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.

Effect of Nutrition Education in NAFLD Patients Undergoing Simultaneous Hyperlipidemia Pharmacotherapy: A Randomized Controlled Trial.

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) have a high prevalence of combined hyperlipidemia. The importance of nutritional education is well-known in NAFLD, but the impact of medical nutrition therapy (MNT) is unclear in patients with NAFLD with hyperlipidemia. The purpose of this study is to investigate the effect of MNT on the improvement of steatohepatitis in patients with NAFLD taking antihyperlipidemic medications. METHODS: Nondiabetic patients with dyslipidemia were prospectively randomized (1:1) either to the MNT group or the control group with standard advice for 48 weeks with simultaneous statin/ezetimibe combination pharmacotherapy at three tertiary centers in Korea. RESULTS: Sixty-six patients were enrolled. Among them, 18 patients dropped out and, overall, 48 patients (MNT group 27, control group 21) were prospectively analyzed in the study. The serum ALT level at 48 weeks between the two groups was not significantly different (66.6 ± 37.7 IU/L vs. 57.4 ± 36.7 IU/L, p = 0.40). Serum liver enzymes, controlled attenuation parameter and fibrosis-4 index were significantly improved within the MNT group after 48 weeks compared to baseline. There was no significant difference between the two groups other than the NAFLD fibrosis score (p = 0.017). CONCLUSIONS: Although there were no significant differences between the two groups in terms of steatosis, metabolic and fibrosis surrogate indicators after 48 weeks, MNT groups showed significant improvement within patient analysis over time. Future studies with a larger number of subjects and a longer study period regarding the effect of MNT are warranted.

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.

Clinical Features of Drug-induced Liver Injury According to Etiology.

Drug-induced liver injury (DILI) is an increasingly common cause of acute hepatitis. We examined clinical features and types of liver injury of 65 affected patients who underwent liver biopsy according DILI etiology. The major causes of DILI were the use of herbal medications (43.2%), prescribed medications (21.6%), and traditional therapeutic preparations and dietary supplements (35%). DILI from herbal medications, traditional therapeutic preparations, and dietary supplements was associated with higher elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than was DILI from prescription medications. The types of liver injury based on the R ratio were hepatocellular (67.7%), mixed (10.8%), and cholestatic (21.5%). Herbal medications and traditional therapeutic preparations were more commonly associated with hepatocellular liver injury than were prescription medications (P = 0.002). Herbal medications and traditional therapeutic preparations induce more hepatocellular DILI and increased elevations in AST and ALT than prescribed medications.

Practical effect of sorafenib monotherapy on advanced hepatocellular carcinoma and portal vein tumor thrombosis.

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.

The clinical features of drug-induced liver injury observed through liver biopsy: focus on relevancy to autoimmune hepatitis.

BACKGROUND/AIMS: Accurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH. METHODS: The clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2±12.8 years (mean±SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively. RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase levels were 662.2±574.8 U/L, 905.4±794.9 U/L, 12.9±10.8 mg/dL, 195.8±123.3 U/L, and 255.3±280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1±519.1 vs. 1043.3±600.5 U/L), globulin levels (2.7±0.4 vs. 3.3±0.5 g/dL), and prothrombin time (12.9±2.4 vs. 15.2±3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7±0.9 in the DILI group and 6.5±0.9 in the AIH group (P<0.001). CONCLUSIONS: Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.