1. THE PRESENCE OF HEPATIC STEATOSIS WHEN NO OTHER CAUSES FOR SECONDARY HEPATIC FAT ACCUMULATION NAFLD MAY PROGRESS TO CIRRHOSIS AND IS LIKELY AN IMPORTANT CAUSE OF CRYPTOGENIC CIRRHOSIS Nonalcoholic fatty liver disease (NAFLD)

2. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS SUBDIVIDED INTO: NONALCOHOLIC FATTY LIVER (NAFL) NONALCOHOLIC STEATOHEPATITIS (NASH). IN NAFL, HEPATIC STEATOSIS IS PRESENT WITHOUT EVIDENCE OF INFLAMMATION IN NASH, HEPATIC STEATOSIS IS ASSOCIATED WITH HEPATIC INFLAMMATION THAT HISTOLOGICALLY IS INDISTINGUISHABLE FROM ALCOHOLIC STEATOHEPATITIS NAFL versus NASH

3. ONE OF THE MOST IMPORTANT RISK FACTORS IS HISTOLOGIC EVIDENCE OF HEPATIC INFLAMMATION. Risk factors for progression

4. ●Older age [10,17,21,22]10,17,21,22 ●Diabetes mellitus [23]23 ●Elevated serum aminotransferases (≥2 times the upper limit of normal in one study) [21-24]21-24 ●Presence of ballooning degeneration plus Mallory hyaline or fibrosis on biopsy [25]25 ●Body mass index ≥28 kg/m 2 [21]21 ●Higher visceral adiposity index, which takes into account waist circumference, body mass index, triglycerides, and high-density lipoprotein level [26]26 ●Coffee consumption has been associated with a lower risk of progression Factor associate with more fibrosis

5. MULTIPLE THERAPIES HAVE BEEN INVESTIGATED WEIGHT LOSS IS THE ONLY THERAPY WITH REASONABLE EVIDENCE SUGGESTING IT IS BENEFICIAL AND SAFE. Therapy

6. OVERWEIGHT OR OBESE PATIENTS: LIFESTYLE MODIFICATIONS BARIATRIC SURGERY PHARMACOLOGIC THERAPY  FAIL DIET AND EXERCISE Weight loss

7. A REASONABLE GOAL FOR MANY PATIENTS IS TO LOSE 0.5 TO 1 KG/WEEK (1 TO 2 LB/WEEK).

8. Histologic improvement has also been observed in some patients with NAFLD or NASH after bariatric surgery [73,75-86]. However, the data are inconsistent and possibly biased. In some observational studies, fibrosis is worsened [86].73,75-8686 At this time, it is not advised to perform a bariatric operation specifically for the purpose of improving NAFLD or NASH, nor is the optimal bariatric procedure yet identified. A retrospective review of obese patients undergoing a bariatric procedure illustrates the latter points

9. A review of 12 studies (seven prospective and five retrospective), ranging from 7 to 116 patients undergoing a RYGB found histologic resolution or improvement in steatosis, inflammation, and fibrosis in most patients with preoperative NAFLD (range 50 to 83 percent). However, a few patients developed worsening or new fibrosis after the RYGB. ●A review of three prospective studies that included a range of 36 to 381 patients undergoing an AGB found improved steatosis, inflammation, and fibrosis in most patients, and a range of approximately 10 to 30 percent with persistent NASH or worsening fibrosis. Limited data are available for the association of a SG and resolution or improvement of NAFLD or NASH. In a retrospective review of 236 patients undergoing a SG using liver function tests as a surrogate marker for NASH, there was a 50 percent reduction in preoperative transaminase levels at 6 and 12 months of follow-up [75].75 Given the potential for worsening fibrosis in some patients following bariatric surgery, patients should continue to have liver function tests monitored closely

10. HISTOLOGIC IMPROVEMENT HAS BEEN OBSERVED AFTER BARIATRIC SURGERY. Histology

11. 21 OBSERVATIONAL STUDIES OF BARIATRIC SURGERY IN PATIENTS WITH NASH: AN IMPROVEMENT IN STEATOSIS WAS REPORTED IN 18 STUDIES DECREASED INFLAMMATION WAS REPORTED IN 11 IMPROVEMENT IN FIBROSIS SCORE WAS REPORTED IN 6 IN FOUR STUDIES THERE WAS SOME WORSENING OF FIBROSIS. Systematic review

12. BARIATRIC SURGERY IS A PROMISING APPROACH IN OBESE PATIENTS WITH NAFLD. GIVEN THE POTENTIAL FOR WORSENING FIBROSIS IN SOME PATIENTS FOLLOWING BARIATRIC SURGERY  PATIENTS SHOULD CONTINUE TO HAVE THEIR LIVER FUNCTION MONITORED CLOSELY Conclusion

13. We recommend weight loss for overweight and obese patients (Grade 1B). In addition to its other health benefits, weight loss, either through lifestyle modifications or bariatric surgery, has been associated with histologic improvement in patients with NAFLD. A reasonable goal for many patients is to lose 0.5 to 1 kg/week (1 to 2lb/weekGrade 1B