Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6.FindingsBetween Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group).InterpretationObeticholic...
Source: The Lancet - Category: General Medicine Source Type: research

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Contributors : Muralidhara R Maradana ; Brendan J O'Sullivan ; Ranjeny ThomasSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusNon-alcoholic fatty liver disease (NAFLD) is a common complication of obesity, where insulin resistance and hepatocyte fat deposition may progress to steatohepatitis (NASH) and fibrosis/ cirrhosis. NASH has no approved treatment. Consequent upon hepatic fat deposition, NF- κB activation in hepatic myeloid cells mediates inflammation and NASH progression. We delivered micro-doses of liposome-encapsulated lipophilic NF-κB inhibitors, curcumin or 1,25-d...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Muralidhara R Maradana ; Brendan J O'Sullivan ; Ranjeny ThomasSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusNon-alcoholic fatty liver disease (NAFLD) is a common complication of obesity, where insulin resistance and hepatocyte fat deposition may progress to steatohepatitis (NASH) and fibrosis/ cirrhosis. NASH has no approved treatment. Consequent upon hepatic fat deposition, NF- κB activation in hepatic myeloid cells mediates inflammation and NASH progression. We delivered micro-doses of liposome-encapsulated lipophilic NF-κB inhibitors, curcumin or 1,25-d...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
In this report, we present the case of a patient who was diagnosed with primary biliary cholangitis and metabolic syndrome. Initial evaluation also revealed diabetes with elevated fasting plasma glucose and glycated hemoglobin. After eight weeks of treatment with ursodeoxycholic acid, a complete normalization of the hepatic biological tests was observed. A few months later, while body weight and abdominal perimeter remained stable, fasting blood glucose and glycated hemoglobin decreased significantly, compatible with diabetes disappearance. This finding supports the concept that the inflamed liver plays a major role in the...
Source: Acta Gastro-Enterologica Belgica - Category: Gastroenterology Tags: Acta Gastroenterol Belg Source Type: research
ConclusionThe health economic models identified in this review are associated with limitations primarily driven by a lack of NASH-specific data. Identified models also largely overlooked the intricate association between NASH and other conditions, including obesity and T2DM, and did not capture the increased risk of cardiovascular events associated with NASH. High-quality, transparent, validated health economic models of NASH will be required to evaluate the cost effectiveness of treatments currently in development, particularly compounds that may target other non-hepatic outcomes.
Source: PharmacoEconomics - Category: Health Management Source Type: research
Non-alcoholic fatty liver disease is a spectrum of liver pathology ranging from simple steatosis to steatohepatitis and can progress to diseases associated with poor outcomes including cirrhosis and hepatocellular carcinoma (HCC). NAFLD research has typically focused on the pathophysiology associated with lipid metabolism, using traditional measures such as histology and serum transaminase assessment; these methods have provided key information regarding NAFLD progression. Although valuable, these techniques are limited in providing further insight into the mechanistic details of inflammation associated with NAFLD. Intravi...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract Nonalcoholic fatty liver disease (NAFLD) includes a variety of changes including non-alcoholic fatty liver, cirrhosis and hepatocellular carcinoma (HCC), which are associated with metabolic disorders and cardiovascular diseases. The pathogenesis of NAFLD is complex and multifactorial. Many studies have shown that estrogen has a protective effect on premenopausal women with metabolic disorders and non-alcoholic fatty liver disease. Estrogen supplements may, at least in theory, prevent the development and progression of NAFLD. Phytoestrogen is extracted from plants, especially legumes´╝îwhose molecular stru...
Source: Mini Reviews in Medicinal Chemistry - Category: Chemistry Authors: Tags: Mini Rev Med Chem Source Type: research
CONCLUSION: Overall, study findings indicate a relationship between microbial composition and NAFLD. Study methods and sequencing techniques influenced these results. PMID: 31910634 [PubMed - in process]
Source: Archives of Iranian Medicine - Category: Middle East Health Authors: Tags: Arch Iran Med Source Type: research
Non-alcoholic fatty liver disease (NAFLD) figures prominently into the clinical hepatology landscape. NAFLD represents a disease spectrum comprising simple steatosis, steatosis with elevated liver enzymes, and non-alcoholic steatohepatitis (NASH), the entity with clear potential for fibrosis progression. Risk factors associated with fibrosis progression in NASH include histologic findings of lobular inflammation and any fibrosis as well as clinical comorbidities that include type 2 diabetes, obesity, and metabolic syndrome. Liver biopsy remains the gold standard in evaluating NASH; however, noninvasive methods are accumula...
Source: Gastroenterology Clinics of North America - Category: Gastroenterology Authors: Source Type: research
CONCLUSION: NAFLD-related HCC was found in non-cirrhotic patients in 42% of cases, alpha-fetoprotein level was normal in 63% and "steatohepatitic HCC" was the predominant histological type. Immunoexpression of K19 and/or Ki-67 occurred in 32% of the nodules and were associated with intratumoral inflammation and ballooning, suggesting that HCC in MtS may be preferentially "an inflammatory, non-proliferative subtype of HCC". PMID: 31858523 [PubMed - as supplied by publisher]
Source: Histology and Histopathology - Category: Cytology Tags: Histol Histopathol Source Type: research
AbstractIntroductionTen percent of cirrhotic patients are known to have a high risk of postoperative complications. Ninety percent of bariatric patients suffer from non-alcoholic fatty liver disease (NAFLD), and 50% of them may develop non-alcoholic steatohepatitis (NASH) which can progress to cirrhosis. The aim of this study was to assess whether the presence of cirrhosis at the time of bariatric surgery is associated with an increased rate and severity of short- and long-term cirrhotic complications.MethodsA cohort of 110 bariatric patients, between May 2003 and February 2018, who had undergone liver biopsy at the time o...
Source: Obesity Surgery - Category: Surgery Source Type: research
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