Dietary habits and behaviors associated with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD)is one of the most frequent causes of health problems in Western(industrialized)countries.Moreover,the incidence of infantile NAFLD is increasing,with some of these patients progressing to nonalcoholic steatohepatitis.These trends depend on dietary habits and life-style.In particular,overeating and its associated obesity affect the development of NAFLD.Nutritional problems in patients with NAFLD include excess intake of energy,carbohydrates,and lipids,and shortages of polyunsaturated fatty acids,vitamins,and minerals.Although nutritional therapeutic approaches are required for prophylaxis and treatment of NAFLD,continuous nutrition therapy is difficult for many patients because of their dietary habits and lifestyle,and because the motivation for treatment differs among patients.Thus,it is necessary to assess the nutritional background and to identify nutritional problems in each patient with NAFLD.When assessing dietary habits,it is important to individually evaluate those that are consumed excessively or insufficiently,as well as inappropriate eating behaviors.Successful nutrition therapy requires patient education,based on assessments of individual nutrients,and continuing the treatment.In this article,we update knowledge about NAFLD,review the important aspects of nutritional assessment targeting treatment success,and present some concrete nutritional care plans which can be applied generally.

Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver

AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively analyzed.Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for ferroportin.As a control,normal liver tissue was obtained from 18 living donors of liver transplantation.Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.RESULTS:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in vivo.Conversely,iron administration suppresses HCV replication in vitro.Therefore,the association between HCV infection and iron metabolism remains unclear.Compared with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and hepcidin.When the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and ferroportin.Expression of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected liver.BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group.HCV infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in hepatocytes.CONCLUSION:Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.

Is the control of dietary cholesterol intake sufficiently effective to ameliorate nonalcoholic fatty liver disease?

In our examination of the distribution of abdominal fat,dietary intake and biochemical data in patients with nonalcoholic fatty liver disease(NAFLD),non-obese NAFLD patients without insulin resistance presented a characteristic pattern of dietary intake.Dietary cholesterol intake was superabundant in non-obese patients compared with obese patients,although total energy and carbohydrate intake was not excessive.Namely,excess cholesterol intake appears to be one of the main factors associated with NAFLD development and liver injury.Therefore,the control of dietary cholesterol intake may lead to an improvement in NAFLD,and the NPC1L1 inhibitor ezetimibe might be a promising treatment for NAFLD.We review one pathogenic aspect of lipid metabolism dysregulation in NAFLD and survey new strategies for NAFLD treatment based on the modification of cholesterol metabolism.

A new treatment strategy for acute liver failure

Acute liver failure (ALF) is a syndrome def ined by coa g ulopathy and encephalopathy and no effective treat ments have been established, except for liver transplantation. However, considering the limited supply of donors, we should endeavor to prevent the progre ssion of this syndrome in its early stage to improve the prognosis of patients with ALF. Recently, several authors have reported that over-activation of intrahepatic macrophages plays an important role in the progression of ALF and we have developed a new treatment method, transcatheter arterial steroid injection therapy (TASIT), to suppress macrophage activation. We have now used TASIT for 5 years and have found that TASIT is effective for patients with over-activation of macrophages in the liver but not for those with les ser activation of macrophages. Therefore, to identify the most appropriate patients for TASIT, we tried to categorize patients with ALF or acute liver injury according to markers for the degree of intrahepatic macrophage activation. This approach was helpful to select the appro-priate treatment including liver transplantation. We believe that it is essential to analyze disease progression in each patient before selecting the most appropriate treatment.

Idiopathic chronic pancreatitis:Beyond antioxidants

Chronic pancreatitis(CP)is a complex disease associated with gene-gene or geneenvironment interactions.The incidence of idiopathic CP has shown an increasing trend,withits phenotypeshaving changed considerably in the last two decades.The diseaseitself can be regulated before it reaches the stage of established CP;however,the etiopathogenesis underlying idiopathic CP remains to be established,making the condition difficult to cure.Unfortunately,there also remains a lack of consensus regarding the beneficial effects of antioxidant therapiesfor CP.It is known that antioxidant therapy does not reduce inflammatory and fibrotic cytokines,making it unlikely that they could modulate the disease process.Although antioxidants are safe,very few studies to date have reported the long-term beneficial effects in patients with CP.Thus,studies are being performed to identify drugs that can improve symptoms and alter the natural history of CP.Statins,with their numerous pleiotropic effects,may play a role in the treatment of CP,butin 2006,their use was found to be associated with the undesirable side effect of promoting pancreatitis.Latter studies showed favourable effects of statins in CP,highlighting the particular benefits of lipophilic statins,such as lovastatin and simvastatin,over the hydrophilic statins,such as rosuvastatin.Ultimately,studies to repurpose N-acetylcysteine as a CP therapy areyielding very promising results.