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ZusammenfassungDie Leitlinie Komplikationen der Leberzirrhose der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) ersetzt die Leitlinie aus dem Jahr 2011. Sie basiert auf den Empfehlungen der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) für eine evidenzbasierte Konsensus-Leitlinie der Entwicklungsstufe S2k und wurde interdisziplinär unter Beteiligung aller relevanten Fachgesellschaften und der Patientenvertretung erstellt. Neben den in der Vorgängerversion behandelten Kapiteln Aszites, spontan bakterielle Peritonitis, hepatorenales Syndrom, hepatischer Hydrothorax und hepatopulmonales Syndrom wurden die Kapitel Diagnostik und Therapie der Hepatischen Enzephalopathie neu aufgenommen.

Preemptive TIPS Individual Data Metanalysis, International Variceal Bleeding Study and Baveno Cooperation Study groups., [Background & Aims] Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS., [Method] We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients., [Results] Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323–0.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307–0.896; P = .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253–0.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy., [Conclusions] In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy., Juan Carlos García-Pagán received support in part through grants from the Spanish Ministry of Education and Science (SAF-2016–75767-R and PIE 15/00027) and from the “Commissioner for Universities and Research of the Generalitat de Catalunya” (AGAUR SGR 2017). CIBERehd is funded by the Instituto de Salud Carlos III. Edilmar Alvarado-Tapias and Anna Baiges are recipients of a "Río Hortega" fellowship grant from the Instituto de Salud Carlos III. The study was partially supported by a GORE grant for statistical support.

Background: To evaluate medical versus interventional treatment (transjugular thrombus fragmentation, local thrombolysis with or without stent implantation) in patients with acute non-cirrhotic, non-malignant portal vein thrombosis (PVT). Methods: This prospective, observational study enrolled 65 patients with acute (

Colonic diverticulosis is a very common condition. Many patients develop diverticulitis or other complications of diverticular disease. Recent genome-wide association studies (GWAS) consistently identified three major genetic susceptibility factors for both conditions, but did not discriminate diverticulititis and diverticulosis in particular due the limitations of registry-based approaches. Here, we aimed to confirm the role of the identified variants for diverticulosis and diverticulitis, respectively, within a well-phenotyped cohort of patients who underwent colonoscopy. Risk variants rs4662344 in Rho GTPase-activating protein 15 (ARHGAP15), rs7609897 in collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) and rs67153654 in family with sequence similarity 155 A (FAM155A) were genotyped in 1,332 patients. Diverticulosis was assessed by colonoscopy, and diverticulitis by imaging, clinical symptoms and inflammatory markers. Risk of diverticulosis and diverticulitis was analyzed in regression models adjusted for cofactors. Overall, the variant in FAM155A was associated with diverticulitis, but not diverticulosis, when controlling for age, BMI, alcohol consumption, and smoking status (ORadjusted 0.49 [95% CI 0.27–0.89], p = 0.002). Our results contribute to the assessment specific genetic variants identified in GWAS in the predisposition to the development of diverticulitis in patients with diverticulosis.

The purpose of this study is to investigate the association of intake of nonsteroidal anti-inflammatory drugs (NSAIDs) and in particular nonaspirin NSAIDs and compare it with other risk factors for the progression of diverticulosis to diverticulitis in patients who underwent colonoscopy. A total of 194 patients who underwent complete colonoscopy in our center between 2012 and 2016 were recruited: 144 with diverticulosis without prior diverticulitis (median age 71 years, 59.7% men) and 50 with diverticulitis (median age 64 years, 54.0% men). Data concerning current and previous medication as well as concomitant diseases were collected using a structured questionnaire and by revision of patients medical charts. Patients with diverticulitis were significantly (p

This guideline provides evidence-based key recommendations for diagnosis and therapy of complications of liver cirrhosis and upgrades the 2011 version. An interdisciplinary team of medical experts and patient support groups developed the guideline following the AWMF recommendations for evidence based consensus guidelines. New chapters concerning diagnosis and therapy of hepatic encephalopathy were added.Die Leitlinie Komplikationen der Leberzirrhose der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) ersetzt die Leitlinie aus dem Jahr 2011. Sie basiert auf den Empfehlungen der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) für eine evidenzbasierte Konsensus-Leitlinie der Entwicklungsstufe S2k und wurde interdisziplinär unter Beteiligung aller relevanten Fachgesellschaften und der Patientenvertretung erstellt. Neben den in der Vorgängerversion behandelten Kapiteln Aszites, spontan bakterielle Peritonitis, hepatorenales Syndrom, hepatischer Hydrothorax und hepatopulmonales Syndrom wurden die Kapitel Diagnostik und Therapie der Hepatischen Enzephalopathie neu aufgenommen.

Renal failure is a severe complication in patients with liver cirrhosis. It is associated with increased mortality and morbidity. Diagnosis is a challenge because it is mainly based on serum creatinine, which does not seem to be an ideal measure of renal function in cirrhosis. The definition of renal failure in these patients has been changed for optimizing treatment and for improving outcome and prognosis. The new criteria are based on the adapted KDIGO (Kidney Disease: Improving Global Outcomes) staging system. The diagnosis of acute kidney injury (AKI) is based on an absolute increase of serum creatinine of >0.3 mg/dl from baseline within 48 h or an increase of >50% from baseline. This means smaller changes in serum creatinine in a shorter time frame which may lead to an early identification of renal failure in cirrhotic patients. The former cirrhotic-specific term hepatorenal syndrome (HRS) is now part of the new diagnostic criteria and is called HRS-AKI. The diagnostic criteria of HRS have changed due to the new criteria for AKI. Due to these criteria for HRS, the medical treatment will be started earlier. First-line treatment for renal AKI-HRS is the combination of a vasoconstrictor and albumin. Most data exist for terlipressin, a vasopressin analog, as vasoconstrictor. Besides this medical treatment, there are other options like the placement of a transjugular intrahepatic portosystemic shunt, renal replacement, and artificial extracorporeal liver support systems. However, these alternative treatment options have limitations. Liver transplantation is the treatment of choice for these patients and represents the definitive treatment. Using new biomarkers like urinary neutrophil gelatinase-associated lipocalin or interleukin-18 for renal failure in cirrhosis should help to differentiate the causes of renal failure and provide an indication regarding the prognosis.

Background Colonic diverticulosis is one of the most common gastroenterological disorders. Although diverticulosis is typically benign, many individuals develop diverticulitis or other aspects of diverticular disease. Diverticulosis is thought to stem from a complex interaction of environmental, dietary, and genetic factors; however, the contributing genetic factors remain unknown. Objective The aim of our present study was to determine the role of genetic variants within genes encoding for collagens of the connective tissue in diverticulosis. Design This was a transsectional genetic association study. Settings This study was conducted at three tertiary referral centers in Germany and Lithuania. Patients Single-nucleotide polymorphisms in COL3A1 (rs3134646, rs1800255) and COL1A1 (rs1800012) were genotyped in 422 patients with diverticulosis and 285 controls of white descent by using TaqMan assays. Main outcome measures The association of colonoscopy-proven diverticulosis with genetic polymorphisms with herniations was assessed in multivariate models. Results The rs3134646, rs1800255, and rs1800012 variants were significantly associated with the risk of developing diverticulosis in the univariate model; however, these associations were not significant in the multivariate logistic regression analysis including additional nongenetic variables. When selectively analyzing sexes, the genotype AA (AA) in rs3134646 remained significantly associated with diverticulosis in men (OR, 1.82; 95% CI, 1.04-3.20; p = 0.04). Limitations Because a candidate approach was used, additional relevant variants could be missed. Within our cohort of patients with diverticulosis, only a small proportion had diverticular disease and thus, we could not examine the variants in these subgroups. Functional studies, including the analysis of the involved collagens, are also warranted. Conclusions Our study shows that a variant of COL3A1 (rs3134646) is associated with the risk of developing colonic diverticulosis in white men, whereas rs1800255 (COL3A1) and rs1800012 (COL1A1) were not associated with this condition after adjusting for confounding factors. Our data provide novel valuable insights in the genetic susceptibility to diverticulosis. See Video Abstract at http://links.lww.com/DCR/A504.

BACKGROUND: The balance between generation and elimination of reactive oxygen species by superoxide dismutase (SOD) is crucially involved in the pathophysiology of liver cirrhosis. Reactive oxygen species damage cells and induce inflammation/fibrosis, but also play a critical role in immune defense from pathogens. As both processes are involved in the development of liver cirrhosis and its complications, genetic variation of the SOD1 gene was investigated. PATIENTS AND METHODS: Two SOD1 single nucleotide polymorphisms (rs1041740 and rs3844942) were analyzed in 49 cirrhotic patients undergoing liver transplantation. In addition, 344 cirrhotic patients with ascites were analyzed in a cohort of 521 individuals in terms of the relationship of these polymorphisms with spontaneous bacterial peritonitis (SBP). RESULTS: Although rs3844942 showed no associations with complications of cirrhosis, we observed a significant association between rs1041740 and the presence of ascites and SBP in the discovery cohort of patients with cirrhosis. Importantly, the association with SBP was not confirmed in the validation cohort of patients with ascites. By contrast, a trend toward lower SBP rates was observed in carriers of rs1041740. In this cohort, rs1041740 was not associated with survival. CONCLUSION: These data suggest a complex role of SOD1 in different processes leading to complications of liver cirrhosis. rs1041740 might be associated with the development of ascites and possibly plays a role in SBP once ascites has developed.

OBJECTIVES: Common nucleotide-binding oligomerization domain containing 2 (NOD2) gene variants have been associated with bacterial infections (BIs) in cirrhosis, in particular, spontaneous bacterial peritonitis, and mortality. Our aim was to evaluate the independent association of NOD2 variants with BI according to the decompensation stage. METHODS: Consecutive patients with cirrhosis in 2 academic medical centers were included and genotyped for the NOD2 variants p.R702W, p.G908R, and c.3020insC. Electronic medical records were screened for BI (requiring antibiotic therapy) and past and present decompensation (as defined by variceal bleeding, encephalopathy, ascites, and/or jaundice). Clinically significant portal hypertension (CSPH) was assessed with liver stiffness and/or hepatic venous pressure gradient measurements. RESULTS: Overall, 735 patients were recruited (men 65%; interquartile age range 53–68 years). Alcoholic cirrhosis was the predominant etiology (n = 406, 55%), and most patients were in the decompensated stage (n = 531, 72%). In total, 158 patients (21%) carried at least one NOD2 variant. BIs were detected in 263 patients (36%), and NOD2 variants were associated with BI (odds ratio = 1.58; 95% confidence interval 1.11–2.27; P = 0.02). In compensated patients, the combination of NOD2 variants and presence of CSPH was the best independent predictors of BI, whereas other factors, such as spleen size and hemoglobin, and decompensations including hepatic encephalopathy or jaundice, gained relevance in decompensated patients. CONCLUSIONS: NOD2 risk variants are associated with BI in cirrhosis. The genetic effect on BI is strongest in compensated patients, whereas in decompensated patients their presence is less relevant. In this situation, CSPH becomes an independent factor associated with BI.

Background & Aims: Refractory ascites (RA) affects 10% of patients with advanced cirrhosis and ascites. Usual therapy includes large volume paracentesis, and in selected patients, a transjugular portosystemic shunt (TIPS). These therapies may be associated with increased morbidity: paracentesis may induce circulatory dysfunction and impair quality of life and TIPS may induce encephalopathy and is associated with increased mortality in patients with severe liver dysfunction. We present the results of a multicenter, non-randomized trial to assess the safety and efficacy of a new automated pump system for treatment of RA. Methods: Forty patients at 9 centers (February 2010-June 2011) received an implanted pump for the automated removal of ascites from the peritoneal cavity into the bladder, from where it was eliminated through normal urination. Patients were followed-up for 6 months. The primary study outcome was safety. Secondary outcomes included recurrence of tense ascites and pump performance. Results: Surgical complications occurred early in the study and became less frequent. The pump system removed 90% of the ascites and significantly reduced the median number of large volume paracentesis per month [3.4 (range 1-6) vs. 0.2 (range 0-4); p

Background & aims Circulating and peritoneal fragments of microbial DNA (bactDNA) are evidence for bacterial translocation in decompensated cirrhosis and may serve as a rational approach for antibiotic therapy when infection is suspected. Methods Prospective multicenter study to investigate whether identification of bactDNA from blood or ascitic fluid (AF) by multiplex polymerase chain reaction (PCR) is associated with increased 90-day mortality in 218 patients with cirrhosis and signs of infection. Results BactDNA in either compartment was detected in 134 (61%) patients, comprising 54 with bactDNA in blood and AF, 48 with AF bactDNA only, and 32 with blood bactDNA only. BactDNA was associated with spontaneous bacterial peritonitis and blood stream infections (SBP/BSI), acute-on-chronic liver failure (ACLF), encephalopathy and markers of inflammation. The prevalence of bactDNA in patients with proven SBP/BSI (36/49; 73%) was similar to that in patients with sterile ACLF (37/52; 71%). Actuarial 90-day survival was 56 ± 5% in the absence of bactDNA in both compartments and did not differ if bactDNA was detected in blood only (63 ± 9%), AF only (63 ± 7%), or in blood and AF (52 ± 7%). Predictors of 90-day mortality were SBP (HR = 3.10; 95% CI: 1.90-5.06), BSI (HR = 4.94; 95% CI: 2.71-9.02), and ACLF (HR = 2.20; 95% CI: 1.44-3.35). The detection of resistance genes in blood or AF in the absence of SBP/BSI (n = 11) was associated with poor 1-year survival (HR = 2.35; 95% CI: 1.03-5.35). Conclusions BactDNA in sterile body fluids did not indicate increased mortality in cirrhotic patients with suspected infection. Using multiplex PCR for risk stratification cannot be recommended in these patients.

Background/aims In cirrhosis portal hypertension can promote bacterial translocation and increase serum endotoxin levels. Vice versa, endotoxin aggravates portal hypertension by induction of systemic and splanchnic vasodilation, and by triggering hepatic inflammatory response via tumor necrosis factor α (TNFα). However, the hepatic elimination of endotoxin in cirrhotic patients with severe portal hypertension, in the absence of acute complications, has not been investigated so far. Methods Twenty patients with alcoholic liver cirrhosis received transjugular intrahepatic portosystemic shunt at an event-free interval for either refractory ascites or recurrent bleeding. During the transjugular intrahepatic portosystemic shunt procedure portal and hepatic venous blood samples were obtained and endotoxin levels were measured by a chromogenic limulus-assay. In 16 of these patients an enzyme-linked immunosorbent assay was used to measure levels of the soluble TNFα-receptors sTNF-R55 and sTNF-R75. Results Portal venous endotoxin levels correlated with portal vein velocity (P=0.03) and arterial systolic blood pressure (P=0.007). Portal endotoxin levels correlated with portal venous sTNF-R75-levels (P=0.039; r=0.521) and hepatic venous sTNF-R55-levels (P=0.009; r=0.669). Hepatic venous levels of both sTNF-R55 and sTNF-R75 correlated directly with the model for end-stage liver disease-score, and inversely with cholinesterase. However, we did not find significant differences in endotoxin levels nor in sTNF-R55-levels and sTNF-R75-levels between portal and hepatic venous blood. Conclusion Endotoxin levels correlated with hemodynamic derangement in cirrhotic severe portal hypertension, and with levels of soluble TNFα-receptors. Soluble TNFα-receptor levels correlated with the severity of liver dysfunction. However, in this study an endotoxin concentration gradient across the liver was absent, suggesting negligible primary hepatic endotoxin elimination in the absence of complications.

The development of hepatorenal syndrome type 1 (HRS1) is associated with a poor prognosis. Liver transplantation improves this prognosis, but the degree of the improvement is unclear. Most patients receive vasoconstrictors such as terlipressin before transplantation, and this may affect the posttransplant outcomes. We examined a cohort of patients with access to liver transplantation from our previously published study of terlipressin plus albumin versus albumin alone in the treatment of HRS1. The purpose of this analysis was the quantification of the survival benefits of liver transplantation for patients with HRS1. Ninety-nine patients were randomized to terlipressin or placebo. Thirty-five patients (35%) received a liver transplant. Among those receiving terlipressin plus albumin, the 180-day survival rates were 100% for transplant patients and 34% for nontransplant patients; among those receiving only albumin, the rates were 94% for transplant patients and 17% for nontransplant patients. The survival rate was significantly better for those achieving a reversal of hepatorenal syndrome (HRS) versus those not achieving a reversal (47% versus 4%, P < 0.001), but it was significantly lower for the responders versus those undergoing liver transplantation (97%). We conclude that the use of terlipressin plus albumin has no significant impact on posttransplant survival. Liver transplantation offers a clear survival benefit to HRS1 patients regardless of the therapy that they receive or the success or failure of HRS reversal. The most likely benefit of terlipressin in patients undergoing liver transplantation for HRS1 is improved pretransplant renal function, and this should make the posttransplant management of this difficult group of patients easier. For patients not undergoing transplantation, HRS reversal with terlipressin and/or albumin improves survival.

Background The aim of this study was to characterize patients and report outcome of diffuse alveolar hemorrhage (DAH) requiring intensive care unit support. Patients and Methods Thirty-seven patients were identified. Clinical characteristics and outcome were determined by chart review. Results Eighty-nine percent of patients presented with shortness of breath, 23% with cough, and 3% with hemoptysis. In 9% of patients, a diagnosis of DAH was suspected on admission. Diagnosis was confirmed by finding a progressively hemorrhagic bronchoalveolar lavage fluid in 89% and by a positive iron stain in 11% of patients. Vasculitis was causative in 19%, drug toxicity in 11%, thrombocytopenia in 27%, stem-cell transplantation in 5%, sepsis-associated lung injury in 22%, and unknown mechanisms in 16%. Thirty-two patients were mechanically ventilated, 4 received noninvasive ventilation, and 1 received supplemental oxygen therapy. Overall, 18 (49%) of 37 patients survived the intensive care unit stay. Survival was markedly different between patients with an immunologic/unknown etiology (82%) and patients with thrombocytopenia and/or sepsis (22%). Discussion Diffuse alveolar hemorrhage should be considered in all patients with persistent pulmonary infiltrates. Both bronchoalveolar lavage fluid and iron stain are mandatory diagnostic means. Patients with an immunologic/idiopathic pathogenetic mechanism have a relatively good prognosis, whereas the outcome in individuals with DAH secondary to cancer therapy or sepsis is poor.

Background Hepatorenal syndrome (HRS) is a frequent complication of end-stage liver cirrhosis. HRS type I has a very poor prognosis. From which of the more or less established therapies, such as use of vasoconstrictors together with albumin or placement of a Transjugular Intrahepatic Portosystemic Shunt patients might profit remains elusive. Therefore, it is important to define parameters that predict an improved outcome in respect to kidney function and survival. Methods The clinical charts of 91 patients with cirrhosis and HRS type I were studied. The parameters associated with response to therapy, defined as a decrease in serum creatinine of more than 1.5 mg/dl on day 14 after diagnosis of HRS, and those associated with survival were assessed by multivariate analysis. Results The median survival was 2.7 (1.5-3.8) months. Three independent predictive factors for survival were identified: Child-Pugh score (P = 0.05), Model of End-Stage Liver Disease (MELD) score less than 20 (P = 0.01), and response to therapy (P = 0.02). The Child-Pugh score (P = 0.00) and MELD score less than 20 (P = 0.02) were the parameters independently associated with the response to therapy, which occurred in 26% of the patients. Conclusion Our data of this large monocentric series with HRS type I confirm the poor prognosis in these patients, especially in those with high Child-Pugh and MELD scores, and in those in whom kidney function does not improve within 2 weeks.

A 55-year-old woman with suspected hilar cholangiocarcinoma presented with jaundice and dilated intrahepatic bile ducts owing to high-grade hepatic duct confluence stenosis. The suspected tumour and the entire extrahepatic bile duct system were resected and Roux-en-Y hepaticojejunostomy was performed. Histological investigations showed perihepatic fibrosis but no signs of malignancy. One year later the patient developed bilateral hydronephrosis caused by ureteral obstruction. Since the patient had a gynaecological history of widespread inflammation, she was referred for transabdominal operative ureterolysis combined with hysterectomy and adnexectomy. Histological investigations as well as fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) findings were compatible with retroperitoneal fibrosis (Ormond's disease). Treatment with tamoxifen was initiated. To the best of our knowledge, only a few cases of intraperitoneal fibroses mimicking cholangiocarcinoma followed by the typical symptoms of retroperitoneal Ormond's disease have been reported.

Bei der Leberzirrhose entstehen aufgrund des portalen Hypertonus Kollateralen, die zur intestinalen Blutung fuhren konnen. Eine Blutung ereignet sich jedoch nicht, wenn der Lebervenenverschlussdruck

Bacterial infections are a well-described complication in patients with cirrhosis of the liver. The development of an infection is associated with a significantly higher mortality. The most common infection in patients with liver cirrhosis is spontaneous bacterial peritonitis (SBP), an infection of ascites without an intraabdominal focus, followed by infections of the unrinary tract, pneumonia and sepsis. Early recognition of SBP results in an early antibiotic threrapy and thus improving survival. Another important role in the development of bacterial infections in cirrhosis is gastrointestinal hemorrhage. In patients with variceal hemorrhage, infection has been shown to be associated with failure to control bleeding and with early rebleeding. For these reasons, a prompt and appropriate antibiotic therapy is important and reduces mortalitiy in cirrhotic patients with bacterial infection.

Background Spontaneous bacterial peritonitis is frequently a fatal infection in patients with liver cirrhosis. We investigated if nuclear dot protein 52 kDa ( NDP52 ), a negative regulator of toll-like receptor (TLR) signalling and autophagy adaptor protein, might be involved. Methods Two cohorts comprising 152 (derivation cohort) and 198 patients (validation cohort) with decompensated liver cirrhosis and 168 healthy controls were genotyped for the rs2303015 polymorphism in the NDP52 gene and prospectively followed-up for spontaneous bacterial peritonitis. Results Overall, 57 (38%) patients in the derivation cohort and 77 (39%) in the validation cohort had spontaneous bacterial peritonitis. Cirrhosis was due to alcohol abuse in 57% of the derivation and 66% of the validation cohort. In patients with alcoholic cirrhosis, patients with spontaneous bacterial peritonitis had an increased frequency of the NDP52 rs2303015 minor variant in the derivation ( p = 0.04) and in the validation cohort ( p = 0.01). Multivariate analysis confirmed this minor variant (odds ratio 4.7, p = 0.002) and the TLR2 −16934 TT variant (odds ratio 2.5, p = 0.008) as risk factors for spontaneous bacterial peritonitis. In addition, presence of the NDP52 minor variant affected survival negatively. Conclusion Presence of the NDP52 rs2303015 minor variant increases the risk for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.

Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP. The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (

There are three major goals in the prophylaxis and treatment of upper gastrointestinal bleeding in portal hypertensive patients: prophylaxis of the first bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding. Several therapeutic options are available: non-selective beta-blockers are the treatment of choice in the primary prophylaxis of the first bleeding episode in patients with large esophageal varices. Alternatively, endoscopic band ligation therapy is an option. Acute bleeding varices should be treated by ligation pharmacological and antibiotic therapy. Prophylaxis of recurrent bleeding is patient-dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A). In patients with refractory ascites and a bilirubin below 3 mg/dl, TIPS is a good option together with recurrent bleeding. At the moment, there are no trials showing that endoscopic ligation therapy is superior to prevent pharmacological therapy. Nevertheless, the first-line treatment in most patients in Germany is endoscopic band ligation. Bleeding from ectopic varices and bleeding from hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.