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Publication Information
Affiliation
Division of Gastroenterology/Hepatology, Indiana University, Indianapolis, IN 46202, USA.
Authors
Abdelmalek MF, Ackermann S, Aouizerat B, Bambha K, Bass M, Bass NM, Behling C, Bell LN, Belt P, Boyett S, Brancati FL, Brandt P, Bringman D, Brunt EM, Buie S, Chalasani N, Chalasani S, Clark JM, Collins J, Colvin R, Contos MJ, Cummings OW, Dasarathy J, Dasarathy S, Diehl AM, Donithan M, Doo EC, Durelle J, Ferrell LD, Fuchs M, Fullenkamp AM, Ghabril M, Gottfried M, Green M, Gu B, Guy C, Hameed B, Hanna M, Hassanein T, Hawkins C, Hollick R, Hoofnagle JH, Isaacson M, Jin WK, Jones A, Kigongo C, Killenberg P, King D, Kleiner DE, Kowdley KV, Kwan S, Lavine JE, Liu YC, Loomba R, Luketic VA, Lydecker A, Mann P, May KP, McCullough AJ, McCullough J, Merriman R, Miriel L, Mooney J, Morgan A, Morris A, Muralidharan S, Nelson J, Neuschwander-Tetri BA, Nguyen A, Nguyen T, Noble K, Nonalcoholic Steatohepatitis Clinical Research Network, Pabst M, Pagadala M, Paiz M, Pan YP, Park J, Patton H, Pierce T, Piercy D, Puri P, Ragozzino L, Robuck PR, Rogers N, Rosenthal M, Sandhu B, Sanyal AJ, Sargeant C, Sargent R, Shaw C, Sherker A, Siegner J, Sirlin C, Smith M, Srivastava S, Stead A, Steel T, Sternberg A, Stewart S, Tandra S, Thompson J, Tonascia J, Unalp-Arida A, Ünalp-Arida A, Van Natta M, Vaughn I, Vuppalanchi R, Wang C, Wang J, White M, Wilson L, Wilson LA, Yates K, Yeh M, Yerian L, Zein C
Citation
Bell LN, Wang J, Muralidharan S, Chalasani S, Fullenkamp AM, Wilson LA, Sanyal AJ, Kowdley KV, Neuschwander-Tetri BA, Brunt EM, McCullough AJ, Bass NM, Diehl AM, Unalp-Arida A, Chalasani N, Nonalcoholic Steatohepatitis Clinical Research Network. 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. Hepatology 2012 Oct;56(4):1311-8. Epub 2012 Aug 21.Abstract
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).