Michael Trauner

Risk factors for development of spontaneous bacterial peritonitis and subsequent mortality in cirrhotic patients with ascites.

Patients with ascites are at risk for developing spontaneous bacterial peritonitis (SBP) – a severe complication associated with high mortality. We aimed to identify risk factors for SBP development and mortality to optimize stratification for primary prophylaxis and therapeutic strategies to improve survival.

Interferon‐free regimens improve portal hypertension and histological necroinflammation in HIV/HCV patients with advanced liver disease

HIV/HCV co‐infected patients show accelerated fibrosis progression and higher risk for complications of portal hypertension (PHT).

Proton Pump Inhibitor Intake neither Predisposes to Spontaneous Bacterial Peritonitis or Other Infections nor Increases Mortality in Patients with Cirrhosis and Ascites

Background and Aim The aim of this study was to assess the impact of proton pump inhibitor (PPI) intake on the development of spontaneous bacterial peritonitis (SBP) or other infections, as well as on mortality, in a thoroughly documented cohort of patients with cirrhosis and ascites. Patients and Methods We performed a retrospective analysis of follow-up data from 607 consecutive patients with cirrhosis undergoing their first paracentesis at a tertiary center. A binary logistic regression model investigating the association between PPI intake and SBP at the first paracentesis was calculated. Competing risk analyses and Cox models were used to investigate the effect of PPIs on the cumulative incidence of SBP or other infections and transplant-free survival, respectively. Adjustments were made for age, hepatocellular carcinoma, history of variceal bleeding, varices and model of end-stage liver disease score. Results Eighty-six percent of patients were receiving PPIs. After adjusting for potential confounding factors, PPI intake was neither associated with increased SBP prevalence at the first paracentesis (odds ratio (OR):1.11,95% confidence interval (95%CI):0.6–2.06; Pu200a=u200a0.731) nor cumulative incidence of SBP (subdistribution hazard ratio (SHR): 1.38; 95%CI:0.63–3.01; Pu200a=u200a0.42) and SBP or other infections (SHR:1.71; 95%CI:0.85–3.44; Pu200a=u200a0.13) during follow-up. Moreover, PPI intake had no impact on transplant-free survival in both the overall cohort (hazard ratio (HR):0.973,95%CI:0.719–1.317; Pu200a=u200a0.859) as well as in the subgroups of patients without SBP (HR:1.01,95%CI:0.72–1.42; Pu200a=u200a0.971) and without SBP or other infections at the first paracentesis (HR:0.944,95%CI:0.668–1.334; Pu200a=u200a0.742). Conclusions The proportion of cirrhotic patients with PPI intake was higher than in previous reports, suggesting that PPI indications were interpreted liberally. In our cohort with a particularly high prevalence of PPI intake, we observed no association between PPIs and SBP or other infections, as well as mortality. Thus, the severity of liver disease and other factors, rather than PPI treatment per se may predispose for infectious complications.

Impact of acute kidney injury on prognosis of patients with liver cirrhosis and ascites: A retrospective cohort study

Acute kidney injury (AKI) is a common complication in patients with liver cirrhosis, and its impact on the clinical course is increasingly recognized. Diagnostic classification systems for AKI in cirrhosis have been suggested. The prognostic significance of the respective AKI stages remains to be evaluated in decompensated cirrhosis with ascites.

The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection

Background Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP) of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear. Methods In this cross-sectional study PNPLA3 (rs738409) and IL28B (rs12979860) SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis—staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP)–and portal hypertension (hepatic venous pressure gradient, HVPG) were compared across PNPLA3 genotypes. Results 75 (42.4%) patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9) showed comparable fibrosis stages (median F2 vs. F2; p = 0.292) and similar amounts of hepatic steatosis (CAP: 203.5±41.9 vs. 215.5±59.7dB/m; p = 0.563) as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253) nor IL28B-genotype (p = 0.628), but with HCV-GT3 (p = 0.003), higher BMI (p = 0.008) and higher age (p = 0.007). Fibrosis progression rate (0.27±0.41 vs. 0.20±0.26 units/year; p = 0.984) and HVPG (3.9±2.6 vs. 4.4±3.0 mmHg; p = 0.472) were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes. Conclusions The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients.

Acid-base disorders in liver disease

Alongside the kidneys and lungs, the liver has been recognised as an important regulator of acid-base homeostasis. While respiratory alkalosis is the most common acid-base disorder in chronic liver disease, various complex metabolic acid-base disorders may occur with liver dysfunction. While the standard variables of acid-base equilibrium, such as pH and overall base excess, often fail to unmask the underlying cause of acid-base disorders, the physical-chemical acid-base model provides a more in-depth pathophysiological assessment for clinical judgement of acid-base disorders, in patients with liver diseases. Patients with stable chronic liver disease have several offsetting acidifying and alkalinising metabolic acid-base disorders. Hypoalbuminaemic alkalosis is counteracted by hyperchloraemic and dilutional acidosis, resulting in a normal overall base excess. When patients with liver cirrhosis become critically ill (e.g., because of sepsis or bleeding), this fragile equilibrium often tilts towards metabolic acidosis, which is attributed to lactic acidosis and acidosis due to a rise in unmeasured anions. Interestingly, even though patients with acute liver failure show significantly elevated lactate levels, often, no overt acid-base disorder can be found because of the offsetting hypoalbuminaemic alkalosis. In conclusion, patients with liver diseases may have multiple co-existing metabolic acid-base abnormalities. Thus, knowledge of the pathophysiological and diagnostic concepts of acid-base disturbances in patients with liver disease is critical for therapeutic decision making.

Interferon-free regimens improve health-related quality of life and fatigue in HIV/HCV-coinfected patients with advanced liver disease: A retrospective study

AbstractHealth-related quality of life (HRQoL) is impaired in HIV/HCV-coinfected patients (HIV/HCV) and further decreased by interferon (IFN)-based therapies. We aimed to investigate the impact of IFN- and ribavirin (RBV)-free therapies on HRQoL and fatigue.Thirty-three HIV/HCV-coinfected patients who underwent HCV therapy with sofosbuvir in combination with daclatasvir or ledipasvir were retrospectively studied and compared to 17 patients who received boceprevir (BOC)/PEGIFN/RBV. HRQoL (mental [MCS] and physical [PCS] component score) and fatigue were assessed using the SF-36 (Short Form 36 Health Survey) and the FSS (Fatigue Severity Scale), respectively. HRQoL/fatigue was evaluated at baseline (BL), midway, and 12 weeks after the end of treatment (FU).At BL, both domains of HRQoL as well as the severity of fatigue were significantly impaired in HIV/HCV, when compared to a healthy population. Already during treatment, IFN/RBV-free therapy improved physical health (PCS: 41.4u200a±u200a9.7 vs. 47.0u200a±u200a11.2; Pu200a<u200a0.01) and reduced fatigue (37.8u200a±u200a14.0 vs. 31.9u200a±u200a15.2; Pu200a=u200a0.01), whereas we observed a substantial worsening of both factors in patients treated with BOC/PEGIFN/RBV. Since these improvements were maintained, patients treated with IFN/RBV-free therapy reported an improvement in physical health (PCS: 41.4u200a±u200a9.7 vs. 45.8u200a±u200a12.7; Pu200a<u200a0.01) and fatigue (37.8u200a±u200a14.0 vs. 30.9u200a±u200a14.8; Pu200a=u200a0.04) at FU. While AIDS-patients had a higher severity of fatigue at BL and showed a reduction of fatigue (42.5u200a±u200a14.0 vs. 31.6u200a±u200a15.7; Pu200a=u200a0.01), mental health only improved in patients without AIDS (MCS: 35.7u200a±u200a5.3 vs.40.7u200a±u200a6.4; Pu200a=u200a0.04). HIV/HCV with severe fatigue at BL (>median BL-FSS) showed most pronounced improvements in severity of fatigue (49.7u200a±u200a7.0 vs. 32.0u200a±u200a16.7; Pu200a<u200a0.01).In contrast to IFN-based regimens, highly effective and well-tolerated IFN-/RBV-free regimens improve HRQoL (especially physical health) and fatigue already during treatment. All patients with HIV/HCV coinfection should be considered for HCV treatment; however, patients with severe fatigue should be prioritized.

Betablockers do not increase efficacy of band ligation in primary prophylaxis but they improve survival in secondary prophylaxis of variceal bleeding.

Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non‐selective beta‐blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used.

The trigger matters – outcome of hepatorenal syndrome vs. specifically triggered acute kidney injury in cirrhotic patients with ascites

Hepatorenal syndrome (HRS) represents a severe form of renal injury in cirrhotic patients with ascites in the absence of certain triggers.

Non-selective beta-blocker treatment does not impact on kidney function in cirrhotic patients with varices

Abstract Goals and background: Non-selective beta-blockers (NSBBs) are used for bleeding prophylaxis in cirrhotic patients with gastroesophageal varices (GEVs). Recent data suggested that NSBB treatment might increase the risk of renal dysfunction in patients with refractory ascites due to an impaired response to acute haemodynamic stress. Study: Retrospective longitudinal assessment of kidney function in a cohort of cirrhotic patients with GEVs with vs. without NSBB therapy. Serum creatinine (SCre), estimated glomerular filtration rate (eGFR), incidence of acute kidney injury (AKI), new onset of large volume ascites and TIPS-/transplant-free survival were compared. Results: Among 176 patients, 93 patients received NSBBs, while 83 did not. Most patients were male (77.8%), had alcoholic aetiology (52.3%) and compensated cirrhosis (51.1% Child-A, MELD: 12.1u2009±u20093.8). Over a 3-year follow-up, renal function was comparable between patients with and without NSBB treatment. Incidence of AKI was similar in NSBB vs. no-NSBB patients (pu2009=u2009.323). Even in potential risk groups (ascites, MAP <90u2009mmHg, baseline creatinineu2009>u2009ULN, hyponatraemia, MELD score ≥15 points, Child–Pugh B/C), there was no difference in SCre or eGFR with vs. without NSBBs (pu2009=u2009n.s. at 74/78 and 76/78 of analysed time points). However, multivariate analysis revealed that the presence of ascites (HR: 3.901, 95%CI: 1.352–11.251; pu2009=u2009.012) and pre-existing renal impairment (HR: 4.315, 95%CI: 1.054–17.672; pu2009=u2009.042) were independent risk factors for AKI. Importantly, NSBB use (HR: 0.319, 95%CI: 0.120–0.848; pu2009=u2009.022) was independently associated with improved TIPS-/transplant-free survival. Conclusions: In our cohort of unselected, mostly compensated cirrhotic patients with GEVs, NSBB treatment was neither associated with worsening of kidney function nor with increased incidence of AKI. On the contrary, NSBB treatment improved TIPS-/transplant-free survival.