre-OLT vs. post-OLT.

Response-guided long-term treatment of chronic hepatitis D patients with bulevirtide-results of a "real world" study.

BACKGROUND AND AIM: Bulevirtide (BLV) blocks the uptake of the hepatitis D virus (HDV) into hepatocytes via the sodium/bile acid cotransporter NTCP. BLV was conditionally approved by the EMA but real-life data on BLV efficacy are limited. METHODS: Patients were treated with BLV monotherapy. Patients who did not achieve further decreases in HDV-RNA after 24 weeks were offered PEG-IFN as an add-on therapy in a response-guided manner. RESULTS: Twenty-three patients (m: 10, f: 13; mean age: 47.9 years, cirrhosis: 16; median ALT: 71 IU/ml; median HDV-RNA: 2.1 × 105 copies/ml) started BLV monotherapy (2 mg/day: 22; 10 mg/day: 1). Twenty-two completed ≥24 weeks of treatment (24-137 weeks): Ten (45%) were classified as BLV responders at week 24. BLV was stopped in two patients with >6 months HDV-RNA undetectability, but both became HDV-RNA positive again. One patient was transplanted at week 25. One patient terminated treatment because of side effects at week 60. Ten patients are still on BLV monotherapy. Adding PEG-IFN in eight patients induced an HDV-RNA decrease in all (1.29 ± 0.19 [SD] log within 12 weeks). HDV-RNA decreased by >2log or became undetectable in 45%(10/22), 55%(11/20), 65% (13/20) and 69% (9/13); and ALT levels normalised in 64% (14/22), 85% (17/20), 90% (18/20) and in 92% (12/13) patients at weeks 24, 36, 48 and 60, respectively. Portal pressure decreased in 40% (2/5) of patients undergoing repeated measurement under BLV therapy. CONCLUSION: Long-term BLV monotherapy is safe and effectively decreases HDV-RNA and ALT-even in patients with cirrhosis. The optimal duration of BLV treatment alone or in combination with PEG-IFN remains to be established. An algorithm for a response-guided BLV treatment approach is proposed.

Prognostic value of depressed cardiac index after STEMI: a phase-contrast magnetic resonance study.

AIMS: An invasively measured cardiac index (CI) of ≤2.2 L/min/m2 is one of the strongest prognostic indicators after ST-elevation myocardial infarction (STEMI), however, knowledge is mainly based on invasive evaluations performed in the pre-stent era. Velocity-encoded phase-contrast cardiac magnetic resonance (PC-CMR) allows non-invasive determination of CI. METHODS AND RESULTS: In this prospective study, CMR was performed in 406 stable and contemporarily revascularized patients a median of 3 days after STEMI. Forward stroke volume was assessed at the level of the ascending aorta by PC-CMR. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were determined by cine CMR. Major adverse cardiac events (MACE) were defined as the composite of death, myocardial infarction, or hospitalization for heart failure. Median CI was 2.52 L/min/m2 and 27% of patients had ≤2.2 L/min/m2. Median LVEF was 53% and median GLS was -12.2%. During a median follow-up of 14.2 [95% confidence interval (95% CI) 13.6-14.7] months, 41 patients (10.1%) experienced a MACE. A depressed CI was significantly associated with MACE after adjustment for LVEF, GLS, Thrombolysis in Myocardial Infarction (TIMI) risk score, and infarct size [hazard ratio = 3.15 (95% CI 1.53-6.47); P = 0.002] and led to significant discrimination improvement [net reclassification improvement 0.61 (95% CI 0.25-0.97); P < 0.001]. CONCLUSIONS: A CI of 2.2 L/min/m2 or less as measured by PC-CMR was present in 27% of clinically stable patients after STEMI and strongly and independently predicted medium-term MACE. The prognostic value of a depressed CI was superior and incremental to LVEF, GLS, TIMI risk score, and infarct size.

Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial.

BACKGROUND: SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin-angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. METHODS: ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596. FINDINGS: Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66-80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00-2·00) vs 1·00 (0·00-3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00-9·25] vs 3·50 [0·00-23·50]; p=0·040), mean SOFA score (0·00 [0·00-0·31] vs 0·12 [0·00-0·78]; p=0·040), and 30-day SOFA score (0·00 [10-90th percentile, 0·00-1·20] vs 0·00 [0·00-24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. INTERPRETATION: Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options. FUNDING: Austrian Science Fund and German Center for Cardiovascular Research.

Baseline LV ejection fraction by cardiac magnetic resonance and 2D echocardiography after ST-elevation myocardial infarction - influence of infarct location and prognostic impact.

OBJECTIVES: The comparability of left ventricular ejection fraction (LVEF) measurements by cardiac magnetic resonance (CMR) and 2D echocardiography (2DE) early after ST-elevation myocardial infarction (STEMI) remains unclear. METHODS: In this study, LVEF measured by CMR and 2DE (Simpson's method) were compared in 221 patients after STEMI treated by primary percutaneous coronary intervention. 2DE image quality was systematically assessed and studies reported by an accredited examiner. Intermodality agreement was assessed by the Bland-Altman method. Major adverse cardiac events (MACE) were defined as the composite of death, myocardial infarction or hospitalisation for heart failure. Patients were followed up for a median of 40.9 months (IQR 28.1-56). RESULTS: After non-anterior STEMI, LVEF measurements by 2DE (single and biplane) were consistently underestimated in comparison to CMR (CMR 55.7 ± 9.5% vs. 2DE-4CV 49 ± 8.2% (p = 0.06), 2DE-2CV 52 ± 8% (p < 0.001), 2DE-biplane 53.5 ± 7.1% (p = 0.01)). After anterior STEMI, there was no significant difference in LVEF measurements by 2DE and CMR with acceptable limits of agreement (CMR 49 ± 11% vs. 2DE-4CV 49 ± 8.2% (p = 0.8), 2DE-2CV 49 ± 9.2% (p = 0.9), 2DE-biplane 49.6 ± 8% (p = 0.5)). In total, 15% of patients experienced a MACE during follow-up. In multivariate Cox regression analysis, reduced LVEF (< 52%) as assessed by either 2DE or CMR was predictive of MACE (2DE HR = 2.57 (95% CI 1.1-6.2), p = 0.036; CMR HR = 2.51 (95% CI 1.1-5.7), p = 0.028). CONCLUSIONS: At baseline after non-anterior STEMI, 2D echocardiography significantly underestimated LVEF in comparison to CMR, whereas after anterior infarction, measurements were within acceptable limits of agreement. Both imaging modalities offered similar prognostic values when a reduced LVEF < 52% was applied. KEY POINTS: • After non-anterior STEMI, 2D-echocardiography significantly underestimated LVEF compared with cardiac MRI • An ejection fraction of < 52% in the acute post-infarct period by both 2D echocardiography and CMR offered similar prognostic values.

Acute liver failure in immunocompetent patients infected with hepatitis E.

In almost all immunocompetent patients an acute hepatitis E virus (HEV) infection is clinically silent with spontaneous viral clearance. So far, only a very small number of severe acute HEV infections have been described. This article reports the case of a 78-year-old immunocompetent, diabetic patient, who presented with a symptomatic acute HEV genotype (GT) 3 infection and that progressed to acute liver failure. After starting with an antiviral therapy with ribavirin, the HEV viral load rapidly decreased with a significant improvement of the laboratory parameters as well as a clinical amelioration of the patient. The treatment was continued for 3 months and led to a complete resolution of this acute fulminant hepatitis E. Although the risk is almost negligible this article clearly demonstrates that an acute liver failure due to HEV should also be considered in immunocompetent patients, especially in older male individuals with diabetes mellitus.

Burden of disease in patients with chronic hepatitis C in the Austrian REAL study.

BACKGROUND: The direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) is approved to treat patients with chronic hepatitis C (CHC) infection genotypes 1 or 4, including compensated cirrhosis. The aim of the prospective, multicenter, observational REAL study was to provide evidence of the effectiveness of this regimen in an Austrian real-world setting and to determine the impact on patient-reported outcomes (PROs). METHODS: Effectiveness was defined as sustained virologic response 12 weeks after the end of treatment (SVR12). EuroQol 5 Dimension 5 Level (EQ-5D-5L) and Work Productivity and Activity Impairment HepC v2.0 (WPAI) questionnaires were used to assess PROs. RESULTS: A total of 173 patients were enrolled. The SVR12 was 95.9% (140/146) in the core population with sufficient follow-up (i. e. patients without SVR12 data not due to efficacy/safety reasons, such as lost to follow-up, were excluded) and 84.8% (140/165) in the core population (CP). Data at all timepoints for the EQ-5D-5L index score and visual analog scale and the total activity impairment score of the WPAI were available for 88, 95 and 72 patients, respectively. All PROs remained generally unaltered during treatment with OBV/PTV/r ± DSV ± RBV but showed a statistically significant (p < 0.01) improvement 12 weeks after the end of treatment versus baseline. CONCLUSIONS: These are the first data on PROs in a real-world setting with OBV/PTV/r ± DSV ± RBV treatment; this study demonstrated that treatment did not negatively impact quality of life. Results from the Austrian REAL study support the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with CHC genotype 1 and 4 in everyday clinical practice.

High incidence of hepatocellular carcinoma and postoperative complications in patients with nonalcoholic steatohepatitis as a primary indication for deceased liver transplantation.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent indication for liver transplantation (LT) across the world. The relative outcomes following transplantation are poorly described in this cohort. We aimed to analyze the incidence and outcome of LT for NASH as compared with other indications. PATIENTS AND METHODS: This is a retrospective analysis of 513 patients who underwent deceased-donor, adult LT between 2002 and 2012 as recorded at the Medical University of Innsbruck, Austria. RESULTS: The prevalence of NASH cirrhosis as indication for liver transplantation was 12.7% (65/513). Patient survival in patients with NASH was comparable to other indications, including alcohol-induced liver steatosis (ALD) and hepatitis C virus (HCV) (P=0.208). Patients with NASH were older, had a higher model of end-stage liver disease score and a higher BMI, but patient survival and graft survival were equivalent to other indications. Patients with hepatocellular carcinoma (HCC) as primary indication for liver transplantation showed significantly inferior overall survival as compared with the other indications (P=0.003). Patients with NASH had coexisting HCC in 53.7% of cases, whereas HCC in ALD, HCV and other indications was prevalent in 31.2, 47.7, and 34.5%, respectively (P<0.0001). Patients with NASH had a higher incidence of advanced HCCs (outside the Milan criteria) than patients with ALD, HCV, and other indications (P=0.034). Postoperative complications were significantly higher in the NASH cohort (P=0.048). CONCLUSION: In this single-center LT database analysis, patients with NASH have a higher incidence and a more rapid progression of HCC as well as an increased incidence of postoperative complications. Our findings warrant confirmation by others.

Disease burden of hepatitis C in the Austrian state of Tyrol - Epidemiological data and model analysis to achieve elimination by 2030.

BACKGROUND: In 2016, the World Health Organization (WHO) and 69th World Health Assembly approved the first global health sector strategy (GHSS) on viral hepatitis with the goal to eliminate hepatitis C virus (HCV) infections worldwide. The aim is a 90% reduction of new infections and 65% reduction of HCV-related deaths by 2030. AIM: This study reports on the epidemiology of HCV infections in the Austrian state of Tyrol (total population 750,000) and uses a predictive model to identify how the WHO strategy for elimination of HCV can be achieved. METHODS: We developed a regional disease burden model based on observed local diagnosis data from 2001 to 2016. Scenarios were developed to evaluate the impact of diagnosis and treatment on HCV-related outcomes (viremic prevalence, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths) from 2015 through 2030. RESULTS: In the last 15 years, 1,721 patients living in Tyrol have been diagnosed with chronic HCV infection. When ageing, mortality and treatment were factored in, there were an estimated 2,043 viremic HCV infections in 2016, of which 1,136 cases had been diagnosed. A baseline model predicts a decrease of 588 HCV cases from 2015 to 2030, which would not translate into the significant reduction of infections needed to achieve WHO global health recommendations. A total of 1,843 infected individuals need to be identified and treated to achieve the WHO goals by 2030 (1,254 averted cases as compared to baseline model). Implementation of this strategy would avoid 523 new HCV infections and decreases HCV-related mortality by 73%. CONCLUSION: HCV elimination and >65% reduction of associated mortality are possible for Tyrol, but requires a significant increase in new diagnoses and treatment rate. The model presented in this study could serve as an example for other regions to reliably predict regional disease burden and estimate how WHO goals can be met in the future.

Follow-up of sustained virological responders with hepatitis C and advanced liver disease after interferon/ribavirin-free treatment.

BACKGROUND: The introduction of direct-acting antivirals (DAA) has increased sustained virological response (SVR) rates in patients with advanced liver disease and chronic hepatitis C(CHC)infection. At present, data on clinical outcome and long-term durability of viral eradication after successful DAA therapy are scarce. AIM: To evaluate the long-term success of viral eradication in patients with advanced fibrosis or cirrhosis treated with DAAs. METHODS: Five hundred and fifty-one patients with advanced fibrosis (n = 158) or cirrhosis (CPS-A:317,CPS-B/C:76) and SVR after interferon and ribavirin-free DAA therapy treated between October 2013 and April 2016 were studied with a median follow-up of 65.6 (13.0-155.3) weeks. Only patients without hepatocellular carcinoma (HCC) at baseline and without liver transplantation were included. RESULTS: Twelve patients (2.2%) died during follow-up: the mortality rate was 0.6% in F3, 2.2% in CPS-A and 5.3% in CPS-B/C patients (P = .08). During follow-up 36 patients with cirrhosis (9.1%) developed a liver related event, including 16 with de-novo HCC (4.1%). Seven patients were transplanted at a median of 9.7 (range 3.8-21.7) months after EOT. History of decompensation was significantly associated with liver related events during follow-up (HR 7.9; 95% CI 2.7-22.6; P < .001), and with mortality (HR 5.5; 95% CI 1.5-20.2, P = .01). CONCLUSIONS: Eradication of HCV by DAA therapy was durable irrespective of the DAA combination used. Most of the cured patients had an excellent long-term clinical prognosis. Nevertheless, the risk of new occurrence of HCC remains worrisome and thus regular surveillance is obligatory even after clinical stabilization and improvement of the patient.

Long-term follow-up of ribavirin-free DAA-based treatment in HCV recurrence after orthotopic liver transplantation.

BACKGROUND & AIMS: Excellent efficacy and safety profile of second-generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT. PATIENTS & METHODS: A total of 62 OLT recipients (male: 50%/81%; age: 60.7 ± 8.5 years [mean ± SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%. RESULTS: Data of at least 96 weeks of FUP after treatment cessation (mean: 120; up to 167 weeks) were analysed. All patients showed on-treatment response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment-free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1 respectively). Reasons for death were: multi-organ failure (N = 4), impaired graft function (N = 1) and unknown (N = 1). CONCLUSION: RBV-free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long-term data show that viral eradication is durable but not necessarily translated into beneficial long-term clinical outcome.

Austrian consensus guidelines on the management and treatment of portal hypertension (Billroth III).

The Billroth III guidelines were developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on 18 February 2017 in Vienna. Based on international guidelines and considering recent landmark studies, the Billroth III recommendations aim to help physicians in guiding diagnostic and therapeutic strategies in patients with portal hypertension.

Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer.

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate between "high-" and "low-benefit" patients. To do so, the concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2,103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (Model for End-Stage Liver Disease, alpha-fetoprotein, Milan-Criteria status, and radiological response) displayed a high effect in terms of delta benefit. According to these risk factors, four benefit groups were identified. Patients with three to four factors ("no-benefit group"; n = 405 of 2,103; 19.2%) had no benefit of LT compared to alternative treatments. Conversely, patients without any risk factor ("large-benefit group"; n = 108; 5.1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The ITT transplant survival benefit presented here allows physicians to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equitable method of organ allocation. Patients without benefit should be de-listed, whereas patients with large benefit ratio should be prioritized for LT. (Hepatology 2017;66:1910-1919).

Polymorphisms in the IL-1 gene cluster influence systemic inflammation in patients at risk for acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrome characterized by acute decompensation, organ failure(s) and high short-term mortality. Recent findings suggest that an overexuberant systemic inflammation plays a primary role in ACLF progression. In this study, we examined whether genetic factors shape systemic immune responses in patients with decompensated cirrhosis. Six single-nucleotide polymorphisms (SNPs) in inflammation-related genes (interleukin [IL]-1 beta [IL-1ß], rs1143623; IL-1 receptor antagonist [IL-1ra], rs4251961; IL-10, rs1800871; suppressor of cytokine signaling-3, rs4969170; nucleotide-binding oligomerization domain-containing protein 2, rs3135500; and chemerin chemokine-like receptor 1, rs1878022) were genotyped in 279 patients with cirrhosis with (n = 178) and without (n = 101) ACLF from the CANONIC study of the CLIF consortium. Among these SNPs, we identified two polymorphisms belonging to the IL-1 gene cluster (IL-1ß and IL-1ra) in strong association with ACLF. Both SNPs were protective against ACLF; IL-1ß (odds ratio [OR], 0.34, 95% confidence interval [CI], 0.13-0.89; P < 0.05) and IL-1ra (OR, 0.58; 95% CI, 0.35-0.95; P < 0.05) under the recessive and overdominant inheritance models, respectively. These protective SNPs translated into reduced circulating levels of IL-1ß, IL-1α, IL-6, granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor, and C-reactive protein at enrollment as well as after 7-14 days of admission. These findings were confirmed in vitro in leukocytes incubated with plasma from patients with decompensated cirrhosis carrying the protective SNP genotypes. Notably, a higher frequency of the protective genotypes was observed in patients without (80%) than in those with (20%) ACLF. Consistently, patients carrying the combined protective genotypes showed a lower 28-day mortality rate. CONCLUSION: These data identify two common functional polymorphisms in the IL-1 gene cluster, which are associated with the inflammatory process related to development of ACLF. (Hepatology 2017;65:202-216).

Indications for liver transplantation in adults : Recommendations of the Austrian Society for Gastroenterology and Hepatology (ÖGGH) in cooperation with the Austrian Society for Transplantation, Transfusion and Genetics (ATX).

Liver transplantation has emerged as an established and well-accepted therapeutic option for patients with acute and chronic liver failure and hepatocellular carcinoma. The disproportion between recipients and donors is still an ongoing problem that has only been solved partially over the last centuries. For several patients no life-saving organs can be distributed. Therefore, objective and internationally established recommendations regarding indication and organ allocation are imperative. The aim of this article is to establish evidence-based recommendations regarding the evaluation and assessment of adult candidates for liver transplantation. This publication is the first Austrian consensus paper issued and approved by the Austrian Society of Gastroenterology and Hepatology in cooperation with the Austrian Society of Transplantation, Infusion and Genetics.