Summary Background The safety of non‐selective β‐blockers in patients with advanced cirrhosis has been questioned in recent years. It was hypothesised that there is a particular therapeutic window. However, the specific limits still need to be determined. Aim To evaluate potential limits of the therapeutic window of non‐selective β‐blocker therapy in patients with cirrhosis and ascites Methods The impact of non‐selective β‐blockers on 28‐day transplant‐free survival was analysed in a cohort of 624 consecutive patients with decompensated cirrhosis and ascites. Three potential limits were investigated: spontaneous bacterial peritonitis, acute‐on‐chronic liver failure, mean arterial blood pressure ≤ 82 and < 65 mm Hg. Results Treatment with non‐selective β‐blockers was associated with a higher 28‐day transplant‐free survival in the overall cohort (hazard ratio: 0.621; P = .035) as well as in patients with acute‐on‐chronic liver failure (hazard ratio: 0.578; P = .031) and those with spontaneous bacterial peritonitis (hazard ratio: 0.594; P = .073). In contrast, survival benefits were markedly attenuated in patients with a mean arterial blood pressure ≤ 82 mm Hg and completely lost in those with mean arterial blood pressure < 65 mm Hg (P = .536). In spontaneous bacterial peritonitis patients with a mean arterial blood pressure < 65 mm Hg non‐selective β‐blocker treatment was associated with renal impairment. Of note, among those with a mean arterial blood pressure ≥ 65 mm Hg non‐selective β‐blocker intake was consistently associated with superior transplant‐free survival (hazard ratio: 0.582; P = .029) irrespective of the presence of spontaneous bacterial peritonitis (hazard ratio: 0.435; P = .028) or acute‐on‐chronic liver failure (hazard ratio: 0.480 P = .034). Conclusions Ascites, acute‐on‐chronic liver failure and spontaneous bacterial peritonitis do not limit the safe use of non‐selective β‐blockers in patients with cirrhosis. Mean arterial blood pressure might represent a better indicator to determine the therapeutic window of non‐selective β‐blocker treatment.

Background & aims Bacterial infections, in particular a spontaneous bacterial peritonitis (SBP), are a major threat in patients with liver cirrhosis. Recently, it has been shown that the impact on mortality might be underestimated by established risk-scores. Onset of infection was suggested to define a distinct stage of cirrhosis. However, it remains unclear whether all stages of decompensated cirrhosis are equally affected. Moreover, if there is such a distinct stage, it must be determined whether it is reversible after the infection has resolved. In this study we aimed to further analyze the impact of a current as well as a resolved SBP in different stages of decompensated liver cirrhosis. Methods A number of 579 patients with liver cirrhosis and ascites were included. MELD-score was used to determine the stage of liver disease. Low (<15), intermediate (15–25) and high (>25) MELD-groups were compared. Patients were followed up for 90 days. Primary endpoint was overall mortality. Statistical analyses were performed using the log-rank test, Cox regression and competing risk analysis. Results Mortality was significantly higher in patients with nosocomial-acquired SBP (nSBP) compared to patients without SBP (p<0.001;HR = 2.05). However, the most prominent difference in mortality was documented in the intermediate MELD-group (nSBP: p = 0.02;HR = 2.10). Importantly, mortality in nSBP patients remained increased even after the initial nSBP episode had resolved (p<0.01;HR = 1.90). Again, this was only significant in those with intermediate MELD-scores (p = 0.02;HR = 2.28). While a current as well as a resolved nSBP were significantly linked to a higher mortality, neither of them did increase the likelihood for liver transplantation. Conclusions Development of nSBP is independently associated with increased mortality supporting the concept of a distinct status of cirrhosis. Importantly, the prognosis remains unfavorable even after resolution of nSBP. This could be particularly relevant for patients with intermediate MELD-scores, who have limited chances for a donor liver.

Background Nosocomial infections are a particular threat for patients with liver cirrhosis. It is not uncommon that individuals develop even several consecutive infections during a single hospital stay. We aimed to investigate the impact and characteristics of multiple, consecutive nosocomial infections. Methods A total of 514 consecutive patients with liver cirrhosis and ascites were included and followed up for 28 days for nosocomial infection, death or liver transplantation (LTx). Laboratory values were assessed at the time of hospitalization as well as at the onset of each new infectious episode. Results 58% ( n = 298) of the patients developed at least one nosocomial infection and in 23% ( n = 119) even multiple infections were documented during a single hospital stay. Consecutive infections usually occurred shortly after the previous episode. Spontaneous bacterial peritonitis (SBP) was the most common infection. However, the proportion of SBP declined from 43% at the first to only 31% at the third nosocomial infection ( p = 0.096). In contrast, the likelihood for other, less common types of infection such as blood stream infections increased. Third nosocomial infections were also more likely to be linked to the detection of fungal pathogens (21% vs. 52%; p = 0.001). Each additional infectious episode had a dramatic detrimental impact on LTx-free survival that was independent from the stage of liver disease (adjusted-HR: 6.76, p = 0.002 for first nosocomial infection; adjusted-HR: 14.69, p<0.001 for second nosocomial infection; adjusted-HR: 24.95, p<0.001 for third nosocomial infection). Conclusion In patients with decompensated liver cirrhosis LTx-free survival significantly decreases with every consecutive infectious episode. Development of prevention strategies is urgently required.

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Acute-on-chronic liver failure (ACLF) is a frequent complication in patients with liver cirrhosis that has high short-term mortality. It is characterized by acute decompensation (AD) of liver cirrhosis, intra- and extrahepatic organ failure, and severe systemic inflammation (SI). In the recent past, several studies have investigated the management of this group of patients. Identification and treatment of precipitants of decompensation and ACLF play an important role, and management of the respective intra- and extrahepatic organ failures is essential. However, no specific treatment for ACLF has been established to date, and the only curative treatment option currently available for these patients is liver transplantation (LT). It has been shown that ACLF patients are at severe risk of waitlist mortality, and post-LT survival rates are high, making ACLF patients suitable candidates for LT. However, only a limited number of patients are eligible for LT due to related contraindications such as uncontrolled infections. In this case, bridging strategies (e.g., extracorporeal organ support systems) are required. Further therapeutic approaches have recently been developed and evaluated. Thus, this review focuses on current management and potential future treatment options.