Mitochondria in nonalcoholic fatty liver disease

Clinics in Liver Disease

Volumn 8, Issue 3, 2004, Pages 595-617

  Caldwell, Stephen H ^a   Chang, Charissa Y ^a   Nakamoto, Robert K ^b   Krugner Higby, Lisa ^c  

^a UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

^c 53726 4098   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; LIPID; MITOCHONDRIAL DNA;

DNA METABOLISM; HUMAN; INSULIN RESISTANCE; LIPID PEROXIDATION; MITOCHONDRION; NONALCOHOLIC FATTY LIVER; OBESITY; PATHOPHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ADENOSINE TRIPHOSPHATE; APOPTOSIS; DNA, MITOCHONDRIAL; FATTY LIVER; HUMANS; ION CHANNELS; LIPID PEROXIDES; MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIA, LIVER; MITOCHONDRIAL PROTEINS; OXIDATIVE PHOSPHORYLATION;

EID: 4344610502     PISSN: 10893261     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cld.2004.04.009     Document Type: Review

References (116)

1. Sayeed M.M. Mitochondrial dysfunction in sepsis: a familiar song with new lyrics. Crit Care Med. 30:2002;2780-2781
2. Mahler H., Pasi A., Kramer J.M., Schulte P., Scoging A.C., Bar W., et al. Fulminant liver failure in association with the emetic toxin of Bacillus cereus. N Engl J Med. 336:1997;1142-1148
3. Jacobsen E.B., Hamberg O., Quisorff B., Ott P. Reduced mitochondrial adenosine triphosphate synthesis in skeletal muscle in patients with Child-Pugh Class B and C cirrhosis. Hepatology. 34:2001;7-12
4. Brealey D., Brand M., Hargreaves L., Heales S., Land J., Smolenski R., et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 360:2002;219-223
5. DiMauro S., Schon E.A. Mitochondrial respiratory-chain diseases. N Engl J Med. 348:2003;2656-2668
6. Carrozzo R., Hirano M., Fromenty B., Casali C., Santorelli F.M., Bonilla E., et al. Multiple mtDNA deletions features in autosomal dominant and recessive diseases suggest distinct pathogeneses. Neurology. 50:1998;99-106
7. Hoek J.B., Cahill A., Pastorino J.G. Alcohol and mitochondria: a dysfunctional relationship. Gastroenterology. 122:2002;2049-2063
8. Gray M.W., Burger G., Lang B.F. Mitochondrial evolution. Science. 283:1999;1476-1481
9. Green D.R., Reed J.C. Mitochondria and apoptosis. Science. 281:1998;1309-1312
10. Marsman W.A., Wiesner R.H., Rodriquez L., Batts K., Porayko M.K., Hay J.E., et al. Use of fatty donor liver is associated with diminished early patient and graft survival. Transplantation. 62:1996;1246-1251
11. Masubuchi Y., Nakayama S., Horie T. Role of mitochondrial permeability transition in diclofenac-induced hepatocyte injury in rats. Hepatology. 35:2002;544-551
12. Berson A., De Beco V., Letteron P., Robin M.A., et al. Steatohepatitis inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology. 114:1998;764-774
13. Caldwell S.H., Hespenheide E.E. Subacute liver failure in obese women. Am J Gastroenterol. 97:2002;2058-2062
14. Bereiter-Hahn J., Voth M. Dynamics of mitochondria in living cells: shape changes, dislocations, fusion and fission of mitochondria. Microsc Res Tech. 27:1994;198-219
15. Phillips M.J., Poucell S., Patterson J., Valencia P. The liver: an atlas and text of ultrastructural pathology. 1987;Raven Press, New York
16. Fletcher L.M., Kwoh-Gain I., Powell E.E., Powell L.W., Halliday J.W. Markers of chronic alcohol ingestion in patients with nonalcoholic steatohepatitis: an aid to diagnosis. Hepatology. 13:1991;455-459
17. Kuroiwa T., Ohta T., Kuroiwa H., Shigeyuki K. Molecular and cellular mechanisms of mitochondrial nuclear division and mitochondriokinesis. Microsc Res Tech. 27:1994;220-232
18. Lea P.J., Temkin R.J., Freeman K.B., Mitchell G.A., Robinson B.H. Variations in mitochondrial ultrastructure and dynamics observed by high resolution scanning electron microscopy (HRSEM). Microsc Res Tech. 27:1994;269-277
19. Di Donato S. Disorders related to mitochondrial membranes: pathology of the respiratory chain and neurodegeneration. J Inherit Metab Dis. 23:2000;247-263
20. Lehmann T.G., Wheeler M.D., Schwabe R.F., Connor H.D., Schoonhoven R., Bunzendahl H., et al. Gene delivery of Cu/Zn-superoxide dismutase improves graft function after transplantation of fatty livers in the rat. Hepatology. 32:2000;1255-1264
21. Dianzani M.U. Uncoupling of oxidative phosphorylation in mitochondria from fatty livers. Biochim Biophys Acta. 14:1954;514-532
22. Dianzani M.U. The content of adenosine polyphosphates in fatty livers. Biochem J. 65:1957;116-124
23. Sternlieb I. Mitochondrial and fatty changes in hepatocytes of patients with Wilson's Disease. Gastroenterology. 55:1968;354-362
24. Chedid A., Mendenhall C.L., Tosch T., Chen T., Rabin L., et al. Significance of megamitochondria in alcoholic liver disease. Gastroenterology. 90:1986;1858-1864
25. Caldwell S.H., Swerdlow R.H., Khan E.M., Iezzoni J.C., et al. Mitochondrial abnormalities in NASH. J Hepatol. 31:1999;430-434
26. Sanyal A.J., Campbell-Sargent C., Mirshani F., Rizzo W.B., et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 120:2001;1183-1192
27. Sternlieb I., Berger J.E. Optical diffraction studies of crystalline structures in electron micrographs. J Cell Biol. 43:1969;448-455
28. Candipan R.C., Sjostrand F.S. An analysis of the contribution of the preparatory techniques to the appearance of condensed and orthodox conformations of liver mitochondria. J Ultrastructure Res. 89:1984;281-294
29. Schmucker D.L., Mooney J.S., Jones A.L. Stereological analysis of hepatic fine structure in the Fischer 344 rat. J Cell Biol. 78:1978;319-337
30. Caldwell S.H., Hespenheide E.E., Redick J.A., Iezzoni J.C., Battle E.H., Sheppard B.L. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastroenterol. 96:2001;519-525
31. Williams W.P., Selstam E., Brain T. X-ray diffraction studies of the structural organization of prolamellar bodies isolated from Zea mays. FEBS Lett. 422:1998;252-254
32. Deng Y., Kohlwein S.D., Manella C.A. Fasting induces cyanide-resistant respiration and oxidative stress in the amoeba Chaos carolinensis : implcations for the cubic structural transition in mitochondrial membranes. Protoplasm. 219:2002;160-167
33. Spycher M.A., Ruttner J.R. Kristalloide Einschlusse in menschlichen Lebermitochondrien. Virch Arch Abt B Zellpath. 1:1968;211-221
34. Wolf S.G., Frenkiel D., Arad T., Finkel S.E., Kolter R., Minsky A. DNA protection by stress-induced biocrystallization. Nature. 400:1999;83-85
35. Petersen P. Ultrastructure of periportal and centrilobular hepatocytes in human fatty liver of various aetiology. Acta Path Microbiol Scand. 85:1977;421-427
36. Hoffsten P.E., Hunter F.E., Gebicki J.M., Weinstein J. Formation of "lipid peroxide" under conditions which lead to swelling and lysis of rat liver mitochondria. Biochem Biophys Res Commun. 7:1962;276-280
37. Le T.H., Caldwell S.H., Redick J.A., Sheppard B.L., Davis C.A., Arseneau K.O., et al. The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis. Hepatology. 39:2004;1423-1429
38. Stadhouders A., Jap P., Walliman T. Biochemical nature of mitochondrial crystals. J Neurol Sci. 98:1990;304-305
39. Dianzani M.U., Scuro S. The effects of some inhibitors of oxidative phosphorylation on the morphology and enzymatic activities of mitochondria. Biochem J. 62:1956;205-215
40. Krahenbuhl S. Alterations in mitochondrial function and morphology in chronic liver disease: pathogenesis and potential for therapeutic intervention. Pharmacol Ther. 60:1993;1-38
41. Vendemiale G., Grattagliano I., Caraceni P., Caraccio G., et al. Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: effect of the nutritional status. Hepatology. 33:2001;808-815
42. Junnila M., Rahko T., Sukura A., Lindberg L.A. Reduction of carbon tetrachloride induced hepatotoxic effects by oral administration of betaine in male Han-Wistar rats: a morphometric histologic study. Veterinary Med. 37:2000;231-238
43. Lehman T.G., Wheeler M.D., Schwabe R.F., Connor H.D., et al. Gene delivery of Cu/Zn-superoxide dismutase improves graft function after transplantation of fatty liver in the rat. Hepatology. 32:2000;1255-1264
44. Trevasani F., Colantoni A., Caraceni P., Van Thiel D.H. The use of donor fatty livers for liver transplantation: a challenge or a quagmire. J Hepatol. 22:1996;114-121
45. Perez-Carrera M., Del Hoya P., Ma M., Rubio J., Martin A., et al. Activity of the mitochondrial respiratory chain enzymes is decreased in the liver of patients with nonalcoholic steatohepatitis. Hepatology. 30:1999;379A
46. Cortez-Pinto H., Chatham J., Chako V.P., Arnold C., Rashid A., Diehl A.M. Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA. 282:1999;1659-1664
47. Kiessling K.H., Pilstrom L. Ethanol and the human liver- structural and metabolic changes in liver mitochondria. Cytobiologie. 4(2):1971;339-348
48. Chavin K.D., Yang S.Q., Lin H.Z., Chatham J., Chakko V.P., et al. Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J Biol Chem. 274:1999;5692-5700
49. Diehl A.M., Hoek J.B. Mitochondrial uncoupling: role of uncoupling protein anion carriers and relationship to thermogenesis and weight control, "the benefits of losing control. J Bioenerg Biomembr. 31:1999;493-506
50. Baffy G., Zhang C.Y., Glickman J.N., Lowell B.B. Obesity-related fatty liver is unchanged in mice deficient for mitochondrial UCP-2. Hepatology. 35:2002;753-761
51. Pessayre D., Mansouri A., Fromenty B. Nonalcoholic steatosis and steatohepatitis V. Mitochondrial dysfunction in steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 282:2002;G193-G199
52. Fournier E., Peresson R., Guy G., Hermier D. Relationship between storage and secretion of hepatic lipids in two breeds of geese with different susceptibility to liver steatosis. Poult Sci. 76:1997;599-607
53. Krugner-Higby L., Shadoan M., Carlson C., Gendron A., Cofta P., Marler C., et al. Type 2 diabetes mellitus, hyperlipidemia, and extremity lesions in California mice (Peromyscus californicus) fed commercial mouse diets. Comp Med. 50:2000;412-418
54. Silva J.E. The thermogenic effect of thyroid hormone and its clinical implications. Ann Intern Med. 139:2003;205-213
55. Dulloo A.G. A sympathetic defense against obesity. Science. 297:2002;780-781
56. Bachman E.S., Dhillon H., Zhang C.Y., Cinti S., Bianco A.C., Kobilka B.K., et al. betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science. 297:2002;843-845
57. Struben V.M.D., Hespenheide E.E., Caldwell S.H. Familial patterns of non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis. Am J Med. 108:2000;9-13
58. Willner I.R., Waters B., Patil S.R., Reuben A., Morelli J., Riely C.A. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency and severity of disease. Am J Gastroenterol. 96:2001;2957-2961
59. Caldwell S.H., Harris D.M., Patrie J., Hespenheide E.E. Are NASH and cryptogenic cirrhosis under diagnosed in African Americans? Am J Gastroenterol. 97:2002;1496-1500
60. Hunt K.K., Gaglio P.J., Arons R.R. Ethnic differences in the prevalence of NASH in the United States - findings from the NHANES III study [abstract]. Gastroenterology. 124:2003;A-702
61. Schapira A.H.V. Mitochondrial disorders: an overview. J Bioenerg Biomembr. 29:1997;105-107
62. Schon E.A., Bonilla E., DiMauro S. Mitochondrial DNA mutations and pathogenesis. J Bioenerg Biomembr. 29:1997;131-149
63. Johns D.R. Mitochondrial DNA and disease. N Engl J Med. 333:1995;638-644
64. Wallace D.C. Mitochondrial diseases in mouse and man. Science. 283:1999;1482-1488
65. Shigenaga M.K., Hagen T.M., Ames B.N. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA. 91:1994;10771-10778
66. Mansouri A., Gaou I., De Kerguenec C., Amsellem S., et al. An alcoholic binge causes massive degradation of hepatic mitochondrial DNA in mice. Gastroenterology. 117:1999;181-190
67. Fromenty B., Grimbert S., Mansouri A., Beaugrand M., et al. Hepatic mitochondrial DNA deletion in alcoholics: association with microvesicular steatosis. Gastroenterology. 108:1995;193-200
68. Mansouri A., Gaou I., Fromenty B., Berson A., et al. Premature oxidative aging of hepatic mitochondrial DNA in Wilson's disease. Gastroenterology. 113:1997;599-605
69. Cote H.C.F., Brumme Z.L., Craib K.J.P., Alexander C.S., et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV infected patients. N Engl J Med. 346:2002;811-820
70. Bohan A., Droogan O., Nolan N., Mayne P., Bonham J., et al. Mitochondrial DNA abnormalities without significant deficiency of intramitochondrial fatty acid beta oxidation enzymes in a well defined subgroup of patients with nonalcoholic steatohepatitis [abstract]. Hepatology. 32:2000;387A
71. Carrozzo R., Hirano M., Fromenty B., Casali C., Santorelli F.M., Bonilla E., et al. Multiple mtDNA deletions features in autosomal dominant and recessive diseases suggest distinct pathogeneses. Neurology. 50:1998;99-106
72. Hinokio Y., Suzuki S., Komatu K., Ohtomo M., Onoda M., Matsumoto M., et al. A new mitochondrial DNA deletion associated with diabetic amyotrophy, diabetic myoatrophy, and diabetic fatty liver. Muscle Nerve. 3:1995;S142-S149
73. Feliciani C., Amerio P. Madelung's disease: inherited from an ancient Mediterranean population? N Engl J Med. 340:1999;1481
74. Vila M.R., Gamez J., Solano A., Playan A., Schwartz S., Santorelli F.M., et al. Uncoupling protein-1 m RNA expression in lipomas from patients bearing pathogenic mitochondrial DNA mutations. Biochem Biophys Res Commun. 278:2000;800-802
75. Guillausseau P.-J., Massin P., Dubois-LaForgue D., Timsit J., Virally M., Gin H., et al. Maternally inherited diabetes and deafness: a multicenter study. Ann Intern Med. 134:2001;721-728
76. Kadowaki H., Tobe K., Mori Y., Sakura H., Sakuta R., et al. Mitochondrial gene mutation and insulin-deficient type of diabetes mellitus. Lancet. 341:1993;893-894
77. Minana J.B., Gomez-Cambronero L., Lloret A., Pallardo F.V., et al. Mitochondrial oxidative stress and CD95 ligand: a dual mechanism for hepatocyte apoptosis in chronic alcoholism. Hepatology. 35:2002;1205-1214
78. Feldsteine A., Canbay A., Angulo P., Taniai M., Burgart L.J., Lindor K.D. Hepatocyte apoptosis in patients with non-alcoholic steatohepatitis. Quantification and clinical relevance. Gastroenterology. 124:2003;703A
79. Feldman G., Haouzi D., Moreau A., Durang-Schneider A.-M., Bringuier A., Berson A., et al. Opening of the mitochondrial permeability transition pore causes matrix expansion and outer membrane rupture in FAS-mediated hepatic apoptosis in mice. Hepatology. 31:2000;674-683
80. Lemasters J.J. Mitochondrial permeability transition pore: from biochemical curiosity to pathophysiological mechanism. Gastroenterology. 115:1998;783-786
81. Rashid A., Wu T.-C., Huang C.C., Chen C.H., Lin H.Z., et al. Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver. Hepatology. 29:1999;1131-1138
82. Selzer M., Rudiger H.A., Sindram D., Madden J., Clavien P.-A. Mechanisms of ischemic injury are different in the steatotic and normal rat liver. Hepatology. 32:2000;1280-1288
83. Calle E., Rodriguez C., Walker-Thurmond K., Thun M. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med. 348(17):2003;1625-1638
84. Powell E., Cooksley W., Hanson R., Searle J., Halliday J., Powell L. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology. 11(1):1990;74-80
85. Cotrim H., Parana R., Braga E., Lyra L. Nonalcoholic steatohepatitis and hepatocellular carcinoma: natural history? Am J Gastro. 95(10):2000;3018-3019
86. Zen Y., Kazuyoshi K., Tsuneyama K., Harada K., Araki I., Nakanuma Y. Hepatocellualr carcinoma arising in non-alcoholic steatohepatitis. Pathol Int. 51(2):2001;127
87. Marrero J., Fontana R., Su G., Conjeevaram H., Emick D., Lok A. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 36:2002;1349-1354
88. Ratzui V., Bonyhay L., Di Martino V., Charlotte F., Cavallaro L., Sayegh-Tainturier M., et al. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. Hepatology. 35:2002;1485-1493
89. Bugianesi E., Leone N., Vanni E., Marchesini G., Brunello F., Carucci P., et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 123(1):2002;134-140
90. Nair S., Mason A., Eason J., Loss G., Perrillo R. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology. 36:2002;150-155
91. Yang S., Lin H., Hwang J., Chacko V., Diehl A. Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition? Cancer Res. 61:2001;5016-5023
92. Wiseman H., Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J. 313:1996;17-29
93. Cerutti P.A. Oxy-radicals and cancer. Lancet. 344:1994;862-863
94. Hu W., Feng Z., Eveleigh J., Iyer G., Pan J., Amin S., et al. The major lipid peroxidation product, trans-4-hydroxy-2 nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma. Carcinogenesis. 23(11):2002;1781-1789
95. Hussain S., Aguilar F., Amstad P., Cerutti P. Oxy-radical induced mutagenesis of hotspot codons 248 and 249 of the human p53 gene. Oncogene. 9(8):1994;2277-2281
96. Moriya K., Nakagawa K., Santa T., Shintani Y., Fujie H., Miyoshi H., et al. Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res. 61:2001;4365-4370
97. 2 generation in liver mitochondria. Carcinogenesis. 21(5):2000;983-989
98. Cortez-Pinto H., Camilo M.E., Baptista A., De Oliveira A.G., De Moura M.C. Non-alcoholic fatty liver: another feature of the metabolic syndrome. Clin Nutr. 18:1999;353-358
99. Marchesini G., Bugianesi E., Forlani G., Cerrelli F., Lenzi M., Manini R., et al. Nonalcoholic fatty liver, steatohepatitis and the metabolic syndrome. Hepatology. 37:2003;917-923
100. Powell E.E., Searle J., Mortimer R. Steatohepatitis associated with limb lipodystrophy. Gastroenterology. 97:1989;1022-1024
101. Degoul F., Sutton A., Mansouri A., Cepanec C., Degott C., Fromenty B., et al. Homozygosity for alanine in the mitochondrial targeting sequence of manganese superoxide dismutase and risk for severe alcoholic liver disease. Gastroenterology. 120:2001;1468-1474
102. Petersen K.F., Befroy D., Dufour S., Dziura J., Ariyan C., Rothman D.L., et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 300:2003;1140-1142
103. Borkman M., Storlien L.H., Pan D.A., Jenkins A.B., Chisholm D.J., Campbell L.V. The relationship between insulin sensitivity and the fatty-acid composition of skeletal muscle phospholipids. N Engl J Med. 328:1993;238-244
104. Sreekumar R., Rosado B., Rasmussen D., Charlton M. Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis. Hepatology. 38:2003;244-251
105. Krahenbuhl S. Alcohol-induced myopathy: what is the role of mitochondria? Hepatology. 34:2001;210-211
106. Hoppeler H., Howald H., Conley K., Lindstedt S.L., Claasen H., Vock P., et al. Endurance training in humans: aerobic capacity and structure of skeletal muscle. J Appl Physiol. 59:1985;320-327
107. Fernandez M.I., Torres M.I., Gil A., Rios A. Steatosis and collagen content in experimental liver cirrhosis are affected by dietary monosaturated and polyunsaturated fatty acids. Scand J Gastroenterol. 32:1997;350-356
108. Tsuboyama-Kasaoka N., Takahashi M., Tanemura K., Kim H.-J., Tange T., Okuyama H., et al. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes. 49:2000;1534-1542
109. Kurihara T., Adachi Y., Yamagata M., Abe K., Akimoto M., Hashimoto H., et al. Role of eicosapentanoic acid in lipid metabolism in the liver with special reference to experimental fatty liver. Clin Ther. 16:1994;830-837
110. Nanji A.A., Sadrzadeh S.M.H., Yang E.K., Fogt F., Meydani M., Dannenberg A.J. Dietary saturated fatty acids: a novel treatment for alcoholic liver disease. Gastroenterology. 109:1995;547-554
111. Caldwell S.H., Hespenheide E.E., Redick J.A., Iezzoni J.C., Battle E.H., Sheppard B.L. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastroenterol. 96:2001;519-525
112. Acosta R.C., Molina E.G., O'Brien C.B., Cobo M.C., Amaro R., Neff G.W., et al. The use of pioglitazone in nonalcoholic steatohepatitis [abstract]. Gastroenterology. 120:2001;546
113. Sanyal A.J., Contos M.J., Sargeant C., Stravitz R.T., Luketic V.A., Sterling R.K., et al. A randomized controlled pilot study of pioglitazone and vitamin E versus vitamin E for non-alcoholic steatohepatitis [abstract]. Hepatology. 36:2002;382
114. Neuschwander-Tetri B.A., Brunt E.M., Bacon B.R., Sponseller C., Wehmeier K.R., Hampton K. Histologic improvement in NASH following increased insulin sensitivity with the PPAR-γ ligand rosiglitazone for 48 weeks[abstract]. Hepatology. 36:2002;379
115. Phillips P.S., Haas R.H., Bannykh S., Hathaway S., Gray N.L., Kimura B.J., et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med. 137:2002;581-585
116. Caldwell S.H., Zaidman J.S., Hespenheide E.E. The liver and statin drug therapy: uncertain navigation in the sea of risk-benefit. Pharmacoepidemiology. 12:2003;1-4