Fernando Bril

• MD
• Assistant Professor at University of Alabama at Birmingham

Introduction and Objective: People with type 2 diabetes (T2D) and obesity appear prone to developing "at-risk" MASH, defined as steatohepatitis with significant fibrosis (stage F≥2), that when present predisposes to cirrhosis. However, the relative impact of T2D and/or BMI remains controversial. We assessed the prevalence of MASLD and "at-risk" MAS...

Hirsutism affects approximately 10% of women globally, with significant economic and quality of life impact. Facial and body terminal hair growth in a male-like pattern is determined by a number of factors, including circulating androgens, and tissue androgen receptor, 5α-reductase, 3α- and 17β-hydroxysteroid dehydrogenase, and ornithine decarboxyl...

Background Polycystic ovary syndrome (PCOS) is one of the most prevalent cardio-metabolic disorders in women. However, PCOS diagnosis is often missed or delayed, which may have serious physical and mental health consequences. The extent of underdiagnosis remains unknown. Objective To estimate the extent to which PCOS is underdiagnosed. Materials...

This mini review explores the increasing prevalence of obesity in type 1 diabetes (T1D) and the challenges patients face in achieving optimal glycemic control with current treatments. It discusses the evidence supporting the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) as potential adjunctive therapy in T1D to reduce weight and improv...

Background Fasting intact insulin concentrations can predict metabolic dysfunction–associated steatotic liver disease (MASLD) in adults without diabetes; however, research in youth is limited. We sought to determine whether fasting intact insulin, measured by liquid chromatography-tandem mass spectrometry, is associated with MASLD in children. Met...

Objective The objective of this study was to determine the prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) in young compared with older adults. Methods Individuals (n = 1420) with (63%) and without type 2 diabetes mellitus (T2D; 37%) who attended internal medicine clinics and did not have a known history of MASLD und...

Background and Aims Recently, a new entity was introduced, MetALD, which includes patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), who consume moderate amounts of alcohol. However, little is known regarding the metabolic and clinical characteristics of these patients. Methods Data from the National Health and Nutriti...

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged females, and women with PCOS are at increased risk for endometrial cancer (EndoCA), the most common gynecological malignancy. Our study sought to assess the economic burden associated with EndoCA in PCOS. Method Using PRISMA systematic review...

Background Polycystic ovary syndrome (PCOS) is a common female cardiometabolic-reproductive disorder. It is unclear whether the global obesity epidemic is impacting the high PCOS prevalence. Objective To determine the association between the prevalence of PCOS and obesity. Materials and methods A systematic review was conducted to identify popula...

Background With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. Metho...

With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. Using the Qualtr...

Background & Aims It has been postulated that carriers of PNPLA3 I148M (CG [Ile/Met] or GG [Met/Met]) develop metabolic dysfunction-associated steatotic liver disease (MASLD) in the absence of insulin resistance or metabolic syndrome. However, the relationship between insulin resistance and MASLD according to the PNPLA3 allele has not been carefull...

This narrative review aims to illustrate the notion that nonalcoholic steatohepatitis (NASH), recently renamed metabolic dysfunction-associated steatohepatitis (MASH), is a systemic metabolic disorder featuring both adverse hepatic and extrahepatic outcomes. In recent years, several NASH trials have failed to identify effective pharmacological trea...

Objective The objective of this study was to assess the performance of noninvasive tests (NITs) across different racial and ethnic groups in a large multiethnic cohort. Methods Data were derived from the National Health and Nutrition Examination Survey (NHANES) 2017 through 2020. Participants without valid transient elastography measurements or wi...

Disclosure: J.S. Lo: None. F. Bril: None. A. Taylor: None. N. Morelli: None. M.A. Ware: None. Y. Garcia-Reyes: None. M.J. McPhaul: Employee; Self; Quest Diagnostics. M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Amino Corp. Adolescents with obesity and polycystic ovary syndrome (PCOS) have significant insulin resistance...

Disclosure: S. Hatoum: None. M. Amiri: None. D. Hopkins: None. R.P. Buyalos: Employee; Self; Fertility & Surgical Associates of California. F. Bril: None. R. Azziz: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Fortress Biotech, Spruce Biosciences, Core Access Surgical Technologies. Grant Recipient; Self; Founda...

Disclosure: C.C. Makwe: None. J.A. Olamijulo: None. M.R. Balogun: None. A.O. Akinkugbe: None. A. Samuel: None. K. Udenze: None. F. Bril: None. R.P. Buyalos: None. J.S. Laven: None. R. Azziz: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Spruce Biosciences, Fortress Biotech, Core Access Surgical Technologies. Gra...

Disclosure: F. Bril: None. S. Kalavalapalli: None. K. Cusi: None. The obesity epidemic has resulted in a significant increase in the prevalence of nonalcoholic fatty liver disease (NAFLD). Some patients with NAFLD progress to more severe forms of the disease, such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Our central hypothesis is that...

Disclosure: L.A. Pace: None. D. Markovic: None. R.P. Buyalos: Employee; Self; Fertility and Surgical Associates of California. F. Bril: None. R. Azziz: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Spruce Biosciences, Fortress Biotech, Core Access Surgical Technologies. Grant Recipient; Self; Foundation for Rese...

Disclosure: M. Amiri: None. S. Hatoum: None. D. Hopkins: None. R.P. Buyalos: Employee; Self; Fertility & Surgical Associates of California. U. Ezeh: Stock Owner; Self; Concentric Analgesics, Inc. L.A. Pace: None. F. Bril: None. R. Azziz: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Fortress Biotech, Spruce Bios...

Disclosure: F. Bril: None. J. Louie: Employee; Self; Quest Diagnostics. D. Shiffman: Consulting Fee; Self; Quest Diagnostics. M.J. McPhaul: Employee; Self; Quest Diagnostics. Stock Owner; Self; Quest Diagnostics. The increasing prevalence of obesity in the US and worldwide has fueled a dramatic increase in the number of patients affected with nonal...

Context While T2D is a risk factor for liver fibrosis in NAFLD, the specific contribution of insulin resistance (IR) relative to other factors is unknown. Objective Assess the impact on liver fibrosis in NAFLD of adipose tissue (Adipo-IR) and liver (HOMA-IR) IR in people with T2D and NAFLD. Design Participants were screened by elastography in the...

The severity of liver fibrosis in patients with NAFLD is a strong predictor of cardiovascular mortality, independently of other well-known cardiovascular risk factors. However, the exact mechanisms leading to cardiovascular disease in patients with advanced liver fibrosis remain incompletely understood. As many of the apolipoproteins are synthesize...

Context The mechanisms leading to increased cardiovascular disease in patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis remain incompletely understood. Objective This study assessed HDL-bound proteins in patients with NAFLD with or without advanced fibrosis. Design Cross-sectional Setting University hospital Pat...

Aim: The optimal screening strategy for advanced liver fibrosis in overweight and obese patients is unknown. The aim of this study is to compare the performance of different strategies to select patients at high risk of advanced liver fibrosis for screening using non-invasive tools. Methods: All patients underwent: liver 1H-MRS and percutaneous...

Bariatric surgery (BarS) is known to improve insulin resistance (IR) , atherogenic dyslipidemia and steatohepatitis in patients (pts) with type 2 diabetes (T2D) . Total ceramides (Cer) and diacylglycerols (DAGs) have been implicated in the development of IR and nonalcoholic fatty liver disease (NAFLD) , but the impact of BarS on their plasma concen...

Patients with T2D remain at high risk of cardiovascular (CV) events despite adequate glycemic and LDL-C control. Changes in HDL particle composition and function may explain part of this increased CV risk. The aim of this study was to determine the proteomic composition of isolated HDL particles in T2D patients, and establish which factors contribu...

Background: Nonalcoholic steatohepatitis (NASH), advanced fibrosis, and subsequent cirrhosis and hepatocellular carcinoma are becoming the most common etiology for liver failure and liver transplantation; however, they can only be diagnosed at these potentially reversible stages with a liver biopsy, which is associated with various complications a...

Background&Aims PPAR-γ agonists decrease hepatic/visceral fat (VF) and improve necroinflammation despite subcutaneous (SC) fat weight-gain. Understanding the impact of changes in VF, VF-to-SC distribution (VF/SC) and adiponectin levels in relation to histological improvement after weight-loss or pioglitazone is relevant as novel PPAR-γ agonists are...

Context Patients with nonalcoholic fatty liver disease (NAFLD) are characterized by insulin resistance and hyperinsulinism. However, insulin resistance measurements have not been shown to be good diagnostic tools to predict NAFLD in prior studies. Objective We aimed to assess a newly validated method to measure intact molecules of insulin by mass...

Background Hypogonadism is reported to occur in non-alcoholic fatty liver disease (NAFLD), but earlier studies used low-sensitivity diagnostic techniques (CT, ultrasound), for NAFLD diagnosis. We hypothesized that if hypogonadism was due to NAFLD, and not solely attributable to underlying obesity/diabetes, it would be more severe in the presence of...

Patients with NAFLD are characterized by insulin resistance (IR) and hyperinsulinism. However, prior studies have been unable to predict NAFLD based on IR measurements. The aim of this study was to explore the application of a newly validated measurement of intact insulin by mass spectrometry to predict NAFLD in patients without diabetes. Ninety-ei...

Dysfunctional mitochondrial function plays an important role in the progression of nonalcoholic steatohepatitis (NASH). Mitochondrial (mt) respiratory function assessed by oxidative phosphorylation/ OXPHOS (activated respiration with mt complex I [OXPHOS CI] and mt complex I + II [OXPHOS CI+II] substrates) and electron transport system capacity [ET...

Background and objectives: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) have become public health problems in the pediatric population. However, the relationship between these two conditions is not well understood. The primary objective of this study was to assess whether treatment of hyperglycemia in obese, treatme...

Objective: Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM). Research design and methods: A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending pr...

Nonalcoholic fatty liver disease (NAFLD) has consolidated as a major public health problem, affecting ~25% of the global population. This percentage is significantly higher in the setting of obesity and/or type 2 diabetes. Presence of NAFLD is associated with severe liver complications, such as nonalcoholic steatohepatitis (NASH; i.e., presence of...

The ADA recommends screening for liver fibrosis in all patients with T2DM and with elevated ALT or steatosis. However, the factors that may predispose to hepatic fibrosis, such as comorbid conditions or insulin resistance (IR), have not been carefully examined. To this end, we studied patients with T2DM and NAFLD/fibrosis screened in an outpatient...

In 2019, the ADA recommended screening for NASH and liver fibrosis in patients with T2DM and steatosis or elevated ALT. However, the true prevalence of liver fibrosis in unselected patients with T2DM in the United States remains unknown. To this end, we screened patients with T2DM attending either internal medicine (IM), family medicine (FM) or end...

Background Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors that are mostly benign. Metastatic disease does occur in about 10% of cases, and for these patients no effective therapies are available. Patients with mutations in the succinate dehydrogenase subunit B (SDHB) gene tend to have metastatic disease. We hypothesize...

Background: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors that are mostly benign. Metastatic disease occurs in about 10% of cases, and for these patients no effective therapies are available. Patients with mutations in the succinate dehydrogenase subunit B (SDHB) gene tend to have metastatic disease with very little t...

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The more severe form is non-alcoholic steatohepatitis (NASH) which can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NASH is more common in patients with type 2 diabetes mellitus (T2DM). However, its true prevalence in unselected patient...

BACKGROUND Central nervous system (CNS) depressants like antipsychotics, opioids, benzodiazepines and zolpidem are frequently used by patients within a wide range of ages. Uncertainty remains about their effect in very old adults (>80 years old) and their potential for pharmacodynamic and pharmacokinetic drug-drug interactions in this population....

While non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of impaired glucose tolerance and type 2 diabetes mellitus (DM) in non-pregnant patients, the clinical significance of NAFLD during pregnancy is still unclear. We hypothesized that sonographic findings of NAFLD during pregnancy would be associated with gestational dia...

Objective: The 2019 Standards of Medical Care in Diabetes suggested that patients with nonalcoholic fatty liver disease (NAFLD) should be evaluated for liver fibrosis. However, the performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and advanced fibrosis has not been care...

Background & aims: Proof-of-concept studies frequently assess changes in intrahepatic triglyceride (IHTG) content by MR-based techniques as a surrogate marker of histology. The aim of this study was to establish how reliable this strategy is to predict changes in liver histology in patients with NASH. Methods: Patients with NASH who had particip...

Exenatide (Exe) is a glucagon-like peptide (GLP)-1 receptor agonist that enhances insulin secretion and is associated with induction of satiety with weight loss. As mitochondrial dysfunction and lipotoxicity are central features of nonalcoholic steatohepatitis (NASH), we tested whether Exe improved mitochondrial function in this setting. We studied...

Pioglitazone (PIO) therapy results in a ∼60% resolution of NASH in patients with prediabetes or T2DM. However, the effects of treatment discontinuation have not been carefully examined. To this end, we assessed plasma aminotransferases (LFTs) after study drug discontinuation among patients who had completed 36 months (n=63) of our randomized, contr...

Objective: This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM). Research design and methods: Patients with T2DM (n = 191) underwent an oral glucose tolerance test, a liver 1H-MRS, and a...

Objective: While vitamin E has shown to improve nonalcoholic steatohepatitis (NASH) in patients without diabetes, information on patients with type 2 diabetes mellitus (T2DM) is lacking. The aim of this study was to determine whether vitamin E, alone or combined with pioglitazone, improves histology in patients with T2DM and NASH. Research design...

The increasing global prevalence of nonalcoholic fatty liver disease (NAFLD) has prompted efforts to identify affected subjects. In particular, the identification of the presence of nonalcoholic steatohepatitis (NASH) and fibrosis in patients with NAFLD has become a priority. The widely-recognized limitations of liver biopsy as ‘gold standard’ for...

Improved understanding of the complex pathophysiology of type 2 diabetes provides a logical basis for target identification and the development of novel glucose-lowering agents. While the major driver of type 2 diabetes is obesity, if β-cells of the pancreatic islets are able to compensate for the obesity-associated insulin resistance by increasing...

Context The relationship between plasma FGF21, insulin resistance and steatohepatitis has not been systematically assessed. Objective To determine if higher plasma FGF21 is associated with worse steatohepatitis on liver biopsy in patients with NAFLD. Design and Setting Cross-sectional study in a University Hospital. Patients Interventions and Mai...

Aim To evaluate the impact of the sodium glucose co‐transporter 2 inhibitor canagliflozin on intrahepatic triglyceride (IHTG) accumulation and its relationship to changes in body weight and glucose metabolism. Materials and methods In this double‐blind, parallel‐group, placebo‐controlled, 24‐week trial subjects with inadequately controlled type 2...

Type 2 diabetes mellitus (T2DM) should be understood as the final common pathway that results from an imbalance between increased insulin resistance (i.e., decreased insulin action) and relative insulinopenia (i.e., impaired insulin secretion). There is consensus that for most patients with T2DM the earliest defect observed is insulin resistance. A...

Non‐alcoholic fatty liver disease (NAFLD) has an estimated prevalence of 25% in the general population, and cirrhosis secondary to Non‐Alcoholic Steatohepatitis (NASH) is predicted to become the leading cause of liver transplantation and yet there is a lack of effective licensed treatments. There is a close relationship between insulin resistance a...

Fibromax is a diagnostic tool composed of the combination of 4 non-invasive biomarker panels for the diagnosis of steatosis (SteatoTest), necrosis and inflammation (ActiTest and NashTest-2) and fibrosis (FibroTest). The purpose of this study was to assess the performance of these biomarker panels in patients with type 2 diabetes mellitus (T2DM). Al...

Background: The effects of pioglitazone on bone metabolism are unclear. The aim of this study was to evaluate the long-term effect of pioglitazone on bone mineral density (BMD) and bone metabolism in patients with prediabetes or type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH). Methods: A total of 92 patients with prediabe...

Pioglitazone is used effectively to treat non-alcoholic steatohepatitis (NASH), but there is marked variability in response. This study examined whether genetic variation contributes to pioglitazone response variability in patients with NASH. This genetic substudy includes 55 participants of a randomized controlled trial designed to determine the e...

Exenatide (Exe) is a glucagon-like peptide-1agonist (GLP-1) that enhances insulin production, slows gastric emptying and reduces appetite. Nonalcoholic fatty liver disease (NAFLD), and its more severe form known as NASH, are frequent complications of T2DM. As mitochondrial dysfunction and lipotoxicity are central features of NASH, we tested whether...

Study Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with elevated risk for metabolic syndrome, type 2 diabetes, cardiovascular disease and cirrhosis. Available diagnostic tools (plasma aminotransferases and liver ultrasound) have low sensitivity. This study screened a broad population of children from an endocrine clinic with a...

Nonalcoholic fatty liver disease (NAFLD) affects a significant number of patients with T2DM and places them at an increased risk of steatohepatitis (NASH) and cirrhosis. However, it is widely underdiagnosed due to lack of a simple, non-invasive test for its diagnosis. The aim of this study was to establish a plasma biomarker profile to identify NAF...

While the use of vitamin E (Vit E) in nondiabetic patients with NASH has proven to be effective in the PIVENS study (NEJM 2010), there is no information about its effect in patients with NASH and T2DM. To examine this, we performed a randomized, double blind, controlled trial assessing the efficacy of Vit E, alone or combined with pioglitazone (PIO...

Pioglitazone is effective in improving insulin resistance and liver histology in patients with nonalcoholic steatohepatitis (NASH). Because dysfunctional mitochondrial metabolism is a central feature of NASH, we hypothesized that an important target of pioglitazone would be alleviating mitochondrial oxidative dysfunction. To this end, we studied he...

Aims: While several non-invasive clinical/metabolic scores have been designed to predict the presence of nonalcoholic steatohepatitis (NASH), none was specifically validated in patients with T2DM. We aimed to assess the utility of existing metabolomics scores to classify liver disease in patients with T2DM. Materials and methods: A total of 220...

Background & aims: Pioglitazone is effective for long-term treatment of patients with nonalcoholic steatohepatitis (NASH) with prediabetes or type-2 diabetes. However, it is not clear how the presence of type-2 diabetes affects the drug's efficacy. We compared metabolic and histologic responses to pioglitazone in patients with NASH and prediabetes...

Objective: There has been a widespread misconception among physicians that African Americans are protected from developing nonalcoholic steatohepatitis (NASH). However, a formal histologic and metabolic comparison against well-matched Caucasians has never been performed. Research design and methods: Sixty-seven African American patients were mat...

Context Patients with NAFLD have a high cardiovascular risk, but statins are rarely prescribed due to fear of hepatotoxicity. Objective To perform a prospective assessment of the long-term safety of statins in patients with prediabetes/T2DM and NASH. Design Post-hoc analysis of statin use during a randomized, controlled trial (RCT) assessing piog...

Background: Pioglitazone is a safe and effective option to manage patients with type 2 diabetes and nonalcoholic steatohepatitis (NASH). However, there is marked variability in treatment response. Aim: To evaluate the relationship between concentrations of pioglitazone and its active metabolites and treatment outcomes in patients with NASH. Met...

Traditionally a disease of hepatologists, nonalcoholic fatty liver disease (NAFLD) has recently become a major concern for a broad spectrum of health care providers. Endocrinologists and those caring for patients with type 2 diabetes mellitus (T2DM) are at center stage, as T2DM appears to worsen the course of NAFLD and the liver disease makes diabe...

Conclusion: IHTG accumulation is strongly associated with adipose tissue insulin resistance, supporting the current theory of lipotoxicity as a driver of IHTG accumulation. Once IHTG accumulation reaches ∼6±2%, skeletal muscle insulin resistance, hypertriglyceridemia, and low HDL-C, become fully established. Histological activity appears to have a...

Nonalcoholic fatty liver disease (NAFLD) is prevalent in patients with obesity or type 2 diabetes. Nonalcoholic steatohepatitis (NASH), encompassing steatosis with inflammation, hepatocyte injury, and fibrosis, predisposes to cirrhosis, hepatocellular carcinoma, and even cardiovascular disease. In rodent models and humans with NAFLD/NASH, maladapta...

Nonalcoholic fatty liver disease (NAFLD) is increasingly common in patients with type 2 diabetes mellitus (T2DM), with an estimated prevalence of 60% to 80%. The relationship of NAFLD and T2DM is complex, with each condition negatively affecting the other. Although NAFLD is associated with more metabolic and cardiovascular complications and worse h...