Perspectives in Clinical Hepatology

You have full text access to this OnlineOpen article

Steatosis: Co-factor in other liver diseases†

  1. Elizabeth E. Powell‡,*,
  2. Julie R. Jonsson,
  3. Andrew D. Clouston

Article first published online: 16 JUN 2005

DOI: 10.1002/hep.20750

Issue

Hepatology

Hepatology

Volume 42, Issue 1, pages 5–13, July 2005

Additional Information

How to Cite

Powell, E. E., Jonsson, J. R. and Clouston, A. D. (2005), Steatosis: Co-factor in other liver diseases. Hepatology, 42: 5–13. doi: 10.1002/hep.20750

Author Information

  1. School of Medicine, Southern Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia

  1. ‡

    fax: (61) 7-3240-2337.

*Director of Clinical Training and Gastroenterologist, Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Brisbane, Queensland 4102, Australia

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 16 JUN 2005
  2. Article first published online: 16 JUN 2005
  3. Manuscript Accepted: 17 APR 2005
  4. Manuscript Received: 17 FEB 2005

Funded by

  • National Health and Medical Research Council, Australia
  • Lions Medical Research Foundation, Australia

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (253K)

References

  • 1
    Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. HEPATOLOGY 2004; 40: 1387–1395.
    Direct Link:
  • 2
    Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. HEPATOLOGY 2003; 37: 1202–1219.
    Direct Link:
  • 3
    Day CP, James OF. Hepatic steatosis: innocent bystander or guilty party? HEPATOLOGY 1998; 27: 1463–1466.
    Direct Link:
  • 4
    Clouston AD, Powell EE. Interaction of non-alcoholic fatty liver disease with other liver diseases. Best Pract Res Clin Gastroenterol 2002; 16: 767–781.
  • 5
    Scheuer PJ, Ashrafzadeh P, Sherlock S, Brown D, Dusheiko GM. The pathology of hepatitis C. HEPATOLOGY 1992; 15: 567–571.
    Direct Link:
  • 6
    Bach N, Thung SN, Schaffner F. The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. HEPATOLOGY 1992; 15: 572–577.
    Direct Link:
  • 7
    Lefkowitch JH, Schiff ER, Davis GL, Perrillo RP, Lindsay K, Bodenheimer HC, Jr., et al. Pathological diagnosis of chronic hepatitis C: a multicenter comparative study with chronic hepatitis B. The Hepatitis Interventional Therapy Group. Gastroenterology 1993; 104: 595–603.
  • 8
    Lonardo A, Adinolfi LE, Loria P, Carulli N, Ruggiero G, Day CP. Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology 2004; 126: 586–597.
  • 9
    Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Host- and disease-specific factors affecting steatosis in chronic hepatitis C. J Hepatol 1998; 29: 198–206.
  • 10
    Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. HEPATOLOGY 1999; 29: 1215–1219.
    Direct Link:
  • 11
    Jonsson JR, Hourigan LF, Purdie D, Clouston A, Macdonald GA, Powell EE. Body composition and hepatic steatosis as precursors of fibrosis in chronic hepatitis C patients - Reply. HEPATOLOGY 1999; 30: 1530–1531.
    Direct Link:
  • 12
    Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. HEPATOLOGY 2001; 33: 1358–1364.
    Direct Link:
  • 13
    Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstal R. Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. J Hepatol 2002; 37: 837–842.
  • 14
    Castera L, Hezode C, Roudot-Thoraval F, Bastie A, Zafrani ES, Pawlotsky JM, et al. Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Gut 2003; 52: 288–292.
  • 15
    Monto A, Alonzo J, Watson JJ, Grunfeld C, Wright TL. Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. HEPATOLOGY 2002; 36: 729–736.
    Direct Link:
  • 16
    Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, et al. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. HEPATOLOGY 2003; 38: 75–85.
    Direct Link:
  • 17
    Patton HM, Patel K, Behling C, Bylund D, Blatt LM, Vallee M, et al. The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol 2004; 40: 484–490.
  • 18
    Ratziu V, Munteanu M, Charlotte F, Bonyhay L, Poynard T. Fibrogenic impact of high serum glucose in chronic hepatitis C. J Hepatol 2003; 39: 1049–1055.
  • 19
    Fartoux L, Chazouilleres O, Wendum D, Poupon R, Serfaty L. Impact of steatosis on progression of fibrosis in patients with mild hepatitis C. HEPATOLOGY 2005; 41: 82–87.
    Direct Link:
  • 20
    Clouston AD, Jonsson JR, Purdie DM, Macdonald GA, Pandeya N, Shorthouse C, et al. Steatosis and chronic hepatitis C: analysis of fibrosis and stellate cell activation. J Hepatol 2001; 34: 314–320.
  • 21
    Wyatt J, Baker H, Prasad P, Gong YY, Millson C. Steatosis and fibrosis in patients with chronic hepatitis C. J Clin Pathol 2004; 57: 402–406.
  • 22
    Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. HEPATOLOGY 1990; 11: 74–80.
    Direct Link:
  • 23
    Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J Hepatol 2004; 40: 578–584.
  • 24
    Moriya K, Yotsuyanagi H, Shintani Y, Fujie H, Ishibashi K, Matsuura Y, et al. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol 1997; 78 (Pt 7): 1527–1531.
  • 25
    Barba G, Harper F, Harada T, Kohara M, Goulinet S, Matsuura Y, et al. Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Natl Acad Sci U S A 1997; 94: 1200–1205.
  • 26
    Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, et al. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 1998; 4: 1065–1067.
  • 27
    Perlemuter G, Sabile A, Letteron P, Vona G, Topilco A, Chretien Y, et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J 2002; 16: 185–194.
  • 28
    Rubbia-Brandt L, Quadri R, Abid K, Giostra E, Male PJ, Mentha G, et al. Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 2000; 33: 106–115.
  • 29
    Su AI, Pezacki JP, Wodicka L, Brideau AD, Supekova L, Thimme R, et al. Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci U S A 2002; 99: 15669–15674.
  • 30
    Hickman IJ, Clouston AD, Macdonald GA, Purdie DM, Prins JB, Ash S, et al. Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C. Gut 2002; 51: 89–94.
  • 31
    Rubbia-Brandt L, Fabris P, Paganin S, Leandro G, Male PJ, Giostra E, et al. Steatosis affects chronic hepatitis C progression in a genotype specific way. Gut 2004; 53: 406–412.
  • 32
    Cardin R, Saccoccio G, Masutti F, Bellentani S, Farinati F, Tiribelli C. DNA oxidative damage in leukocytes correlates with the severity of HCV-related liver disease: validation in an open population study. J Hepatol 2001; 34: 587–592.
  • 33
    Farinati F, Cardin R, Bortolami M, Rugge M. The mechanisms underlying hepatitis C virus genotype 3-mediated liver damage. J Hepatol 2003; 39: 292–294.
  • 34
    Younossi ZM, McCullough AJ, Ong JP, Barnes DS, Post A, Tavill A, et al. Obesity and non-alcoholic fatty liver disease in chronic hepatitis C. J Clin Gastroenterol 2004; 38: 705–709.
  • 35
    Zatloukal K, Stumptner C, Fuchsbichler A, Fickert P, Lackner C, Trauner M, et al. The keratin cytoskeleton in liver diseases. J Pathol 2004; 204: 367–376.
    Direct Link:
  • 36
    Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003; 125: 437–443.
  • 37
    Walsh MJ, Vanags DM, Clouston AD, Richardson MM, Purdie DM, Jonsson JR, et al. Steatosis and liver cell apoptosis in chronic hepatitis C: a mechanism for increased liver injury. HEPATOLOGY 2004; 39: 1230–1238.
    Direct Link:
  • 38
    Bantel H, Lugering A, Heidemann J, Volkmann X, Poremba C, Strassburg CP, et al. Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury. HEPATOLOGY 2004; 40: 1078–1087.
    Direct Link:
  • 39
    Ratziu V, Saboury M, Poynard T. Worsening of steatosis and fibrosis progression. Gut 2003; 52: 1386–1387.
  • 40
    Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology 2003; 125: 1695–1704.
  • 41
    Sud A, Hui JM, Farrell GC, Bandara P, Kench JG, Fung C, et al. Improved prediction of fibrosis in chronic hepatitis C using measures of insulin resistance in a probability index. HEPATOLOGY 2004; 39: 1239–1247.
    Direct Link:
  • 42
    Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 2004; 126: 840–848.
  • 43
    Hickman IJ, Powell EE, Prins JB, Clouston AD, Ash S, Purdie DM, et al. In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy. J Hepatol 2003; 39: 1042–1048.
  • 44
    Svegliati-Baroni G, Ridolfi F, Di Sario A, Casini A, Marucci L, Gaggiotti G, et al. Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. HEPATOLOGY 1999; 29: 1743–1751.
    Direct Link:
  • 45
    Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. HEPATOLOGY 2001; 34: 738–744.
    Direct Link:
  • 46
    Romero-Gomez M, Castellano-Megias VM, Grande L, Irles JA, Cruz M, Nogales MC, et al. Serum leptin levels correlate with hepatic steatosis in chronic hepatitis C. Am J Gastroenterol 2003; 98: 1135–1141.
  • 47
    Piche T, Vandenbos F, Abakar-Mahamat A, Vanbiervliet G, Barjoan EM, Calle G, et al. The severity of liver fibrosis is associated with high leptin levels in chronic hepatitis C. J Viral Hepat 2004; 11: 91–96.
    Direct Link:
  • 48
    Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? HEPATOLOGY 2004; 40: 46–54.
    Direct Link:
  • 49
    Kaser S, Moschen A, Cayon A, Kaser A, Crespo J, Pons-Romero F, Ebenbichler CF, et al. Adiponectin and its receptors in non-alcoholic steatohepatitis. Gut 2005; 54: 117–121.
  • 50
    Zhang BH, Hornsfield BP, Farrell GC. Chronic ethanol administration to rats decreases receptor-operated mobilization of intracellular ionic calcium in cultured hepatocytes and inhibits 1,4,5-inositol trisphosphate production: relevance to impaired liver regeneration. J Clin Invest 1996; 98: 1237–1244.
  • 51
    Yang SQ, Lin HZ, Mandal AK, Huang J, Diehl AM. Disrupted signaling and inhibited regeneration in obese mice with fatty livers: implications for nonalcoholic fatty liver disease pathophysiology. HEPATOLOGY 2001; 34: 694–706.
    Direct Link:
  • 52
    Roskams T, Yang SQ, Koteish A, Durnez A, DeVos R, Huang X, et al. Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease. Am J Pathol 2003; 163: 1301–1311.
  • 53
    Yang S, Koteish A, Lin H, Huang J, Roskams T, Dawson V, et al. Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease. HEPATOLOGY 2004; 39: 403–411.
    Direct Link:
  • 54
    Sell S. Heterogeneity and plasticity of hepatocyte lineage cells. HEPATOLOGY 2001; 33: 738–750.
    Direct Link:
  • 55
    Lewindon PJ, Pereira TN, Hoskins AC, Bridle KR, Williamson RM, Shepherd RW, et al. The role of hepatic stellate cells and transforming growth factor-beta(1) in cystic fibrosis liver disease. Am J Pathol 2002; 160: 1705–1715.
  • 56
    Ramm GA, Greco SA, Bridle KR, Rutherford PS, Hoskins AC, Lewindon PJ. Monocyte chemotaxis protein-1, derived from hepatocytes isolated from bile duct-ligated rats, causes recruitment of hepatic stellate cells [abstr.]. HEPATOLOGY 2002; 36: 260A.
  • 57
    Ezure T, Sakamoto T, Tsuji H, Lunz JG III, Murase N, Fung JJ, et al. The development and compensation of biliary cirrhosis in interleukin-6-deficient mice. Am J Pathol 2000; 156: 1627–1639.
  • 58
    Clouston AD, Powell EE, Walsh MJ, Richardson MM, Demetris AJ, Jonsson JR. Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis. HEPATOLOGY 2005; 41: 809–818.
    Direct Link:
  • 59
    Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 2004; 53: 413–419.
  • 60
    Bressler BL, Guindi M, Tomlinson G, Heathcote J. High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. HEPATOLOGY 2003; 38: 639–644.
    Direct Link:
  • 61
    Lam NP, Pitrak D, Speralakis R, Lau AH, Wiley TE, Layden TJ. Effect of obesity on pharmacokinetics and biologic effect of interferon-alpha in hepatitis C. Dig Dis Sci 1997; 42: 178–185.
  • 62
    Bellentani S, Tiribelli C. The spectrum of liver disease in the general population: lesson from the Dionysos study. J Hepatol 2001; 35: 531–537.
  • 63
    Naveau S, Giraud V, Borotto E, Aubert A, Capron F, Chaput JC. Excess weight risk factor for alcoholic liver disease. HEPATOLOGY 1997; 25: 108–111.
    Direct Link:
  • 64
    Raynard B, Balian A, Fallik D, Capron F, Bedossa P, Chaput JC, et al. Risk factors of fibrosis in alcohol-induced liver disease. HEPATOLOGY 2002; 35: 635–638.
    Direct Link:
  • 65
    Diehl AM. Obesity and alcoholic liver disease. Alcohol 2004; 34: 81–87.
  • 66
    Lieber CS. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol 2004; 34: 9–19.
  • 67
    Mezey E. Dietary fat and alcoholic liver disease. HEPATOLOGY 1998; 28: 901–905.
    Direct Link:
  • 68
    Robertson G, Leclercq I, Farrell GC. Nonalcoholic steatosis and steatohepatitis. II. Cytochrome P-450 enzymes and oxidative stress. Am J Physiol Gastrointest Liver Physiol 2001; 281: G1135–1139.
  • 69
    Bunout D, Munoz C, Lopez M, de la Maza MP, Schlesinger L, Hirsch S, et al. Interleukin 1 and tumor necrosis factor in obese alcoholics compared with normal-weight patients. Am J Clin Nutr 1996; 63: 373–376.
  • 70
    Nair S, Mason A, Eason J, Loss G, Perrillo RP. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? HEPATOLOGY 2002; 36: 150–155.
    Direct Link:
  • 71
    El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 2004; 126: 460–468.
  • 72
    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 2002; 123: 134–140.
  • 73
    Ratziu V, Bonyhay L, Di Martino V, Charlotte F, Cavallaro L, Sayegh-Tainturier MH, et al. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. HEPATOLOGY 2002; 35: 1485–1493.
    Direct Link:
  • 74
    Ohata K, Hamasaki K, Toriyama K, Matsumoto K, Saeki A, Yanagi K, et al. Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection. Cancer 2003; 97: 3036–3043.
    Direct Link:
  • 75
    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 2001; 61: 4365–4370.
  • 76
    Kato T, Miyamoto M, Date T, Yasui K, Taya C, Yonekawa H, et al. Repeated hepatocyte injury promotes hepatic tumorigenesis in hepatitis C virus transgenic mice. Cancer Sci 2003; 94: 679–685.
    Direct Link:
  • 77
    Lerat H, Honda M, Beard MR, Loesch K, Sun J, Yang Y, et al. Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology 2002; 122: 352–365.
  • 78
    Fausto N. Mouse liver tumorigenesis: models, mechanisms, and relevance to human disease. Semin Liver Dis 1999; 19: 243–252.
  • 79
    Sell S. The role of progenitor cells in repair of liver injury and in liver transplantation. Wound Repair Regen 2001; 9: 467–482.
    Direct Link:
  • 80
    Theise ND, Yao JL, Harada K, Hytiroglou P, Portmann B, Thung SN, et al. Hepatic 'stem cell' malignancies in adults: four cases. Histopathology 2003; 43: 263–271.
    Direct Link:
  • 81
    Boelsterli UA. Animal models of human disease in drug safety assessment. J Toxicol Sci 2003; 28: 109–121.
  • 82
    Pessayre D, Mansouri A, Fromenty B. Nonalcoholic steatosis and steatohepatitis. V. Mitochondrial dysfunction in steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2002; 282: G193–199.
  • 83
    Farrell GC. Drugs and steatohepatitis. Semin Liver Dis 2002; 22: 185–194.
  • 84
    Langman G, Hall PM, Todd G. Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol 2001; 16: 1395–1401.
    Direct Link:
  • 85
    Brunt EM, Ramrakhiani S, Cordes BG, Neuschwander-Tetri BA, Janney CG, Bacon BR, et al. Concurrence of histologic features of steatohepatitis with other forms of chronic liver disease. Mod Pathol 2003; 16: 49–56.
  • 86
    Bonkovsky HL, Lambrecht RW, Shan Y. Iron as a co-morbid factor in nonhemochromatotic liver disease. Alcohol 2003; 30: 137–144.
  • 87
    Mendler MH, Turlin B, Moirand R, Jouanolle AM, Sapey T, Guyader D, Le Gall JY, et al. Insulin resistance-associated hepatic iron overload. Gastroenterology 1999; 117: 1155–1163.
  • 88
    George DK, Goldwurm S, MacDonald GA, Cowley LL, Walker NI, Ward PJ, et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998; 114: 311–318.
  • 89
    Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, Cobb J, Lambrecht RW, et al. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol 1999; 31: 421–429.
  • 90
    Chitturi S, Weltman M, Farrell GC, McDonald D, Kench J, Liddle C, et al. HFE mutations, hepatic iron, and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. HEPATOLOGY 2002; 36: 142–149.
    Direct Link:
  • 91
    Bugianesi E, Manzini P, D'Antico S, Vanni E, Longo F, Leone N, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. HEPATOLOGY 2004; 39: 179–187.
    Direct Link:
  • 92
    Loria P, Lonardo A, Carulli N. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. HEPATOLOGY 2004; 39: 1748; author reply 1749.
    Direct Link:
  • 93
    Vigano M, Vergani A, Trombini P, Paleari F, Piperno A. Insulin resistance influences iron metabolism and hepatic steatosis in type II diabetes. Gastroenterology 2000; 118: 986–987.
  • 94
    Piperno A, Vergani A, Salvioni A, Trombini P, Vigano M, Riva A, et al. Effects of venesections and restricted diet in patients with the insulin-resistance hepatic iron overload syndrome. Liver Int 2004; 24: 471–476.
    Direct Link:
  • 95
    Facchini FS, Hua NW, Stoohs RA. Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 931–939.
  • 96
    Valenti L, Fracanzani AL, Fargion S. Effect of iron depletion in patients with nonalcoholic fatty liver disease without carbohydrate intolerance. Gastroenterology 2003; 124: 866; author reply 866–867.
  • 97
    Fletcher LM, Dixon JL, Purdie DM, Powell LW, Crawford DH. Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis. Gastroenterology 2002; 122: 281–289.
  • 98
    Bowlus CL, Willner I, Zern MA, Reuben A, Chen P, Holladay B, et al. Obesity predisposes to advanced liver disease in adults with alpha-1 antitrypsin deficiency [Abstract]. HEPATOLOGY 2004; 40(Suppl): 71A.
  • 99
    Mihm S, Fayyazi A, Hartmann H, Ramadori G. Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype. HEPATOLOGY 1997; 25: 735–739.
    Direct Link:
  • 100
    Kumar D, Farrell GC, Fung C, George J. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. HEPATOLOGY 2002; 36: 1266–1272.
    Direct Link:
  • 101
    Camps J, Crisostomo S, Garcia-Granero M, Riezu-Boj JI, Civeira MP, Prieto J. Prediction of the response of chronic hepatitis C to interferon alfa: a statistical analysis of pretreatment variables. Gut 1993; 34: 1714–1717.
  • 102
    Kaserer K, Fiedler R, Steindl P, Muller CH, Wrba F, Ferenci P. Liver biopsy is a useful predictor of response to interferon therapy in chronic hepatitis C. Histopathology 1998; 32: 454–461.
    Direct Link:
  • 103
    Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol 2005; 42: 218–224.
View Full Article (HTML) Get PDF (253K)