Long-Term Carbohydrate-Containing Late-Evening Snack Significantly Improves the Ratio of Branched Chain Amino Acids to Aromatic Amino Acids in Adults with Liver Cirrhosis due to Hepatitis B.

BACKGROUND: The liver is the primary organ for amino acid metabolism, and metabolic disorder of amino acids is common in liver disease. However, the characteristics of plasma amino acid profiles in patients with HBV-related cirrhosis and the impacts of late-evening snack (LES) on cirrhosis are unclear. OBJECTIVES: To investigate the characteristics of plasma amino acid profiles in patients with HBV-related chronic hepatitis, cirrhosis, and the effects of late-evening snacks on plasma amino acid profiles. METHODS: 86 patients with HBV-related cirrhosis and eighty patients with chronic hepatitis B were included in this study. The plasma amino acid profiles were measured by the amino acid analyzer. Patients were randomly divided into two groups, of which the liver cirrhosis group was to receive daily LES (n = 43) or non-LES (n = 43) for 6 months. Plasma amino acid profiles and biochemical parameters were measured in both groups at baseline and after 1, 3, and 6 months. RESULTS: Compared to healthy controls, the plasma concentration in the liver cirrhosis group of threonine, serine, glycine, glutamine, cysteine, tyrosine, phenylalanine, arginine, and methionine increased significantly (P < 0.05), while the ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA) decreased significantly (P < 0.05). A carbohydrate-predominant LES treatment resulted in a significant increase in BCAA/AAA and decrease in the level of ammonia and glutamine compared with baseline after 6 months of supplementation (P < 0.05). Patients with Child-Pugh B and C are more responsive to changes in amino acid profiles than those with Child-Pugh A. CONCLUSIONS: The application of an LES carbohydrate module for six months in liver cirrhosis patients was associated with increased BCAA/AAA and decreased level of ammonia. Patients with Child-Pugh B and C grades were the most beneficial population.

Usefulness of nutritional therapy recommended in the Japanese Society of Gastroenterology/Japan Society of Hepatology evidence-based clinical practice guidelines for liver cirrhosis 2020.

BACKGROUND: The JSGE/JSH guidelines for the management of patients with liver cirrhosis revised in 2020 recommends new strategies for nutritional assessment and intervention, although their usefulness in daily clinical practice is unclear. METHODS: A total of 769 patients with cirrhosis were classified into low-, intermediate-, and high-risk groups according to hypoalbuminemia and sarcopenia, the criteria established for initiating the nutritional therapy algorithm in the guidelines. The association between these groups and mortality was analyzed using a Cox proportional hazards model. The effect of branched-chain amino acids (BCAAs) on survival was evaluated using propensity score matching. RESULTS: Of the enrolled patients, 495 (64%) were men with a median age of 73 years, 428 (56%) had hypoalbuminemia, 156 (20%) had sarcopenia, and 288 (37%) were receiving BCAAs. During a median follow-up period of 1.5 years, 276 (36%) patients died. The intermediate-risk [hazard ratio (HR), 1.60; 95% confidence interval (CI), 1.18-2.18] and high-risk (HR, 2.85; 95% CI, 1.92-4.23) groups independently predicted mortality. Among the propensity score-matched 250 patients, 49 (39%) BCAA-treated and 58 (46%) untreated died. Overall survival was higher in BCAA-treated patients than in untreated patients (HR, 0.67; 95% CI, 0.46-0.98). The survival benefit of BCAAs was pronounced in the intermediate-risk (HR, 0.50; 95% CI, 0.31-0.80) and high-risk (HR, 0.38; 95% CI, 0.16-0.91) groups. CONCLUSIONS: The 2020 JSGE/JSH guidelines for liver cirrhosis are useful in stratifying the mortality risk and providing effective nutritional interventions for malnourished patients with cirrhosis.

Coffee and nonalcoholic fatty liver disease: A review.

Nonalcoholic fatty liver disease (NAFLD) is widely prevalent globally and has no effective treatment. Coffee is one of the most popular beverages in the world and can therefore have a significant impact on public health on account of its health-promoting properties. Evidence from observational, clinical, and animal studies suggests that coffee may play an important role in human health. This article summarizes the effects of coffee on liver health, especially on nonalcoholic fatty liver disease (NAFLD) and its progression: liver fibrosis, cirrhosis and hepatocellular carcinoma. In addition, this article describes the pathogenesis, prevalence, diagnosis, and nutrition guidelines relating to NAFLD. Possible mechanisms responsible for the effects of coffee on the liver are also suggested.

Japan's Practical Guidelines for Zinc Deficiency with a Particular Focus on Taste Disorders, Inflammatory Bowel Disease, and Liver Cirrhosis.

Zinc deficiency is common in Japan, yet awareness on this disorder is lacking. The Japanese Society of Clinical Nutrition recently issued the Japan's Practical Guideline for Zinc Deficiency 2018 setting forth criteria for diagnosing zinc deficiency, i.e., (a) one or more symptoms of zinc deficiency or low serum alkaline phosphatase, (b) ruling out other diseases, (c) low serum zinc, and (d) alleviation of symptoms upon zinc administration. Serum zinc <60 µg/dL and 60-80 µg/dL indicate zinc deficiency and marginal deficiency, respectively. Zinc deficiency symptoms vary and include dermatitis and taste disorders among others. Zinc administration improves taste in 50-82% of patients suffering from taste disorders (a common symptom of zinc deficiency). Effects of zinc administration do not appear immediately, and therapy should be continued for at least three months. Zinc deficiency often accompanies various diseases and conditions. Here, we focus on inflammatory bowel diseases and liver cirrhosis. As zinc deficiency enhances intestinal inflammation via macrophage activation, we discuss the pathological mechanism for inflammation and zinc deficiency in the context of IBD. Zinc deficiency can also lead to a nitrogen metabolic disorder in patients with liver cirrhosis. Zinc supplementation can improve not only the ammonia metabolism, but also the protein metabolism. We also discuss directions for future studies of zinc deficiency.

Review article: malnutrition/sarcopenia and frailty in patients with cirrhosis.

BACKGROUND: Malnutrition/sarcopenia and frailty are common in patients with cirrhosis and are associated with poor outcomes. AIM: To provide an overview of data on the importance, assessment and management of malnutrition/sarcopenia and frailty in cirrhosis. METHODS: A literature search was conducted in PubMed and other sources, using the search terms "sarcopenia," "muscle," "malnutrition," "cirrhosis," "liver" and "frailty" from inception to April 2019, to identify the relevant studies and international guidelines. RESULTS: The prevalence of malnutrition/sarcopenia in cirrhosis is 23%-60%. Frailty generally overlaps with malnutrition/sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition/sarcopenia in cirrhosis is complex/multifactorial and not just reduction in protein/calorie intake. Hyperammonemia appears to be the main driver of sarcopenia in cirrhosis through several molecular signalling pathways. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, they, and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. CONCLUSIONS: Malnutrition/sarcopenia and frailty are unique, inter-related and multi-dimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.

Omega-3 polyunsaturated fatty acids prevent progression of liver fibrosis and promote liver regeneration after partial hepatectomy in cirrhotic rats.

OBJECTIVE: To assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on liver regeneration of rats with liver cirrhosis after hepatectomy and antifibrosis. MATERIALS AND METHODS: Omega-3 polyunsaturated fatty acids were intravenously injected in n-3 PUFA group 3 days before the operation to 1 day after partial hepatectomy. 70% hepatectomy was performed in rats, which were subsequently divided into 4 groups, namely normal and hepatectomy group (PH); liver cirrhosis and hepatectomy group (LC+PH); liver cirrhosis, n-3 PUFA (1 mL/kg), and hepatectomy group (LC+n-3 PUFA+PH); liver cirrhosis, n-3 PUFA (2 mL/kg) and hepatectomy group (LC+n-3PUFA*+PH). Body/liver weight ratios, serum parameters, histopathological examination, immunostaining, inflammatory cytokine and quantification of mRNA expression were also investigated. RESULTS: Liver regeneration was significantly delayed compared with PH group 7 days after hepatectomy (PH) in LC+PH group. Besides, liver regeneration of LC+n-3 PUFA*+PH group increased significantly compared with LC+PH group 7 days after PH. In LC+PH group, liver cirrhotic was significantly higher compared with LC+n-3 PUFA+PH group 7 days after PH. In the meantime, liver cirrhosis of LC+n-3 PUFA*+PH group was significantly reduced compared with LC+n-3 PUFA+PH group 7 days after PH. Anti-inflammatory cytokine IL-10 was increased and pro-inflammatory cytokine IL-6 was decreased in LC+n-3 PUFA*+PH group compared with LC+PH group. N-3 PUFA also suppressed increments in mRNA expression for transforming growth factor-ß and up-regulated the expression of matrix metalloproteinase-9 and matrix metalloproteinase-1 in the liver. CONCLUSIONS: The mentioned results clearly show that n-3 PUFA reduces liver fibrosis and promotes liver regeneration, even under cirrhotic conditions. This could be a potentially useful treatment for liver cirrhosis.

Mastiha (Pistacia lentiscus) Improves Gut Microbiota Diversity, Hepatic Steatosis, and Disease Activity in a Biopsy-Confirmed Mouse Model of Advanced Non-Alcoholic Steatohepatitis and Fibrosis.

SCOPE: As a result of the obesity epidemic, the prevalence of non-alcoholic steatohepatitis (NASH) is increasing. No drug is approved for the treatment of NASH. In this study, the effect of a nutritional supplement, Mastiha or Chios mastic gum, on metabolic and histological parameters and on the gut microbiome in mice with NASH and fibrosis was investigated. METHODS AND RESULTS: Advanced NASH was induced by feeding C57BL/6J mice a diet rich in fat, sucrose, and cholesterol for 41 weeks. After randomization, animals received the NASH-inducing diet with or without 0.2% (w/w) Mastiha for a further 8 weeks. Disease activity was assessed by liver histology and determination of plasma transaminase activities. Fecal microbiota DNA extraction and 16S rRNA amplicon sequencing were used to determine the composition of the gut microbiome. Mastiha supplementation led to a significant reduction in circulating alanine aminotransferase (ALT) activity, improvement in hepatic steatosis and collagen content, and a reduction in NAFLD activity score. Furthermore, it resulted in a partial but significant recovery of gut microbiota diversity and changes in identity and abundance of specific taxa. CONCLUSION: This is the first study demonstrating an improvement in disease activity in mice with advanced NASH with fibrosis by a diet containing Mastiha.

[Nutrition in Liver Cirrhosis: Clinical Practice Recommendations]. / Ernährung bei Leberzirrhose: wichtige Tipps für Klinik und Praxis.

Liver disease and nutritional status affect each other mutually. Hepatic function is impaired by malnutrition and can be improved by nutrition therapy. Liver cirrhosis leads to prognostically relevant malnutrition in a stage dependent manner. Protein depletion and sarcopenia are its key features. Patients with liver cirrhosis should undergo systematic screening for risk of malnutrition and if positive sarcopenia should be assessed and a nutrition plan devised. In cirrhotic patients, spontaneous food intake frequently does not meet requirements and prolonged (> 12 h) periods of fasting must be avoided. In a stepwise fashion nutritional counseling, oral nutritional supplements, enteral tube feeding and parenteral nutrition as third-line-therapy should be used. In cirrhotic patients, nutrition therapy can improve morbidity and mortality by ensuring the adequate provision of energy, protein and micronutrients.

Mechanistic evaluation of AMPK/SIRT1/FXR signaling axis, inflammation, and redox status in thioacetamide-induced liver cirrhosis: The role of Cichorium intybus linn (chicory)-supplemented diet.

Liver cirrhosis is a scene profitable to the advance of hepatocellular carcinoma (HCC). The current work was engrossed to weigh the potential role of Cichorium intybus linn against thioacetamide (TAA)-induced liver cirrhosis and their probable underlying biochemical and molecular mechanisms. farnesoid-X-receptor (FXR) expression, proliferating cell nuclear antigen (PCNA) immunoreactivity, and activated AMP protein kinase (pAMPK), sirtuin-1 (SIRT1), and interleukin-6 (IL6) levels were estimated in hepatic tissue by real-time PCR, immunohistochemistry, and immunoassay, respectively. C. intybus linn supplementation caused a significant improvement in serum liver enzymes, albumin, bilirubin levels, tissues redox status and hepatic histological features in addition to decreased IL6 level, hydroxylproline content, and PCNA immunoreactivity. On contrary, increased pAMPK/SIRT1 levels and upregulated FXR gene expression were observed. C. intybus linn could feasibly protect against TAA-induced hepatic damage, fibrosis, and cirrhosis by relieving oxidative stress and by interruption of the inflammatory pathway via AMPK/SIRT1/FXR signaling. PRACTICAL APPLICATIONS: No specific therapies are available until now to target the underlying mechanisms for protection against liver diseases. Herbal protection is widely available and cheap with no side effect. Cichorium intybus linn, a natural supplement, is proved in this current work to have the potential of being hepatoprotectant, antioxidant, and anti-inflammatory agents, thus reducing the risk of hepatic cirrhosis.

Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis.

BACKGROUND: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. AIM: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT). METHODS: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine-mediated cancer pathways inclusive of MAPK and NF-kappa B were tested. RESULTS: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1-40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12-0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029). CONCLUSIONS: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells.

Effects of branched chain amino acid supplementation on patient care outcomes in adults and children with liver cirrhosis: A systematic review.

BACKGROUND & AIMS: Malnutrition is highly prevalent in chronic liver disease (CLD) due to alterations in nutrient utilization, malabsorption and poor intake. Low serum concentrations of branched chain amino acids (BCAA) in the presence of elevated aromatic acid concentrations is commonly observed in adult and children with liver cirrhosis and is associated with malnutrition and other adverse patient outcomes. The efficacy of BCAA supplementation has not been well established in adults and children with CLD. The purpose of this review was to critically evaluate the literature regarding the impact of BCAA supplementation related to changes in body composition, muscle strength, liver biomarkers, medical and hepatic complications (hepatic encephalopathy (HE), ascites, edema) and patient care outcomes (event free survival, health related quality of life, length of hospitalization). METHODS: A total of 40 articles retrieved from PubMed or Web of Science databases (1989-2017) were included. RESULTS: BCAA supplementation may be beneficial in improving muscle strength, ascites and edema with potential clinically significant improvements in HE in adult liver patients. In children, limited data have shown that BCAA supplementation may exert favourable effects on weight, fat mass, fat free mass and serum albumin level. CONCLUSIONS: Heterogeneity of study findings attributed to variability in BCAA dose (total, relative proportions), duration, disease severity and lack of uniformity in tools used for assessing patient outcomes limit overall conclusions. Longitudinal studies examining the efficacy of BCAA supplementation as a therapeutic treatment of malnutrition in chronic liver disease is warranted.

Dietary management and supplementation with branched-chain amino acids in cirrhosis of the liver. / Manejo dietético y suplementación con aminoácidos de cadena ramificada en cirrosis hepática.

One of the most important characteristics of malnutrition is the loss of muscle mass and the severe depletion of the protein reserve, secondarily affecting energy metabolism. That impacts nutritional status and the progression of disease-related complications. Nutritional treatment is one of the main factors in the comprehensive management of those patients. Achieving adequate energy intake that provides the macronutrients and micronutrients necessary to prevent or correct malnutrition is attempted through dietary measures. ESPEN, the European Society for Clinical Nutrition and Metabolism, recommends a caloric intake of 30-40kcal/kg/day, in which carbohydrates provide 45-60% of the daily energy intake and proteins supply 1.0-1.5g/kg/day. The remaining portion of the total energy expenditure should be covered by lipids. The administration of branched-chain amino acids has been shown to be beneficial not only in counteracting malnutrition, but also as a coadjuvant treatment in specific complications, thus playing a favorable role in outcome and quality of life. Therefore, branched-chain amino acids should be considered part of nutritional treatment in patients with advanced stages of cirrhosis of the liver, particularly in the presence of complications.

The Benefit of Supplemental Nutrition Education for Severely Malnourished Patients Awaiting Liver Transplant.

INTRODUCTION: Nutritional interventions improve patient outcomes and reduce mortality in patients with cirrhosis by reducing infection risk, ascites, length of stay in hospital and intensive care unit, and mortality. Follow-up phone calls have been found to be useful in improving patient adherence to therapy. PROBLEM: The purpose of this quality improvement project was to determine whether supplemental nutrition education would improve nutrition and outcomes among patients with cirrhosis who are undergoing a liver transplant evaluation. In addition, we sought to measure patient adherence with nutritional recommendations and whether patients perceived this additional education improved their nutrition status. METHODS: The Plan-Do-Study-Ask methodology was used. PROCESSES: Addressed 8 patients were enrolled to participate in the supplemental nutrition education, after which they received 3 follow-up phone calls. A retrospective review of data from 10 patients meeting project inclusion criteria were identified by the nutrition specialist and were used as a comparison group. Data were analyzed using descriptive statistics; comparing data from before and after implementation of the supplemental nutrition education was done. OUTCOMES: At the end of the 8-week project period, 4 (66.7%) patients reported weight loss since the time of enrollment (nutrition education class), and the median patient-generated subjective global assessment score increased by 4 points, rather than decreasing as expected. However, all patients reported they believed the phone calls improved their nutrition status. IMPLICATIONS: With a multidisciplinary approach, this additional patient education may improve patient care and outcomes.

Nutritional issues in patients with obesity and cirrhosis.

Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.

Omega-3 fatty acids and non-alcoholic fatty liver disease: Evidence of efficacy and mechanism of action.

For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised trials in both adults and children with NAFLD; and finally to discuss key 'known unknowns' that need to be considered, before planning future studies that are focussed on testing the effects of omega-3 fatty acid treatment in patients with NAFLD.

Rare cause of isolated severe coagulation failure in cirrhosis: traditional healing with fenugreek.

Patients with cirrhosis develop decompensation events during the natural history of the disease that encompass ascites, variceal bleeding, hepatic encephalopathy and jaundice. Coagulation failure, defined using the international normalised ratio, even though not a decompensation event, is important in patients with stratifying cirrhosis into those who require liver transplantation for long-term survival. Isolated coagulation failure in cirrhosis is rare and usually occurs with use of anticoagulants in the setting of vascular diseases. We reported the case of a patient with compensated cirrhosis in whom, isolated severe coagulation failure was found to be due to excessive use of fenugreek milk porridge as part of traditional healing. The coagulation failure was promptly reversed with avoidance of fenugreek and supplementation with vitamin K.

Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis induces marked metabolic disorders, protein-energy malnutrition, and sarcopenia. The objective of the study reported here was to investigate the effects of dietary branched-chain amino acids (BCAAs) on systemic glucose metabolism, skeletal muscle, and prognosis of patients with liver cirrhosis. METHODS: Japanese patients with liver cirrhosis (n = 21) were enrolled into a longitudinal study in which their diets were supplemented with BCAAs. We evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI) and intramuscular adipose tissue content (IMAC) using computed tomography. RESULTS: After 48 weeks of supplementation with BCAAs, there were no changes in glucose metabolism and skeletal muscle findings. In patients with ameliorated hypoalbuminemia, IMAC was significantly decreased and SAI was preserved concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels (P < 0.01 each). In patients without increased albumin levels, IMAC was significantly increased and the SAI was significantly decreased (P < 0.01 each). Liver-related event-free survival rates for 72 months were 63.6% in patients with decreased IMAC and 20.0% in patients with increased IMAC. CONCLUSIONS: Amelioration of hypoalbuminemia associated with BCAA supplementation correlated with decreased fat accumulation in skeletal muscle, maintenance of skeletal muscle mass, and improved glucose sensitivity, all factors which may contribute to improving the survival of patients with liver cirrhosis.

Effect of a high-protein, high-fiber diet plus supplementation with branched-chain amino acids on the nutritional status of patients with cirrhosis. / Efecto de una dieta rica en proteínas y alta en fibra más la suplementación con aminoácidos de cadena ramificada sobre el estado nutricional de pacientes con cirrosis.

INTRODUCTION AND OBJECTIVES: The potential benefits of branched-chain amino acids (BCAAs) in cirrhosis extend beyond just the improvement of nutritional status. Their effects include improvement of glucose tolerance, oxidative stress, and inflammatory markers, as has been shown in several studies. A dual nutritional approach of a high-protein, high-fiber diet plus BCAAs in cirrhosis could have additional benefits, compared with BCAAs alone. Such an approach has not been explored and therefore the aim of the present study was to evaluate the effect of a combination of a high-protein, high-fiber diet plus BCAA supplementation over a 6-month period of time on the nutritional status of patients with cirrhosis, as well as its safety and tolerability for those same patients. METHODS: An open, randomized clinical trial was conducted. Patients were randomized to one of two groups: the BCAAs+HPHF diet intervention group: a high-protein, high-fiber diet with 1.2g/kg protein and 30g of fiber plus supplementation with oral branched-chain amino acids 110g daily and the HPHF diet control group: a high-protein, high-fiber diet with 1.2g/kg protein and 30g of fiber. The differences between the treatment groups were compared using the unpaired T test and the differences at the end of treatment were compared using the paired T test. RESULTS: A total of 72 patients were included, 37 in the intervention group and 35 in the control group. At the end of the study period, ammonia and glucose levels showed no significant increase in either group, reflecting the safety of the BCAA supplement. Furthermore, muscle and fat mass were evaluated through triceps skinfold thickness and mid-arm muscle circumference measurements. There was an increase in muscle mass and a decrease in fat mass in the BCAA group, but not in the control group. After the intervention, there were no significant changes in the Psychometric Hepatic Encephalopathy Score or the Critical Flicker Frequency score results in either group, and no episodes of hepatic encephalopathy were observed during the treatment period. CONCLUSION: Supplementation with branched-chain amino acids plus a high-fiber, high-protein diet is a safe intervention in patients with cirrhosis. It helps increase muscle mass and does not raise the levels of ammonia or glucose, nor is it associated with the development of hepatic encephalopathy.

Effects of branched-chain amino acids (BCAAs) on the progression of advanced liver disease: A Korean nationwide, multicenter, retrospective, observational, cohort study.

Evidence of the potential benefits of long-term oral branched-chain amino acid (BCAA) supplementation in reducing the severity of liver disease is limited.Patients who were diagnosed with liver cirrhosis with a Child-Pugh (CP) score of 8-10 were included. The BCAA group consumed BCAAs daily for at least 6 months, and the control group consumed a diet without BCAA. We analyzed the improvements based on the model for end-stage liver disease (MELD) score, CP score, incidence of cirrhosis-related complications, and event-free survival over 2 years. Among the 867 recruited patients, 307 (166 in the BCAA group and 141 in the control group) were analyzed. The BCAA group was divided into 3 subgroups, whose patients consumed 4.15 g, 8.3 g, or 12.45 g of BCAAs daily for the analysis. There were significant differences in the CP score, albumin, and hepatic encephalopathy between the 2 groups at baseline. After matching the propensity scores, we analyzed patients in the BCAA-12.45 g group (12.45 g of BCAAs daily, n = 41) and matched control group (n = 41). The MELD score significantly improved in the BCCA-12.45 g group compared to the matched control group (P = .004). The changes in the serum bilirubin level (P = .014) and CP score (P = .033) over time also differed significantly between the 2 groups. The incidence rates of cirrhosis-related complications (P = .973) and development of hepatocellular carcinoma (2 cases each) did not differ significantly between the 2 groups.Long-term oral BCAA supplementation has beneficial effects in patients with advanced liver cirrhosis. A further large-scale prospective study is needed to delineate these beneficial effects.

Protective effects of coffee against oxidative stress induced by the tobacco carcinogen benzo[α]pyrene.

AIMS: Coffee consumption has been epidemiologically associated with a lower risk for liver cirrhosis and cancer. UDP-glucuronosyltransferases (UGT1A) catalyze the detoxification of reactive metabolites thereby acting as indirect antioxidants. Aim of the study was to examine UGT1A regulation in response to Benzo[α]pyrene (BaP) to elucidate the potentially protective effects of coffee on BaP-induced oxidative stress and toxicity. RESULTS: In cell culture (HepG2, KYSE70 cells) and in htgUGT1A-WT mice, UGT1A transcription was activated by BaP, while it was reduced or absent htgUGT1A-SNP (containing 10 commonly occurring UGT1A-SNPs) mice. siRNA-mediated knockdown identified aryl hydrocarbon receptor (AhR) and nuclear factor erythroid2-related factor-2 (Nrf2) as mediators of BaP-induced UGT1A upregulation. Exposure to coffee led to a reduction of BaP-induced production of reactive oxygen species in vitro and in htgUGT1A-WT and -SNP mice. After UGT1A silencing by UGT1A-specific siRNA in cell culture, the coffee-mediated reduction of ROS production was significantly impaired compared to UGT1A expressing cells. CONCLUSION: A common UGT1A haplotype, prevalent in 9% (homozygous) of the White population, significantly impairs the expression of UGT1A enzymes in response to the putative tobacco carcinogen BaP and is likely to represent a significant risk factor for reduced detoxification and increased genotoxicity. Coffee was demonstrated to inhibit BaP-induced production of oxidative stress by UGT1A activation, and is therefore an attractive candidate for chemoprotection in risk groups for HCC or other tumors.