Browsing by Author "Unalp-Arida, Aynur"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Histologic Abnormalities in Children with Nonalcoholic Fatty Liver Disease and Normal or Mildly Elevated Alanine Aminotransferase Levels.
    (Elsevier, 2014-04) Molleston, Jean P.; Schwimmer, Jeffrey B.; Yates, Katherine P.; Murray, Karen F.; Cummings, Oscar W.; Lavine, Joel E.; Brunt, Elizabeth M.; Scheimann, Ann O.; Unalp-Arida, Aynur; Department of Pediatrics, IU School of Medicine
    Objectives: To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26–50 U/L boys, 23–44 U/L girls), or elevated (> 50 boys, > 44 girls) serum alanine aminotransferase (ALT) levels. Study design: The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) enrolls children 5–18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy within 180 days of ALT, and compared them with 392 children with elevated ALT. Results: Of 91 children, 17 (19%) had normal and 74 (81%) had mildly elevated ALT levels. Overall, 45% of biopsies had ≥ 33% steatosis, lobular inflammation grade was ≥ 2 in 22%, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had “suspicious/borderline” steatohepatitis, and 8% had definite NASH, 34% had NAFLD activity score (NAS) ≥ 4. Overall, 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in mildly elevated vs normal, with no difference in ballooning, inflammation, or NAS ≥ 4. Fibrosis stage 3/4 was seen in none of the children with normal ALT, and in 9% of the mildly elevated and 15% of the elevated. Conclusions: Liver biopsies of children with NAFLD with normal or mildly elevated ALT levels show significant histologic abnormalities, including advanced fibrosis in children with mildly elevated ALT. ALT thus may underestimate liver injury in NAFLD. Appropriate ALT cut-off levels can help identify children at risk for more severe disease.
  • Thumbnail Image
    Item
    Relationship between adipose tissue insulin resistance and liver histology in nonalcoholic steatohepatitis: a pioglitazone versus vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis trial follow-up study
    (Wolters Kluwer, 2012) Bell, Lauren N.; Wang, Jiangxia; Muralidharan, Sriya; Chalasani, Sadhana; Fullenkamp, Allison M.; Wilson, Laura A.; Sanyal, Arun J.; Kowdley, Kris V.; Neuschwander-Tetri, Brent A.; Brunt, Elizabeth M.; McCullough, Arthur J.; Bass, Nathan M.; Diehl, Anna Mae; Unalp-Arida, Aynur; Chalasani, Naga; Nonalcoholic Steatohepatitis Clinical Research Network; Medicine, School of Medicine
    The PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis [NASH]) trial demonstrated that pioglitazone and vitamin E improved liver histology to varying degrees, but the mechanisms are unknown. We conducted a study to examine the changes in adipose tissue insulin resistance (Adipo-IR) during the PIVENS trial and its relationship to histological endpoints. Adipo-IR (fasting nonesterified fatty acids [NEFAs] × fasting insulin) was calculated at baseline and after 16 and 96 weeks of therapy. Compared to placebo, the baseline Adipo-IR was not different in either the vitamin E group (P = 0.34) or the pioglitazone group (P = 0.29). Baseline Adipo-IR was significantly associated with fibrosis score (P = 0.02), but not with other histological features or nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 16 weeks, compared to placebo, the pioglitazone group had a significant reduction in Adipo-IR (-15.7 versus -1.91; P = 0.02), but this effect did not persist at 96 weeks (-3.25 versus -4.28; P = 0.31). Compared to placebo, Adipo-IR in the vitamin E group did not change significantly either after 16 weeks (P = 0.70) or after 96 weeks (P = 0.85). Change in Adipo-IR at week 16 was not associated with changes in any histological parameters at week 96, but improvement in Adipo-IR at week 96 was significantly associated with improvement in ballooning (P = 0.03), fibrosis (P = 0.004), and NAS (P = 0.01). Conclusion: Vitamin E improved liver histology independent of changes in Adipo-IR, and pioglitazone treatment acutely improved Adipo-IR, but this was not sustained. Changes in Adipo-IR were associated with changes in liver histology, including fibrosis.