Vitamin E for people with non-alcoholic fatty liver disease.

RATIONALE: Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is the most common liver disease worldwide, affecting an estimated 3 in 10 people. The available treatment is far from optimal. Diet and lifestyle changes to promote weight loss and weight loss maintenance are the basic management of NAFLD, but these are difficult to achieve and maintain. Vitamin E has shown beneficial effects on oxidative stress, which plays a major role in the pathogenesis of NAFLD. However, there is uncertainty about the effects of vitamin E for people with NAFLD. OBJECTIVES: To evaluate the beneficial and harmful effects of vitamin E alone, or vitamin E in combination with other vitamins or minerals, versus placebo or no intervention in people with NAFLD. SEARCH METHODS: We used recommended Cochrane search methods. The latest search was performed on 2 February 2024. ELIGIBILITY CRITERIA: We included randomised clinical trials that compared vitamin E alone, or in combination with other vitamins or minerals, at any dose, duration, and route of administration, versus placebo or no intervention, in people with NAFLD of any age, sex, or ethnic origin. We included participants with imaging techniques or histology-proven NAFLD and minimal alcohol intake, and participants with steatohepatitis who had liver biopsies. OUTCOMES: Our critical outcomes were all-cause mortality, liver-related mortality, and serious adverse events. Our important outcomes were liver-related morbidity, health-related quality of life, non-serious adverse events, biochemical response, and imaging assessment of the degree of fatty liver. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias for each of the predefined outcomes. SYNTHESIS METHODS: We used standard Cochrane methods. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES: We included 16 randomised clinical trials involving 1066 paediatric and adult participants with NAFLD. Experimental groups received vitamin E alone (14 trials) or vitamin E in combination with vitamin C (2 trials). Control groups received placebo in 13 trials and no intervention in three trials. Daily dosages of oral vitamin E ranged from 298 international units (IU) to 1000 IU. Co-interventions were lifestyle and low-calorie diet interventions in 13 trials, ursodeoxycholic acid in one trial, unchanged diet and physical activity in one trial, and baseline treatments for type 2 diabetes in one trial. Nine trials had more than two intervention groups, but we used only the groups in which vitamin E alone or vitamin E in combination with vitamin C were compared with placebo or no intervention. In total, 7.9% (84/1066) of participants dropped out. Follow-up ranged from 2 months to 24 months. SYNTHESIS OF RESULTS: Vitamin E versus placebo or no intervention The effects of vitamin E versus placebo or no intervention on all-cause mortality (risk ratio (RR) 3.45, 95% confidence interval (CI) 0.57 to 20.86; 3 trials, 351 participants; very low certainty evidence) and serious adverse events (RR 1.91, 95% CI 0.30 to 12.01; 2 trials, 283 participants; very low certainty evidence) are very uncertain. There were no data on liver-related mortality or liver-related morbidity. The effects of vitamin E versus placebo or no intervention on physical health-related quality of life (mean difference (MD) 0.74, 95% CI -0.52 to 2.01; 2 trials, 251 participants; higher scores indicate better quality of life; very low certainty evidence); psychosocial health-related quality of life (MD -0.57, 95% CI -4.11 to 2.97; 2 trials, 251 participants; higher scores indicate better quality of life; very low certainty evidence); and non-serious adverse events (RR 0.86, 95% CI 0.64 to 1.17; 2 trials, 283 participants; very low certainty evidence) are also very uncertain. There were no data on proportion of participants without a decrease in liver enzymes. Vitamin E likely slightly reduces serum alanine transaminase (ALT) (MD -9.29, 95% CI -13.69 to -4.89; 11 trials, 708 participants; moderate certainty evidence) and aspartate aminotransferase (AST) (MD -4.90, 95% CI -7.24 to -2.57; 11 trials, 695 participants; moderate certainty evidence) levels compared with placebo or no intervention. Vitamin E may slightly reduce serum alkaline phosphatase (ALP) levels (MD -5.21, 95% CI -9.88 to -0.54; 5 trials, 416 participants; very low certainty evidence), but the evidence is very uncertain. Vitamin E plus vitamin C versus placebo There were no data on all-cause mortality, liver-related mortality, serious adverse events, liver-related morbidity, health-related quality of life, and non-serious adverse events. The effects of vitamin E plus vitamin C on reducing serum ALT (MD -0.50, 95% CI -4.58 to 3.58; 2 trials, 133 participants; very low certainty evidence), AST (MD 0.09, 95% CI -3.39 to 3.57; 1 trial, 88 participants; very low certainty evidence), and gamma-glutamyl transferase (GGT) levels (MD 1.58, 95% CI -3.22 to 6.38; 1 trial, 88 participants; very low certainty evidence) are very uncertain. We identified three ongoing trials, and six trials are awaiting classification. AUTHORS' CONCLUSIONS: Given the very low certainty evidence, we do not know if long-term treatment (18 months to 24 months) with vitamin E administered alone affects all-cause mortality, serious adverse events, quality of life, or non-serious adverse events in people with NAFLD when compared with placebo or no intervention. We found no data on liver-related mortality, liver-related morbidity, or proportion of participants without a decrease in liver enzymes. Vitamin E likely reduces ALT and AST slightly when compared with placebo, but whether this has any impact on the clinical course in people with NAFLD is unknown. The trials on vitamin E plus vitamin C did not report on all-cause mortality, liver-related mortality, serious adverse events, liver-related morbidity, health-related quality of life, or non-serious adverse events. Given the very low certainty evidence, we do not know the effects of vitamin E plus vitamin C on liver enzymes in people with NAFLD when compared with placebo. FUNDING: Three trials disclosed no external funding. Five trials were industry funded. Five trials were funded by organisations with no vested interests. Three trials did not provide any information on clinical trial support or sponsorship. REGISTRATION: Protocol: doi.org/10.1002/14651858.CD015033.

Increased ARPP-19 expression is associated with hepatocellular carcinoma.

The cAMP-regulated phosphoprotein 19 (ARPP-19) plays a key role in cell mitotic G2/M transition. Expression of ARPP-19 was increased in human hepatocellular carcinoma (HCC) compared to adjacent non-tumorous liver tissues in 36 paired liver samples, and the level of ARPP-19 in HCC tissues was positively correlated with the tumor size. To determine the interrelationship between ARPP-19 expression and HCC, we silenced ARPP-19 expression in the human hepatocarcinoma HepG2 and SMMC-7721 cells using lentivirus encoding ARPP-19 siRNA. HepG2 and SMMC-7721 cells with ARPP-19 knockdown displayed lowered cell growth rate, retarded colony formation and increased arrest at the G2/M phase transition. Silencing ARPP-19 in HCC cells resulted in decreased protein levels of phospho-(Ser) CDKs substrates and increased levels of inactivated cyclin division cycle 2 (Cdc2). Therefore, ARPP-19 may play a role in HCC pathogenesis through regulating cell proliferation.

Qingchang decoction retention enema may induce clinical and mucosal remission in left-sided ulcerative colitis: A case report.

BACKGROUND: Ulcerative colitis (UC) is a chronic autoimmune disease characterized by relapsing-remitting abdominal pain, diarrhea, mucopurulent discharge and rectal bleeding. To date, the etiology of the disease remains unknown; therefore, medical therapy is not yet available. Left-sided UC is mainly treated with oral and topical mesalazine. However, due to its modest clinical effect, endoscopic mucosal remission is not achieved in all patients. CASE SUMMARY: A 44-year-old man presented to Longhua Hospital with a history of left-sided UC for more than 6 years and slight bloody diarrhea over time. Endoscopy suggested hyperemia, edema, and erosive mucosa involving the rectum and sigmoid colon. The Traditional Chinese medicine Qingchang decoction (QCD) enema treatment was initiated once a day combined with a previous standard dose of mesalazine for 8 wk, and rectal bleeding ceased after 4 wk of treatment. Another QCD enema treatment was provided after symptom relapse due to drug withdrawal for nearly 6 mo. At the 2-mo follow-up, the colonoscopy results indicated mucosal healing with no erosion or ulcers. CONCLUSION: The Chinese formula QCD retention enema represents a potential treatment for left-sided UC with predominant rectal bleeding to achieve clinical and mucosal remission.

Chinese medicine formula lingguizhugan decoction improves Beta-oxidation and metabolism of Fatty Acid in high-fat-diet-induced rat model of Fatty liver disease.

Lingguizhugan decoction (LGZG), a classic traditional Chinese medicine (TCM) formula, has been used to treat obesity and hyperlipidemia in recent years, but the related mechanisms underlying the regulation of lipid metabolism by LGZG are not clear yet. Here, we reported the effectiveness and possible mechanisms of LGZG on rats with fatty liver disease induced by high-fat diet (HFD). Our results demonstrated that LGZG significantly attenuated HFD-induced fatty liver disease, as measured by body weight, liver index, epididymal fat pad-body weight ratio (EFP/BW), liver injury, and hepatic triglycerides (TG) probably through increasing serum thyroid hormone levels, improving beta-oxidation (via modulation of TR ß 1 and CPT1A expression), metabolism and transport (through modulation of SREBP-1c, ACSL and ApoB100 expression) of fatty acid. In addition, we discovered the herbal combination with the properties of warming yang to relieve water retention in the formula and proposed the biological basis of LGZG conventional effect via further study on disassembled formula. This study, for the first time, revealed the mechanisms through which LGZG regulates lipid metabolism. Furthermore, our study suggested that it might be feasible to understand the scientific implications of TCM from the perspective of classic formulas' conventional efficacy.