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. @*Conclusions@#Twenty-four weeks of L-carnitine supplementation was safe but ineffective in improving quality of life and liver function.

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 adverseeffects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). @*Conclusions@#Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.

Effects of DA-9701, a Novel Prokinetic Agent, on Phosphorylated Extracellular Signal-Regulated Kinase Expression in the Dorsal Root Ganglion and Spinal Cord Induced by Colorectal Distension in Rats

BACKGROUND/AIMS: DA-9701, a standardized extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that exhibits an analgesic effect on the abdomen. We investigated whether DA-9701 affects visceral pain induced by colorectal distension (CRD) in rats. METHODS: A total of 21 rats were divided into three groups: group A (no CRD+no drug), group B (CRD+no drug), and group C (CRD+DA-9701). Expression of pain-related factors, substance P (SP), c-fos, and phosphorylated extracellular signal-regulated kinase (p-ERK) in the dorsal root ganglion (DRG) and spinal cord was determined by immunohistochemical staining and Western blotting. RESULTS: The proportions of neurons in the DRG and spinal cord expressing SP, c-fos, and p-ERK were higher in group B than in group A. In the group C, the proportion of neurons in the DRG and spinal cord expressing p-ERK was lower than that in group B. Western blot results for p-ERK in the spinal cord indicated a higher level of expression in group B than in group A and a lower level of expression in group C than in group B. CONCLUSIONS: DA-9701 may decrease visceral pain via the downregulation of p-ERK in the DRG and spinal cord.

Nonalcoholic Fatty Liver Disease: Lifestyle Modification / 대한내과학회지

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. The prevalence of NAFLD is growing gradually worldwide with increases in obesity, sedentary lifestyles, and an unbalanced diet. NAFLD ranges from simple steatosis without inflammation to steatohepatitis that can progress to cirrhosis. There is no single effective treatment that has widespread effects in NAFLD. The cornerstone of treatment is lifestyle modification, including weight reduction, diet, and physical activity. An approximately 7-10% weight reduction via diet or physical activity can improve the liver histopathology. Risk factors for NAFLD include a high-calorie diet, high-lipid diet, high-carbohydrate diet, saturated fatty acids, trans fatty acids, cholesterol, high fructose intake, and low-choline diet. Factors that protect against NAFLD include a low-calorie diet, low-carbohydrate diet, low-lipid diet, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), dietary fiber, coffee, green tea, and light alcohol consumption. Physical activity also helps to manage NAFLD with or without weight reduction. Recent reports found that resistance training is as effective as aerobic training. Lifestyle modification has very low compliance. To maintain a treatment program, a multidisciplinary team approach is required that includes physicians, dietitians, physical trainers, and psychologists.

Augmenting Effect of DA-9601 on Ghrelin in an Acute Gastric Injury Model

BACKGROUND/AIMS: Acute gastric injury by alcohol or indomethacin has been reported to be prevented by DA-9601, an extract of the herb Artemisia asiatica. Ghrelin, an endogenously produced gastrointestinal peptide hormone, has also been demonstrated to play a role in gastric mucosal defense. The aim of this study was to investigate the effects of DA-9601 on ghrelin in an acute gastric injury model induced by alcohol or indomethacin. METHODS: A total of 140 Sprague-Dawley rats were divided into two groups, a placebo group and a DA-9601-pretreated group. Thirty minutes later, half of the rats in each group received ethanol injury and the other half received indomethacin injury. Levels of serum ghrelin and gastric mucosal ghrelin mRNA were measured by ELISA and RT-PCR, respectively. RESULTS: Immediately after ethanol administration, ghrelin increased in both groups pretreated with DA-9601 and placebo. However, the increase occurred more rapidly and was higher in the DA-9601-pretreated rats than in the controls that did not receive DA-9601-pretreatment. Similarly, from 30 minutes to 2 hours after indomethacin administration, the DA-9601-pretreated rats showed a significant increase in serum and gastric mucosal ghrelin concentrations, whereas placebo-pretreated rats showed only a mild increase. CONCLUSIONS: DA-9601 potentiates the endogenous production and secretion of ghrelin in acute gastric injury models induced by ethanol or indomethacin.

Nutrition and Chronic Liver Disease / 한양의대학술지

Malnutrition is very commonly seen in end stage liver disease. More than 65% of patients with chronic liver disease and more than 90% of patients with end-stage liver disease suffer malnutrition. Multiple reports have clearly shown that malnourishment is a relevant factor in complications and mortality due to chronic liver disease. It is essential that all patients with chronic liver disease have a full assessment of nutritional status at presentation. Supplementary enteral nutrition is indicated when chronic liver disease patients are unable to meet their nutritional requirements in their usual daily diet. Non-alcoholic fatty liver disease (NAFLD) is another type of chronic liver condition characterized by overnutrition and ectopic hepatic fat accumulation and/or hepatic inflammation. Patients diagnosed with obesity, insulin resistance, and/or dyslipidemia are at the greatest risk for developing or having NAFLD. A recent hypothesis is that NAFLD is one manifestation of metabolic syndrome or insulin resistance. Unfortunately, there is no consensus as to what dietary approach is most beneficial for preventing the progression of NAFLD. It seems likely that there will not be any single correct dietary plan for all NAFLD patients, so that diet and life-style modifications will best be tailored for the individual needs of the patient.