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insulin treatment in patient with cirrhosis

Herbert Tilg, Alexander R Moschen, Michael Roden
The liver constitutes a key organ in systemic metabolism, contributing substantially to the development of insulin resistance and type 2 diabetes mellitus (T2DM). The mechanisms underlying these processes are not entirely understood, but involve hepatic fat accumulation, alterations of energy metabolism and inflammatory signals derived from various cell types including immune cells. Lipotoxins, mitochondrial function, cytokines and adipocytokines have been proposed to play a major part in both NAFLD and T2DM...
October 12, 2016: Nature Reviews. Gastroenterology & Hepatology
Hugo Perazzo, Jean-François Dufour
Non-alcoholic steatohepatitis (NASH) is characterized by lobular inflammation and hepatocellular ballooning, and may be associated with liver fibrosis leading to cirrhosis and its complications. A pharmacological approach is necessary to treat NASH because of failure to change dietary habits and lifestyle in most patients. Insulin resistance with an increased release of free fatty acids, oxidative stress and activation of inflammatory cytokines seem to be key features for disease progression. Thiazolidinediones, such as pioglitazone and antioxidant agents, such as vitamin E, were the first pharmacological options to be evaluated for NASH...
October 11, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Alberto A Chiappori, Gregory A Otterson, Afshin Dowlati, Anne M Traynor, Leora Horn, Taofeek K Owonikoko, Helen J Ross, Christine L Hann, Taher Abu Hejleh, Jorge Nieva, Xiuhua Zhao, Michael Schell, Daniel M Sullivan
LESSONS LEARNED: Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials.Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC.Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients...
October 2016: Oncologist
Wai Gin Lee, Rinki Murphy, John L McCall, Edward J Gane, Mattias Soop, Andrea Tura, Lindsay D Plank
BACKGROUND: Liver cirrhosis is frequently complicated by portal hypertension leading to increased mortality from variceal bleeding and hepatic decompensation. Non-cardioselective β-blockers reduce portal hypertension and prevent variceal bleeding in cirrhosis, but also impair glucose tolerance and insulin sensitivity in other settings. This study aimed to determine whether non-selective β-blockade with nadolol impairs glucose metabolism in liver cirrhosis. METHODS: A randomized, double-blind, placebo-controlled, cross-over trial of nadolol in cirrhotic patients examined insulin sensitivity, disposition index and glucose tolerance...
September 26, 2016: Diabetes/metabolism Research and Reviews
Xiaomin He, Yu Hong, Xiaomei Wang, Xiaohong Zhang, Jiang Long, Hai Li, Bei Zhang, Suhong Chen, Qiqi Liu, Hongyi Li, Xiaoming Wang, Xiaojuan Ou, Jian Huang
Chronic hepatitis B (CHB) is prevalent worldwide and can develop into liver cirrhosis and liver carcinoma. Early discrimination of liver cirrhosis from chronic hepatitis is critical for effective treatment and optimal prognosis. The aim of the present study was to assess the diagnostic value of a panel of cellular proteins that can be recognized by autoantibodies in patient serum for hepatitis B virus (HBV)‑related liver cirrhosis. Twenty‑two candidate autoantigens screened using a serum proteomics assay in our previous study were assessed retrospectively in 443 participants, comprising 89 patients with HBV‑related liver cirrhosis, 89 patients with CHB, and 265 healthy controls...
September 14, 2016: Molecular Medicine Reports
Mazen Noureddin, Alice Zhang, Rohit Loomba
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60-80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). A subset of patients with hepatic steatosis progress to NASH, while 15-20% of patients with NASH develop cirrhosis...
September 2016: Expert Opinion on Emerging Drugs
Manoj Amrutkar, Urszula Chursa, Matthias Kern, Esther Nuñez-Durán, Marcus Ståhlman, Silva Sütt, Jan Borén, Bengt R Johansson, Hanns-Ulrich Marschall, Matthias Blüher, Margit Mahlapuu
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and 10-20% of patients with NAFLD progress to nonalcoholic steatohepatitis (NASH) with a high risk of cirrhosis, liver failure, and hepatocellular carcinoma. Despite its high medical importance, the molecular mechanisms controlling progression from simple liver steatosis to NASH remain elusive. We recently identified serine/threonine protein kinase (STK)25 as a critical regulator of ectopic lipid deposition, systemic glucose, and insulin homeostasis...
July 15, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Nadine Gehrke, Marcus A Wörns, Yvonne Huber, Moritz Hess, Beate K Straub, Nadine Hövelmeyer, Ari Waisman, Yong Ook Kim, Detlef Schuppan, Peter R Galle, Jörn M Schattenberg
BACKGROUND & AIMS: The pathomechanisms underlying non-alcoholic fatty liver disease (NAFLD) and the involved molecular regulators are incompletely explored. The nuclear factor-kappa B (NF-κB)-cofactor gene B cell leukemia-3 (Bcl-3) plays a critical role in altering the transcriptional capacity of NF-κB - a key inducer of inflammation - but also of genes involved in cellular energy metabolism. METHODS: To define the role of Bcl-3 in non-alcoholic steatohepatitis (NASH), we developed a novel transgenic mouse model with hepatocyte-specific overexpression of Bcl-3 (Bcl-3(Hep)) and employed a high-fat, high-carbohydrate dietary feeding model...
July 9, 2016: Journal of Hepatology
André Thá Nassif, Thais Ayumi Nagano, Sulamita Okayama, Luís Sérgio Nassif, Alcides Branco Filho, José Sampaio Neto
BACKGROUND: Nonalcoholic fatty liver disease incidence is related to the presence of obesity and insulin resistance. A treatment of this disease in patients with morbid obesity is bariatric surgery and its diagnosis is extremely important due to the possible progression to cirrhosis or hepatocellular carcinoma. The development of clinical-laboratorial analysis tools to this disease and its complications is necessary as the gold standard for its diagnosis is an invasive procedure. The objective of the study is to evaluate the use of BARD score in the selection of patients who should undergo liver biopsy during bariatric surgery...
July 8, 2016: Obesity Surgery
Sreejith Vasudevan, Amit Kavimandan, Nancy Kalra, Baibaswata Nayak, Bhaskar Thakur, Prasenjit Das, Siddhartha Datta Gupta, Subrat Kumar Panda, Subrat Kumar Acharya
BACKGROUND & OBJECTIVES: Standard of care for chronic hepatitis C (CHC) in India is peginterferon and ribavirin (RBV). The response to treatment in real life stetting is unclear. The objectives of this study were to evaluate the demographic profile and assess the virological response and predictors of response in CHC patients. METHODS: Consecutive patients with CHC were included in this study. Detailed clinical history, risk factors, and predictive factors of response were noted...
March 2016: Indian Journal of Medical Research
Niki Katsiki, Dimitri P Mikhailidis, Christos S Mantzoros
Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma. Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression. NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking. NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction...
August 2016: Metabolism: Clinical and Experimental
Sami A Gabr, Ahmad H Alghadir, Ahmed A Allam, Jamaan Ajarem, Ghada Al-Basher, Mostafa A Abdel-Maksoud, Ayman A Ghfar, Alaa Aboud
BACKGROUND: Vitamin D levels play a pivotal role in most biological processes and differ according to age. A deficiency of vitamin D in chronic hepatitis C (CHC) patients has been shown to be linked with the severity of liver fibrosis, but little is known about the mechanism of this association. OBJECTIVE: In this study, we evaluate the potential interrelation between vitamin D levels, oxidative stress, and apoptosis, based on liver fibrosis in geriatric patients infected with hepatitis C virus (HCV) genotype 4...
2016: Clinical Interventions in Aging
Kenneth Cusi
Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions in patients with type 2 diabetes. Patients with NAFLD are at increased risk of more aggressive liver disease (non-alcoholic steatohepatitis [NASH]) and at a higher risk of death from cirrhosis, hepatocellular carcinoma and cardiovascular disease. Dysfunctional adipose tissue and insulin resistance play an important role in the pathogenesis of NASH, creating the conditions for hepatocyte lipotoxicity. Mitochondrial defects are at the core of the paradigm linking chronic excess substrate supply, insulin resistance and NASH...
June 2016: Diabetologia
Ashish Kumar, Varun Gupta, Praveen Sharma, Naresh Bansal, Vikas Singla, Anil Arora
BACKGROUND: Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response. Whether IL-28b genotypes also influence other nontreatment related clinical parameters is unclear. METHODS: Patients with HCV-related chronic liver diseases who attended our department during 2012-2014 were retrospectively analyzed. The single nucleotide polymorphisms (SNPs) of rs12979860 (IL-28B) were correlated with various clinical parameters...
March 28, 2016: Journal of Clinical and Translational Hepatology
Soo Ryang Kim, Ke Ih Kim
Clinical identity of nonalcoholic steatohepatitis (NASH) has established it as a chronic liver disease since the 1990s in the USA and in the 21st century in Japan, although its significance is not well recognized in Japanese society. It is characterized as a chronic liver disease, differentiated from viral liver disease and alcoholic liver disease. Nonalcoholic fatty liver disease (NAFLD) comprises nonalcoholic fatty liver (NAFL) and NASH. NASH is considered to be the hepatic manifestation of a metabolic syndrome...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
S N Batskikh, I V Karandashova, A D Neverov, V P Chulanov
AIM: To clarify the role of virus resistance in the efficiency of antiviral therapy with protease inhibitors (PIs) chronic hepatitis C (CHC) patients, with moderate sensitivity to interferon-α. MATERIALS AND METHODS: Eight Caucasian patients (4 men and 4 women) aged 21 to 65 years (median 52.5 years) with genotype 1b hepatitis C virus (HCV) infection were included in the study. Two patients were diagnosed with liver cirrhosis; 4 had been ineffectively treated with peginterferon in combination with ribavirin...
2016: Terapevticheskiĭ Arkhiv
Tsuyoshi Mashitani, Ryuichi Noguchi, Yasushi Okura, Tadashi Namisaki, Akira Mitoro, Hitoshi Ishii, Toshiya Nakatani, Eiryo Kikuchi, Hiroto Moriyasu, Masami Matsumoto, Shinya Sato, Tatsuichi An, Hiroshi Morita, Sigeyuki Aizawa, Yasunori Tokuoka, Masatoshi Ishikawa, Yoshinobu Matsumura, Hiromasa Ohira, Atsuko Kogure, Kazuhiro Noguchi, Hitoshi Yoshiji
Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease worldwide and is characterized by chronic liver inflammation and fibrosis leading to cirrhosis and increased risk of liver cancer in a proportion of patients. Effective anti-fibrotic agents have yet to be approved for the treatment of NAFLD. The present study aimed to evaluate the efficacy of dipeptidyl peptidase 4 inhibitors (DPP4-I) in the prevention of NAFLD progression in NAFLD patients with type 2 diabetes...
February 2016: Biomedical Reports
L I Tkachenko, V V Maleev, I V Sannikova, M V Titorenko
AIM: To determine the general characteristics of patients with chronic viral hepatitis C (CVHC) from the data of a registry of patients with viral hepatitis (VH) in the Stavropol Territory and to estimate possible predictors for the inefficiency of antiviral therapy (AVT) for treatment optimization. SUBJECTS AND METHODS: The results of examining and treating patients with CVHC were retrospectively analyzed from the data of the registry of HV patients in the Stavropol Territory in 2008-2013...
2015: Terapevticheskiĭ Arkhiv
Ming-Ling Chang
In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown...
January 28, 2016: World Journal of Gastroenterology: WJG
Hilla Knobler, Stephen Malnick
Chronic hepatitis C virus (HCV) infection has been shown to be linked to a higher prevalence of type 2 diabetes compared with the general population or with patients with chronic hepatitis B infection and diabetes is the most common extra-hepatic manifestation of HCV. The HCV-diabetes association is due to insulin resistance (IR) that occurs early in the course of the disease even in patients without or with minimal fibrosis. The mechanisms for HCV-induced IR are only partly understood and include a direct inhibitory effect of HCV on insulin signaling pathway...
January 18, 2016: World Journal of Hepatology
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