Objective: We conducted this umbrella review of meta-analysis on randomized controlled trials to clarify the effects of vitamin E administration on alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), degrees of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).
Methods: PubMed, MEDLINE, SCOPUS, EMBASE, and Web of Science were searched to identify pertinent articles published up to June 2023. To calculate the overall effect size (ES) and confidence intervals (CI), random-effects model was used.
Results: Six meta-analyses were included in the umbrella review. By pooling ES based on the random-effects model, we found that vitamin E supplementation significantly decreased ALT (ES -6.47, 95% CI -11.73 to -1.22,P = 0.01), AST (ES -5.35, 95% CI -9.78 to -0.93,P = 0.01), degrees of fibrosis (ES -0.24, 95% CI -0.36 to -0.12,P < 0.001) and steatosis (ES -0.67, 95% CI -0.88 to -0.45,P < 0.001) in NAFLD patients, but had no effect on GGT. In the subgroup analyses, we detected that fibrosis scores notably decreased when vitamin E dosage was >600 IU/day (ES -0.25, 95% CI -0.41 to -0.10,P = 0.002) and when the treatment duration was ≥12 months (ES -0.24, 95% CI -0.37 to -0.12,P < 0.001).
Conclusion: Vitamin E administration improves ALT, AST, fibrosis, and steatosis in NAFLD subjects. Fibrosis scores were significantly reduced when vitamin E dosage exceeded 600 IU/day or with a treatment duration of at least 12 months.
Objectives: Bone loss is a common morbidity in patients with inflammatory bowel disease (IBD). Bone mineral density (BMD) measurement is recommended for IBD patients at a high risk of osteoporosis. However, there is a lack of evidence in the need of BMD measurement in patients who are young at the first disease onset. In this study we aimed to investigate the prevalence of low BMD in patients with newly diagnosed Crohn’s disease (CD) at 20–50 years of age and the potential risk factors.
Methods: A single-center, retrospective cross-sectional study was conducted. Medical records of the patients were reviewed and their demographics, clinical characteristics and laboratory test results were collected. Dual energy X-ray absorptiometry (DEXA) scan was performed for BMD measurements; low BMD was defined as Z-score or T-score <-1.0 standard deviation (SD). Univariate and multivariate logistic regression analyses were used to determine the risk factors for low BMD.
Results: A total of 221 patients with CD were included; osteopenia and osteoporosis were identified in 23.1% and 8.6%, and 39.4% and 7.2% of the patients using Z-score and T-score, respectively. Female gender and a higher BMI at diagnosis were protective factors for low BMD.
Conclusions: Low BMD is common in patients with newly diagnosed CD aged 20–50 years. Female gender and a higher BMI at diagnosis might protect CD patients from bone loss. Therefore, BMD measurement and early intervention with calcium and vitamin D are recommended for these patients.
Objectives: As a critical component of the autophagic machinery, autophagy-related gene 5 (ATG5) is essential for autophagosome formation. Autophagy participates in the transformation and progression of various malignant tumors, but the role of ATG5 in hepatocellular carcinoma (HCC) remains to be illustrated. In this study we aimed to investigate the prognostic significance of ATG5 in HCC.
Methods: ATG5 expression was evaluated in 89 pairs of HCC tissues and adjacent non-tumor tissues. The relationship between ATG5 expression and patients’ clinicopathological characteristics and prognosis were evaluated. Moreover, subgroup analyses were performed regarding patients’ age and number of tumors. Nomograms estimating overall survival (OS) and disease-free survival (DFS) were conducted.
Results: ATG5 expression was increased in HCC specimens rather than adjacent non-tumor tissues. The upregulated ATG5 expression was positively associated with serum α-fetoprotein (AFP) level. Moreover, cases with a strong ATG5 expression had a poorer disease-free survival (DFS) and overall survival (OS) than those with a weak ATG5 expression. Multivariate analysis showed that a strong expression of ATG5 was related to a poor OS and DFS in patients with HCC. Further analysis indicated that cases with a higher ATG5 expression had a poorer OS and DFS in the young patients (≤55 years) and those with solitary tumor. The nomogram suggested that there was a coherence between nomogram prediction and the actual situation of patient survival related to ATG5.
Conclusion: ATG5 promotes tumor progression in HCC, making it a potential biomarker in the diagnosis and a therapeutic target of HCC.
Objectives: To determine whether hyperammonemia has a direct impact on steatohepatitis in mice fed with a high-fat diet (HFD).
Methods: Male C57BL/6 mice were divided into two groups receiving either chow diet or HFD. After 12-week NASH modeling, hyperammonemia was induced by intragastric administration of ammonium chloride solution (NH4Cl) or liver-specific carbamoyl phosphate synthetase 1 (Cps1) knockdown. In vitro experiments were performed in HepG2 cells induced by free fatty acid (FFA) and NH4Cl.
Results: NH4Cl administration led to increased levels of plasma and hepatic ammonia in NASH mice. NH4Cl-induced hyperammonemia did not influence liver histological changes in mice fed with HFD; however, elevated plasma cholesterol level, and an increasing trend of liver lipid content were observed. No significant effect of hyperammonemia on hepatic inflammation and fibrosis in NASH mice was found. In vitro cell experiments showed that NH4Cl treatment failed to increase the lipid droplet content and the expressions of de novo lipogenesis genes in HepG2 cells induced by FFA. The knockdown of Cps1 in HFD-fed mice resulted in elevated plasma ammonia levels but did not cause histological change in the liver.
Conclusions: Our study revealed a limited role of ammonia in aggravating the progression of NASH. Further studies are needed to clarify the role and mechanism of ammonia in NASH development.
Objectives: Primary biliary cholangitis (PBC) is a rare disease characterized by intrahepatic cholestasis, whereas gallstone disease (GD) is common. In this study, we aimed to investigate the prevalence and impact of GD on the prognosis of PBC in China.
Methods: Medical records of the PBC patients were retrospectively reviewed and their follow-up data were obtained via regular structured, standardized telephone interviews. GD was defined as gallstones on ultrasonography or a history of cholecystectomy for gallstones. Propensity score matching (PSM) and Cox regression analysis were performed. The primary end-point was liver-related death and/or liver transplantation.
Results: A total of 985 ursodeoxycholic acid (UDCA)-treated PBC patients were enrolled with a median follow-up duration of 5.3 years (range 1.0–20.9 years). Among them, 258 (26.2%) had GD, including 157 (22.9%) of non-cirrhotic and 101 (33.8%) of cirrhotic patients. Compared with PBC without GD, those with GD were older, more often had type 2 diabetes mellitus, and had a more severe liver disease at baseline. After PSM (1:2), 229 PBC patients with GD were matched with 458 PBC patients without GD based on age, sex, cirrhosis, and total bilirubin level. The transplant-free survival and incidence of hepatic events were similar between the two groups. Furthermore, multivariate Cox regression analysis showed that concomitant GD was not independently associated with a worse prognosis for PBC patients.
Conclusion: Concomitant GD was common but was not associated with long-term outcomes in patients with UDCA-treated PBC.
Objectives: To systematically evaluate the patient and procedural risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among patients receiving rectal indomethacin.
Methods: Data from a randomized controlled trial (RCT) of high-risk patients undergoing ERCP who received rectal indomethacin with or without topical epinephrine was evaluated. PEP was defined based on the consensus criteria. Pancreatic stenting was excluded to avoid confounding results with the role of epinephrine spray. Multivariable logistic regression analysis was used to identify patient and procedural risk factors for PEP.
Results: Among 960 patients enrolled in the RCT, the PEP incidence was 6.4%. An increased risk of PEP was seen with age <50 years and female gender (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.35–4.26), malignant biliary stricture(s) (OR 3.51, 95% CI 1.52–8.10), >2 guidewire passes into the pancreatic duct (PD) (OR 2.84, 95% CI 1.43–5.64), and pancreatic brush cytology (OR 6.37, 95% CI 1.10–36.90), whereas a decreased risk of PEP was seen with contrast- over guidewire-assisted cannulation (OR 0.14, 95% CI 0.02–0.99) and the use of lactated Ringer’s (LR) over other fluid types (OR 0.52, 95% CI 0.27–0.98). There was a significant trend between the number of guidewire passes into the PD and PEP risk (P = 0.002).
Conclusions: More than two guidewire passes into the PD and pancreatic brush cytology increased while the use of LR decreased the risk of PEP among high-risk patients receiving rectal indomethacin. Pancreatic stent placement and/or LR should be considered in patients with >2 guidewire passes into the PD.