Download PDF
Semin Liver Dis 2005; 25(1): 52-64
DOI: 10.1055/s-2005-864781
Published in 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Liver Biopsy in Chronic Hepatitis C: A View from the Other Side of the Microscope

David E. Kleiner1
  • 1Director, Clinical Operations, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland
Further Information

Publication History

Publication Date:
25 February 2005 (online)

    Permissions and Reprints

ABSTRACT

The liver biopsy has long been the gold standard for the evaluation of the state of liver disease in patients with chronic hepatitis C. Although a liver biopsy continues to be a recommended part of the work-up of this disease, its routine use is challenged by the increasing effectiveness of therapy and by surrogate biochemical tests that give information about the stage of disease. Nevertheless, recent studies have shown that histological features other than stage may have predictive value for disease progression and therapeutic response to interferon-based regimens. Pathologists can increase the relevance and utility of the liver biopsy in chronic hepatitis C by the systematic reporting of steatosis and iron accumulation in addition to stage and grade, and by identifying certain potential confounding liver diseases, such as steatohepatitis and hereditary hemochromatosis. Clinicians can then make best use of the information derived from the liver biopsy to help them advise patients on the natural history of their disease and the therapeutic options that are available.

KEYWORDS

Liver biopsy - chronic hepatitis C - progression - therapeutic response

REFERENCES

  • 1 National Institutes of Health Consensus Development Conference Panel statement . Management of hepatitis C.  Hepatology. 1997;  26 2S-10S
    CrossrefPubMedGoogle Scholar
  • 2 EASL International Consensus Conference on hepatitis C . Consensus statement February 26-27, 1999; Paris, France.  J Hepatol. 1999;  31(suppl 1) 3-8
    CrossrefPubMedGoogle Scholar
  • 3 Booth J C, O'Grady J, Neuberger J. Clinical guidelines on the management of hepatitis C.  Gut. 2001;  49(suppl 1) 1-21
    CrossrefPubMedGoogle Scholar
  • 4 National Institutes of Health Consensus Development Conference Statement . Management of hepatitis C-June 10-12, 2002.  Hepatology. 2002;  36 S3-20
    CrossrefPubMedGoogle Scholar
  • 5 Tillman H L, Manns M P, Rudolph K L. Merging models of hepatitis C virus pathogenesis.  Semin Liver Dis. 2005;  25 84-92
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Perrillo R P. The role of liver biopsy in hepatitis C.  Hepatology. 1997;  26 57S-61S
    CrossrefPubMedGoogle Scholar
  • 7 Dienes H P, Drebber U, von Both I. Liver biopsy in hepatitis C.  J Hepatol. 1999;  31(suppl 1) 43-46
    CrossrefPubMedGoogle Scholar
  • 8 Poynard T, Ratziu V, Bedossa P. Appropriateness of liver biopsy.  Can J Gastroenterol. 2000;  14 543-548
    PubMedGoogle Scholar
  • 9 Garcia G, Keeffe E B. Liver biopsy in chronic hepatitis C: routine or selective.  Am J Gastroenterol. 2001;  96 3053-3055
    CrossrefPubMedGoogle Scholar
  • 10 Saadeh S, Cammell G, Carey W D et al.. The role of liver biopsy in chronic hepatitis C.  Hepatology. 2001;  33 196-200
    CrossrefPubMedGoogle Scholar
  • 11 Yusoff I F, Mollison L, Totten L et al.. Liver biopsy in hepatitis C: reassessing its role in 2001.  Med J Aust. 2002;  176 89-90
    PubMedGoogle Scholar
  • 12 Dienstag J L. The role of liver biopsy in chronic hepatitis C.  Hepatology. 2002;  36 S152-S160
    CrossrefPubMedGoogle Scholar
  • 13 Gebo K A, Herlong H F, Torbenson M S et al.. Role of liver biopsy in management of chronic hepatitis C: a systematic review.  Hepatology. 2002;  36 S161-S172
    CrossrefPubMedGoogle Scholar
  • 14 Scheuer P J. Classification of chronic viral hepatitis: a need for reassessment.  J Hepatol. 1991;  13 372-374
    CrossrefPubMedGoogle Scholar
  • 15 Ishak K G. Chronic hepatitis: morphology and nomenclature.  Mod Pathol. 1994;  7 690-713
    PubMedGoogle Scholar
  • 16 Desmet V J, Gerber M, Hoofnagle J H et al.. Classification of chronic hepatitis: diagnosis, grading and staging.  Hepatology. 1994;  19 1513-1520
    CrossrefPubMedGoogle Scholar
  • 17 Batts K P, Ludwig J. Chronic hepatitis. An update on terminology and reporting.  Am J Surg Pathol. 1995;  19 1409-1417
    CrossrefPubMedGoogle Scholar
  • 18 Ishak K, Baptista A, Bianchi L et al.. Histological grading and staging of chronic hepatitis.  J Hepatol. 1995;  22 696-699
    CrossrefPubMedGoogle Scholar
  • 19 The French METAVIR Cooperative Study Group . Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C.  Hepatology. 1994;  20 15-20
    CrossrefPubMedGoogle Scholar
  • 20 Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group.  Hepatology. 1996;  24 289-293
    CrossrefPubMedGoogle Scholar
  • 21 Knodell R G, Ishak K G, Black W C et al.. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis.  Hepatology. 1981;  1 431-435
    CrossrefPubMedGoogle Scholar
  • 22 Deugnier Y M, Turlin B, Powell L W et al.. Differentiation between heterozygotes and homozygotes in genetic hemochromatosis by means of a histological hepatic iron index: a study of 192 cases.  Hepatology. 1993;  17 30-34
    CrossrefPubMedGoogle Scholar
  • 23 Searle J, Leggett B A, Crawford D HG et al.. Iron storage diseases. In: MacSween RN, Burt AD, Portmann BC, et al, Pathology of the Liver, 4th ed London, England; Churchill Livingstone 2002: 257-272
    Google Scholar
  • 24 Regev A, Berho M, Jeffers L J et al.. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection.  Am J Gastroenterol. 2002;  97 2614-2618
    CrossrefPubMedGoogle Scholar
  • 25 Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C.  Hepatology. 2003;  38 1449-1457
    CrossrefPubMedGoogle Scholar
  • 26 Colloredo G, Guido M, Sonzogni A et al.. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease.  J Hepatol. 2003;  39 239-244
    CrossrefPubMedGoogle Scholar
  • 27 Siddique I, El-Naga H A, Madda J P et al.. Sampling variability on percutaneous liver biopsy in patients with chronic hepatitis C virus infection.  Scand J Gastroenterol. 2003;  38 427-432
    CrossrefPubMedGoogle Scholar
  • 28 Guido M, Rugge M. Liver biopsy sampling in chronic viral hepatitis.  Semin Liver Dis. 2004;  24 89-97
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Poynard T, Ratziu V, McHutchison J 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
    CrossrefPubMedGoogle Scholar
  • 30 Shiffman M L, Di Bisceglie A M, Lindsay K L et al.. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.  Gastroenterology. 2004;  126 1015-1023
    CrossrefPubMedGoogle Scholar
  • 31 Myers R P, Patel K, Pianko S et al.. The rate of fibrosis progression is an independent predictor of the response to antiviral therapy in chronic hepatitis C.  J Viral Hepat. 2003;  10 16-22
    CrossrefPubMedGoogle Scholar
  • 32 Imbert-Bismut F, Ratziu V, Pieroni L et al.. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study.  Lancet. 2001;  357 1069-1075
    CrossrefPubMedGoogle Scholar
  • 33 Fortunato G, Castaldo G, Oriani G et al.. Multivariate discriminant function based on six biochemical markers in blood can predict the cirrhotic evolution of chronic hepatitis.  Clin Chem. 2001;  47 1696-1700
    PubMedGoogle Scholar
  • 34 Forns X, Ampurdanes S, Llovet J M et al.. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model.  Hepatology. 2002;  36 986-992
    CrossrefPubMedGoogle Scholar
  • 35 Wai C T, Greenson J K, Fontana R J et al.. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.  Hepatology. 2003;  38 518-526
    PubMedGoogle Scholar
  • 36 Sud A, Hui J M, Farrell G 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
    CrossrefPubMedGoogle Scholar
  • 37 Poynard T, McHutchison J, Manns M et al.. Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin.  Hepatology. 2003;  38 481-492
    PubMedGoogle Scholar
  • 38 Shakil A O, Conry-Cantilena C, Alter H J et al.. Volunteer blood donors with antibody to hepatitis C virus: clinical, biochemical, virologic, and histologic features. The Hepatitis C Study Group.  Ann Intern Med. 1995;  123 330-337
    PubMedGoogle Scholar
  • 39 Kyrlagkitsis I, Portmann B, Smith H et al.. Liver histology and progression of fibrosis in individuals with chronic hepatitis C and persistently normal ALT.  Am J Gastroenterol. 2003;  98 1588-1593
    CrossrefPubMedGoogle Scholar
  • 40 Monto A, Alonzo J, Watson J J et al.. Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol.  Hepatology. 2002;  36 729-736
    CrossrefPubMedGoogle Scholar
  • 41 Hourigan L F, Macdonald G A, Purdie D et al.. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis.  Hepatology. 1999;  29 1215-1219
    CrossrefPubMedGoogle Scholar
  • 42 Asselah T, Boyer N, Guimont M C et al.. Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C.  Gut. 2003;  52 1638-1643
    CrossrefPubMedGoogle Scholar
  • 43 Wyatt J, Baker H, Prasad P et al.. Steatosis and fibrosis in patients with chronic hepatitis C.  J Clin Pathol. 2004;  57 402-406
    CrossrefPubMedGoogle Scholar
  • 44 Rubbia-Brandt L, Fabris P, Paganin S et al.. Steatosis affects chronic hepatitis C progression in a genotype specific way.  Gut. 2004;  53 406-412
    CrossrefPubMedGoogle Scholar
  • 45 Hezode C, Lonjon I, Roudot-Thoraval F et al.. Impact of moderate alcohol consumption on histological activity and fibrosis in patients with chronic hepatitis C, and specific influence of steatosis: a prospective study.  Aliment Pharmacol Ther. 2003;  17 1031-1037
    CrossrefPubMedGoogle Scholar
  • 46 Poynard T, Ratziu V, Charlotte F et al.. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C.  J Hepatol. 2001;  34 730-739
    CrossrefPubMedGoogle Scholar
  • 47 Wali M, Lewis S, Hubscher S et al.. Histological progression during short-term follow-up of patients with chronic hepatitis C virus infection.  J Viral Hepat. 1999;  6 445-452
    CrossrefPubMedGoogle Scholar
  • 48 Matsumura H, Moriyama M, Goto I et al.. Natural course of progression of liver fibrosis in Japanese patients with chronic liver disease type C-a study of 527 patients at one establishment.  J Viral Hepat. 2000;  7 268-275
    CrossrefPubMedGoogle Scholar
  • 49 Ghany M G, Kleiner D E, Alter H et al.. Progression of fibrosis in chronic hepatitis C.  Gastroenterology. 2003;  124 97-104
    CrossrefPubMedGoogle Scholar
  • 50 Wright M, Goldin R, Fabre A et al.. Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study.  Gut. 2003;  52 574-579
    CrossrefPubMedGoogle Scholar
  • 51a Fontaine H, Nalpas B, Poulet B et al.. Haptatitis activity index is a key factor in determining the natural history of chronic hepatitis C.  Hum Pathol. 2001;  32 904-909
    CrossrefPubMedGoogle Scholar
  • 51b Guido M, Fagiuoli S, Tessari G et al.. Histology predicts cirrhotic evolution of post transplant hepatitis C.  Gut. 2002;  50 697-700
    CrossrefPubMedGoogle Scholar
  • 52 Zarski J P, Mc Hutchison J, Bronowicki J P et al.. Rate of natural disease progression in patients with chronic hepatitis C.  J Hepatol. 2003;  38 307-314
    CrossrefPubMedGoogle Scholar
  • 53 Ryder S D, Irving W L, Jones D A et al.. Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study.  Gut. 2004;  53 451-455
    CrossrefPubMedGoogle Scholar
  • 54 Lefkowitch J H, Schiff E R, Davis G L 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
    PubMedGoogle Scholar
  • 55 Serfaty L, Poujol-Robert A, Carbonell N et al.. Effect of the interaction between steatosis and alcohol intake on liver fibrosis progression in chronic hepatitis C.  Am J Gastroenterol. 2002;  97 1807-1812
    CrossrefPubMedGoogle Scholar
  • 56 Friedenberg F, Pungpapong S, Zaeri N et al.. The impact of diabetes and obesity on liver histology in patients with hepatitis C.  Diabetes Obes Metab. 2003;  5 150-155
    CrossrefPubMedGoogle Scholar
  • 57 Hwang S J, Luo J C, Chu C W et al.. Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation.  J Gastroenterol Hepatol. 2001;  16 190-195
    CrossrefPubMedGoogle Scholar
  • 58 Kumar D, Farrell G C, Fung C et al.. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: Reversal of hepatic steatosis after sustained therapeutic response.  Hepatology. 2002;  36 1266-1272
    CrossrefPubMedGoogle Scholar
  • 59 Hickman I J, Clouston A D, Macdonald G A et al.. Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C.  Gut. 2002;  51 89-94
    CrossrefPubMedGoogle Scholar
  • 60 Adinolfi L E, Gambardella M, Andreana A et al.. 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
    CrossrefPubMedGoogle Scholar
  • 61 Hu K Q, Kyulo N L, Esrailian E et al.. Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States.  J Hepatol. 2004;  40 147-154
    PubMedGoogle Scholar
  • 62 Walsh M J, Vanags D M, Clouston A D et al.. Steatosis and liver cell apoptosis in chronic hepatitis C: a mechanism for increased liver injury.  Hepatology. 2004;  39 1230-1238
    CrossrefPubMedGoogle Scholar
  • 63 Clouston A D, Jonsson J R, Purdie D M et al.. Steatosis and chronic hepatitis C: analysis of fibrosis and stellate cell activation.  J Hepatol. 2001;  34 314-320
    CrossrefPubMedGoogle Scholar
  • 64 Ong J P, Younossi Z M, Speer C et al.. Chronic hepatitis C and superimposed nonalcoholic fatty liver disease.  Liver. 2001;  21 266-271
    CrossrefPubMedGoogle Scholar
  • 65 Sanyal A J, Contos M J, Sterling R K et al.. Nonalcoholic fatty liver disease in patients with hepatitis C is associated with features of the metabolic syndrome.  Am J Gastroenterol. 2003;  98 2064-2071
    CrossrefPubMedGoogle Scholar
  • 66 Akuta N, Suzuki F, Tsubota A et al.. Efficacy of interferon monotherapy to 394 consecutive naive cases infected with hepatitis C virus genotype 2a in Japan: therapy efficacy as consequence of tripartite interaction of viral, host and interferon treatment-related factors.  J Hepatol. 2002;  37 831-836
    CrossrefPubMedGoogle Scholar
  • 67 Bjoro K, Bell H, Hellum K B et al.. Effect of combined interferon-alpha induction therapy and ribavirin on chronic hepatitis C virus infection: a randomized multicentre study.  Scand J Gastroenterol. 2002;  37 226-232
    CrossrefPubMedGoogle Scholar
  • 68 Van Thiel D H, Friedlander L, Fagiuoli S et al.. Response to interferon alpha therapy is influenced by the iron content of the liver.  J Hepatol. 1994;  20 410-415
    CrossrefPubMedGoogle Scholar
  • 69 Olynyk J K, Reddy K R, Di Bisceglie A M et al.. Hepatic iron concentration as a predictor of response to interferon alfa therapy in chronic hepatitis C.  Gastroenterology. 1995;  108 1104-1109
    PubMedGoogle Scholar
  • 70 Barton A L, Banner B F, Cable E E et al.. Distribution of iron in the liver predicts the response of chronic hepatitis C infection to interferon therapy.  Am J Clin Pathol. 1995;  103 419-424
    PubMedGoogle Scholar
  • 71 Ikura Y, Morimoto H, Johmura H et al.. Relationship between hepatic iron deposits and response to interferon in chronic hepatitis C.  Am J Gastroenterol. 1996;  91 1367-1373
    PubMedGoogle Scholar
  • 72 Kaserer K, Fiedler R, Steindl P et al.. Liver biopsy is a useful predictor of response to interferon therapy in chronic hepatitis C.  Histopathology. 1998;  32 454-461
    CrossrefPubMedGoogle Scholar
  • 73 Piperno A, Vergani A, Malosio I et al.. Hepatic iron overload in patients with chronic viral hepatitis: role of HFE gene mutations.  Hepatology. 1998;  28 1105-1109
    CrossrefPubMedGoogle Scholar
  • 74 Kazemi-Shirazi L, Datz C, Maier-Dobersberger T et al.. The relation of iron status and hemochromatosis gene mutations in patients with chronic hepatitis C.  Gastroenterology. 1999;  116 127-134
    PubMedGoogle Scholar
  • 75 Hezode C, Cazeneuve C, Coue O et al.. Liver iron accumulation in patients with chronic active hepatitis C: prevalence and role of hemochromatosis gene mutations and relationship with hepatic histological lesions.  J Hepatol. 1999;  31 979-984
    CrossrefPubMedGoogle Scholar
  • 76 Thorburn D, Curry G, Spooner R et al.. The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C.  Gut. 2002;  50 248-252
    CrossrefPubMedGoogle Scholar
  • 77 Smith B C, Gorve J, Guzail M A et al.. Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C.  Hepatology. 1998;  27 1695-1699
    CrossrefPubMedGoogle Scholar
  • 78 Bonkovsky H L, Troy N, McNeal K et al.. Iron and HFE or TfR1 mutations as comorbid factors for development and progression of chronic hepatitis C.  J Hepatol. 2002;  37 848-854
    CrossrefPubMedGoogle Scholar
  • 79 Giannini E, Mastracci L, Botta F et al.. Liver iron accumulation in chronic hepatitis C patients without HFE mutations: relationships with histological damage, viral load and genotype and alpha-glutathione S-transferase levels.  Eur J Gastroenterol Hepatol. 2001;  13 1355-1361
    CrossrefPubMedGoogle Scholar
  • 80 Fong T L, Han S H, Tsai N C et al.. A pilot randomized, controlled trial of the effect of iron depletion on long-term response to alpha-interferon in patients with chronic hepatitis C.  J Hepatol. 1998;  28 369-374
    CrossrefPubMedGoogle Scholar
  • 81 Di Bisceglie A M, Bonkovsky H L, Chopra S et al.. Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: a multicenter, prospective, randomized, controlled trial.  Hepatology. 2000;  32 135-138
    CrossrefPubMedGoogle Scholar
  • 82 Fontana R J, Israel J, LeClair P et al.. Iron reduction before and during interferon therapy of chronic hepatitis C: results of a multicenter, randomized, controlled trial.  Hepatology. 2000;  31 730-736
    CrossrefPubMedGoogle Scholar
  • 83 Fargion S, Fracanzani A L, Rossini A et al.. Iron reduction and sustained response to interferon-alpha therapy in patients with chronic hepatitis C: results of an Italian multicenter randomized study.  Am J Gastroenterol. 2002;  97 1204-1210
    PubMedGoogle Scholar
  • 84 Yano M, Hayashi H, Wakusawa S et al.. Long term effects of phlebotomy on biochemical and histological parameters of chronic hepatitis C.  Am J Gastroenterol. 2002;  97 133-137
    CrossrefPubMedGoogle Scholar
  • 85 Tung B Y, Emond M J, Bronner M P et al.. Hepatitis C, iron status, and disease severity: relationship with HFE mutations.  Gastroenterology. 2003;  124 318-326
    CrossrefPubMedGoogle Scholar
  • 86 Erhardt A, Maschner-Olberg A, Mellenthin C et al.. HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis.  J Hepatol. 2003;  38 335-342
    CrossrefPubMedGoogle Scholar
  • 87 Larson A M, Taylor S L, Bauermeister D et al.. Pilot study of the relationship between histologic progression and hepatic iron concentration in chronic hepatitis C.  J Clin Gastroenterol. 2003;  37 406-411
    PubMedGoogle Scholar
  • 88 Bressler B L, Guindi M, Tomlinson G et al.. High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C.  Hepatology. 2003;  38 639-644
    PubMedGoogle Scholar
  • 89 Gochee P A, Jonsson J R, Clouston A D et al.. Steatosis in chronic hepatitis C: association with increased messenger RNA expression of collagen I, tumor necrosis factor-alpha and cytochrome P450 2E1.  J Gastroenterol Hepatol. 2003;  18 386-392
    CrossrefPubMedGoogle Scholar
  • 90 Petit J M, Benichou M, Duvillard L et al.. Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load, steatosis, and liver fibrosis.  Am J Gastroenterol. 2003;  98 1150-1154
    PubMedGoogle Scholar
  • 91 Czaja A J, Carpenter H A, Santrach P J et al.. Host- and disease-specific factors affecting steatosis in chronic hepatitis C.  J Hepatol. 1998;  29 198-206
    CrossrefPubMedGoogle Scholar
  • 92 Sharma P, Balan V, Hernandez J et al.. Hepatic steatosis in hepatitis C virus genotype 3 infection: does it correlate with body mass index, fibrosis, and HCV risk factors?.  Dig Dis Sci. 2004;  49 25-29
    CrossrefPubMedGoogle Scholar
  • 93 Brunt E M, Ramrakhiani S, Cordes B G et al.. Concurrence of histologic features of steatohepatitis with other forms of chronic liver disease.  Mod Pathol. 2003;  16 49-56
    CrossrefPubMedGoogle Scholar
  • 94 Romero-Gomez M, Castellano-Megias V M, Grande L et al.. Serum leptin levels correlate with hepatic steatosis in chronic hepatitis C.  Am J Gastroenterol. 2003;  98 1135-1141
    PubMedGoogle Scholar

 Dr.
David E Kleiner

Laboratory of Pathology/NCI, Bldg. 10/ Room 2N212, Bethesda, MD 20892

Email: kleinerd@mail.nih.gov

      >