SummaryThe 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.

AimsLp(a) concentrations represent a major cardiovascular risk factor and are almost entirely controlled by one single locus (LPA). However, many genetic factors in LPA governing the enormous variance of Lp(a) levels are still unknown. Since up to 70% of the LPA coding sequence are located in a difficult to access hypervariable copy number variation named KIV-2, we hypothesized that it may contain novel functional variants with pronounced effects on Lp(a) concentrations. We performed a large scale mutation analysis in the KIV-2 using an extreme phenotype approach.Methods and ResultsWe compiled an discovery set of 123 samples showing discordance between LPA isoform phenotype and Lp(a) concentrations and controls. Using ultra-deep sequencing, we identified a splice site variant (G4925A) in preferential association with the smaller LPA isoforms. Follow-up in a European general population (n = 2892) revealed an exceptionally high carrier frequency of 22.1% in the general population. The variant explains 20.6% of the Lp(a) variance in carriers of low molecular weight (LMW) apo(a) isoforms (P = 5.75e-38) and reduces Lp(a) concentrations by 31.3 mg/dL. Accordingly the odds ratio for cardiovascular disease was reduced from 1.39 [95% confidence interval (CI): 1.17–1.66, P = 1.89e-04] for wildtype LMW individuals to 1.19 [95%CI: 0.92; 1.56, P = 0.19] in LMW individuals who were additionally positive for G4925A. Functional studies point towards a reduction of splicing efficiency by this novel variant.ConclusionA highly frequent but until now undetected variant in the LPA KIV-2 region is strongly associated with reduced Lp(a) concentrations and reduced cardiovascular risk in LMW individuals.

Acute-on-chronic liver failure (ACLF) is characterized by high short-term mortality. Liver transplantation (LT) is a potential therapy for patients who do not improve with supportive measures, but the efficacy of LT has not been shown. The aim of this study was to investigate the feasibility of LT and to determine the postoperative outcomes of patients with ACLF. All patients referred to our liver unit between 2002 and 2010 were registered in a database. The diagnosis of ACLF was made in accordance with the Asian Pacific Association for the Study of the Liver consensus. The post-LT outcomes were compared with the outcomes of a cohort of patients with chronic liver disease who underwent transplantation for other indications during the same period. One hundred forty four of 238 patients fulfilled the ACLF criteria. In an intention-to-treat analysis, the median transplant-free survival time was 48 days. Multiorgan failure was the most common cause of death. Ninety-four patients (65%) were evaluated for LT, 71 patients (49%) were listed, and 33 patients (23%) finally underwent deceased donor LT; this resulted in a wait-list mortality rate of 54%. Patients who developed infectious complications (particularly pneumonia and/or sepsis) and patients who received renal replacement therapy or mechanical ventilation were less likely to undergo LT. The 1-and 5-year survival rates of 87% and 82% were comparable to the rates for non-ACLF patients.In conclusion, this study shows that LT remains the only therapeutic option for the vast majority of patients with ACLF. However, LT was feasible in less than one fourth of the patients with a 5-year survival rate greater than 80%.

We compared the calibration of hepatic iron based on R2* relaxometry and liver biopsy with similar studies that have already been published to investigate the transferability of published calibration curves. Materials and Methods: 17 patients with clinically suspected hepatic iron overload (HIO) were enrolled. All patients underwent liver biopsy and MRI of the liver using a multi-echo gradient echo sequence (TR = 200 ms; TE-initial 0.99 ms; Delta-TE 1.41 ms; 12 echos; flip-angle: 20°). R2* parameter maps were analyzed using manually placed regions of interest and R2* values were correlated with liver iron concentration (LIC) obtained from liver biopsy. In addition, the results of our study were compared with 6 similar, already published studies. Results: A linear relationship between R2* and LIC was found. Regression analysis yielded a correlation coefficient of 0.926, a slope of 0.024 (s mg/g) [95 % CI 0.013 -0.024] and an intercept of 0.277 (mg/g) [95 % CI -0.328 -2.49]. We found a significant correlation between the calibration curves obtained from our study in comparison to 3/6 similar studies. The other 3 studies used a different reference standard or sequence parameters which lead to a significant difference for slope, intercept or both in comparison to our data. Conclusion: Calibration curves from published studies that are based on a correlation of liver biopsy and R2* can be used for the estimation of liver iron concentration, although different scanning parameters and post-processing protocols were used. Low initial TEs might be a prerequisite for pooling data for liver iron quantification.