COMMENTARY

The Increasing Pace of Progress in Hepatology

Digestive Disease Week (DDW) 2015

William F. Balistreri, MD

Disclosures

November 05, 2015

In This Article

Author's Note:
At this year's Digestive Disease Week (DDW), it was clear that several key advances had been made in the clinical practice of hepatology. Many important abstracts were presented that, collectively, highlight the increasing pace of progress in diagnosing and managing commonly encountered clinical issues, such as obesity-related issues, hepatitis B virus (HBV) infection, autoimmune liver diseases, and the role of the microbiome.

NASH in Young Patients

The increasing prevalence of obesity is an undeniable global public health concern, and multiple presentations focused on one of its more significant long-term consequences: the development of nonalcoholic fatty liver disease (NAFLD). A particular concern with NAFLD is its potential progression to nonalcoholic steatohepatitis (NASH), with its associated risk for cirrhosis and liver failure.

Alkhouri and colleagues[1] used data from the 1987-2012 United Network for Organ Sharing and Organ Procurement and Transplantation Network (UNOS/OPTN) database to characterize patient and graft survival for 330 children and young adults who underwent liver transplantation for NASH cirrhosis. Age at time of the transplantation ranged from as young as 4 years to 40 years (mean, approximately 34 years), with 14 patients younger than 18 years and 20 between the ages of 18 and 25 years.

A progressive increase in NASH as the primary indication for liver transplantation in young patients was seen from 2001 to 2012. During follow-up after liver transplantation (approximately 46 months), 30% of patients died and 12% were retransplanted, with one third being performed for NASH recurrence. These sobering findings strongly indicate that childhood obesity must be aggressively addressed to prevent the progression of NAFLD to NASH, and then to end-stage liver disease.

Although NASH is histologically defined as steatosis plus inflammation, ballooning, and fibrosis, there is also a need for predictors of progression that do not rely on liver biopsies. The NAFLD fibrosis score has been proposed as a novel tool to predict the presence of advanced liver fibrosis. NAFLD-associated metabolic syndrome has been recognized as a risk factor for cardiovascular disease, leading Madan and colleagues[2] to hypothesize that the NAFLD fibrosis score also may predict coronary artery disease (CAD).

They reported that a high NAFLD fibrosis score was associated with an increased body mass index (BMI), and the presence of diabetes, hypertension, dyslipidemia, higher aspartate aminotransferase levels, and lower platelet count. A high score also was associated with a greater prevalence of CAD, triple-vessel CAD, and a higher mean vessel score. Further studies are warranted to document the applicability of the NAFLD fibrosis score, not only as a simple and noninvasive tool to assess liver fibrosis but also to predict angiographic CAD.

The Genetic Underpinnings of NAFLD

There is significant variability in the clinical expression of NAFLD and the rate of progression to NASH.

Zarrinpar and colleagues[3] hypothesized that various microRNAs (miRs) could explain this discordance in clinical features. They found that miRs exert control of cell processes by silencing target mRNA or by repressing the synthesis of proteins. In studying two individuals who are genetically similar, they postulate that epigenetic mechanisms, such as miRs, could account for discordance in the presence or absence of NAFLD.

The researchers performed miR profiling of serum samples from 43 well-phenotyped adult twin-pairs; six pairs of twins were discordant for NAFLD. They identified a total of 818 unique miRs, with 203 present in over 70% of participants. Comparison of serum miRs between the six pairs of discordant twins identified 10 miRs that were significantly different between those with and without NAFLD. Two of these miRs, miR-331 and miR-30c, were also among the 21 miRs that were different between the non-NAFLD and NAFLD groups.

In looking for a common mechanistic pathway, an interactome analysis of these two miRs showed seven common target genes, especially pathways involved in ubiquitin-mediated proteolysis and cell growth regulation. This important observation may allow the development of prognostic markers as well the discovery of targeted therapeutic interventions.

Motilin and Gastric Bypass Surgery

The degree of weight loss after Roux-en-Y gastric bypass (RYGB) bariatric surgery is known to vary. In an effort to explain why, Deloose and colleagues[4] postulated that changes in the gut hormones may play an important role in the metabolic reprogramming that occurs after RYGB surgery. The researchers reviewed studies indicating that specific gastric phases of the migrating motor complex are associated with hunger peaks in healthy lean volunteers, which can be induced through the administration of the motilin receptor agonist erythromycin.

In trying to define the role of motilin as a hunger-inducing factor in obese patients and determine the effect of RYGB surgery on plasma motilin levels, the authors observed a positive correlation between BMI and plasma motilin levels. They also noted that after RYGB surgery, the magnitude of change of plasma motilin levels was significantly reduced. The positive correlation between BMI and plasma motilin levels indicates that the latter plays an important role in the pathogenesis of obesity. The investigators postulate that motilin is a component of counterregulatory mechanisms to decrease hunger in obese patients.

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