An overwhelming majority of NAFLD patients are treated in general care and endocrinology settings. This article presents the AACE and AASLD recommendations for the screening, diagnosis and treatment of fatty liver diseases.

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NAFLD and NASH

The primary line of treatment for NAFLD patients is provided in the general care and endocrinology settings. Patients are only sent to liver specialists when their condition has reached an advanced stage. We must thus be the ones identifying and treating these individuals since there are insufficient liver experts to do so.

The spectrum of NAFLD includes nonprogressive steatosis, nonalcoholic steatohepatitis NASH, fibrotic NASH, and NASH cirrhosis at the end-stage. In turn, NASH is a leading cause of liver cancer. Furthermore, NAFLD is closely linked to insulin resistance, type 2 diabetes, atherogenesis, and cardiac dysfunction.

The prevalence of NAFLD is around 25 per cent, whereas that of NASH is between 12 and 14 per cent. Recent research indicated that more than 70% of patients with type 2 diabetes and more than 90% of patients with type 2 diabetes who had a body mass index (BMI) over 35 kg/m2 also had NAFLD, and more than 20% of these individuals had severe liver fibrosis.

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Prevalence in India

An estimated 16-32 per cent of India's general population (about 120 million people) has NAFLD, and among them, almost 31 per cent have been diagnosed with NASH. The rising incidence of NAFLD in the Indian population is attributable to industrialization, changes in lifestyle and nutrition characterised by reduced physical exercise and an increase in calorie-dense foods.

Also, it is projected that 63 million Indians have Type 2 diabetes, with 70% of them having NAFLD (44 million). And it is expected that one-third of the NAFLD population has NASH (13 million). It is also possible that 5% of NASH patients (650,000) may acquire liver cancer.

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The irony of disease 

Unfortunately, relatively few individuals are aware they have either condition. In reality, the majority of NAFLD cases are discovered through ultrasounds or CT scans performed for other reasons. In around 70% of instances, liver enzymes are normal, and these individuals receive liver workups seldom.

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Treatment approach to fatty liver: Latest recommendations and FAQs

The American Association of Clinical Endocrinology AACE and the American Association for the Study of Liver Diseases (AASLD) have released new clinical practice recommendations for the diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD). These are the first to be aimed exclusively at primary care and endocrinology clinical settings.

They contain suggestions for screening, diagnosis, treatment, and referral based on scientific evidence. The AACE guideline is very applicable and simple to implement in general care and endocrinology settings.

1. Which adults with NAFLD should be considered to have a "high risk" of clinically significant fibrosis (stages F2-F4) and cirrhosis?

Clinicians should consider individuals with obesity and/or symptoms of Metabolic syndrome, those with prediabetes or T2D, and those with hepatic steatosis on any imaging examination and/or consistently increased plasma aminotransferase levels (over 6 months) to be at "high risk" for NAFLD and advanced fibrosis, and test these individuals for NAFLD and advanced fibrosis.

2. What Blood Tests (eg, Diagnostic Panels and Specific Biomarkers) Can Be Used to Diagnose NAFLD With Clinically Significant Fibrosis (Stages F2-F4) in Adults?

To determine the risk of NAFLD in patients with liver fibrosis, clinicians should apply hepatic fibrosis prediction calculations. The fibrosis-4 index is the first noninvasive test of choice (FIB-4). The recommended screening test is the fibrosis-4 (FIB-4) index, calculated using the patient's age, AST level, platelet (PLT) count, and ALT level: FIB-4 score = age (years) x AST (U/L)/[PLT (109/L) x ALT ½ (U/L)].

A score of <1.45 and >3.25 enables the correct identification of patients who have moderate or significant fibrosis, respectively, and could avoid liver biopsy examination. The FIB-4, which was recently authorised by the US Food and Drug Administration (FDA), has been shown to aid in the diagnosis of liver disease in primary care settings. The FIB-4 classifies people as having a low, moderate, or high risk of developing liver fibrosis. Individuals at low risk may be handled in general practice or endocrinology settings with an emphasis on obesity management and cardiovascular disease prevention.

A second noninvasive test, either a liver stiffness assessment by elastography or an enhanced liver fibrosis (ELF) test, is recommended for people at moderate risk. If the patient is determined to be at high risk or if the results of two non-invasive tests are inconclusive, referral to a liver specialist for further testing, including a potential biopsy, is recommended.

Those with a high FIB-4 risk score should also be sent to hepatology. The recommendations recommend multidisciplinary care, including a hepatologist, endocrinologist, and other specialists, for both intermediate- and high-risk populations to avoid cardiovascular disease and the development of cirrhosis.

3. What imaging tests may be used to diagnose NAFLD in adults with clinically significant fibrosis (stages F2-F4)?

As the most proven method to diagnose advanced illness and predict liver-related consequences, VCTE Vibration Controlled Transient Elastography (Fibroscan) should be preferred by doctors for staging the risk of fibrosis in patients with NAFLD. Alternative imaging techniques, such as shear wave elastography (SWE) (less well-proven) and/or magnetic resonance imaging (MRE), may be examined (most accurate but with a high cost and limited availability; best if ordered by a liver specialist for selected cases).

4. Should All Diabetics Be Tested for Clinically Significant Fibrosis (Stages F2-F4) Linked to NAFLD?

Even if a person with T2D has normal liver enzyme values, doctors should consider screening for clinically significant fibrosis (stages F2-F4) with the FIB-4.

5. When Should an Adult Be Referred to a Gastroenterologist/Hepatologist for Management?

Persons with persistently elevated ALT or aspartate aminotransferase (AST) levels and/or with hepatic steatosis on imaging and indeterminate risk (FIB-4, 1.3- 2.67; LSM, 8-12 kPa; or ELF test, 7.7-9.8) or high risk (FIB-4, >2.67; LSM, >12 kPa; or ELF test, >9.8) based on blood tests and/or imaging should be referred to a gastroenterologist or hepatologist for further assessment, which may include a liver biopsy.

6. How Should Cardiometabolic Risk and Other Extrahepatic Complications Be Managed in the Setting of NAFLD?

Clinicians must treat patients with NAFLD for obesity, Metabolic syndrome, prediabetes, diabetes mellitus, dyslipidemia, hypertension, and cardiovascular disease in accordance with the current standards of care.

7. In adults with NAFLD or NASH, what lifestyle modifications (dietary intervention and exercise) should be recommended?

Clinicians should recommend lifestyle changes to individuals with excess adiposity and NAFLD with a goal of at least 5 per cent, preferably 10 per cent weight loss, as greater weight loss is frequently associated with greater liver histologic and cardiometabolic benefit, depending on individual risk assessments. When feasible, clinicians must encourage involvement in an organised weight reduction programme customised to the individual's lifestyle and preferences.

8. What Medications Have Proven Effective for the Treatment of Liver Disease and Cardiometabolic Disorders Related to NAFLD or NASH?

Pioglitazone or GLP-1 RAs are recommended for persons with T2D and biopsy-proven NASH.

9. What obesity drugs have been shown to help treat liver disease and cardiometabolic conditions in adults who have NAFLD or NASH?

Clinicians should offer obesity medication as a supplementary treatment to lifestyle change for persons with obesity and NAFLD or NASH with a target of at least 5 per cent, preferably 10 per cent, weight reduction, since higher weight loss is frequently linked with a better liver histologic and cardiometabolic benefit when this is not adequately accomplished by lifestyle modification alone.

10. How Does Bariatric Surgery Affect Liver Disease and Cardiometabolic Disorders Associated With NAFLD or NASH in Adults?

Clinicians should consider bariatric surgery as an option to treat NAFLD (Grade B; Intermediate Strength of Evidence) and improve cardiometabolic health (Grade A; High/Intermediate Strength of Evidence; upgraded based on the cardiometabolic and all-cause mortality benefits in all persons with or without NAFLD) in persons with NAFLD and a BMI of ≥35 kg/m2 (≥32.5 kg/m2 in Asian populations), particularly if T2D is present. It should also be considered an option in those with a BMI of ≥30 to 34.9 kg/m2 (≥27.5 to 32.4 kg/m2 in Asian populations) (Grade B; Intermediate/Weak Strength of Evidence;).

11. In children, Who Should Be Screened for NAFLD and Comorbidities?

Children of any age and adolescents with obesity or T2D, but not T1D, should be screened for NAFLD using serum ALT.

12. What Tests Can Be Used to Diagnose Pediatric NAFLD?

Clinicians should use plasma aminotransferases to test children at high risk of NAFLD.

13. What Are the Lifestyle, Medical, and Surgical Treatment Options for Pediatric NAFLD, and What Role Does Endocrine Disorder-Specific Pharmacotherapy Play in the Treatment of Pediatric NAFLD?

Clinicians should prescribe lifestyle modifications to children with NAFLD, supporting the adoption of dietary adjustments to produce an energy deficit, with a decrease in sugar intake as the first-line lifestyle modification and an increase in a physical activity aiming to optimise BMI.

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Conclusion

Lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, especially glucagon-like peptide-1 receptor agonists; and bariatric surgery, for those who are obese, as well as certain diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes, may be used to manage NAFLD. In addition to promoting cardiometabolic health and reducing the elevated cardiovascular risk associated with this complicated disease, management should also include cardiometabolic wellness.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Monish Raut is a practising super specialist from New Delhi.