insulin resistance and metabolic syndrome in normal level alanin aminotransferase non-alcoholic fatty liver disease

SUMMARY`THE INSULIN RESISTANCE AND METABOLIC SYNDROME INNORMAL LEVEL ALANIN AMİ NOTRANSFERASE NON-ALCOHOLİCFATTY LIVER DISEASE?In light of few studies about patients with chronic transaminase increase andnon-alcoholic steatohepatitis (NASH),non-alcoholic fatty liver disease (NAFLD)now is accepted as a part of metabolic syndrome (MS). On the other hand sinceNAFLD with normal alanine aminotransferase (ALT) levels is generally acceptedas a moderate condition this group has not been studied if it has anypredisposition to MS. In a study it has been shown that some patients who havenormal transaminase levels may have NASH in histopathologic examination.Normal ALT level NAFLD which could lead severe histopathologic damage isnot known if it could cause any predisposition to MS.The aim of the study is to investigate insulin resistance and MS criterionin NAFLD with normal ALT levels which is prevalent in the community.Randomised 50 people with normal ALT levels and hepatosteatosisdetected by ultrasonografia (US) consisted the study group and againrandomised 50 people with normal ALT levels and having no hepatosteatosisdetected by US consisted the control group. All participants were questionnedabout drug and alcohol intake, surgical intervention, and family history for liverdisease. Liver function tests and viral hepatitis markers were studied. Threesubjects with hepatosteatosis and one subject with no hepatosteatosis wereexcluded because of high transaminase levels were detected. Body mass index(BMI), waist-hip ratio (WHR) and blood pressures were measured of all subjects?in both groups. In non-diabetics, glucose tolerance level was determined by oralglucose tolerance test (OGTT). HOMA-IR value were calculated according tofasting glucose and insulin levels. Lipid profile( triglyceride, HDL) of allsubjects? were studied. Microalbuminuria amount of each individual wasdetected from 24-hour urine sample. Subjects with hepatosteatosis were groupedas grade I,II,III. Each group was evaluated with respect to MS diagnosis criteriaaccording to world healthy organization (WHO) and National Cholesterole40Education Programe-Adult Treatment Panel III (NCEP-ATP III). MS frequenciesdetermined for each criterion were compared to control groupThe mean age was 49.2 (range in the study group and 29 (58%) personswere female, while 21 (42%) were male. The mean age was 47.6 (range in thecontrol group and 36 (72%) persons were female, 14 (28%) were male.When the groups were compared, HOMA-IR value were foundsignificantly higher in the group NAFLD with normal ALT levels (p=0.042).Although ALT and aspartat aminotransferase (AST) levels were in normal range,they were significantly higher in the study group compared to control group(P=0.016 and P<0.001). However there were no differences in respect to otherclinical and laboratory findings. Estimated MS frequency according to WHO was36% and 64% in control and study groups respectively and this was significant(p=0.005). On the other hand estimated MS frequency according to NCEP-ATPIII was 44% and 60% in control and study groups respectively and no differencewas found between the groups (p=0.08).When the study group was considered as to hepatosteatose grades whichdetected by US; it has been noted that as grade was increasing both AST andALT levels were also significantly increased (p<0.001 and p=0.004). The ratio ofinsulin resistance (HOMA-IR> 2.5) and impared glucose tolerance (IGT) weresignificantly different between the groups (p=0.044 and p=0.001). Whilehepatosteatose grade was increasing, the rate of insulin resistance was alsoincreasing significantly. However, MS rates estimated as to both WHO andNCEP-ATP III, were showed no differences between the groups.In conclusion, MS rates were higher as to both WHO and NCEP-ATP IIIin normal ALT level NAFLD as it was in NASH. But in NAFLD the criteria thatwas gaved significantly higher MS rates compared to control group were WHOcriteria. For this reason the use of WHO MS crtiteria for insulin resistance ismore reasonable in NAFLD caused by insulin resistance. In our study althoughsubjects with steatosis have normal range transaminase levels, these levels werefound to be significantly higher than subjects who have no steatosis this findingalong with coexisting significantly higher insulin resistance have suggested thatin some of these individuals inflammation could be exist.41Considering all of these results as a whole; until now individuals withNAFLD to be considered important when their ALT levels were high should bescreened especially with respect to insulin resistance, obesity and MSindependently from ALT levels. It should be kept in mind that clinical course ofnormal ALT level NAFLD might not be innocent and some preventions such asweight loss by diet directed to reduce insulin resistance should be taken withoutwaiting for an increase in ALT level. The effects of insulin resistance reducingdrugs like metformin and roziglitazon on normal ALT level NAFLD should beresearched by new studies evaulating hepatic histopathology if necessary.42