The associations of alcoholic liver disease and nonalcoholic fatty liver disease with bone mineral density and the mediation of serum 25-Hydroxyvitamin D: A bidirectional and two-step Mendelian randomization.

BACKGROUND: Reduced bone mineral density (BMD) and osteoporosis are common in chronic liver diseases. However, the causal effect of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) on BMD remains uncertain. OBJECTIVES: This study uses a two-sample Mendelian randomization (MR) design to evaluate the genetically predicted effect of ALD and NAFLD on BMDs using summary data from publically available genome-wide association studies (GWASs). METHODS: The GWAS summary statistics of ALD (1416 cases and 213,592 controls) and NAFLD (894 cases and 217,898 controls) were obtained from the FinnGen consortium. BMDs of four sites (total body, n = 56,284; femoral neck, n = 32,735; lumbar spine, n = 28,498; forearm, n = 8143) were from the GEnetic Factors for OSteoporosis Consortium. Data for alcohol consumption (n = 112,117) and smoking (n = 33,299) and serum 25-Hydroxyvitamin D (25-OHD) level (n = 417,580) were from UK-biobank. We first performed univariate MR analysis with the Inverse Variance Weighted (IVW) method as the primary analysis to investigate the genetically predicted effect of ALD or NAFLD on BMD. Then, multivariate MR and mediation analysis were performed to identify whether the effect was mediated by alcohol consumption, smoking, or serum 25-OHD level. RESULTS: The MR results suggested a robust genetically predicted effect of ALD on reduced BMD in the femoral neck (FN-BMD) (IVW beta = -0.0288; 95% CI: -0.0488, -0.00871; P = 0.00494) but not the other three sites. Serum 25-OHD level exhibited a significant mediating effect on the association between ALD and reduced FN-BMD albeit the proportion of mediation was mild (2.21%). No significant effects of NAFLD, alcohol consumption, or smoking on BMD in four sites, or reverse effect of BMD on ALD or NAFLD were detected. CONCLUSION: Our findings confirm the genetically predicted effect of ALD on reduced FN-BMD, and highlight the importance of periodic BMD and serum 25-OHD monitoring and vitamin D supplementation as needed in patients with ALD. Future research is required to validate our results and investigate the probable underlying mechanisms.

Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models.

Despite its increased recognition as a major public health issue, alcohol use disorder is mostly underdiagnosed and undertreated. The undertreatment and underdiagnosis of alcohol use disorder is most concerning in the management of patients with alcohol-associated liver disease, which is one of the main medical consequences of chronic and excessive alcohol use. Dual pathology (alcohol use disorder and alcohol-associated liver disease) requires multidisciplinary care involving hepatologists and addiction specialists. Such integrated care models are widely accepted as optimal care for treating comorbid medical and mental health conditions. However, the implementation of such models in clinical practice is challenging and often represents the exception, rather than the rule, in managing patients with alcohol use disorder and alcohol-associated liver disease. Barriers at the patient, clinician, and system levels are encountered in treating patients with alcohol use disorder and alcohol-associated liver disease. In this Viewpoint, we synthesise the emerging literature on the potential barriers encountered in caring for patients with alcohol-associated liver disease and alcohol use disorder and focus on how integrated models of care could overcome these barriers. We provide our perspective on why these barriers exist and propose strategies to overcome them.

In vitro effects of Pueraria extract on ethanol-exposed microglia and neurons.

Predominant health impacts from alcoholism are chronic neurologic deficits and hepatic dysfunction. Pueraria extract (PE) is a solution obtained from the dried root of Pueraria lobate and can reverse alcohol-induced hepatic damage. The present study aimed to elucidate the effects of PE on ethanol-induced injury in microglia and neurons. To confirm the reliability of the experimental approach, an in vivo demonstration of PE activity was used to verify its impact on hepatic damage in mice exposed to ethanol (ETOH). Subsequently, an in vitro assay was used to verify the effects of PE on ETOH-exposed microglia and neurons.PE reversed fibrosis and hyperplasia, adipocyte infiltration, hepatomegaly, hepatic function, lipid metabolism, indicators of oxidative stress, and morphological changes in hepatic cells, induced by ETOH exposure. The reliability of the experimental approach was thus confirmed. PE also reversed the activation of microglia and inflammatory-related cytokines and proteins induced by ETOH exposure. PE showed protective effects on neurons via inhibition of mitochondrial fission. in vivo and in vitro evidence indicated that PE might be useful in the treatment of both hepatic injury and neurologic deficits commonly observed in chronic alcoholism.

Mortality rates among individuals diagnosed with hepatitis C virus (HCV); an observational cohort study, England, 2008 to 2016.

BackgroundMonitoring trends in mortality for individuals diagnosed with hepatitis C virus (HCV) infection are important as we expand treatment and move towards World Health Organization elimination targets.AimTo estimate mortality rates for individuals aged ≥ 15 years diagnosed with HCV infection in England 2008-16.MethodsAn observational cohort study whereby death certificate information was linked to the Sentinel Surveillance of Blood Borne Virus Testing in England. Age-sex standardised mortality rates (ASMR) for individuals diagnosed with HCV infection (2008-16) were calculated and compared to the general population.ResultsOf 43,895 individuals with HCV infection, 2,656 (6.3%) died. All-cause ASMRs were 2,834.2 per 100,000 person years (PY), 2.3 times higher than in the general population. In individuals aged 30-69 years, all-cause mortality rates were 1,768.9 per 100,000 PY among individuals with HCV, 4.7 times higher than in the general population. ASMRs had not decreased between 2010 (2,992) and 2016 (2,340; p=0.10), with no change from 2014 (p = 0.058). ASMRs were 441.0 times higher for hepatitis, 34.4 times higher for liver cancer, 8.1 times higher for end stage liver disease and 6.4 times higher for external causes than in the general population.ConclusionsMortality was higher in individuals with diagnosed HCV infection compared to the general population, highlighting health inequalities. There is a need to improve HCV diagnosis, engagement in care and treatment rates. The high mortality from external causes highlights the importance of integrated health and social care strategies and addressing the needs of this vulnerable population.

Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol-induced liver dysfunction: Rescue effect of ginger extract.

The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent.

Malnutrition and Nutritional Support in Alcoholic Liver Disease: a Review.

Malnutrition is associated with alcoholic liver disease (ALD) and related complications such as hepatic encephalopathy and increased rate of infections. Avoidance of prolonged fasting and overly restrictive diets is important to avoid poor nutrition. Adequate intake of calories, protein, and micronutrients via frequent small meals and evening supplements and/or enteral and parenteral nutrition when indicated has been associated with reduced mortality and morbidity in patients with ALD. Modification of protein/fat sources and composition in addition to probiotic supplementation are promising interventions for decreased progression of ALD and its complications.

Effects of Sex, Drinking History, and Omega-3 and Omega-6 Fatty Acids Dysregulation on the Onset of Liver Injury in Very Heavy Drinking Alcohol-Dependent Patients.

BACKGROUND: Heavy alcohol consumption frequently causes liver inflammation/injury, and certain fatty acids (FAs) may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking and the changes in the FA levels involved in the ω-6 (pro-inflammatory) and ω-3 (anti-inflammatory) state in alcohol-dependent (AD) patients who had no clinical manifestations of liver injury. We aimed to identify sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking. METHODS: A total of 114 heavy drinking AD female and male patients aged 21 to 65 years without clinical manifestations of liver injury, who were admitted to an alcohol dependence treatment program, were grouped by the alanine aminotransferase (ALT) levels: ≤40 IU/l, as no liver injury (GR.1), and >40 IU/l, as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic panel, comprehensive FA panel, and drinking history data were evaluated. RESULTS: Elevated ALT and aspartate aminotransferase (AST) showed close association with markers of heavy alcohol intake. In the patients with mild biochemical liver injury (GR.2), females showed significantly higher AST level than males. Significant association of AST and total drinks in past 90 days (TD90) in females, and AST and heavy drinking days in past 90 days (HDD90) in males was observed. The ω-6:ω-3 ratio showed a significant pro-inflammatory response only in females with mild liver injury (GR.2) when adjusted by drinking history marker, TD90. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were increased in males with liver injury, while females did not show any comparable rise in EPA; and DHA levels were lower. CONCLUSIONS: Measures of heavy drinking, TD90 and HDD90, predicted changes in liver injury. Changes in the ω-3 and ω-6 FA levels and the ω-6:ω-3 ratio showed a pro-inflammatory shift in patients with biochemical liver injury with a significant effect in females. Changes in FAs involved in the inflammatory state may represent one mechanism for liver inflammation/injury in response to heavy alcohol drinking.

Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.

BACKGROUND: Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. METHODS: C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. RESULTS: Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. CONCLUSIONS: This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD.

Supplementary management of functional, temporary alcoholic hepatic damage with Robuvit® (French oak wood extract).

BACKGROUND: The aim of this registry study was to evaluate Robuvit® (French oak wood extract) supplementation in the evolution of moderate functional hepatic failure (MTHF) due to alcohol. Recent studies have indicated the protective effect of oak wood (QR) extracts on liver injury. This registry included patients with MTHF characterized by: decreased albumin levels; increased total bilirubin, altered hepatic functions enzymes, increased oxidative stress, negative viral hepatitis markers. METHODS: The two groups resulted divided into a best management (BM) group and a comparative group (BM + Robuvit®): 23 Robuvit® patients and 21 comparable controls completed the 12-week registry. At inclusion, blood parameters in the two groups were comparable. RESULTS: During the observation period, the increase in albumin levels was significantly (P<0.05 at 6 weeks) faster and higher in the Robuvit® group in comparison with controls. The decrease in ALT-SGPT and AST-ASAT were significantly more important in the supplement group (P<0.05 at 6 and 12 weeks). Alkaline phosphatase was significantly lower at 6 and 12 weeks in Robuvit® patients; (Robuvit® group's values were significantly better; P<0.05). Total bilirubin improved more in Robuvit® subjects at 6 weeks. Results were statistically significant in comparison with controls (P<0.05). Also, direct bilirubin values were higher in the Robuvit® group at 6 and 12 weeks (P<0.05). Gamma GT values were normalized at 6 and 12 weeks in the Robuvit® group. There was a less important decrease in controls (P<0.05) without normalization at 12 weeks. Plasma free radicals, high at inclusion, showed a more significant decrease in Robuvit® subjects (at 6 and 12 weeks), with normalization at 12 weeks. Persisting high values in controls were observed even at 12 weeks (P<0.05). Erythrocytes sedimentation rate (ESR) decreased in both groups with a more important decrease in the Robuvit® group (P<0.05). Hepatitis markers were negative when repeated at 6 and 12 weeks. CONCLUSIONS: In conclusion, observations from this pilot, supplement registry study indicate a significant protective activity of the supplementation with Robuvit®, associated with a very good safety profile, in patients with temporary alcoholic hepatic failure. The activity of Robuvit® seems to be mediated by its anti-inflammatory activity associated to its important action on oxidative stress.

Nutrition and Alcoholic Liver Disease: Effects of Alcoholism on Nutrition, Effects of Nutrition on Alcoholic Liver Disease, and Nutritional Therapies for Alcoholic Liver Disease.

Malnutrition is the most frequent and nearly universal consequence in alcoholic liver disease (ALD) that adversely affects clinical outcomes. Sarcopenia or skeletal muscle loss is the major component of malnutrition in liver disease. There are no effective therapies to prevent or reverse sarcopenia in ALD because the mechanisms are not well understood. Consequences of liver disease including hyperammonemia, hormonal perturbations, endotoxemia and cytokine abnormalities as well as the direct effects of alcohol and its metabolites contribute to sarcopenia in ALD. This article focuses on the prevalence, methods to quantify malnutrition, specifically sarcopenia and potential therapies including novel molecular targeted treatments.

Bone health and vitamin D status in alcoholic liver disease.

Alcohol consumption is harmful to many organs and tissues, including bones, and it leads to osteoporosis. Hepatic osteodystrophy is abnormal bone metabolism that has been defined in patients with chronic liver disease (CLD), including osteopenia, osteoporosis, and osteomalacia. Decreased bone density in patients with CLD results from decreased bone formation or increased bone resorption. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is between 34 % and 48 %, and the prevalence of osteoporosis is between 11 % and 36 %. Cirrhosis is also a risk factor for osteoporosis. The liver has an important role in vitamin D metabolism. Ninety percent of patients with alcoholic liver cirrhosis have vitamin D inadequacy (<80 nmol/L). The lowest serum vitamin D levels were observed in patients with Child-Pugh class C. Bone densitometry is used for the definitive diagnosis of osteoporosis in ALD. There are no specific controlled clinical studies on the treatment of osteoporosis in patients with ALD. Alcohol cessation and abstinence are principal for the prevention and treatment of osteoporosis in ALD patients, and the progression of osteopenia can be stopped in this way. Calcium and vitamin D supplementation is recommended, and associated nutritional deficiencies should also be corrected. The treatment recommendations of osteoporosis in CLD tend to be extended to ALD. Bisphosphonates have been proven to be effective in increasing bone mineral density (BMD) in chronic cholestatic disease and post-transplant patients, and they can be used in ALD patients. Randomized studies assessing the management of CLD-associated osteoporosis and the development of new drugs for osteoporosis may change the future. Here, we will discuss bone quality, vitamin D status, mechanism of bone effects, and diagnosis and treatment of osteoporosis in ALD.

Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation.

BACKGROUND: Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. METHODS: We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. RESULTS: One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 ± 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 ± 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 ± 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 ± 3.5 months, 95% CI: 45.4-59.3; P = 0.001). CONCLUSIONS: Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long-term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients.

Diagnosis and treatment of nutritional deficiencies in alcoholic liver disease: Overview of available evidence and open issues.

Malnutrition is common in alcoholic liver disease and is associated with high rates of complications and mortality. In this article, the current literature was reviewed to highlight the relevance of proper nutritional management providing levels of evidence, when available. A PubMed search was performed for English-language publications from 1980 through 2014 with the keywords: alcoholic liver disease, nutritional deficiencies, nutritional support, enteral nutrition, parenteral nutrition, and protein-energy malnutrition. Manuscripts focused on nutritional approach in patients with alcoholic liver disease were selected. Although nutritional support for malnourished patients improves the outcome of hospitalization, surgery, transplantation and reduces the complications of liver disease and the length of hospital stay, specific guidelines are scanty. Both enteral and parenteral nutrition appear to improve nutritional parameters and liver function; however data on survival is often conflicting. As micronutrient depletion is common in alcoholic liver disease and each deficiency produces specific sequelae, all cirrhotic patients should be screened at baseline for deficiencies of micronutrient and supplemented as needed. In summary, protein-energy malnutrition and micronutrient depletion are clinical concerns in alcoholic liver disease. Nutritional therapy, including enteral nutrition, parenteral nutrition and micronutrient supplementation should be part of the multidisciplinary management of these patients.

Multidisciplinary Approach in Hepatocellular Carcinoma in a Level II Hospital: The First Decade of Hospital Universitario Fundacion Alcorcon.

BACKGROUND/AIMS: Mean survival in hepatocellular carcinoma remains low. Many efforts have been done during the last years through screening, diagnosis and treatment to improve the results. The aim of this work is to present the experience of our hospital multidisciplinary group during the first decade of this century. METHODOLOGY: The patients with hepatocellullar carcinoma presented at the multidisciplinary meeting from 1999 to 2009 were prospectively studied. According to the tumor and functional status they were treated through the current available guidelines by transplant, partial hepatectomy, local/regional procedures, systemic or symptomatic treatment. RESULTS: One hundred and forty two patients were studied. Median tumor size was 3 cm. A single tumor was diagnosed in 64.8% of the patients. Eighteen patients had liver resection (6 transplantation and 12 with partial resection), 53 tumors were not treated due to advanced stage or liver dysfunction, and in the remaining patients radiofrequency, ethanol or embolization treatments were used, single or combined. CONCLUSIONS: a multidisciplinary approach of hepatocellular carcinoma in a second level hospital with trained professionals permits a diagnosis in early tumoral and functional stages in the majority of patients, and a variety of possible treatments with adequate survival outcomes.

Marked 25-hydroxyvitamin D deficiency is associated with poor prognosis in patients with alcoholic liver disease.

BACKGROUND & AIMS: Vitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD. METHODS: Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D. RESULTS: Severe deficiency in 25(OH)D (<10 ng/ml) was significantly associated with higher aspartate aminotransferase levels (p=1.00 × 10(-3)), increased hepatic venous pressure gradient (p=5.80 × 10(-6)), MELD (p=2.50 × 10(-4)), and Child-Pugh scores (p=8.50 × 10(-7)). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18-3.84, p=0.013) and mortality (HR=4.33, 95% CI=1.47-12.78, p=7.94 × 10(-3)) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p=3.00 × 10(-3)), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p=0.04). CONCLUSIONS: Low 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD.

Alcoholic liver disease and changes in bone mineral density.

Osteoporosis and osteopenia are alterations in bone mineral density (BMD) that frequently occur in the context of chronic liver disease (CLD). These alterations have been studied predominantly in chronic cholestatic disease and cirrhosis of the liver. Alcohol consumption is an independent risk factor for the onset of osteoporosis, whose estimated prevalence in patients with alcoholic liver disease (ALD) ranges between 5 % and 40 %. The loss of BMD in ALD is the result of an imbalance between bone formation and resorption. Its pathogenesis is multifactorial and includes the toxic effects of alcohol on bone and endocrine and nutritional disorders secondary to alcoholism and a deficiency of osteocalcin, vitamin D and insulin growth factor-1. The diagnosis of BMD alterations in ALD is based on its measurement using bone densitometry. Treatment includes smoking and alcohol cessation and general measures such as changes in nutrition and exercise. Calcium and vitamin D supplements are recommended in all patients with ALD and osteoporosis. Bisphosphonates are the most commonly prescribed drugs for the specific treatment of this condition. Alternatives include raloxifene, hormone replacement therapy and calcitonin.This review will address the most important aspects involved in the clinical management of abnormal BMD in the context of ALD, including its prevalence, pathogenesis and diagnosis. We will also review the treatment of osteoporosis in CLD in general, focusing on specific aspects related to bone loss in ALD.

Nutrition in alcoholic liver disease.

The liver plays an important role in the metabolism, synthesis, storage, and absorption of nutrients. Patients with cirrhosis are prone to nutritional deficiencies and malnutrition, with a higher prevalence among patients with decompensated disease. Mechanisms of nutritional deficiencies in patients with liver disease are not completely understood and probably multifactorial. Malnutrition among patients with cirrhosis or alcoholic liver disease correlates with poor quality of life, increased risk of infections, frequent hospitalizations, complications, mortality, poor graft and patient survival after liver transplantation, and economic burden. Physicians, including gastroenterologists and hepatologists, should be conversant with assessment and management of malnutrition and nutritional supplementation.

[Analysis of major herbs in Chinese herbal formula Jianpi Huoxue Decoction for improving intestinal permeability based on uniform design].

OBJECTIVE: To investigate the herbal medicines which play a main role in Chinese herbal formula Jianpi Huoxue Decoction for improving intestinal permeability and protect alcohol-induced liver injury and intestine damage, and to explore the analysis method for the material base of pharmacological effects of the Chinese herbal compound. METHODS: Sprague Dawley rats were given Lieber-DeCarli ethanol liquid diet once daily for 6 weeks to induce alcoholic liver injury. In step one, U(17)(17(16)) table of uniform design was adopted to design the experiment and the eight herbs of Jianpi Huoxue Decoction were screened to seek the herbs which play the main role. Three and a half hours before the rats were killed, each rat was administered lipopolysaccharide once, then blood sample was collected from portal vein and endotoxin content in plasma was detected as the index of intestinal permeability. The data were analyzed by stepwise regression to find the herbal drugs which had the best effects and the compatibility ratio of these drugs. In step two, the rats with Lieber-DeCarli liquid diet-induced liver injury were divided into four groups to test and verify the results. RESULTS: According to the obtained regression equation, Rasux Paeonia Alba (Baishao), Rhizoma Alismatis (Zexie) and Fructus Schisandrae Chinensis (Wuweizi) were the main herbal drugs in Jianpi Huoxue Decoction in improving intestinal permeability, and the doses for rats were 1.33, 0.50 and 0.17 g/kg respectively. In the verification experiment, combination of Baishao, Zexie and Wuweizi significantly decreased the endotoxin level in plasma of rats with Lieber-DeCarli-induced liver injury and showed reliability. CONCLUSION: Baishao, Zexie and Wuweizi are the major herbs of Jianpi Huoxue Decoction for improving intestinal permeability. Uniform design is efficient in screening the major herbs or their optimal combination in a certain Chinese compound.

Current status of liver diseases in Korea: toxic and alcoholic liver diseases.

The study of the epidemiology of toxic liver injury has been limited in Korea. The number of hospitalizations for toxic liver injury has been estimated to be 2,400 persons per year. About 30~40% of fulminant hepatitis was attributed to toxic hepatitis. The frequent causative agents of toxic hepatitis in Korea are herbal medicines (34-40%), folk remedies (23-34%), and prescribed medicines (24-55%). However, the most common agents causing severe liver injury including fulminant hepatitis are herbal medicine and folk remedies. Antituberculosis drugs and acetaminophen are two common causes of fulminant hepatitis among prescribed drugs. Alcohol is one of the leading causes of chronic liver disease in Korea. No nationwide study on the epidemiology of alcoholic liver disease (ALD) has been carried out, but 7-31% of cirrhosis has been reported to be alcoholic in a few single-center studies. Alcohol could be a risk factor for the development of hepatocellular carcinoma (HCC) in chronic viral hepatitis. Several studies have shown that alcohol increased the risk of HCC in liver cirrhosis with HBsAg or anti-HCV. Furthermore, alcoholic cirrhosis with occult hepatitis B virus infection increased the risk of HCC.