The risk factors and clinical outcomes in hepatitis B seropositive and seronegative renal transplant patients.

INTRODUCTION: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients. METHODS: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival. RESULTS: We identified 337 patients (47.5 ± 12 years) were enrolled in our final cohort. Fifty-two (15.4%) had HBsAg positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pre-transplant anti-HBV medication [hazard ratio (HR), 5.95; 95% confidence interval (CI), 1.31-27.02; P = 0.021 or an absence of lifelong antiviral therapy [HR, 3.14; 95% CI, 1.01-9.74; P = 0.047] Conclusion: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pre-transplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.

Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway.

BACKGROUNDS/AIMS: The present study explores the potential of chronic treatment with the Foresaid X receptor (FXR) agonist obeticholic acid (OCA), which inhibits oxidative stress-related pathogenesis, in ascitic cirrhotic rats with hepatorenal syndrome (HRS) developed 6 weeks after bile duct ligation (BDL). METHODS: Systemic, splanchnic, and renal hemodynamics and pathogenic cascades were measured in ascitic BDL and sham rats receiving 2-weeks of either vehicle or OCA treatments (sham-OCA and BDL-OCA groups), and NRK-52E cells, rat kidney tubular epithelial cells. RESULTS: Chronic OCA treatment significantly normalized portal hypertension, glomerular filtration rate, urine output, renal blood flow; decreased ascites, renal vascular resistance, serum creatinine, and the release of renal tubular damage markers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury moleculae-1 (uKim-1) in BDL-OCA rats. In the BDL group, inhibition of the renal oxidative stress (8-iso-PGF2α)-activated cyclooxygenase-thromboxane A2 [COX-TXA2] pathway, apoptosis, and tubular injury accompanied by a decrease in hyper-responsiveness to the vasoconstrictor 8-iso-PGF2α in perfused kidneys. In vitro experiments revealed that 8-iso-PGF2α induced oxidative stress, release of reactive oxygen species, and cell apoptosis, which were reversed by concomitant incubation with the FXR agonist. CONCLUSIONS: Through the inhibition of renal 8-iso-PGF2α production and the down-regulation of the COX-TXA2 pathway, our study suggests that chronic OCA treatment can ameliorate the HRS in ascitic cirrhotic rats. Thus, OCA is an agent with antioxidative stress, antivasoconstrictive, antiapoptotic properties which benefit ascitic, cirrhotic rats with systemic, hepatic, and renal abnormalities.

Non-Selective Beta-Blockers Decrease Infection, Acute Kidney Injury Episodes, and Ameliorate Sarcopenic Changes in Patients with Cirrhosis: A Propensity-Score Matching Tertiary-Center Cohort Study.

BACKGROUND: Cirrhotic complications resulting from portal hypertension can be considerably reduced by non-selective beta-blockers (NSBBs); however, scarce studies have investigated therapeutic agents for other complications. We aimed to investigate the effects of NSBBs on common cirrhotic complications of infection, acute kidney injury (AKI), chronic renal function declination, and sarcopenic changes. METHODS: Medical records of hospitalization for cirrhosis with at least a 4-year follow-up were analyzed and selected using propensity-score matching (PSM). Generalized estimating equation (GEE) was applied to assess the association of NSBBs with infection requiring hospitalization and AKI. Chronic renal function declination was evaluated by slope of regression lines derived from reciprocal of the serum creatinine level. The covariates of CT-measured skeletal muscle index (SMI) alterations were analyzed by generalized linear mixed model. RESULTS: Among the 4946 reviewed individuals, 166 (83 NSBB group, 83 non-NSBB group) were eligible. Using GEE, Charlson comorbidity index, Child-Pugh score and non-NSBB were risk factors for infection; non-NSBB group revealed a robust trend toward AKI, showed no significant difference with chronic renal function declination of NSBB group, and was negatively associated with SMI alteration. CONCLUSION: Chronic NSBB use lowered the episodes of infection requiring hospitalization and AKIs, whereas non-NSBB was associated with sarcopenic changes.

Urinary fatty acid and retinol binding protein-4 predict CKD progression in severe NAFLD patients with hypertension: 4-year study with clinical and experimental approaches.

Detection of the chronic kidney disease (CKD) progression can begin early intervention to improve the prognosis of severe non-alcoholic fatty liver disease (NAFLD). This bi-directional cross-sectional study evaluates the roles of fatty acid-binding protein (FABP) and retinol binding protein (RBP4), which are produced from inflamed liver, adipose tissue and immune cells, for the prediction of CKD progression in severe NAFLD. Ninety severe NAFLD patients with hypertension and proteinuria (NAFLDHTN) were enrolled and divided into CKD (n = 39) and non-CKD groups (n = 51). Among 39 NAFLDHTN patients, 18 cases were categorized as CKD progression group. In comparison with CKD stable group (n = 21), the positive correlation between fold change values of hepatic fibrotic score (KPa), urinary FABP4 or urinary RBP4 versus severity of albuminuria were noted among CKD progression group. On multivariate analysis, high body mass index (BMI, >25 kg/m), high hepatic fibrosis score (>9.5 KPa), high urinary level of vascular cell adhesion molecule-1 (VCAM-1, >2239 µg/g cr), high urinary level of FABP4 (>115 ng/g cr) and high urinary level of RBP4 (>33.5 mg/g cr) are 5 independent predictors for progressive CKD during 24 months of follow-up. Synergetic effect was noted among these 5 risk factors for the prediction of CKD progression in NAFLDHTN patients. The in vitro experiments revealed that both FABP4 and RBP4 directly enhanced albumin-induced ER stress and apoptosis of human renal tubular epithelial cell line HK-2 cells and human podocytes cell lines. Through clinical and experimental approaches, this study revealed new 5 synergetic predictors including high BMI, hepatic fibrosis score, urinary level of VCAM-1, urinary level of FABP4 and RBP4, for the CKD progression in severe NAFLD patients with hypertension and proteinuria.

Propranolol Is Associated with Lower Risk of Incidence of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Tertiary-Center Study and Indirect Comparison with Meta-Analysis.

Alcoholic cirrhosis (AC) leads to enormous disease burden and occupies a substantial proportion in the etiology of hepatocellular carcinoma (HCC), but scarce attention has been paid to this topic. Besides, propranolol has been reported to decrease the rate of HCC in viral hepatitis. We conducted a retrospective tertiary-center cohort study to identify the HCC incidence in AC patients with or without propranolol. A total of 1,046 AC patients with hospitalization had been screened, and those with regular follow-up for three years or otherwise until the date of malignancy diagnosis without meeting exclusion criteria were enrolled; finally, 23 AC patients with propranolol and 46 AC patients without propranolol were analyzed after twofold propensity-score matching. The cumulative incidence of HCC was lower in the propranolol group (log-rank test, P = 0.046). Furthermore, we undertook the meta-analysis of annual incidence of HCC in AC patients, and 1,949 publications were screened, within which eight studies were analyzed; the pooled annual incidence was 2.41%, which was higher than the calculated annual incidence of HCC in our AC cohort with propranolol (1.45%). In conclusion, propranolol is associated with decreased risk of HCC incidence in patients with AC.

SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice.

BACKGROUND: In non-alcoholic steatohepatitis (NASH), muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice. METHODS: In vivo and in vitro study, we evaluate the SIRT1-dependent mechanisms and effects of resveratrol administration for 6 weeks with high-fat-methionine and choline deficient diet-induced NASH mice and palmitate-pretreated C2C12 myoblast cells. RESULTS: Resveratrol treatment improved grip strength and muscle mass of limbs, increased running distance and time on exercise wheels in NASH mice. There is a negative correlation between muscular SIRT1 activity and 3-nitrotyrosine levels of NASH and NASH-resv mice. The SIRT1-dependent effect of muscle wasting was associated with the suppression of oxidative stress, upregulation of antioxidants, inhibition of protein degradation, activation of autophagy, suppression of apoptotic activity, upregulation of lipolytic genes and the reduction of fatty infiltration in limb muscles of NASH mice. In vitro, resveratrol alleviated palmitate acid-induced oxidative stress, lipid deposition, autophagy dysfunction, apoptotic signals, and subsequently reduced fusion index and myotube formation of C2C12 cells. The beneficial effects of resveratrol were abolished by EX527. CONCLUSIONS: Our study suggests that chronic resveratrol treatment is a potential strategy for amelioration of hepatic steatosis and muscle wasting in NASH mouse model.