Different Associations of Coffee Consumption with the Risk of Incident Metabolic Dysfunction-Associated Steatotic Liver Disease and Advanced Liver Fibrosis.

Although coffee has a potential hepatoprotective effect, evidence of the relationship between coffee consumption and metabolic dysfunction-associated steatotic liver disease (MASLD) remains conflicting. There is limited evidence regarding the most appropriate coffee intake to prevent advanced liver fibrosis (ALF) in patients with MASLD. We investigated the effect of coffee consumption on MASLD and ALF among 5266 participants without MASLD and 1326 with MASLD but without ALF. Participants were grouped by coffee intake: non-consumers, >0 and <1 cups/day, ≥1 and <2 cups/day, and ≥2 cups/day. Over a median follow-up of 11.6 years for MASLD and 15.7 years for ALF, coffee consumption did not significantly affect the incidence of MASLD, with 2298 new cases observed. However, a notable inverse association was found with ALF risk in patients with MASLD among those consuming coffee ≥2 cups/day (adjusted HR 0.57, 95% CI: 0.37-0.90, p = 0.014), especially among those consuming coffee ≥2 and <3 cups/day (adjusted HR 0.51, 95% CI: 0.30-0.89, p = 0.018). This suggests a potential hepatoprotective effect of coffee, especially in preventing the progression of liver fibrosis in patients with MASLD. These findings propose that coffee consumption could be a simple and effective approach to mitigate the risk of ALF in individuals with MASLD.

Effect of L-carnitine on quality of life in covert hepatic encephalopathy: a randomized, double-blind, placebo-controlled study.

BACKGROUND/AIMS: L-carnitine is potentially beneficial in patients with hepatic encephalopathy (HE). We aimed to evaluate the impact of L-carnitine on the quality of life and liver function in patients with liver cirrhosis and covert HE. METHODS: We conducted an investigator-initiated, prospective, multi-center, double- blind, randomized phase III trial in patients with covert HE. A total of 150 patients were randomized 1:1 to L-carnitine (2 g/day) or placebo for 24 weeks. Changes in quality of life and liver function were assessed at 6 months. The model for end-stage liver disease (MELD), the 36-Item Short Form Survey (SF-36), the psychometric hepatic encephalopathy score (PHES), and the Stroop Test were evaluated in all patients. RESULTS: The total SF-36 score significantly improved in the L-carnitine group after 24 weeks (difference: median, 2; interquartile range, 0 to 11; p < 0.001); however, these values were comparable between the two groups. Furthermore, there was a significant ordinal improvement in PHES scores among patients with minimal HE who were in the L-carnitine group (p = 0.007). Changes in the total carnitine level also positively correlated with improvements in the Stroop test in the L-carnitine group (color test, r = 0.3; word test, r = 0.4; inhibition test, r = 0.5; inhibition/switching test, r = 0.3; all p < 0.05). Nevertheless, the MELD scores at week 24 did not differ between the groups. CONCLUSION: Twenty-four weeks of L-carnitine supplementation was safe but ineffective in improving quality of life and liver function.

Twelve-month post-treatment parameters are superior in predicting hepatocellular carcinoma in patients with chronic hepatitis B.

BACKGROUND & AIMS: There are currently several prediction models for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) receiving oral antiviral therapy. However, most models are based on pre-treatment clinical parameters. The current study aimed to develop a novel and practical prediction model for HCC by using both pre- and post-treatment parameters in this population. METHODS: We included two treatment-naïve CHB cohorts who were initiated on oral antiviral therapies: the derivation cohort (n = 1480, Korea prospective SAINT cohort) and the validation cohort (n = 426, the US retrospective Stanford Bay cohort). We employed logistic regression, decision tree, lasso regression, support vector machine and random forest algorithms to develop the HCC prediction model and selected the most optimal method. RESULTS: We evaluated both pre-treatment and the 12-month clinical parameters on-treatment and found the 12-month on-treatment values to have superior HCC prediction performance. The lasso logistic regression algorithm using the presence of cirrhosis at baseline and alpha-foetoprotein and platelet at 12 months showed the best performance (AUROC = 0.843 in the derivation cohort. The model performed well in the external validation cohort (AUROC = 0.844) and better than other existing prediction models including the APA, PAGE-B and GAG models (AUROC = 0.769 to 0.818). CONCLUSIONS: We provided a simple-to-use HCC prediction model based on presence of cirrhosis at baseline and two objective laboratory markers (AFP and platelets) measured 12 months after antiviral initiation. The model is highly accurate with excellent validation in an external cohort from a different country (AUROC 0.844) (Clinical trial number: KCT0003487).

Effects of vitamin D supplements in patients with chronic hepatitis C: a randomized, multi-center, open label study.

BACKGROUND/AIMS: We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC). METHODS: Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). RESULTS: One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverse effects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). CONCLUSION: Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.

Fermented Soymilk Alleviates Lipid Accumulation by Inhibition of SREBP-1 and Activation of NRF-2 in the Hepatocellular Steatosis Model.

Ingredients of soy and fermented soy products have been widely utilized as food supplements for health-enhancing properties. The aim of this study was to evaluate the effects of fermented soymilk (FSM) and soymilk (SM) on free fatty acid-induced lipogenesis in the hepatocellular steatosis model. HepG2 cells were incubated with palmitic acid (PA) for 24 h to induce lipogenesis and accumulation of intracellular lipid contents. The PA-treated cells were co-incubated with FSM, SM, genistein, and estrogen, respectively. Lipid accumulation in the PA-treated HpG2 cells was significantly decreased by co-incubation with FSM. Treatment of HepG2 cells with PA combined with genistein or estrogen significantly increased the expression of SREBP-1. However, FSM co-incubation significantly attenuated SREBP-1 expression in the PA-treated HepG2 cells; in addition, expression of NRF-2 and phosphorylation of ERK were significantly increased in the PA and FSM co-incubated cells. PA-induced ROS production was significantly reduced by FSM and SM. Our results suggested that the bioactive components of FSM could protect hepatocytes against the lipid accumulation and ROS production induced by free fatty acids. These effects may be mediated by the inhibition of SREBP-1 and the activation of NRF-2 via the ERK pathway in HepG2 cells.

Associations between intakes of individual nutrients or whole food groups and non-alcoholic fatty liver disease among Korean adults.

BACKGROUND AND AIM: Dietary factors are closely associated with the risk of non-alcoholic fatty liver disease (NAFLD). Asian and Western diets differ in energy-nutrient composition, fatty-acid composition, and main nutritional sources; therefore, the implications would be limited if the Western-oriented study results were applied to Asian patients. We aimed to identify the nutrient and food group intakes of a typical Asian diet and assess their effects on NAFLD risk. METHODS: In total, 348 subjects were recruited from 5 participating hospitals. Information on sociodemographic characteristics and health-related behaviors were obtained through face-to-face interviews. NAFLD was diagnosed by ultrasound. Dietary intakes were assessed with a 24-h recall applying a multiple-pass approach and 4-day food records that included 1 or 2 weekend days. RESULTS: There were no significant differences in health-related behaviors between the cases and controls except for smoking behavior. The cases had elevated triacylglycerol, fasting glucose, and low-density lipoprotein cholesterol levels compared with the controls. In men, after adjusting for variables, low intakes of vitamin C (odds ratio [OR], 4.23), vitamin K (OR, 3.93), folate (OR, 3.37), omega-3 fatty acids (OR, 2.16), and nuts and seeds (OR, 3.66) were associated with a significantly higher risk for developing NAFLD. In women, vitamin K (OR, 2.54) and vegetable (OR, 4.11) intakes showed a significant beneficial effect for lowering NAFLD risk. CONCLUSIONS: Adequate intakes of vitamin C, vitamin K, folate, omega-3 fatty acids, nuts and seeds, and vegetables may help in preventing NAFLD in Korean adults.