Let’s Rewind: Recognizing Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in the Primary Care Clinic

Let’s Rewind: Recognizing Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in the Primary Care Clinic

At least 30% of the US population (about 110 million people) has nonalcoholic fatty liver disease (NAFLD), and in as many as 4.5 million, the disease is diagnosed in an advanced stage.¹ As many as 1 in every 3 patients seen by a primary care provider (PCP) in a given day will have a fatty liver, and many of these patients will be asymptomatic.

Fatty liver encompasses a spectrum of disease, ranging from only fat to fat and inflammation (known as nonalcoholic steatohepatitis [NASH]), fat and scarring or fibrosis, and cirrhosis.²

While NAFLD is very common, it is often silent, and diagnosis can be tricky. Clinicians may not recognize the problem until an event occurs because the risk factors for NAFLD are easy to miss. Elevated liver enzymes should prompt a PCP to look for fatty liver, but many patients with fatty liver have normal liver enzymes.

When PCPs identify patients with early disease, progression can be prevented.³ Patients who have fatty liver have problems that PCPs see every day in practice. Typically, patients with early-stage fatty liver disease have one or a combination of three medical issues: Hyperlipidemia, usually with hypertriglyceridemia or low high-density lipoprotein levels, type 2 diabetes mellitus (T2DM), obesity, or metabolic syndrome. A fraction of these patients are silently developing progressive liver disease, and they will ultimately develop cirrhosis, even though many of them do not drink alcohol. Thus, when PCPs see patients with these types of underlying problems, they need to consider fatty liver, identify patients with this disease, and intervene to prevent progression.

Missed opportunity

Consider the case of a 35-year-old woman who has hypertension and elevated liver enzymes. On physical examination, her body mass index is 31.1 kg/m² and her blood pressure is 158/90 mm Hg. She has previously been prescribed metformin for T2DM and lisinopril for her hypertension. Table 1 lists laboratory test results for this patient.

In this case, the PCP discussed the patient’s lab results, hypertension, recent weight gain, and T2DM with her. The patient expressed concern about having gained weight for no apparent reason. She also noted that she is always tired and looks bloated and swollen. The PCP recommended adjusting the metformin and lisinopril dosage, gave the patient educational material about healthy eating and exercise, and asked her to come back for a follow-up visit in 6 months.

In this scenario, this is a missed opportunity because the PCP should have recognized the risk factors of NAFLD, scheduled an ultrasound, assessed the patient's alcohol intake, calculated a FIB-4, and potentially referred the patient to a specialist.

NAFLD assessments and referral

For patients with signs and symptoms suggestive of NAFLD, in addition to ordering a complete metabolic panel, PCPs should order an ultrasound to evaluate for steatosis.^4,5 Some patients need to be referred to a specialist, but many do not. When PCPs identify NAFLD at an early stage, they can intervene with the intention of preventing the development of advanced liver disease. However, patients who need additional evaluation, based on the results of their laboratory tests and ultrasound, should be referred to a specialist.⁶

Fibrosis-4

Fibrosis-4 (FIB-4) is an easily calculated, noninvasive screening test that can help PCPs differentiate between patients they can manage with a plan of diet and exercise and those who need to be referred to a specialist for further testing to determine if they have advanced disease.⁵

The FIB-4 score is based on a patient’s alanine transaminase and aspartate transaminase levels, platelet count, and age.⁵ A computer program quickly generates the patient’s FIB-4 score using these 4 parameters. A risk stratification score of <1.3 excludes advanced fibrosis; ≥1.3 – 2.67 is indeterminate; and a score of >2.67 signifies a high risk for advanced fibrosis. A low score indicates that the patient does not have significant liver scarring and can be followed by the PCP without referral.

If the FIB-4 score is high, the patient almost definitely has significant fibrosis, or even cirrhosis, and requires timely referral. An intermediate or indeterminate score also indicates a need for referral to a specialist for further testing. Many patients do have significant disease.

Guidelines for screening and referral include the following: 1) Signs of metabolic risk factors are central obesity, high triglycerides, low high-density lipoprotein cholesterol, hypertension, prediabetes, or insulin resistance; 2) For patients aged >65, FIB-4 <2.0 is the lower cutoff; the higher cutoff does not change; and 3) Referral to a hepatologist should be considered for patients with hepatic steatosis on ultrasound who are indeterminate or high risk based on FIB-4.⁵

Patients with a high or intermediate FIB-4 score require more intervention, which includes lifestyle modifications. If a patient has hyperlipidemia, the condition needs to be treated. Statins are not contraindicated in patients with NAFLD.^7,8 T2DM also needs to be appropriately treated. For patients who are overweight, aggressive attempts at weight loss are prudent. In fact, some of these patients benefit from referral to a lifestyle clinic, if there is one in their local community.

Medications including resmetirom and lanifibranor are in late-stage development for the treatment of patients who have NASH.⁹ If approved by the US Food and Drug Administration, their use will be based on liver disease stage, as determined by tests such as the FIB-4.

Of note, patients with advanced liver disease, including individuals with fatty liver and those who are asymptomatic, are at increased risk for hepatocellular carcinoma.^10,11 The standard of care for these patients, regardless of their physical presentation or lab results, is to perform an ultrasound to screen for liver cancer every 6 months. In addition, specialists often evaluate serum alpha-fetoprotein levels. Such surveillance and testing are other reasons to refer patients with advanced liver disease to a specialist who can implement these very important diagnostic and screening strategies.

Conclusion

NAFLD and NASH are conditions that are common in patients seen in a primary care setting. The occurrence of both NAFLD and NASH is high because the factors that lead to their development are so widespread in the US population. Regardless of the degree of fibrosis, or even cirrhosis associated with NAFLD and NASH, patients with these conditions are usually asymptomatic. Liver disease is frequently silent, and it progresses if it is not identified and treated. Therefore, it is critical for PCPs to be aware of NAFLD and NASH and consider these diagnoses. Elevated liver enzymes need to be taken seriously, but even patients with normal levels may have liver disease and require treatment. When a patient’s lipid profile, weight, and/or comorbidities suggest the possibility of liver disease, PCPs should screen for fatty liver with an ultrasound and then calculate the patient’s FIB-4 fibrosis score in order to determine an appropriate plan for management and whether there is a need for referral to a specialist.

References

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