Clinical and Histologic Spectrum of Nonalcoholic Fatty Liver Disease Associated With Normal Alt Values

Abstract

A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with NAFLD and normal ALT were identified and compared with 50 consecutive subjects with NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained hepatomegaly (n ‫؍‬ 21) and evaluation as a potential donor for living donor liver transplantation (n ‫؍‬ 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the metabolic syndrome, the major risk factor for NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of NAFLD. A total of 12 subjects with normal ALT levels had bridging fibrosis, whereas 6 had cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced fibrosis (bridging fibrosis or cirrhosis) by multivariate analysis (relative risk: 2.3, P < .01). The mean steatosis (1.6 vs. 2.16, P < .04) and perisinusoidal fibrosis scores (0.35 vs. 0.9, P < .049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying steatohepatitis with advanced fibrosis.

Metabolic and histological features of non‐alcoholic fatty liver disease patients with different serum alanine aminotransferase levels

“…16,18 One possibility is that those were spurious results because of the use of inappropriate ALT cutoffs.…”

“…The length of liver samples was 18 AE 3 mm (median, 17; interquartile range, [16][17][18][19][20], and the number of portal tracts per sample was 7 AE 2 (median 6; interquartile range, 5-8). The ALT level had moderate correlation with steatosis grade (R = 0.32, P < 0.001), fibrosis stage (R = 0.20, P = 0.008) and the NAFLD activity score (R = 0.28, P < 0.001).…”

“…15 Significant fibrosis has been reported among NAFLD patients with normal ALT. [16][17][18][19] Last but not least, most previous studies only evaluated one ALT level and neglected the potential variability of ALT.…”

Review and Recommendations for the Component Tests in the Liver Function Test Profile

“…It has long been recognised that ALT elevation is poorly correlated with the severity of histologic liver disease in chronic liver disease [24,25]. Mofrad et al [26] reported on a cohort of patients with normal ALT levels who were diagnosed as having NAFLD histologically and identified clinically (persistent hepatomegaly) or because the subjects were live liver transplant donors. There was no relation in this group between fibrosis stage (histologic) and ALT level.…”

Nonalcoholic fatty liver disease in a district general hospital: clinical presentation and risk factors

“…Although NAFLD has no specific clinical or laboratory features, a presumed diagnosis of NAFLD can often be made in a patient with a combination of a mildly elevated liver biochemistry, negative liver screen, ''bright'' liver on abdominal ultrasonography (USS), and the presence of metabolic risk factors such as hypertension, noninsulindependent diabetes mellitus and insulin-resistance, hyperlipidemia, and obesity [2][3][4]. The definitive diagnosis of NAFLD is made on a liver biopsy [5,6] as patients with NAFLD may present with ''normal'' liver biochemistry [7][8][9] and at least 20% of people with persistently abnormal alanine aminotransaminase values have an alternative diagnosis. More important, a liver biopsy is currently the only reliable method in distinguishing simple steatosis from NASH and allows an assessment of disease severity [5,6].…”