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Digestive Diseases: Nonalcoholic fatty liver disease and obesity

BY ALI TARKAN DURAL, M.D., F.A.C.G DIGESTIVE SPECIALISTS, P.A.

Nonalcoholic fatty liver disease (NAFLD) term encompasses benign simple fatty liver-steatosis, nonalcoholic steatohepatitis (NASH) and SHassociated cirrhosis. NAFLD is probably the most common liver disorder in the world which might affect 2.8% to 24 % of the general population (Sleisenger & Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management. 8th edition.).

Obesity is the most commonly reported condition associated with NAFLD (http:// digestive.niddk.nih.gov/ddiseases/pubs/nash ) . NAFLD might be also caused by other acquired metabolic disorders (i.e., diabetes mellitus, hyperlipidemia, starvation), cytotoxic drugs (i.e., methotrexate, bleomycin), metals (i.e., thallium and uranium compounds), inborn errors of metabolism (i.e., abetalipoproteinemia ), surgical procedures (i.e., biliopancreatic diversion, extensive small bowel resection), other drugs ( i.e., amiodarone, estrogens, highly active antiretroviral therapy, tamoxifen) and miscellaneous conditions( i.e., prolonged total parenteral nutrition, jejunal diverticulosis with bacterial overgrowth, inflammatory bowel disease, industrial exposure to petrochemicals).

According to CDC web site (http://www. cdc.gov/obesity/data/trends.html ), obesity is defined as a body mass index (BMI) of 30 or greater. During the past 20 years there has been a significant increase in obesity in the U.S. In 2008, only one state (Colorado) had a prevalence of obesity less than 20%. Thirty-two states had prevalence equal to or greater than 25%; six of these states (Alabama, Mississippi, Oklahoma, South Carolina, Tennessee, and West Virginia) had a prevalence of obesity equal to or greater than 30%. Obesity is becoming a serious health concern for children and adolescents (http://www.cdc.gov/obesity/ childhood/prevalence.html ). Data from NHANES surveys (1976–1980 and 2003– 2006) show that the prevalence of obesity has increased: for children aged 2–5 years, prevalence increased from 5.0% to 12.4%; for those aged 6–11 years, prevalence increased from 6.5% to 17.0%; and for those aged 12–19 years, prevalence increased from 5.0% to 17.6%.

To diagnose NAFLD, alcohol consumption history, imaging tests and aminotransferase levels are utilized. Other etiologies, i.e., autoimmune, viral hepatitis and hemochromatosis need to be ruled out. By imaging and laboratory tests, it is difficult to distinguish benign steatosis from NASH and NASH-associated cirrhosis. However, higher BMI, age more than 45, AST > ALT, ALT > 2 x ULN, high ferritin, low platelets, sleep apnea, and features of severe insulin resistance are surrogate markers of NASH. Liver biopsy is still the gold standard test to establish diagnosis of NASH which can lead to cirrhosis. There are some emerging noninvasive surrogate markers like Fibro Test which might help to diagnose NASHassociated cirrhosis (http://www.ncbi.nlm. nih.gov/pubmed/15723588 ). Patients with NAFLD are also at high risk for other health issues including increased cardiovascular events.

The potential treatments for NASH include weight loss (diet and exercise counseling, possibly bariatric surgery), insulin sensitizers (metformin, Thiazolidinediones-TZDs, i.e., pioglitazone, rosiglitazone), UDCA, antioxidants (Vitamin E, betaine), orlistat, antilipemics (gemfibrozil, statins), losartan and TNF alfa-inhibitors. However, there is no single established treatment for NAFLD yet.

Weight loss by diet and exercise is the initial recommendation of choice. Further studies are needed to recommend bariatric surgery specifically for treatment of NASH patients. However, the studies have shown significant improvement in liver biopsies of patients who underwent gastric restriction with bypass surgery in Pittsburgh (Manar et al. Annals of Surgery 2005; 242: 610-620). Bariatric surgery can be performed safely in NASH and NASH related cirrhotic patients as long as prominent portal hypertension is absent (absence of esophageal and intraabdominal varices by upper endoscopy and imaging tests).

Insulin sensitizers might also play an important role in treatment of NASH. Recently in PIVENS trial (http://www.ncbi. nlm.nih.gov/pubmed/18804555 ), Vitamin E 800 IU/daily also showed promising results.

Cardiovascular events are most common cause of death in patients with NAFLD. We need to remember that statins can be used safely in NAFLD patients as long as guidelines are followed. Some case series have shown improvement in liver biopsies of NASH patients who take statins.

As a clinician, I have noticed more NAFLD cases in younger adults and even in teenagers in recent years. It is my opinion that increasing incidence of NAFLD due to childhood obesity is a clear and present danger that will negatively impact healthcare in the near future.