Pulmonary hypertension is associated with an increased incidence of NAFLD: A retrospective cohort study of 18,910 patients.

BACKGROUND: Pulmonary hypertension (PH) represents a multicausal disease with increasing global incidence that eventually leads to right ventricular failure. In addition to cardiac sequelae, noncardiac comorbidities appear to be of increasing relevance, especially in times of improved therapeutic options that often result in long-term survival. Here, we examined a potential association between PH and nonalcoholic fatty liver disease (NAFLD) as well as liver cirrhosis in an outpatient cohort in Germany. METHODS: A total of 9455 PH patients followed in general and internist practices between 2005 and 2019 were matched by propensity scoring based on age, sex, yearly consultation frequency and relevant comorbidities (obesity, diabetes, heart failure, lipid metabolism disorders) to a cohort of equal size without PH. The association between PH and NAFLD/liver cirrhosis was evaluated using Cox regression models. RESULTS: Within 10 years from the index date, cumulative incidence rates of NAFLD were significantly higher amongst patients with PH (7.3%) compared to non-PH patients (3.5%, log-rank p < 0.001). In regression analysis, this association was significant for both female (HR: 1.93, p < 0.001) and male (HR: 1.51, p = 0.005) patients and was most prominent amongst patients > 80 years (HR: 3.30, p = 0.001). Moreover, PH patients showed a strong trend towards higher incidence rates of liver cirrhosis compared to non-PH patients (1.4 vs. 1.1%, p = 0.066). CONCLUSION: Our data suggest that incidence rates of NAFLD are strongly elevated in patients with PH. This finding should trigger awareness of noncardiac comorbidities in these patients and argues for potential liver-directed screening programs in patients with PH.

Self-limited HBV infection of the recipient does not reactivate after liver transplantation: Observations from a 30-year liver transplant program.

BACKGROUND: A self-limited hepatitis B infection can reactivate in patients under immunosuppression or chemotherapy (reappearance of hepatitis B surface antigen (HBsAg) or HBV-DNA). Exact circumstances of HBV reactivation in patients undergoing liver transplantation (LT) for end-stage liver diseases (ESLD) unrelated to HBV are unknown, and recommendations on HBV prophylaxis remain unclear. PATIENTS AND METHODS: Among 1273 liver transplants, 168 patients with a self-limited HBV hepatitis B infection prior to LT were identified from our prospective liver transplant database. Patients with underlying chronic HBV infection and recipients of an anti-HBc-positive liver were not included in the analysis. Demographic, laboratory, serological, and virological data were analyzed retrospectively. Appearance of HBsAg or HBV-DNA was defined as reactivation. RESULTS: The median follow-up after LT was 12.0 years (0.6-30.7 years). The rate of HBV reactivation was 0% independent of antiviral prophylaxis (n = 7; 4.2%), the etiology of ESLD, hepatitis C treatment, or the anti-HBs concentration. The overall patient survival with a history of a self-limited HBV infection before LT did not significantly differ from the rest of the cohort. CONCLUSION: Antiviral treatment with nucleos(t)ide analogues post-liver transplantation in order to prevent HBV reactivation in patients with a resolved self-limited hepatitis B infection prior to LT seems to be omittable since the main viral reservoir is removed by the hepatectomy. These findings may clarify the current uncertainty in the recommendations regarding the risk of HBV reactivation in patients with self-limited hepatitis B prior to LT.

Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis.

Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.

Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis.

OBJECTIVE: Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants ('Pi*Z' and 'Pi*S'), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse. DESIGN: We analysed multicentric case-control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed. RESULTS: The Pi*Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p<0.0001). Accordingly, the Pi*Z variant increased the risk of NAFLD subjects to develop cirrhosis (adjusted OR=7.3 (95% CI 2.2 to 24.8)). Likewise, the Pi*Z variant presented in 6.2% of alcohol misusers with cirrhosis but only in 2.2% of alcohol misusers without significant liver injury (p<0.0001). Correspondingly, alcohol misusers carrying the Pi*Z variant were prone to develop cirrhosis (adjusted OR=5.8 (95% CI 2.9 to 11.7)). In contrast, the Pi*S variant was not associated with NAFLD-related cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19)). CONCLUSION: The Pi*Z variant is the hitherto strongest single nucleotide polymorphism-based risk factor for cirrhosis in NAFLD and alcohol misuse, whereas the Pi*S variant confers only a weak risk in alcohol misusers. As 2%-4% of Caucasians are Pi*Z carriers, this finding should be considered in genetic counselling of affected individuals.

Insufficient evidence of benefit regarding mortality due to albumin substitution in HCC-free cirrhotic patients undergoing large volume paracentesis.

BACKGROUND: Current guidelines for clinical practice recommend the infusion of human albumin after large volume paracentesis. After inspecting the current evidence behind this recommendation, we decided to conduct a systematic review and meta-analysis in order to address the effect of albumin on mortality and morbidity in the context of large volume paracentesis. METHODS: We performed a comprehensive search of large databases and abstract books of conference proceedings up to March 15th 2016 for randomized controlled trials, testing the infusion of human albumin against alternatives (vs no treatment, vs plasma expanders; vs vasoconstrictors) in HCC-free patients suffering from cirrhosis. We analyzed these trials with regard to mortality, changes in plasma renin activity (PRA), hyponatremia, renal impairment, recurrence of ascites with consequential re-admission into hospital and additional complications. We employed trial sequential analysis in order to calculate the number of patients required in controlled trials to be able to determine a statistically significant advantage of the administration of one agent over another with regard to mortality. RESULTS: We were able to include 21 trials totaling 1277 patients. While the administration of albumin prevents a rise in PRA as well as hyponatremia, no improvement in strong clinical endpoints such as mortality could be demonstrated. Trial sequential analysis showed that at least 1550 additional patients need to be recruited into RCTs and analyzed with regard to this question in order to detect or disprove a 25% mortality effect. CONCLUSIONS: There is insufficient evidence that the infusion of albumin after LVP significantly lowers mortality in HCC-free patients with advanced liver disease.

Fecal Microbiota Transplant in Patients With Recurrent Clostridium Difficile Infection.

BACKGROUND: The clinical effectiveness of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridium difficile infections (rCDI) has been demonstrated in randomized controlled trials. To assess the current status of FMT in Germany with respect to active centers, local standards, clinical effectiveness and safety, the MicroTrans Registry (NCT02681068) was established. METHODS: In a long-term retrospective multicenter observational study by the German Clinical Microbiome Study Group (GCMSG), primary and secondary cure on day 30 and 90, as well as occurrence of treatment-related adverse events were assessed. In addition to patient demographic data, we provide an overview of the FMT procedures and techniques used at different centers. RESULTS: Overall, 133 eligible patients from 33 centers were included, of which 64.7% were female (n = 86). The mean age was 75 years (interquartile range: 59.5-81.5). Administration via the duodenal route (n = 59; 44.4%) was the most frequently applied option, followed by colonic (n = 55; 41.1%), capsule (n = 13; 9.8%), and gastric administration (n = 4; 3.0%). Primary cure on day 30 and 90 was achieved in 84.2% (n = 101/120) and 78.3% (n = 72/92) of patients, respectively. Including re-treatment, secondary response was achieved in 87.5% (d 30; n = 105/120) and 85.9% (d 90; n = 79/92), respectively. Treatment- elated adverse events were documented in 16 patients (12.0%). CONCLUSION: FMT is a safe and effective treatment option for rCDI. However, FMT is currently available only in few centers in Germany, and treatment options vary from one center to another.

A Novel Easy-to-Use Prediction Scheme for Upper Gastrointestinal Bleeding: Cologne-WATCH (C-WATCH) Risk Score.

Acute upper gastrointestinal bleeding (UGIB) is the leading indication for emergency endoscopy. Scoring schemes have been developed for immediate risk stratification. However, most of these scores include endoscopic findings and are based on data from patients with nonvariceal bleeding. The aim of our study was to design a pre-endoscopic score for acute UGIB--including variceal bleeding--in order to identify high-risk patients requiring urgent clinical management. The scoring system was developed using a data set consisting of 586 patients with acute UGIB. These patients were identified from the emergency department as well as all inpatient services at the University Hospital of Cologne within a 2-year period (01/2007-12/2008). Further data from a cohort of 322 patients who presented to our endoscopy unit with acute UGIB in 2009 served for external/temporal validation.Clinical, laboratory, and endoscopic parameters, as well as further data on medical history and medication were retrospectively collected from the electronic clinical documentation system. A multivariable logistic regression was fitted to the development set to obtain a risk score using recurrent bleeding, need for intervention (angiography, surgery), or death within 30 days as a composite endpoint. Finally, the obtained risk score was evaluated on the validation set. Only C-reactive protein, white blood cells, alanine-aminotransferase, thrombocytes, creatinine, and hemoglobin were identified as significant predictors for the composite endpoint. Based on the regression coefficients of these variables, an easy-to-use point scoring scheme (C-WATCH) was derived to estimate the risk of complications from 3% to 86% with an area under the curve (AUC) of 0.723 in the development set and 0.704 in the validation set. In the validation set, no patient in the identified low-risk group (0-1 points), but 38.7% of patients in the high-risk group (≥ 2 points) reached the composite endpoint. Our easy-to-use scoring scheme is able to distinguish high-risk patients requiring urgent endoscopy, from low-risk cases who are suitable candidates for outpatient management or in whom endoscopy may be postponed. Based on our findings, a prospective validation of the C-WATCH score in different patient populations outside the university hospital setting seems warranted.

Patient- and procedure-related factors affecting proximal and distal detection rates for polyps and adenomas: results from 1603 screening colonoscopies.

BACKGROUND: Screening colonoscopy is less effective in reducing the incidence of proximal compared to distal colorectal cancer, presumably because of missed adenomas and advanced lesions during endoscopy. Thus, effectiveness and success of colorectal cancer (CRC) screening programs depend decisively on the quality of the endoscopic procedures. METHODS: A retrospective analysis of 1603 average risk screening colonoscopies to calculate and to identify determinants of separate detection rates for proximally and distally located polyps, adenomas, and advanced adenomas was performed. RESULTS: 56.1 % of 1603 individuals included were men, and the mean age was 60.2 ± 10.2 years. Distal detection rates were markedly higher compared to proximal detection rates for polyps (40.9 vs. 23.8 %), adenomas (21.3 vs. 16.2 %), and advanced adenomas (4.0 vs. 2.0 %). A gradual increase in detection rates with increasing age was found for proximal and distal localization. Gender difference was also seen for polyps and adenomas, but not for advanced adenomas. In multivariate analysis, age <65.0 years and female gender were independently associated with a lower separate polyp detection rate (PDR) and adenoma detection rate (ADR). The use of propofol was the only procedure-related variable significantly associated with higher polyp detection rate. CONCLUSION: Since age and gender affect detection rates of proximally and distally located polyps and adenomas, the requirement of a specific gender-related limit in total detection rates may be insufficient as a quality indicator for screening colonoscopies.