Gastro Flash
Gastro Flash 2015 › Gastro Flash Vol-1, No-1, 2015

Management of NAFLD with Bariatric Surgery

Non-alcoholic fatty liver disease (NAFLD) is universally considered as the hepatic manifestation of the metabolic syndrome.1Yilmaz Y. Review article: is non-alcoholic fatty liver disease a spectrum, or are steatosis and non-alcoholic steatohepatitis distinct conditions? Aliment Pharmacol Ther 2012; 36: 815-23.   It is most commonly associated with insulin resistance/type 2 diabetes mellitus and obesity; and manifested by steatosis, steatohepatitis, cirrhosis, and rarely, hepatocellular carcinoma.2Tolman KG. Dalpiaz AS. Treatment of non-alcoholic fatty liver disease. Therapeutics and Clinical Risk Management 2007:3(6) 1153-63.  

‘Multiple-hit’ Pathogenesis of NAFLD

NAFLD is currently conceptualised as a clinical spectrum that results from a ‘multiple-hit’ process which begins with simple steatosis (first hit) and may progresses, more serious liver injuries like non-alcoholic steatohepatitis (NASH) and subsequently cirrhosis may develop (second hit). As depicted in figure 1, the initial or first hit is insulin resistance leading to an increased uptake and synthesis of free fatty acids resulting in simple fatty liver. One of the second hits involves oxidative stress from reactive oxygen species (ROS) and an altered production of adipokines. These pathways probably play the most prominent role in the pathogenesis of NASH and can be potentially involved in promoting the negative impact of superimposed insults ultimately leading to progressive liver disease.1Yilmaz Y. Review article: is non-alcoholic fatty liver disease a spectrum, or are steatosis and non-alcoholic steatohepatitis distinct conditions? Aliment Pharmacol Ther 2012; 36: 815-23.  

Risk Associated with NAFLD

The long-term risk associated with NAFLD is variable. Most patients with non-NASH NAFLD have significant metabolic disease (diabetes, dyslipidaemia and cardiovascular disease) but are not likely to develop advanced fibrosis of the liver. Patients with NASH, however, may have complications of liver disease in addition to cardiovascular disease.3Wattacheril J, Chalasani N. Management of Nonalcoholic Fatty Liver Disease: Role of Bariatric Surgery. Clinical Liver Disease, Vol. 1, No. 4, August 2012; 119-21.   Table 1 depicts the risk factors and its associated conditions with NAFLD/NASH, as given by the World Gastroenterology Organisation.4Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. World Gastroenterology Organisation Global Guidelines. 2012 June.  

Diagnosis of NAFLD/NASH

World Gastroenterology Organisation Global Guidelines has recommended various diagnostic options for NAFLD/NASH, as shown in figure 2.

Current Therapies for NAFLD

Treatment of NAFLD falls into two categories (Figure 3):
1. Targeting on the steatosis or
2. Targeting the pathogenesis of progression.

Bariatric Surgery: Best Current Treatment for NAFLD and NASH

Bariatric surgery is said to offer several advantages, when performed by skilled surgeons:5Hafeez S, Ahmed MH. Bariatric Surgery as Potential Treatment for Nonalcoholic Fatty Liver Disease: A Future Treatment by Choice or by Chance? Journal of Obesity 2013;1-11.  

  • It is safe and effective in reducing weight.
  • It improves quality of life.
  • It decreases obesity related disease.
  • It increases life expectancy.

On the basis of their mechanism of action, procedures can be divided into 3 major categories:5Hafeez S, Ahmed MH. Bariatric Surgery as Potential Treatment for Nonalcoholic Fatty Liver Disease: A Future Treatment by Choice or by Chance? Journal of Obesity 2013;1-11.  

1. Restrictive procedures:
These procedures in bariatric surgery aim to restrict the amount of food that can be eaten by surgically reducing the size of the stomach. Most commonly performed restrictive procedures are vertical banded gastroplasty, laparoscopic adjustable gastric banding and sleeve gastrectomy (Figure 4 a and b).

 

 

 

 

2. Malabsorptive procedures:
These procedures aim to bypass a segment of the small bowel so that less food is absorbed (biliopancreatic diversion, biliopancreatic diversion with duodenal pouch). These procedures are less popular than restrictive procedures, as they are more technically demanding and patients often develop nutritional deficiencies.

3. Hybrid procedure:
It aims to restrict food intake by creating a small gastric pouch which also limits absorption by bypassing the proximal small bowel-the procedure is called Roux-en-Y gastric bypass (RYGB), as shown in Figure 5. This is the most common surgical bariatric procedure performed. It leaves 95% of the small bowel intact and so avoids many of the unwanted malabsorptive side effects such as diarrhoea and nutritional deficiencies.

Potential Benefits of Various Techniques used in Bariatric Surgery in the Treatment of NAFLD: Clinical Evidences

In a meta-analysis by Hafeez and Ahmed,5Hafeez S, Ahmed MH. Bariatric Surgery as Potential Treatment for Nonalcoholic Fatty Liver Disease: A Future Treatment by Choice or by Chance? Journal of Obesity 2013;1-11.   various techniques used in bariatric surgery showed their benefits in the treatment of NAFLD.

 

 

 

Factors Associated with Bariatric Surgery having Potential Role in the Treatment of NAFLD

There are several factors (Figure 6) that are associated with bariatric surgery and contribute to the treatment of NAFLD.

Long-term Effect of Bariatric Surgery on Liver Enzymes: Swedish Obese Subjects (SOS) Study

Elevated serum transaminase levels are frequently associated with obesity and with progression to chronic liver disease, including NAFLD. A non-randomised, matched, prospective controlled intervention study called “The Swedish Obese Subjects (SOS) study”6Burza MA, Romeo S, Kotronen A, et al. Long-Term Effect of Bariatric Surgery on Liver Enzymes in the Swedish Obese Subjects (SOS) Study. PLoS ONE 2013; 8(3): e60495.   was designed to examine the long-term effects of bariatric surgery on transaminase levels in obese individuals. This study compared the long-term effects of bariatric surgery and usual care in obese subjects.

Methodology : A total of 3,570 obese participants (aged 37-60 years and BMI ≥34 kg/m2 for men and ≥38 kg/m2 ) for women with no excess of alcohol consumption at baseline were included in the analyses and were divided into 2 groups:

  • Control group (n=1,795): Patients received the conventional treatment for obesity (such as advanced lifestyle modification, other or no treatment).
  • Surgery group (n=1,775): Patients in the surgery group underwent either nonadjustable or adjustable banding (n= 376), vertical banded gastroplasty (n= 1369) or gastric bypass (n =265).

Patients who earlier had bariatric surgery, earlier surgery for gastric or duodenal ulcer, gastric ulcer during the past six months, ongoing malignancy, active malignancy during the past five years,

 

myocardial infarction during the past six months, bulimic eating pattern, psychiatric or cooperative problems contraindicating bariatric surgery, regular use of cortisone or non-steroidal antiinflammatory treatment; excess of alcohol intake and alcohol or drug abuse and other severe illnesses, were excluded from the study.

The current and past health status was assessed and daily alcohol consumption was collected. The baseline examination took place approximately four weeks before the date of bariatric surgery for both the surgery patients and the matched control individuals. Anthropometric, clinical and biochemical parameters were measured at baseline examination and after 2 and 10 years. Analysis of blood samples obtained in the morning after an overnight fast was also done. Changes in serum transaminase levels and body weight were calculated as the difference between follow up (2 or 10 years) and baseline values. Also analysis of the incidence of high transaminase during follow-up and remission from high transaminase at baseline was done. High transaminase group was defined by AST levels ≥ 33 U/L or 29 U/L and ALT levels ≥ 43 U/L or 30 U/L in men or women, respectively, as cut-offs.

 

Results:6Burza MA, Romeo S, Kotronen A, et al. Long-Term Effect of Bariatric Surgery on Liver Enzymes in the Swedish Obese Subjects (SOS) Study. PLoS ONE 2013; 8(3): e60495.  

  • As compared to the control group, bariatric surgery was associated with a significant and sustained decrease in body weight.
  • Both ALT and AST were reduced in the surgery group, while there was no change in the control group, after two years of follow-up (Figure 7A).
  • ALT reduced in both the groups, but there was significantly smaller increase in AST in the surgery group than in the control group, after 10 years (Figure 7B).
  • Serum transaminase level changes were positively correlated to body weight changes at both 2- (ALT: r = 0.500, p 0.001; AST: r =0.289, p 0.001) and 10-year (ALT: r = 0.357, p < 0.001; AST: r = 0.160, p < 0.001) follow up when the surgery and control groups were pooled (Figure 8A and B).
  • Continuous reduction in ALT levels was observed with increasing weight loss for both the 2- and 10-year follow-up. In the same way, serum AST level were related to weight loss. (Figure 8 A).
  • AST levels were associated with weight change, but as compared to baseline there was no reduction in the AST levels irrespective of the weight change categories, at 10-year follow up (Figure 5B).
  • Weight gain was associated with increased serum transaminases at both 2- and 10-year follow-up (Figure 8 A and B).
  • The incidence of high serum transaminase (HT) was lower in the surgery compared to the control group at both 2-year (6% and 21%, for surgery and control groups, respectively p<0.001) and at 10-year (18% and 27%, p,0.001) follow up (Figure 9). A reduced risk for HT onset was observed in the surgery group at 2 and 10 years (OR: 0.26 (95% confidence interval 0.18-0.36, p<0.001) and 0.61 (95% confidence interval 0.46-0.81, p< 0.001, respectively).

Finally, the proportion of individuals with an ALT/AST < 1 was calculated in the control and in the surgery group in the follow-up (Figure 10). The prevalence of ALT/AST < 1 was lower in the surgery compared to the control group at both 2-year (14% vs. 25%

respectively, p < 0.001) and 10-year follow up (31 vs. 38% respectively, p = 0.001).

The prevalence of ALT/AST ratio >1 is expressed as proportion of individuals. The differences in the prevalence of ALT/AST ratio >1 between the control and the surgery group has been analysed by Fisher’s exact test.

Conclusion: Thus, this recent study concluded that in obese people bariatric surgery is more beneficial as it results in a sustained decrease in transaminase levels.

Summary

Nonalcoholic fatty liver disease is a chronic liver disease with a wide spectrum of histopathology, ranging from simple steatosis to cirrhosis. Morbid obesity is strongly associated with NAFLD. There is no evidence-based approved drug therapy for NAFLD/NASH. Lifestyle change is critical in any attempt to reverse the course of this disease, whose overall goal is to reduce excess weight. Bariatric surgery is the best alternative option for weight reduction, if lifestyle modifications and pharmacological therapy have not yielded long-term success. There are several factors that are suggested to be associated with bariatric surgery and have a potential role in the treatment of NAFLD, though this mechanism is not completely understood. It is believed that in addition to weight loss, bariatric surgery normalises insulin resistance and decreases dyslipidaemia and inflammation. Thus, bariatric surgery may be a choice for treatment of the most progressive type of NAFLD.

References

  1. Yilmaz Y. Review article: is non-alcoholic fatty liver disease a spectrum, or are steatosis and non-alcoholic steatohepatitis distinct conditions? Aliment Pharmacol Ther 2012; 36: 815-23.
  2. Tolman KG. Dalpiaz AS. Treatment of non-alcoholic fatty liver disease. Therapeutics and Clinical Risk Management 2007:3(6) 1153-63.
  3. Wattacheril J, Chalasani N. Management of Nonalcoholic Fatty Liver Disease: Role of Bariatric Surgery. Clinical Liver Disease, Vol. 1, No. 4, August 2012; 119-21.
  4. Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. World Gastroenterology Organisation Global Guidelines. 2012 June.
  5. Hafeez S, Ahmed MH. Bariatric Surgery as Potential Treatment for Nonalcoholic Fatty Liver Disease: A Future Treatment by Choice or by Chance? Journal of Obesity 2013;1-11.
  6. Burza MA, Romeo S, Kotronen A, et al. Long-Term Effect of Bariatric Surgery on Liver Enzymes in the Swedish Obese Subjects (SOS) Study. PLoS ONE 2013; 8(3): e60495.
Back to Gastro Flash Vol-1, No-1, 2015