Use of Bacterial DNA Concentration in Ascites as a Marker for Spontaneous Bacterial Peritonitis.

Background and aims: Spontaneous bacterial peritonitis (SBP) is a common and serious complication in patients with decompensated cirrhosis. Precise quantification of bacterial DNA (bactDNA) and the related inflammatory response might add further information on the course of disease. The aim of the study was to evaluate the association between bactDNA, cytokine levels and clinical outcome. Methods: Ascites and serum samples of 98 patients with decompensated liver cirrhosis (42 with SBP and 56 without SBP) as well as serum samples of 21 healthy controls were collected. BactDNA in ascites and serum was detected and quantified by 16S rRNA PCR. Concentrations of IL-1ß, TNF-α, IL-6, IL-8 and IL-10 were measured by a LEGENDplexTM multi-analyte flow assay. Clinical data were collected and analyzed retrospectively. Results: BactDNA was detected more frequently in ascites of patients with SBP (n = 24/42; 57.1%) than in ascites of patients without SBP (n = 5/56; 8.9%; P < 0.001). Additionally, IL-6 levels in both ascites and serum were significantly higher in patients with SBP (ascites P < 0.001, serum P = 0.036). The quantity of bactDNA in ascites was strongly correlated with polymorphonuclear neutrophil count in ascites (r = 0.755; P < 0.001) as well as ascites IL-6 levels (r = 0.399; P < 0.001). Receiver operating characteristic (ROC) curve analysis to diagnose SBP provided an AUC of 0.764 (95% CI: 0.661-0.867) for serum IL-6 levels, an AUC of 0.810 (95% CI: 0.714-0.905) for ascites IL-6 levels, and an AUC of 0.755 (95% CI: 0.651-0.858) for bactDNA levels in ascites. Conclusions: The correlation between the amount of bactDNA and IL-6 confirms the pathophysiological relevance of bactDNA and IL-6 as potential biomarkers for the diagnosis of SBP.

Body fat composition determines outcomes before and after liver transplantation in patients with cirrhosis.

Cachexia occurs in late stages of liver cirrhosis, and a low-fat mass is potentially associated with poor outcome. This study compared different computed tomography (CT)-derived fat parameters with respect to its prognostic impact on the development of complications and death before and after liver transplantation. Between 2001 and 2014, 612 patients with liver cirrhosis without hepatocellular carcinoma listed for liver transplantation met the inclusion criteria, including abdominal CT scan (±200 days to listing). A total of 109 patients without cirrhosis served as controls. The subcutaneous fat index (SCFI), the paraspinal muscle fat index, and the visceral fat index were assessed at L3/L4 level and normalized to the height (cm2 /m2 ). Data were collected and analyzed retrospectively. Low SCFI was associated with a higher rate of ascites and increased C-reactive protein levels (p < 0.001). In addition, multivariate Cox regression analysis adjusting for sex, age, body mass index (BMI), and Model for End-Stage Liver Disease showed that decreasing SCFI was also associated with an increased risk of cirrhosis-related complications (p = 0.003) and death on the transplant wait list (p = 0.013). Increased paraspinal and visceral fat were not only positively correlated with creatinine levels (p < 0.001), BMI, and metabolic comorbidities (all p < 0.001) before transplantation, but also predictive for 1-year mortality after transplantation. Conclusion: The distribution of body fat is a major determinant for complications and outcome in cirrhosis before and after liver transplantation.

Current State and Future Possibilities in Liver Transplantation.

Due to medical and surgical progress, liver transplantation (LT) is is nowadays a routine treatment for terminal liver failure and hepatic malignancies. However, in recent years there has been a change in the indications for LT. Especially in western industrialized countries, the use of LT for chronic hepatis B and hepatitis C cirrhosis is continuously decreasing since the introduction of effective antiviral drugs. Liver cirrhosis due to non-alcoholic steatohepatitis (NASH), alcoholic liver disease and hepatocellular carcinoma (HCC) in cirrhosis are now among the leading indications for LT. Due to tremendous progress in oncology, immunology, and technical aspects, multidisciplinary cancer treatment increasingly includes LT for non-HCC hepatobiliary malignancies. Excellent 5-year survival rates of 75 to 80% can now be achieved after LT. However, in patients with liver cirrhosis, the implementation of a 'sickest first' principle for liver allocation has led to an increasing number of critically ill patients undergoing liver transplantation. This results in an increased morbidity and mortality after liver transplantation. Moreover, donor characteristics have markedly shifted to less ideal grafts due to an increasing shortage of donor organs in many countries. In this context, normothermic machine perfusion with oxygenated blood components using pulsatile flow has been shown to reduce liver damage despite a prolonged preservation time and might be able to provide viability testing for otherwise discarded organs. With favorable donor and recipient conditions, excellent long-term results can be obtained with a 10-year survival rate of close to 70%. However, in patients with a high MELD score (>30), survival rates markedly decrease by 12-18%. Future research should focus on optimization of organ allocation, optimization of immunosuppression including tolerance induction, and on increasing the donor organ pool to further improve and the numbers of successful LT.

[Liver transplantation - current trends]. / Aktuelle Entwicklungen bei der Lebertransplantation ­ Wo stehen wir?

INDICATION OF TRANSPLANTATION: There is an ongoing change in the indications of orthotopic liver transplantation (OLT) with non-alcoholic and alcoholic liver disease and hepatocellular carcinoma (HCC) becoming the main indications whereas the numbers of cirrhosis due to chronic viral hepatitis are declining. 6-MONTH ABSTINENCE RULE: : The directive of the German Federal Medical Association requires absolute abstinence from alcohol for at least 6 months. New data show that patients with severe alcoholic hepatitis for the first time who do not show a response to medical treatment may benefit from OLT. For these patients an individual exception for OLT listing can be requested. HCC BEYOND MILAN CRITERIA: New data show that patients with HCC outside the Milan criteria may have a favorable prognosis, which can be comparable to patients with HCC within the Milan criteria, if effective pre-transplant "down-staging" therapies but also alfa fetoprotein levels are taken into consideration. TOO SICK TO TRANSPLANT?: Even patients with decompensated cirrhosis and multi-organ dysfunction, defined as acute-on-chronic liver failure, may undergo OLT successfully with a beneficial long-term prognosis. However, the timeframe to realize OLT is short. ORGAN SHORTAGE: OLT using organs from HBV- or HCV-infected patients represents a relevant strategy to mitigate organ shortage and can be safely and effectively be performed due to the excellent therapeutic options against these infections which are available now. In addition, machine perfusion, a novel tool for organ conservation and conditioning, may help preserving organs for transplantation that formerly could not be used.