An Obese Man With Elevated Transaminases and Abnormal Liver Ultrasonography Findings

Author:
Ronald N. Rubin, MD—Series Editor

Citation:
Rubin RN. An obese man with elevated transaminases and abnormal liver ultrasonography findings. Consultant. 2019;59(11):341-342, 352.

A 60-year-old man presents for evaluation of abnormalities discovered during a biannual employment physical examination. He is a midlevel executive at a financial services company that requires a relatively comprehensive examination every 2 years for such executives. Specifically, the findings in question included obesity, abnormal blood glucose and glycated hemoglobin (HbA_1c) levels, and hyperlipidemia. The examiner also appreciated an enlarged liver, which was confirmed by point-of-care ultrasonography.

History reveals a 60-year-old man who believes himself to be in “excellent health.” His job is mainly deskbound, with occasional travel required. He denies chest pain or exertional dyspnea, but when specifically questioned, he says his only physical effort is occasional trips up and down steps at home and recreational golf a couple of weekends per month using a golf cart. He knows he is overweight, which has been a problem for some time. He takes no chronic medications. He says he consumes alcohol “moderately,” which specific questioning reveals to be daily but never more than 2 drinks a day, with a single evening drink being most common.

Physical examination of the man reveals a blood pressure of 152/96 mm Hg, a pulse rate of 88 beats/min, and a body mass index of 32 kg/m². Findings of a head, eyes, ears, nose, and throat examination are unremarkable, as are cardiac and pulmonary examination findings. The abdomen shows ample girth with protuberant adipose anteriorly. The liver and spleen are not palpable, but the abdominal girth precludes accuracy in this regard. No other abnormal findings are noted.

Laboratory tests reveal a normal complete blood cell count. A comprehensive metabolic panel reveals a random serum glucose level of 160 mg/dL, a creatinine level of 1.1 mg/dL, and an alanine aminotransferase (ALT) level of 111 U/L (reference value, <75 U/L). The HbA_1c level is 6.3% (reference value, <6.0%). Lipoprotein electrophoresis shows a triglyceride (TG) level of 188 mg/dL with an elevated ratio of TG to high-density lipoprotein cholesterol. Abdominal ultrasonography reveals mild hepatomegaly and the presence of increased fat in the liver (hepatic steatosis). Results of serum iron studies, including iron level, iron-binding capacity, and ferritin level, were normal.

Answer: A, statins are indicated to aid in the management of dyslipidemia and can be safely used in patients like this one.

The presented patient manifests nonalcoholic fatty liver disease (NAFLD) based on the criteria of evidence of hepatic steatosis and a lack of secondary causes (eg, excessive alcohol consumption, long-term use of known steatogenic drugs such as corticosteroids).

The global incidence rate of NAFLD in the general population, as determined with imaging documentation (ultrasonography, magnetic resonance imaging, or transient elastography), is in the 10% to 15% range, while the global prevalence rate may approach or even surpass 25%.^1,2 For patients who reach the stage of liver biopsy for any indication, the prevalence rate of NAFLD approaches 60%.^1,2 Thus, NAFLD is extremely common such that its termination in cirrhosis is the second most common reason for liver transplant in the United States and will shortly surpass hepatitis C to become the most common reason, especially in light of current excellent curative regimens for hepatitis C.^3,4

Within the broad definition of NAFLD is an order of conditions as the disease progresses or worsens: nonalcoholic fatty liver, which is the presence of 5% or greater hepatic steatosis but without evidence of hepatocellular injury (ie, ballooning of hepatocytes or fibrosis of any kind); nonalcoholic steatohepatitis (NASH), which is 5% or greater hepatic steatosis with hepatocyte injury but without fibrosis; NASH cirrhosis; and, finally, cryptogenic cirrhosis, wherein a patient first reaches medical attention in cirrhotic state (without known prior NAFLD) but has demographics consistent with risk factors for NAFLD. In fact, it is quite likely that cryptogenic cirrhosis is in actuality burned-out NAFLD.

The ever more common metabolic syndrome patient personifies the major risk factors for NAFLD. Obesity is the No. 1 risk factor for NAFLD, followed by type 2 diabetes mellitus and dyslipidemias. Obesity/metabolic syndrome has indeed become a major US public health concern and is associated with striking morbidity and mortality statistics and outcomes. Although NAFLD is a liver disease, the most common cause of mortality is cardiovascular disease, not liver disease, making Answers B and D above incorrect. Both hepatic failure and hepatocellular carcinoma are high on the list of mortality causation in the universe of NAFLD patients, but both rank below cardiovascular disease.^1,2 This is not surprising in view of the triad of obesity, type 2 diabetes and dyslipidemia, which comprises the demographic predisposing to the development of NAFLD in the first place.

We can screen high-risk patients with a variety of noninvasive studies. Unexpected and sustained abnormal serum transaminase levels (especially ALT) are often the initial abnormality that triggers further evaluation. Also very common is the incidental finding of hepatic steatosis on imaging studies for other problems. Subsequent more-refined and focused studies include high-resolution ultrasonography, computed tomography, and magnetic resonance imaging, all of which are capable of identifying fatty liver. However, none of these can reliably reflect the precise nature or extent of abnormality in liver histology, the gold standard of which remains liver biopsy. Coupling the techniques with evaluating liver stiffness (elastography) seems a useful predictive technique for evolving fibrosis and can serve as a indicator of when to proceed with liver biopsy.^1,2 A variety of index schemes combining serum biomarkers, imaging, and elastography can be used to assess the likelihood of advanced fibrosis in patients and thus when to proceed to biopsy in such high-risk patients.^1,2

Treatment approaches depend on where a given patient is on the spectrum of NAFLD. For any patient, attention to the classical risk factors must be addressed, which means a program of weight loss of at least 5% to 10% (the more the better), diabetes control, and dyslipidemia management will be the backbone of any therapy program. This includes the use of statins as needed despite the theoretical risks of hepatotoxicity from such agents, making Answer A the correct choice here. Also, limiting alcohol intake is a good idea in these patients. Meanwhile, the use of further pharmacotherapy—such as the thiazolidinediones or glitazones, which have been shown in trials to be capable of improving histology once either steatohepatitis or even fibrosis has presented⁵—for now is only indicated when advanced lesions are present, and not for fatty liver (NAFLD) alone, making Answer C incorrect and an excessive intervention for now.

Patient Follow-Up

After prolonged discussion with the patient, the decision was made to proceed with a liver biopsy in light of the imaging documented hepatic steatosis and concomitant presence of metabolic syndrome components. The biopsy proceeded without complications and revealed only histologic evidence of hepatic steatosis without NASH or fibrosis. 

Management will consist of attempts at significant weight loss (5% to 10% or more) by combining decreased caloric intake, exercise, and abstinence from alcohol. He will have scheduled follow-up visits for interval assessment of his ALT levels and hepatic ultrasonography.

Ronald N. Rubin, MD, is a professor of medicine at the Lewis Katz School of Medicine at Temple University and is chief of clinical hematology in the Department of Medicine at Temple University Hospital in Philadelphia, Pennsylvania.

TAKE-HOME MESSAGE

NAFLD is an increasingly common clinical entity in the world today due to the increasing incidence of its 3 core epidemiological demographic risk factors of obesity, type 2 diabetes, and dyslipidemia. Initial triggers for evaluation and diagnosis include incidental findings of elevated transaminases on routine blood testing and the demonstration of hepatic steatosis on incidentally obtained imaging studies. The gold standard for confirmation of the diagnosis is liver biopsy, the results of which will categorize where on the NAFLD spectrum the specific patient’s condition is located. Therapeutics will depend on these definitions. Thus, hepatic steatosis without either steatohepatitis or fibrosis is treated and will respond to aggressive weight loss and tighter control of type 2 diabetes and dyslipidemia. When there has been progression to steatohepatitis or fibrosis, glitazone pharmacotherapy has been shown to be able to reverse this pathology. Treatment of NAFLD is important, since this population has a significant risk for cardiovascular, hepatic, and carcinoma-related morbidity and mortality.

References:

1. Paul S, Davis AM. Diagnosis and management of nonalcoholic fatty liver disease. JAMA. 2018;320(23):2474-2475.
2. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357.
3. Cusi K, Orsak B, Bril F, et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016;165(5):305-315.
4. Singal AK, Hasanin M, Kaif M, Weisner R, Kuo Y-F. Nonalcoholic steatohepatitis is the most rapidly growing indication for simultaneous liver kidney transplantation in the United States. Transplantation. 2016;100(3):607-612.
5. Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547-555.