The diagnosis and management of nonalcoholic fatty liver disease: A patient‐friendly summary of the 2018 AASLD guidelines

Abstract

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^{Bahirwani R, Griffin C. The diagnosis and management of nonalcoholic fatty liver disease: A patient‐friendly summary of the 2018 AASLD guidelines. Clinical Liver Disease. 2022;19:222–226. https://doi.org/10.1002/cld.1216BahirwaniR, GriffinC. The diagnosis and management of nonalcoholic fatty liver disease: A patient‐friendly summary of the 2018 AASLD guidelines. Clinical Liver Disease. 2022;19:222–226. https://doi.org/10.1002/cld.1216}

NON‐ALCOHOLIC FATTY LIVER DISEASE

Non‐alcoholic fatty liver disease (NAFLD) is defined by the presence of fat in the liver without evidence of other causes of fat accumulation in the liver such as alcohol use, hepatitis C, or certain medications. It is commonly associated with obesity, diabetes, and elevated cholesterol. Currently, about 25% of the global population has a diagnosis of NAFLD. In about 6% of patients with NAFLD the fatty accumulation causes liver inflammation, and this condition is known as non‐alcoholic steatohepatitis (NASH). Individuals with NAFLD are at increased risk of cardiovascular disease and patients with NASH are also at risk of developing long‐term liver injuries, and permanent scarring of the liver known as cirrhosis.

DIAGNOSIS

Guideline statement:

• Patients with unsuspected Hepatic steatosis (HS) detected on imaging who have symptoms or signs attributable to liver disease or have abnormal liver chemistries should be evaluated as though they have suspected NAFLD and worked up accordingly.
• Initial evaluation of patients with suspected NAFLD should carefully consider the presence of commonly associated comorbidities such as obesity, dyslipidemia, diabetes, hypothyroidism, polycystic ovary syndrome, and sleep apnea.
• Routine screening in high‐risk groups is not currently recommended. Systemic screening of family members for NAFLD is not recommended currently.

Patient Summary: Fatty liver is commonly seen on liver ultrasounds or other forms of radiographic studies. When this happens with an increase in liver blood tests (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), patients should be evaluated for NAFLD. This evaluation should include an assessment for metabolic risk factors such as diabetes, hypertension, obesity, or elevated cholesterol. Routine screening for NAFLD is not recommended, and family members of patients with NAFLD do not need to be screened.

Key Point: People with metabolic diseases such as type 2 diabetes, obesity, or metabolic syndrome are at high risk for NAFLD. However screening is not currently recommended. This could always change as new tests and treatments for NAFLD are developed.

Guideline statement:

• When evaluating a patient with suspected NAFLD, it is essential to exclude competing etiologies for steatosis and coexisting Common CLD.
• Ongoing or Recent alcohol consumption >21 standard drinks on average per week in men and >14 standard drinks per week in women is a reasonable threshold for significant alcohol consumption when evaluating patients with suspected NAFLD
• High serum titers of autoantibodies in association with other features suggestive of autoimmune liver disease (>5 ULN aminotransferases, high globulins, or high total protein to albumin ratio) should prompt a work‐up for autoimmune liver disease.

Patient summary: Several liver diseases can cause a fatty liver or elevated liver enzymes. NAFLD can only be diagnosed once other forms of chronic liver disease are ruled out. A common alternative cause of fatty liver disease is significant alcohol consumption (defined as more than 21 drinks a week for men, and more than 14 drinks a week for women), although fatty liver can occur with lower alcohol intake. Another cause is autoimmune hepatitis (AIH) which can lead to very high increases in liver blood tests. Other possible causes include hepatitis C, hepatitis B, certain medications such as amiodarone or methotrexate, or other genetic diseases. The diagnostic steps are summarized in Figure 1.

FIGURE 1: Diagnosing and assessing severity of NAFLD

Key Point: When evaluating patients with NAFLD, it is important to rule out other causes of fatty liver and evaluate for other common causes of chronic liver disease.

ASSESSING THE SEVERITY OF LIVER DISEASE

Guideline Statement:

• There should be a high index of suspicion for NAFLD and NASH in patients with Type 2 Diabetes. Clinical decision aids such as the NAFLD fibrosis score (NFS) or fibrosis‐4 index (fib‐4) or vibration controlled transient elastography (VCTE) can be used to identify those at low or high risk for advanced fibrosis.
• NFS or FIB‐4 index are clinically useful tools for identifying NAFLD patients with higher likelihood of having bridging fibrosis (stage 3) or cirrhosis (stage 4).
• VCTE or magnetic resonance elastography (MRE) are clinically useful tools for identifying advanced fibrosis in patients with NAFLD.

Patient summary: Patients with many metabolic risk factors, diabetes, or elevated liver blood tests may need further non‐invasive testing to see if there is liver damage or scarring. These tests include bloodwork, which can create predictive scores for advanced liver scarring (fibrosis) or cirrhosis such as the fibrosis‐4 score, or imaging studies such as ultrasound, CT, or MRI. Additionally, “liver stiffness” can be evaluated by various imaging techniques such as ultrasound elastography to determine degree of scar without performing a biopsy.

Key Point: NAFLD can cause fibrosis and cirrhosis and blood work and imaging studies are frequently done to assess the severity of the liver disease.

Guideline statement:

• In patients with suspected NAFLD, persistently high serum ferritin, and increased iron saturation, especially in the context of homozygote or heterozygote C282Y HFE mutation, a liver biopsy should be considered
• Liver biopsy should be considered in patients with NAFLD who are at increased risk of having steatohepatitis (SH) and/or advanced fibrosis.
• Liver biopsy should be considered in patients with suspected NAFLD in whom competing etiologies for hepatic steatosis (HS) and the presence and/or severity of coexisting CLDs cannot be excluded without a liver biopsy.
• Current evidence does not support routinely repeating a liver biopsy in patients with NAFL or NASH, but this may be considered on a case‐by‐case basis.

Patient summary: Sometimes non‐invasive testing cannot determine if an individual has advanced liver disease or not. In these cases, a piece of liver tissue is collected by a biopsy to see how much scarring is present in the liver. This evaluation can also rule out other causes of liver disease if there is any uncertainty of the diagnosis of NAFLD. Methods of evaluating for fibrosis are summarized in Figures 2 and 3.

FIGURE 2: Stages of liver damage

FIGURE 3: Methods for evaluating degree of fibrosis

Key Point: Patients with NAFLD may need a biopsy to rule out other causes of chronic liver disease and to assess the liver for cirrhosis.

TREATMENT

Guideline statement:

• Weight loss generally reduces HS, achieved either by hypocaloric diet alone or in conjunction with increased physical activity. A combination of a hypocaloric diet (daily reduction by 500–1000 kcal) and moderate‐intensity exercise is likely to provide the best likelihood of sustaining weight loss over time.
• Weight loss of at least 3%–5% of body weight appears necessary to improve steatosis, but a greater weight loss (7%–10%) is needed to improve the majority of the histopathological features of NASH, including fibrosis.
• Pharmacological treatments aimed primarily at improving liver disease should generally be limited to those with biopsy‐proven NASH and fibrosis.
• It is premature to consider foregut bariatric surgery as an established option to specifically treat NASH.
• The type, safety, and efficacy of foregut bariatric surgery in otherwise eligible obese individuals established cirrhosis attributed to NAFLD are not established. In otherwise eligible patients with compensated NASH or cryptogenic cirrhosis, foregut bariatric surgery may be considered on a case‐by‐case basis by an experienced bariatric surgery program.

Patient summary: Weight loss is the key to preventing harm from NAFLD. Eating 500–1000 Calories a day with moderate‐intensity exercise is the best way to lose weight. Losing 7%–10% of body weight can improve liver fat and inflammation in patients with NASH and can even help reverse scarring. Medications are not recommended for treatment unless patients have severe scarring and proven NASH. Bariatric surgery can lead to weight loss in patients with NAFLD, but there is not enough data on safety or efficacy to recommend bariatric surgery as a treatment for NAFLD alone. Although it’s not mentioned in the guideline, it is important for patients with NAFLD to avoid alcohol, which could cause additional harm to the liver.

Key Point: Weight loss is key to preventing long‐term injury from NAFLD. Medications are only recommended if patients have severe inflammation or scarring in the liver.

Guideline statement:

• Patients with NAFLD are at high risk for cardiovascular morbidity and mortality. Thus, aggressive modification of cardiovascular risk factors should be considered in all patients with NAFLD.
• Patients with NAFLD or NASH are not at higher risk for serious liver injury from statins. Thus, statins can be used to treat dyslipidemia in patients with NAFLD and NASH. While statins may be used in patients with NASH cirrhosis, they should be avoided in patients with decompensated cirrhosis.

Patient summary: It is common for patients with NAFLD to have other metabolic diseases such as hypertension, diabetes, and coronary artery disease. Thus, NAFLD patients are at high risk for death due to cardiovascular disease, including strokes and heart attacks. It is important for patients to have these other disease states evaluated and managed to reduce risk. Statin medications to decrease cholesterol and improve cardiovascular disease risk are safe unless a patient has extremely advanced cirrhosis.

Key Point: Evaluating and treating potential diabetes, hypertension, coronary artery disease, and high cholesterol is important in patients with NAFLD as they are at an increased risk of cardiovascular disease. Statins are safe to use unless the patient has very advanced cirrhosis.

Guideline statement:

• Pioglitazone improves liver histology in patients with and without T2DM with biopsy‐proven NASH. Therefore, it may be used to treat these patients. Risks and benefits should be discussed with each patient before starting therapy.
• Vitamin E administered at a daily dose of 800 IU/day improves liver histology in nondiabetic adults with biopsy‐proven NASH and therefore may be considered for this patient population. Risks and benefits should be discussed with each patient before starting therapy. Vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis

Patient summary: Some medications have been shown to reduce inflammation in patients with NASH. These include pioglitazone, which is a medication used to reduce blood sugar in patients with diabetes, and vitamin E, which is an anti‐oxidant thought to reduce inflammation. Both of these medicines come with risks and thus should not be started unless it is proven the patient has NASH. This will likely involve getting a biopsy and patients should not start these medications without discussing them with their doctor. There are new medications being studied which will likely be recommended in the next update of the guidelines. This includes two other classes of medications that are used to lower blood sugar, and some examples include dulaglutide, semaglutide, liraglutide, dapagliflozin, empagliflozin, and canagliflozin.² Deciding on which medication to take for diabetes depends on many patient specific factors and will require a decision with a doctor. Treatments are summarized in Table 1.

TABLE 1 - Treatment of NAFLD based on fibrosis

Management	Low risk for fibrosis	Intermediate risk	High risk
Weight loss and lifestyle intervention	Yes	Yes	Yes
Medications for NASH	Not recommended	Consider	Consider
Cardiovascular risk reduction	Yes	Yes	Yes

Key Point: There are medical treatments for patients with NASH that can be used in conjunction with losing weight. These medicines do have risks which need to be discussed with a physician before starting.

Guideline statement:

• Patients with NASH cirrhosis should be screened for gastroesophageal varices according to the AASLD and ACG practice guidelines.
• Patients with cirrhosis suspected because of NAFLD should be considered for HCC screening according to the AASLD practice guidelines.
• Current evidence does not support routine screening and surveillance for HCC in patients with noncirrhotic NASH.

Patient summary: If patients develop cirrhosis from NASH they will need screening for liver cancer and varices. Varices are blood filled veins in the patient’s esophagus (throat) which can bleed in patients with cirrhosis and require evaluation and treatment. This is done by a camera evaluation of the esophagus and stomach called an upper endoscopy. This screening is done in all patients with cirrhosis and patients with NASH without cirrhosis do not need screening.

Key Point: NASH can lead to cirrhosis which requires patients to have tests that screen for liver cancer and varices in the esophagus.

CHILDREN

Guideline statement:

• Children with fatty liver who are very young or not overweight should be tested for monogenic causes of CLD such as fatty acid oxidation defects, lysosomal storage diseases, and peroxisomal disorders, in addition to those causes considered for adults.
• Liver biopsy in children with suspected NAFLD should be performed in those in whom the diagnosis is unclear or in whom there is possibility of multiple diagnoses, or before initiating potentially hepatotoxic medical therapy.
• Intensive lifestyle modification improves aminotransferases and liver histology in children with NAFLD and thus should be the first line of treatment.
• Vitamin E 800 IU/day offers histological benefits to some children with biopsy proven NASH. Long‐term safety of high‐dose vitamin E in children is unknown. Vitamin E may be used to treat NASH in children, but risks and benefits should be discussed with each patient.

Patient summary: NAFLD is common in children, however some genetic disorders can present the same and may need to be evaluated. Biopsy is considered when the diagnosis is uncertain and treatment is similar to that of adults with lifestyle modification being the first line of treatment. Vitamin E can be used but the long‐term safety is unknown in children.

Key Point: Children are treated the same as adults for NAFLD. Ruling out genetic disorders must be done as well as a standard evaluation and lifestyle modification is the first step in treatment.