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.