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Search Results: 1 - 10 of 2132 matches for " Makoto Nakamuta "
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Is the control of dietary cholesterol intake sufficiently effective to ameliorate nonalcoholic fatty liver disease?
Munechika Enjoji, Makoto Nakamuta
World Journal of Gastroenterology , 2010,
Abstract: 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.
Metabolic Disorders and Steatosis in Patients with Chronic Hepatitis C: Metabolic Strategies for Antiviral Treatments
Munechika Enjoji,Motoyuki Kohjima,Kazuhiro Kotoh,Makoto Nakamuta
International Journal of Hepatology , 2012, DOI: 10.1155/2012/264017
Abstract: It has been reported that hepatitis C virus (HCV) infection is closely associated with hepatic metabolic disorders. Hepatic steatosis and insulin resistance are both relatively common in patients with chronic hepatitis C. Recent investigations suggest that HCV infection changes the expression profile of lipid-metabolism-associated factors in the liver, conferring advantages to the life cycle of HCV. Moreover, insulin resistance and steatosis are independent predictors of impaired response to antiviral treatment in chronic hepatitis C. In this paper, we summarize our current knowledge of hepatic metabolic disorders and describe how HCV leads to and exploits these hepatic disorders. We also discuss the clinical significance of insulin sensitizers used to improve insulin resistance and lipid modulators used to manage lipid metabolism as potential treatment options for chronic hepatitis C.
Nutrition and Nonalcoholic Fatty Liver Disease: The Significance of Cholesterol
Munechika Enjoji,Kenichiro Yasutake,Motoyuki Kohjima,Makoto Nakamuta
International Journal of Hepatology , 2012, DOI: 10.1155/2012/925807
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that ranges in severity from simple steatosis to cirrhosis. NAFLD is considered to be associated with hepatic metabolic disorders, resulting in overaccumulation of fatty acids/triglycerides and cholesterol. The pathogenesis and progression of NAFLD are generally explained by the “two-hit theory.” Most studies of lipid metabolism in the NAFLD liver have focused on the metabolism of fatty acids/triglycerides; therefore, the impact of cholesterol metabolism is still ambiguous. In this paper, we review recent studies on NAFLD from the viewpoint of hepatic lipid metabolism-associated factors and discuss the impact of disordered cholesterol metabolism in the etiology of NAFLD. The clinical significance of managing cholesterol metabolism, an option for the treatment of NAFLD, is also discussed.
A new treatment strategy for acute liver failure
Kazuhiro Kotoh, Masaki Kato, Motoyuki Kohjima, Makoto Nakamuta, Munechika Enjoji
World Journal of Hepatology , 2010,
Abstract: Acute liver failure (ALF) is a syndrome defined by coagulopathy and encephalopathy and no effective treatments have been established, except for liver transplantation. However, considering the limited supply of donors, we should endeavor to prevent the progression 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 lesser 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 appropriate treatment including liver transplantation. We believe that it is essential to analyze disease progression in each patient before selecting the most appropriate treatment.
Metabolic Disorders and Steatosis in Patients with Chronic Hepatitis C: Metabolic Strategies for Antiviral Treatments
Munechika Enjoji,Motoyuki Kohjima,Kazuhiro Kotoh,Makoto Nakamuta
International Journal of Hepatology , 2012, DOI: 10.1155/2012/264017
Abstract: It has been reported that hepatitis C virus (HCV) infection is closely associated with hepatic metabolic disorders. Hepatic steatosis and insulin resistance are both relatively common in patients with chronic hepatitis C. Recent investigations suggest that HCV infection changes the expression profile of lipid-metabolism-associated factors in the liver, conferring advantages to the life cycle of HCV. Moreover, insulin resistance and steatosis are independent predictors of impaired response to antiviral treatment in chronic hepatitis C. In this paper, we summarize our current knowledge of hepatic metabolic disorders and describe how HCV leads to and exploits these hepatic disorders. We also discuss the clinical significance of insulin sensitizers used to improve insulin resistance and lipid modulators used to manage lipid metabolism as potential treatment options for chronic hepatitis C. 1. Introduction Hepatic steatosis is a well-documented histological characteristic of chronic hepatitis C virus (HCV) infection [1]. Insulin resistance or impaired glucose metabolism, is linked to hepatic steatosis in patients with chronic hepatitis C (CH-C). It is widely considered that hepatic steatosis in patients with CH-C is caused by lipid metabolic disorders, in which insulin resistance plays an important role [2]. Fat accumulation promotes oxidative stress and inflammatory reactions. A considerable number of studies have also suggested that various HCV proteins lead to alterations in lipid synthesis, catabolism and transport. In particular, HCV core protein was reported to contribute to these metabolic changes and induce reactive oxygen species generation [3, 4]. Clinically, hepatic steatosis and insulin resistance in CH-C patients are associated with hepatic fibrosis, an increased frequency of hepatocellular carcinoma, and a poor response to pegylated interferon (peg-IFN) plus ribavirin combination therapy [5]. 2. HCV Infection and Insulin Resistance It has been reported that hepatic steatosis is correlated with viral load; approximately 50% of patients with CH-C have hepatic steatosis, which enhances disease progression [6, 7]. Recent studies have shown that, as in nonalcoholic fatty liver disease (NAFLD), insulin resistance and an increased fatty acid supply to the liver are important pathogeneses of steatosis in CH-C [8]. In CH-C patients, the occurrence of insulin resistance is independent of visceral adipose tissue and hepatic steatosis and irrespective of the HCV genotype [9]. In our experience, insulin resistance is frequently observed in nonobese
Nutrition and Nonalcoholic Fatty Liver Disease: The Significance of Cholesterol
Munechika Enjoji,Kenichiro Yasutake,Motoyuki Kohjima,Makoto Nakamuta
International Journal of Hepatology , 2012, DOI: 10.1155/2012/925807
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that ranges in severity from simple steatosis to cirrhosis. NAFLD is considered to be associated with hepatic metabolic disorders, resulting in overaccumulation of fatty acids/triglycerides and cholesterol. The pathogenesis and progression of NAFLD are generally explained by the “two-hit theory.” Most studies of lipid metabolism in the NAFLD liver have focused on the metabolism of fatty acids/triglycerides; therefore, the impact of cholesterol metabolism is still ambiguous. In this paper, we review recent studies on NAFLD from the viewpoint of hepatic lipid metabolism-associated factors and discuss the impact of disordered cholesterol metabolism in the etiology of NAFLD. The clinical significance of managing cholesterol metabolism, an option for the treatment of NAFLD, is also discussed. 1. Introduction Histological features of nonalcoholic fatty liver disease (NAFLD) include steatosis, hepatocellular ballooning, the formation of Mallory bodies, apoptosis/necrosis, and inflammation [1]. Around 10–20% of patients with NAFLD have nonalcoholic steatohepatitis (NASH), which can develop into cirrhosis and hepatocellular carcinoma [2–5]. Because excess nutrition intake is one of the main causes, NAFLD is often accompanied by obesity, insulin resistance, hypertension, and/or dyslipidemia, which are manifestations of the metabolic syndrome [6]. Therefore, nutritional management and therapeutic exercise are fundamental steps to treat NAFLD. The “two-hit theory” is increasingly being adopted to explain the pathogenesis of NAFLD and NASH [7]. In this theory, the first hit consists of the accumulation of fatty acids/triglycerides in the liver, while the second hit involves oxidative stress, mitochondrial dysfunction, and inflammation, which ultimately cause liver damage. It is also clear that inflammatory cytokines and insulin resistance are closely associated with fatty liver during the progression of NAFLD. In previous studies that examined lipid metabolism in the context of NAFLD, dysregulation of cholesterol metabolism has received much less attention than have fatty acids and triglycerides. In this paper, we focus on the role of cholesterol and its metabolites on the pathogenesis of NAFLD, and also the validity of cholesterol management as a method of treating this disease. 2. Fatty Acid Metabolism in the NAFLD Liver Hepatic lipid homeostasis represents a balance between lipid uptake, synthesis, catabolism, and secretion. Therefore, steatosis, a typical characteristic of NAFLD, is
Nutrition Therapy for Liver Diseases Based on the Status of Nutritional Intake
Kenichiro Yasutake,Motoyuki Kohjima,Manabu Nakashima,Kazuhiro Kotoh,Makoto Nakamuta,Munechika Enjoji
Gastroenterology Research and Practice , 2012, DOI: 10.1155/2012/859697
Abstract: The dietary intake of patients with nonalcoholic fatty liver disease (NAFLD) is generally characterized by high levels of carbohydrate, fat, and/or cholesterol, and these dietary patterns influence hepatic lipid metabolism in the patients. Therefore, careful investigation of dietary habits could lead to better nutrition therapy in NAFLD patients. The main treatment for chronic hepatitis C (CHC) is interferon-based antiviral therapy, which often causes a decrease in appetite and energy intake; hence, nutritional support is also required during therapy to prevent undernourishment, treatment interruption, and a reduction in quality of life. Moreover, addition of some nutrients that act to suppress viral proliferation is recommended. As a substitutive treatment, low-iron diet therapy, which is relatively safe and effective for preventing hepatocellular carcinoma, is also recommended for CHC patients. Some patients with liver cirrhosis (LC) have decreased dietary energy and protein intake, while the number of LC patients with overeating and obesity is increasing, indicating that the nutritional state of LC patients has a broad spectrum. Therefore, nutrition therapy for LC patients should be planned on an assessment of their complications, nutritional state, and dietary intake. Late evening snacks, branched-chain amino acids, zinc, and probiotics are considered for effective nutritional utilization. 1. Introduction The liver is one of the main organs of nutritional metabolism, including protein synthesis, glycogen storage, and detoxification. These functions become damaged to a greater or lesser extent in patients with liver diseases, resulting in various metabolic disorders, and their disturbed nutritional condition is associated with disease progression. Therefore, dietary counseling and nutritional intervention can support other medical treatments in some liver diseases. Nonalcoholic fatty liver disease (NAFLD) is a disease caused by excessive dietary intake, which leads to hepatocytic triglyceride accumulation, obesity, and insulin resistance; hence, nutrition therapy is a basic treatment for NAFLD. NAFLD has a wide spectrum of pathologic conditions from simple steatosis to steatosis with necroinflammation and fibrosis, the condition termed nonalcoholic steatohepatitis (NASH). Nutritional intake in NAFLD patients is characterized as energy overload by a high-carbohydrate and high-fat diet, or excessive cholesterol intake. In patients with chronic hepatitis C (CHC), nutritional support is expected to promote the effect of antiviral treatment, for example,
A new parameter using serum lactate dehydrogenase and alanine aminotransferase level is useful for predicting the prognosis of patients at an early stage of acute liver injury: A retrospective study
Kazuhiro Kotoh, Munechika Enjoji, Masaki Kato, Motoyuki Kohjima, Makoto Nakamuta, Ryoichi Takayanagi
Comparative Hepatology , 2008, DOI: 10.1186/1476-5926-7-6
Abstract: To confirm this hypothesis, we developed a new parameter with serum alanine aminotransferase (ALT) and LDH: the ALT-LDH index = serum ALT/(serum LDH - median of normal LDH range). We analyzed retrospectively 33 patients suffering acute liver injury (serum ALT more than 1000 U/L or prothrombin time expressed as international normalized ratio over 1.5 at admission) and evaluated the prognostic value of the ALT-LDH index, comparing data from the first 5 days of hospitalization with the Model for End-Stage Liver Disease (MELD) score. Patients whose symptoms had appeared more than 10 days before admission were excluded from this study. Among those included, 17 were conservative survivors, 9 underwent liver transplantation (LT) and 7 died waiting for LT. We found a rapid increase in the ALT-LDH index in conservative survivors but not in fatal patients. While the prognostic sensitivity and specificity of the ALT-LDH index was low on admission, at day 3 they were superior to the results of MELD.ALT-LDH index was useful to predict the prognosis of the patients with acute liver injury and should be helpful to begin preparation for LT soon after admission.Acute liver failure (ALF) or fulminant liver failure is a disease characterized by abrupt onset and high mortality. Liver transplantation (LT) is the only effective treatment for ALF and many patients die before undergoing LT because of rapid progression of the disease [1,2]. Therefore, a prompt decision regarding LT is required following an early determination of prognosis. Among the various clinical selection criteria proposed for LT, the King's College criteria and the Model for End-Stage Liver Disease (MELD) criteria have been applied widely [3,4]. However, those criteria include some factors reflecting multiple or systemic organ failure, which means that many patients fulfilling the criteria are already too unwell for transplantation to be contemplated. The poor prognosis of ALF seems to be attributable to the definition
Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods
Makoto Nakamuta, Motoyuki Kohjima, Shusuke Morizono, Tsuyoshi Yoshimoto, Yuzuru Miyagi, Hironori Sakai, Munechika Enjoji, Kazuhiro Kotoh
Comparative Hepatology , 2006, DOI: 10.1186/1476-5926-5-10
Abstract: A block of pig liver sealed in a rigid plastic case was used as a model of an HCC tumor with a capsule. The multi-step method with the LeVeen electrode resulted in the lowest pressure as compared with the single-step or cool-tip methods. There was no significant difference in the ablation time between the multi-step and cool-tip ablation methods, although the single-step methods had longer ablation times than the other ablation procedures. In HCC cases, the multi-step method had a significantly shorter ablation time than the single-step or cool-tip methods.We demonstrated that the multi-step method was useful to reduce the ablation time and to suppress the increase in pressure. The multi-step method using a LeVeen needle may be a clinically applicable procedure for RFA.Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Most of HCC patients suffer from virus-induced liver injury and most have underlying liver cirrhosis [1]. Percutaneous ethanol injection therapy (PEIT) has been used widely for the treatment of unresectable HCC [2]. Many reports showed that the efficacy of PEIT for small HCC tumors was comparable to that of hepatic resection; however, PEIT demands multiple sessions to achieve complete necrosis, resulting in protracted hospitalization [3]. Furthermore, many patients suffer from local recurrence after PEIT, which is attributable to intra-tumor septa that prevent the injected ethanol from infiltrating the entire tumor [4,5]. We reported that local recurrence after PEIT should be prevented as much as possible because it is one of the most important negative prognostic factors for HCC patients [6].It has been reported that radio frequency ablation (RFA) is an effective procedure for hepatocellular carcinoma (HCC) as well as for metastatic liver tumors [7,8]. However, it has also been shown that it is not uncommon for RFA to cause various complications [9,10]. During or just after the procedure, peritoneal bleeding, hepatic abscess,
NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease
Munechika Enjoji, Kazuyuki Machida, Motoyuki Kohjima, Masaki Kato, Kazuhiro Kotoh, Kazuhisa Matsunaga, Manabu Nakashima, Makoto Nakamuta
Lipids in Health and Disease , 2010, DOI: 10.1186/1476-511x-9-29
Abstract: We reviewed a year of follow-up data of non-obese NAFLD patients treated with Niemann-Pick C1 like 1 inhibitor ezetimibe to evaluate its therapeutic effect on clinical parameters related to NAFLD. Without any dietary or exercise modification, 10 mg/day of ezetimibe was given to 8 patients. In 4 of 8 patients, ezetimibe was administered initially. In the remaining 4 patients, medication was switched from ursodeoxycholic acid to ezetimibe.In each patient, body mass index was maintained under 25 kg/m2 during the observation period. Serum ALT levels significantly decreased within 6 months and in 4 patients levels reached the normal range (<30 U/L), which was accompanied with at least a 10% decrease in serum total cholesterol and LDL-cholesterol. However, ultrasonographic findings of fatty liver did not show obvious improvement for a year.We conclude that the cholesterol absorption inhibitor ezetimibe can suppress hepatic injury in non-obese patients with NAFLD and that ezetimibe may offer a novel treatment for NAFLD.Nonalcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, is a common cause of abnormal liver function and its incidence is increasing in many countries. Many NAFLD patients progress to a severe form of nonalcoholic steatohepatitis that can lead to cirrhosis, hepatic failure and hepatocellular carcinoma [1,2]. Although obesity and/or insulin resistance are considered to be a common cause of NAFLD, a large proportion of NAFLD patients are non-obese individuals [3,4]. Because onset and progression of NAFLD seem to be affected by nutritional intake, we have compared the distribution of abdominal fat, dietary intake and biochemical data between obese and non-obese patients with NAFLD to identify potential nutritional factors that affect NAFLD [5,6]. Waist circumference, total abdominal fat levels and subcutaneous fat levels were significantly higher in the obese group, whereas visceral fat levels were not significantly different betw
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