Advances in Liver Disease

Digestive Disease Week (DDW) 2014

William F. Balistreri, MD


June 19, 2014

In This Article

Editor's Note: Significant advances in the clinical practice of hepatology were presented at the recent Digestive Disease Week (DDW) meeting in Chicago. This review focuses on a few of the most relevant concepts that emerged from this meeting, and also highlights the pace of progress in the diagnosis and management of the common forms of liver disease.

Nonalcoholic Fatty Liver Disease


Nonalcoholic fatty liver disease (NAFLD) affects people of all ages, including those at the extremes of life. With the epidemic of childhood obesity, NAFLD has become the most common cause of chronic liver disease in the pediatric population. In a review of data from autopsies performed in New York City, Fernandes and colleagues detected NAFLD in 14% of 564 children.[1] Hispanic children had the highest prevalence, at 21%.

At the other end of the age spectrum, a prospective study[2] provided data on the prevalence of NAFLD in an older population. Of 440 Australian individuals (mean age, 78 years), NAFLD was present in 43% and was "largely unrecognized." Given these high prevalence rates, enhanced detection methods are needed.


Liver biopsy remains the gold standard to diagnose NAFLD and also the more severe disease of nonalcoholic steatohepatitis (NASH). There is, however, a perceived lack of uniformity in the interpretation of the results from liver biopsy.

Vanderbeck and colleagues[3] postulated that automatic quantification of cardinal histologic features of NAFLD/NASH may reduce observer variability and allow valid assessment of injury. They developed an automated classifier to detect and quantify macrosteatosis with high precision and sensitivity (≥ 95%). When correlated with the average of 2 expert pathologists' semiquantitative grading, the model had a Spearman rank correlation coefficient of 91% for steatosis, 45% for lobular inflammation, and 46% for ballooning.

One of the prime objectives is to develop simple, valid, noninvasive measures to assess patients at risk. Eltawil and colleagues[4] reported that assessment of alanine aminotransferase (ALT) values as the sole screening strategy in obese children will miss a substantial proportion of cases. They suggest that a better, albeit imperfect, alternative is to use a combination of ALT and ultrasonography to screen for NAFLD and to determine the need for further testing.

Predictive hepatic "fibrosis scores" are another option and have been developed and validated for use in adult patients. However, these perform poorly in diagnosing advanced fibrosis in children with NAFLD. Therefore, Alkhouri and colleagues[5] attempted to develop a new, pediatric-specific fibrosis score. In consecutive children with biopsy-proven NAFLD, advanced fibrosis was significantly associated with the presence of hypertension, as well as elevated serum triglyceride, ALT, aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) levels. Alkhouri and colleagues used these data to develop a multivariable logistic regression model that can reliably predict advanced fibrosis.

Ultimately, biomarkers may become valid indicators of NAFLD and provide discrimination from NASH. For example, serum proteomic signatures may reflect hepatic fat and fibrosis. Nikrad and colleagues[6] obtained serum samples from 577 obese patients who had liver biopsy during bariatric surgery for weight loss. Protein biomarker panels that indicated the presence of steatosis or fibrosis were developed and validated.

Investigators also reported systemic changes in the metabolome associated with spontaneous improvement in liver histology in patients with NASH.[7] Metabolomic profiling revealed that spontaneous histologic improvement in NASH was associated with decreased utilization of arginine-ornithine, osmotic stress, and bile acids, and increased purine synthesis and caffeinated product intake.

These observations have identified candidate biomarkers, and perhaps therapeutic pathways, for further study. Although promising, these proposed strategies must be validated in a large independent sample set of adults and children.


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