Statins and NASH

Background & Aims: Despite availability of diagnostic and management reference guidelines outlining standard of care for patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), national and regional guidelines are lacking, resulting in variations in patient management between regions. We retrospectively analyzed patient characteristics and management data from the Adelphi Real World NASH Disease Specific Programme™ for patients with NASH in the EU5, Canada, and the Middle East to identify gaps between real-world practice and that advocated by reference guidelines, irrespective of clinician awareness or consultation of guidelines...

Non-alcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease. The range is extensive, including hepatocellular carcinoma, cirrhosis, fibrosis, fatty liver, and non-alcoholic steatohepatitis (NASH). NASH is a condition related to obesity, overweight, metabolic syndrome, diabetes, and dyslipidemia. It is a dynamic condition that can regress to isolated steatosis or progress to fibrosis and cirrhosis. Statins exert anti-inflammatory, proapoptotic, and antifibrotic effects. It has been proposed that these drugs could have a relevant role in NASH...

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of fatty infiltration, inflammation, and fibrosis of the liver caused by metabolic factors. It is projected to become the leading cause of cirrhosis and need for liver transplantation in the United States. Guidelines from the American Association for the Study of Liver Diseases (AASLD) do not recommend routine screening of patients at high risk of NAFLD. European guidelines recommend testing for certain high-risk patients. Hepatic steatosis and nonalcoholic steatohepatitis (NASH) are difficult to diagnose and often go unrecognized until patients have advanced fibrosis or cirrhosis...

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, and 25% of patients with NAFLD progress to non-alcoholic steatohepatitis (NASH). NAFLD is predicted to be the most common indication for liver transplantation by 2030. Despite associated high morbidity and mortality, there is currently no approved therapy for NASH. PCSK9 inhibitors are approved for reducing LDL in patients who are statin-intolerant or need further LDL reduction. Increased LDL levels are independently associated with an elevated risk of NAFLD...

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. There is no universally accepted effective treatment for NAFLD. Although various studies propose statins effective in lowering liver enzymes and in improving liver histology, their potency in the treatment and development of NAFLD remains unknown. PURPOSE: We conducted this meta-analysis to evaluate the efficacy of statins in the treatment and the development of NAFLD...

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and NAFLD-related cirrhosis in the United States and globally highlights the need to better understand the mechanisms causing progression of hepatic steatosis to fibrosing steatohepatitis and cirrhosis in a small proportion of patients with NAFLD. Accumulating evidence suggests that lipotoxicity mediated by hepatic free cholesterol (FC) overload is a mechanistic driver for necroinflammation and fibrosis, characteristic of nonalcoholic steatohepatitis (NASH), in many animal models and also in some patients with NASH...

BACKGROUND: There are increasing data on the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). AIM: To summarise evidence on the association between NAFLD and CVD in the clinical setting and provide potential therapeutic implications. METHODS: We searched PubMed. Evidence was primarily derived from meta-analyses. and then, if data were insufficient, from clinical trials, and then from observational studies...

In many countries worldwide, the burden of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing. Preventive strategies are needed to counteract this trend. In this review, we provide an overview of the evidence on preventive strategies in NAFLD-associated HCC. We consider the impact of lifestyle factors such as weight loss, physical activity, smoking, dietary patterns and food items, including coffee and alcohol, on both HCC and NAFLD/NASH...

BACKGROUND: SARS-CoV-2 (COVID-19) disease causes significant morbidity and mortality through increased inflammation and thrombosis. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are states of chronic inflammation and indicate advanced metabolic disease. OBJECTIVE: The purpose of this observational study was to characterize the risk of hospitalization for COVID-19 in patients with NAFLD/NASH and evaluate the mitigating effect of various metabolic treatments...

INTRODUCTION: To estimate the annual incidence of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis, to determine the risk factors for the development of HCC, and to evaluate the chemoprotective effect of statin use stratified by fibrosis stage. METHODS: We conducted a retrospective study at 2 US tertiary academic centers, including patients with NASH-related advanced liver fibrosis (bridging fibrosis [F3] and cirrhosis [F4]) followed between July 2002 and June 2016...

Recurrent Clostridioides difficile infections (rCDI) have a substantial impact on healthcare systems, with limited and often expensive therapeutic options. Nonalcoholic fatty liver disease (NAFLD) affects about 25% of the adult population and is associated with metabolic syndrome, changes in gut microbiome and bile acids biosynthesis, all possibly related with rCDI. The aim of this study was to determine whether NAFLD is a risk factor associated with rCDI. A retrospective cohort study included patients ≥ 60 years hospitalized with CDI...

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which ranks only second to viral hepatitis and poses an increasingly serious challenge to global public health and economy. NAFLD has attracted more and more attention, but there is no drugs with exact curative effects are available. The commonly used drugs for the treatment of NAFLD in clinical practice are statins, such drugs, inevitably increase the burden on the live...

The obesity pandemic has led to a significant increase in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). While dyslipidemia, type 2 diabetes mellitus and cardiovascular diseases guide treatment in patients without signs of liver fibrosis, liver related morbidity and mortality becomes relevant for MAFLD's progressive form, non-alcoholic steatohepatitis (NASH), and upon development of liver fibrosis. Statins should be prescribed in patients without significant fibrosis despite concomitant liver diseases but are underutilized in the real-world setting...

In non-alcoholic steatohepatitis (NASH), decreased nitric oxide and increased endothelin-1 (ET-1, also known as EDN1) released by sinusoidal endothelial cells (LSEC) induce hepatic stellate cell (HSC) contraction and contribute to portal hypertension (PH). Statins improve LSEC function, and ambrisentan is a selective endothelin-receptor-A antagonist. We aimed to analyse the combined effects of atorvastatin and ambrisentan on liver histopathology and hemodynamics, together with assessing the underlying mechanism in a rat NASH model...

Patients with nonalcoholic fatty liver disease (NAFLD) are at an increased risk of cardiovascular disease. Hydoxy-3-methyglutaryl-coenzyme reductase inhibitors, statins, reduce the risk of cardiovascular events.1 Studies have shown that statins are safe among patients with liver disease, including those with compensated cirrhosis,2 and their use is associated with lower mortality, hepatic decompensation, and possibly hepatocellular carcinoma.3 , 4 Despite these data, statins are under prescribed among patients with liver disease due to concerns about hepatotoxicity...

BACKGROUND: The clinical significance of rare mutations in LDL metabolism genes on nonalcoholic fatty liver disease (NAFLD) severity is not well understood. OBJECTIVE: To examine the significance of mutations in LDL metabolism genes including apolipoprotein B (APOB), proprotein convertase subtilisin kexin 9 (PCSK9) and LDL receptor (LDLR) in patients with NAFLD. METHODS: Patients with biopsy-confirmed NAFLD from the NASH Clinical Research Network studies were stratified into 3 groups of LDL-C (≤50 mg/dL, 130-150 mg/dL, ≥ 190 mg/dL) and then 120 (40 per group) were randomly selected from the strata...

PURPOSE OF REVIEW: Adoption of poor lifestyles (inactivity and energy-dense diets) has driven the worldwide increase in the metabolic syndrome, type 2 diabetes mellitus and non-alcoholic steatohepatitis (NASH). Of the defining features of the metabolic syndrome, an atherogenic dyslipidaemia characterised by elevated triglycerides (TG) and low plasma concentration of high-density lipoprotein cholesterol is a major driver of risk for atherosclerotic cardiovascular disease. Beyond lifestyle intervention and statins, targeting the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) is a therapeutic option...

INTRODUCTION: Familial hypercholesterolemia (FH) is a genetic disorder that causes elevated low-density lipoprotein-cholesterol (LDL-C) levels. If undiagnosed and untreated in childhood, affected individuals can suffer premature health complications. Statins reduce the risks of complications for adults, but less is known about children. This systematic review examined the effectiveness of statin therapy for lowering LDL-C levels in children with FH. METHOD: Medline Ovid, Embase, CINAHL, and Allied Health Literature Plus were searched for studies that examined the effectiveness of stains in children ages 1-18 years with heterozygous FH...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality globally. Given the limited therapeutic efficacy in advanced HCC, prevention of HCC carcinogenesis could serve as an effective strategy. Patients with chronic fibrosis due to viral or metabolic etiologies are at a high risk of developing HCC. Primary prevention seeks to eliminate cancer predisposing risk factors while tertiary prevention aims to prevent HCC recurrence. Secondary prevention targets patients with baseline chronic liver disease...

In recent years, rapid growth of incidence of metabolic syndrome, obesity and diabetes has been noted worldwide. Concurrent non-alcoholic steatohepatitis (NASH) has become a dominant factor of hepatic cirrhosis and hepatocellular carcinoma (HCC). The most important risk factors of transition from NASH to HCC are the degree of liver fibrosis, diabetes, obesity, age and male gender. Body mass index (BMI) reduction and increase of physical activity limit the risk of occurrence of HCC. Also, treatment of diabetes with metformin and application of statins have potential anticancer effects...