Updates in characteristics and survival rates of cirrhosis in a nationwide cohort of real-world U.S. patients, 2003-2021.

BACKGROUND: Adverse outcomes of cirrhosis remain a top priority. AIMS: We examined the distribution of cirrhosis causes, HCC incidence and mortality and related changes over time in a nationwide U.S. METHODS: A retrospective study of a national sample of commercially insured patients with cirrhosis from Optum's de-identified Clinformatics® Data Mart Database (CDM). RESULTS: A total of 628,743 cirrhosis cases were identified with 45% having NAFLD, 19.5% HCV, and 16.3% ALD. African Americans had the highest rate of decompensation (60.6%), while Asians had the highest rate of HCC (2.4%), both p < 0.001. African Americans more frequently had HCV (28.4%) while Hispanic/Latinos more frequently had NAFLD (49.2%, p < 0.001). Patients in the 2014-2021 cohort were significantly older (63.0 ± 12.8 vs. 57.0 ± 14.3), less frequently decompensated (54.5% vs. 58.3%) but more frequently had HCC (1.7% vs. 0.6%) and NAFLD (46.5% vs. 44.2%), all p < 0.001. The overall annual incidence of HCC was 0.76% (95% CI: 0.75-0.77) with a 5-year cumulative incidence of 4.03% (95% CI: 3.98-4.09), with significant variation by sex, race/ethnicity, and cirrhosis aetiology. The overall median years of survival were 11.4 (95% CI: 11.3-11.5) with a 5-year cumulative survival of 73.4% (95% CI: 73.3%-73.6%), also with significant disparities in similar subgroups (lowest in cryptogenic cirrhosis and worse in 2014-2021 vs. 2003-2013). The 2014-2021 period was independently associated with worse survival (aHR: 1.14, 95% CI: 1.08-1.20). CONCLUSIONS: HCC incidence and survival vary by aetiology among patients with cirrhosis, with cryptogenic cirrhosis having the lowest survival and lower survival in the more recent time period.

Systematic review with meta-analysis: prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B.

BACKGROUND: As the prevalence of hepatitis steatosis (HS) increases, the prevalence of HS among those with chronic hepatitis B (CHB) may also be increasing but data on the effect of HS on CHB disease progression are lacking. AIMS: To determine the prevalence of HS in CHB and associated factors, prevalence of fibrosis and its association with HS. METHODS: Two researchers independently searched the literature and extracted data. We included full-length original articles of adults with CHB that evaluated. Prevalence estimates were pooled using a random-effects model. Associations between HS and fibrosis were assessed by pooled odds ratios (ORs) or mean differences (MD). RESULTS: Of the 2821 records screened, 54 eligible studies (28 648 patients) were analysed. The pooled prevalence of HS in CHB was 32.8% (95% CI, 28.9-37.0) with higher prevalence in men and obese patients. Older age, male sex and metabolic factors were associated with HS while an inverse association was observed between HS and HBeAg (OR 0.82, 95% CI, 0.75-0.91) and HBV DNA levels (MD -0.38, 95% CI -1.16--0.42). The pooled prevalence of significant fibrosis (≥F2 or ≥F3) was similar between patients with CHB with or without HS (40.1% vs 42.22%, P = 0.68). HS was not significantly associated with fibrosis (pooled OR 0.87, 95% CI 0.54-1.39, 20 studies, 6232 patients). CONCLUSIONS: Approximately 30% of patients with CHB had HS, which was positively associated with male sex, diabetes and metabolic factors, and was negatively associated with HBeAg and HBV DNA. HS was not significantly associated with increased fibrosis.

Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis.

BACKGROUND: Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir (TDF) and entecavir (ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV. AIM: To investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis. METHODS: Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies (NRSs) using the keywords "CHB", "Tenofovir", and "Entecavir", and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and 24 mo. RESULTS: Nine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo [mean difference (MD) = 0.03 mg/dL; 95%CI: 0.02-0.04; I 2 = 0%], 12 mo (MD = 0.05 mg/dL; 95%CI: 0.02-0.08; I 2 = 78%), and 24 mo (MD = 0.07 mg/dL; 95%CI: 0.01-0.13; I 2 = 93%). The change in estimated glomerular filtration rate (eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo [standardized mean difference (SMD), -0.22; 95%Cl: -0.36--0.08; I 2 = 0%], 12 mo (SMD = -0.24; 95%Cl: -0.43--0.05; I 2 = 50%), and 24 mo (-0.35; 95%Cl: -0.61- -0.09; I 2 = 67%). CONCLUSION: TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence. However, the differences are negligible.

Redox Regulation of Metabolic Syndrome: Recent Developments in Skeletal Muscle Insulin Resistance and Non-alcoholic Fatty Liver Disease (NAFLD).

Several new discoveries over the past decade have shown that metabolic syndrome, a cluster of metabolic disorders, including increased visceral obesity, hyperglycemia, hypertension, dyslipidemia and low HDL-cholesterol, is commonly associated with skeletal muscle insulin resistance. More recently, non-alcoholic fatty liver disease (NAFLD) was recognized as an additional condition that is strongly associated with features of metabolic syndrome. While the pathogenesis of skeletal muscle insulin resistance and fatty liver is multifactorial, the role of dysregulated redox signaling has been clearly demonstrated in the regulation of skeletal muscle insulin resistance and NAFLD. In this review, we aim to provide recent updates on redox regulation with respect to (a) pro-oxidant enzymes (e.g. NAPDH oxidase and xanthine oxidase); (b) mitochondrial dysfunction; (c) endoplasmic reticulum (ER) stress; (d) iron metabolism derangements; and (e) gut-skeletal muscle or gut-liver connection in the development of skeletal muscle insulin resistance and NAFLD. Furthermore, we discuss promising new therapeutic strategies targeting redox regulation currently under investigation for the treatment of skeletal muscle insulin resistance and NAFLD.