Identification of High-Risk Patients With Nonalcoholic Fatty Liver Disease in Endocrinology Clinics.

The twin epidemics of obesity and type 2 diabetes continue to increase worldwide, so does the associated chronic liver disease, nonalcoholic fatty liver disease (NAFLD). Although NAFLD has been thought of as a benign liver disease, current evidence suggests that it is a complex liver disease that, for approximately 20% of patients, can progress to fibrosis, cirrhosis, hepatocellular carcinoma, liver transplant, and death. It is important to note that, given NAFLD's association with metabolic syndrome, the number one cause of death among those with NAFLD is related to cardiovascular diseases. In addition, NAFLD is associated with impaired patient-reported outcomes and a significant economic burden. As such, efforts are now aimed at using noninvasive tests (NITs) to identify patients with NAFLD and those who are at risk of liver disease progression and adverse outcomes in endocrinology practices whereby appropriate risk stratification and referrals can be undertaken. In this review, we discuss the most common NITs used and provide a simple clinically relevant algorithm using these NITs to identify patients with NAFLD who are at risk of adverse outcomes and subsequent clinical management and referral.

American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm - 2023 Update.

OBJECTIVE: This consensus statement provides (1) visual guidance in concise graphic algorithms to assist with clinical decision-making of health care professionals in the management of persons with type 2 diabetes mellitus to improve patient care and (2) a summary of details to support the visual guidance found in each algorithm. METHODS: The American Association of Clinical Endocrinology (AACE) selected a task force of medical experts who updated the 2020 AACE Comprehensive Type 2 Diabetes Management Algorithm based on the 2022 AACE Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan and consensus of task force authors. RESULTS: This algorithm for management of persons with type 2 diabetes includes 11 distinct sections: (1) Principles for the Management of Type 2 Diabetes; (2) Complications-Centric Model for the Care of Persons with Overweight/Obesity; (3) Prediabetes Algorithm; (4) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Dyslipidemia; (5) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Hypertension; (6) Complications-Centric Algorithm for Glycemic Control; (7) Glucose-Centric Algorithm for Glycemic Control; (8) Algorithm for Adding/Intensifying Insulin; (9) Profiles of Antihyperglycemic Medications; (10) Profiles of Weight-Loss Medications (new); and (11) Vaccine Recommendations for Persons with Diabetes Mellitus (new), which summarizes recommendations from the Advisory Committee on Immunization Practices of the U.S. Centers for Disease Control and Prevention. CONCLUSIONS: Aligning with the 2022 AACE diabetes guideline update, this 2023 diabetes algorithm update emphasizes lifestyle modification and treatment of overweight/obesity as key pillars in the management of prediabetes and diabetes mellitus and highlights the importance of appropriate management of atherosclerotic risk factors of dyslipidemia and hypertension. One notable new theme is an emphasis on a complication-centric approach, beyond glucose levels, to frame decisions regarding first-line pharmacologic choices for the treatment of persons with diabetes. The algorithm also includes access/cost of medications as factors related to health equity to consider in clinical decision-making.

American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD).

OBJECTIVE: To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders. METHODS: The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RECOMMENDATION SUMMARY: This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base. CONCLUSION: NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.

Intrahepatic hypothyroidism in MASLD: Role of liver-specific thyromimetics including resmetirom.

BACKGROUND AND AIMS: Thyroid hormones are important regulators of hepatic lipid homeostasis and whole-body energy expenditure. Recent evidence suggests that euthyroid individuals with metabolic dysfunction-associated steatohepatitis (MASH) develop intrahepatic hypothyroidism that promotes progression of MASH. METHODS: A literature search was performed with Medline (PubMed), Scopus and Google Scholar electronic databases from inception till March 2024, using the following keywords: hypothyroidism and nonalcoholic fatty liver disease; MASLD and thyroid function; intrahepatic hypothyroidism; TRß agonists; and resmetirom. Relevant studies were extracted that described pathogenesis of MASH in the context of thyroid functions. RESULTS: In euthyroid individuals with MASH, there is decreased conversion of prohormone thyroxine (T4) to bioactive tri-iodothyronine (T3) and increased conversion of T4 to inactive metabolite reverse T3 (rT3). Consequently, reduced levels of T3 results in impaired intrahepatic TRß signaling, a state of intrahepatic hypothyroidism, which promotes progression of MASH. Hepatic TRß activation leads to metabolically beneficial effects in the liver including mitochondrial fatty acid uptake and ß-oxidation, mitochondrial biogenesis, increasing surface low-density lipoprotein (LDL) receptor density and lowering of circulatory LDL-cholesterol. In recent years, selective thyroid hormone mimetics that exhibit TRß-selective binding and liver-selective uptake have been designed. Resmetirom, a liver-specific thyromimetic, improves intrahepatic TRß signaling and in clinical trials significantly improved liver inflammation, fibrosis and lipid profile in patients with MASH. CONCLUSIONS: In euthyroid individuals with MASH, development of intrahepatic hypothyroidism results in further progression of the disease. In clinical trials, resmetirom treatment results in a significant improvement in steatosis, inflammation and fibrosis and is the first drug approved by the US Food and Drug Administration (FDA) for the treatment of noncirrhotic MASH with moderate to advanced fibrosis.

Nonalcoholic Fatty Liver Disease.

Management of nonalcoholic fatty liver disease (NAFLD) is crucial for type 2 diabetes (T2D) remission because they are linked through the common pathophysiology of insulin resistance and lipotoxicity. One in three patients with T2D has nonalcoholic steatohepatitis leading to fibrosis, cirrhosis, and hepatocellular carcinoma. Noninvasive testing with imaging and/or serum biomarkers can assess the risk for advanced liver disease. A liver biopsy is only necessary in select patients where there is diagnostic doubt. Treatments for NAFLD parallel T2D remission strategies focusing on weight loss and managing comorbid conditions through lifestyle modification, antiobesity medications, and/or bariatric surgery, and T2D medications with proven efficacy.

A practical use of noninvasive tests in clinical practice to identify high-risk patients with nonalcoholic steatohepatitis.

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) or other components of metabolic syndrome are at high risk for disease progression. We proposed an algorithm to identify high-risk NAFLD patients in clinical practice using noninvasive tests (NITs). METHODS: Evidence about risk stratification of NAFLD using validated NITs was reviewed by a panel of NASH Experts. Using the most recent evidence regarding the performance of NITs and their application in clinical practice were used to develop an easy-to-use algorithm for risk stratification of NAFLD patients seen in primary care, endocrinology and gastroenterology practices. RESULTS: The proposed algorithm uses a three-step process to identify NAFLD patients who are potentially at high risk for adverse outcomes. The first step is to use clinical data to identify most patients who are at risk for having potentially progressive NAFLD (e.g. having T2D or multiple components of metabolic syndrome). The second step is to calculate the FIB-4 score as a NIT that can further risk stratifying individuals who are at low risk for progressive liver disease and can be managed by their primary healthcare providers to manage their cardiometabolic comorbidities. The third step is to use second-line NITs (transient elastography or enhanced liver fibrosis tests) to identify those who at high risk for progressive liver disease and should be considered for specially care by providers with NASH expertise. CONCLUSIONS: The use of this simple clinical algorithm can identify and assist in managing patients with NAFLD at high risk for adverse outcomes.

Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes.

Admission hyperglycemia has been associated with increased hospital mortality in critically ill patients; however, it is not known whether hyperglycemia in patients admitted to general hospital wards is associated with poor outcome. The aim of this study was to determine the prevalence of in-hospital hyperglycemia and determine the survival and functional outcome of patients with hyperglycemia with and without a history of diabetes. We reviewed the medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center, a community teaching hospital in downtown Atlanta, GA, from July 1, 1998, to October 20, 1998. New hyperglycemia was defined as an admission or in-hospital fasting glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations. Hyperglycemia was present in 38% of patients admitted to the hospital, of whom 26% had a known history of diabetes, and 12% had no history of diabetes before the admission. Newly discovered hyperglycemia was associated with higher in-hospital mortality rate (16%) compared with those patients with a prior history of diabetes (3%) and subjects with normoglycemia (1.7%; both P < 0.01). In addition, new hyperglycemic patients had a longer length of hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility. Our results indicate that in-hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.