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Abstract Background Patients with cirrhosis and portal hypertension may have alterations in intestinal barrier resulting in increased susceptibility for infections. We investigated the effect of propranolol in gastrointestinal motility, permeability and bacterial overgrowth in cirrhosis. Methods Patients with cirrhosis and esophageal varices were studied before and after a build-up dose of propranolol according to standard guidelines. Serum TNF-a, IL-6, IL-1b, LPS and bacterial DNA were measured before and during propranolol therapy. Oro-caecal transit time (OCTT) and bacterial overgrowth (BO) have been evaluated with H2 breath testing. Intestinal paracellular (IP), cellular passive non-carrier (ICNC), cellular passive carrier-mediated (ICCM), and gastric permeability (GP) were evaluated by measurement of lactulose, mannitol, D-xylose and sucrose respectively in urine, with high performance liquid chromatography (HPLC). Results 35 patients with cirrhosis and portal hypertension with median age was 59.6 years (range 42–86) were included in the study. Twenty one had viral hepatitis and 25 were classified as having advanced cirrhosis (Child-Pugh B: 14 or C: 11). Median dose of administrated propranolol was 40 mg/day. After 7 days propranolol treatment BO was resolved in 15 out of 16 patients (93.7%, p = 0.0001) and OCTT was reduced significantly from 180 min to 139 min (SD 58.5, difference − 4 1 min, p = 0.0001). Serum IL-6 levels were reduced in 21/35 (60%) patients from 41.1 to 19 pg/ml (p = 0.01), TNF-a in 10/35 (28.5%) patients from 10.7 to 5.6 pg/ml (p = 0.007) and LPS in 20/35 (57%) from 7.1 to 5.2 mg/L (p = 0.1). No bacterial DNA was detected in serum of all patients either baseline or under propranolol treatment. IP was significantly reduced (0.2 to 0.16, p = 0.04) whereas ICNC (p = 0.9), ICCM (p = 0.4) and GP (p = 0.7) were not affected significantly. Intestinal Permeability (PI) index (Lactulose to Mannitol ratio) was significantly reduced (0.027 to 0.02, p = 0.03). Conclusion In patients with cirrhosis and portal hypertension, propranolol use is associated with reduction in BO, increase in intestinal motility and amelioration in intestinal permeability. Moreover IL-6 and LPS levels are being decreased in the majority of patients under propranolol.

Abstract Background Preventing disease progression and viral suppression are the main goals of antiviral therapy in chronic hepatitis B (CHB). Liver stiffness measurement (LSM) by transient elastography is a reliable non-invasive method to assess liver fibrosis in patients with CHB. Our aim was to explore factors that may affect changes in LSMs during long term tenofovir (TDF) monotherapy in a well characterized cohort of patients with compensated CHB. Methods We analyzed serial LSMs in 103 adult patients with CHB who were on TDF monotherapy and had at least three LSMs over a period of 90 months. Results Twenty-five (24%) patients had advanced fibrosis at baseline. A significant decline in mean LSM between baseline and last visit (8.7 ± 6.2 kPa vs. 6.7 ± 3.3, p = 10− 3) was observed. Twenty-four (23%) patients had progression of liver fibrosis with mean increase in liver stiffness of 2.8 kPa (range: 0.2–10.2 kPa). Multivariate analysis showed that BMI ≥ 25 (OR, 0.014; 95% CI, 0.001–0.157; p = 0.001) and advanced fibrosis (OR, 5.169; 95% CI, 1.240–21.540; p = 0.024) were independently associated with a fibrosis regression of > 30% of liver stiffness compared to baseline value. Conclusions In CHB patients TDF monotherapy resulted in liver fibrosis regression, especially in patients with advanced fibrosis. Despite the successful antiviral effect of TDF, 1 out of 4 patients had liver fibrosis progression. Obesity and advanced fibrosis at baseline were independently associated with significant liver fibrosis regression.

BackgroundBacterial infections are associated with the risk of variceal bleeding through complex pathophysiologic pathways.ObjectivesThe primary objective of the present case-control study was to investigate the role of bacterial translocation and intestinal barrier dysfunction in the pathogenesis of variceal bleeding. A secondary objective was to determine independent predictors of key outcomes in variceal bleeding, including bleeding-related mortality.MethodsEighty-four (n = 84) consecutive patients participated in the study, 41 patients with acute variceal bleeding and 43 patients with stable cirrhosis, and were followed up for 6 weeks. Peripheral blood samples were collected at patient admission and before any therapeutic intervention.ResultsChild-Pugh (CP) score (OR: 1.868; p = 0.044), IgM anti-endotoxin antibody levels (OR: 0.954; p = 0.016) and TGF-β levels (OR: 0.377; p = 0.026) were found to be significant predictors of variceal bleeding. Regression analysis revealed that albumin (OR: 0.0311; p = 0.023), CRP (OR: 3.234; p = 0.034) and FABP2 levels (OR:1.000, p = 0.040), CP score (OR: 2.504; p = 0.016), CP creatinine score (OR: 2.366; p = 0.008), end-stage liver disease model (MELD), Na (OR: 1.283; p = 0.033), portal vein thrombosis (OR: 0.075; p = 0.008), hepatocellular carcinoma (OR: 0.060; p = 0.003) and encephalopathy (OR: 0.179; p = 0.045) were significantly associated with 6-week mortality.ConclusionsBacterial translocation and gut barrier impairment are directly related to the risk of variceal bleeding. Microbiota-modulating interventions and anti-endotoxin agents may be promising strategies to prevent variceal bleeding.