Skip to main content
Top
Published in: Digestive Diseases and Sciences 9/2015

01-09-2015 | Original Article

Concurrent Obesity, Diabetes, and Steatosis Increase Risk of Advanced Fibrosis Among HCV Patients: A Systematic Review

Authors: Harleen K. Dyal, Maria Aguilar, Taft Bhuket, Benny Liu, Edward W. Holt, Sharon Torres, Ramsey Cheung, Robert J. Wong

Published in: Digestive Diseases and Sciences | Issue 9/2015

Login to get access

Abstract

Background

Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease among patients with chronic hepatitis C virus infection (HCV) may contribute to more rapid disease progression.

Aim

To evaluate the impact of concurrent obesity, DM, and steatosis on disease progression among HCV patients.

Methods

A systematic review using structured keyword search of MEDLINE and EMBASE from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of obesity, DM, and steatosis with advanced fibrosis (AF) among adults with chronic HCV. Studies involving HCV patients coinfected with human immunodeficiency virus, hepatitis B virus, hepatocellular carcinoma, or other chronic liver diseases were excluded. Quality assessment utilized Newcastle–Ottawa Scale.

Results

Twenty cohort studies met inclusion criteria for analyses. Obesity was associated with increased risk of AF in seven studies with effect size ranging from OR 1.08 to 7.69. However, four studies did not demonstrate a significant association between obesity and AF. The presence of advanced steatosis among HCV patients was associated with increased risk of AF in 12 studies (OR 1.80–14.3). Concurrent DM was associated with increased risk of AF in six studies (OR 2.25–9.24). Thirteen studies were good quality, and seven studies were fair quality.

Conclusion

Concurrent DM and steatosis are associated with increased risk of AF among chronic HCV patients. The majority of studies demonstrated significant associations of obesity with AF. Targeted interventions to optimize management of obesity-related diseases among HCV patients may help mitigate HCV disease progression.
Appendix
Available only for authorised users
Literature
1.
go back to reference Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005;5:558–567.CrossRefPubMed Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005;5:558–567.CrossRefPubMed
2.
go back to reference Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45:529–538.CrossRefPubMed Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45:529–538.CrossRefPubMed
3.
go back to reference Hu SX, Kyulo NL, Xia VW, et al. Factors associated with hepatic fibrosis in patients with chronic hepatitis C: a retrospective study of a large cohort of US patients. J Clin Gastroenterol. 2009;43:758–764.CrossRefPubMed Hu SX, Kyulo NL, Xia VW, et al. Factors associated with hepatic fibrosis in patients with chronic hepatitis C: a retrospective study of a large cohort of US patients. J Clin Gastroenterol. 2009;43:758–764.CrossRefPubMed
4.
go back to reference Everhart JE, Lok AS, Kim HY, HALT-C Trial Group, et al. Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology. 2009;137:549–557.PubMedCentralCrossRefPubMed Everhart JE, Lok AS, Kim HY, HALT-C Trial Group, et al. Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology. 2009;137:549–557.PubMedCentralCrossRefPubMed
5.
go back to reference Younossi ZM, McCullough AJ, Ong JP, et al. Obesity and non-alcoholic fatty liver disease in chronic hepatitis C. J Clin Gastroenterol. 2004;38:705–709.CrossRefPubMed Younossi ZM, McCullough AJ, Ong JP, et al. Obesity and non-alcoholic fatty liver disease in chronic hepatitis C. J Clin Gastroenterol. 2004;38:705–709.CrossRefPubMed
6.
go back to reference El Ray A, Asselah T, Moucari R, et al. Insulin resistance: a major factor associated with significant liver fibrosis in Egyptian patients with genotype 4 chronic hepatitis C. Eur J Gastroenterol Hepatol. 2013;25:421–427.PubMed El Ray A, Asselah T, Moucari R, et al. Insulin resistance: a major factor associated with significant liver fibrosis in Egyptian patients with genotype 4 chronic hepatitis C. Eur J Gastroenterol Hepatol. 2013;25:421–427.PubMed
7.
go back to reference Petta S, Cammà C, Di Marco V, et al. Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection. Liver Int. 2011;31:507–515.CrossRefPubMed Petta S, Cammà C, Di Marco V, et al. Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection. Liver Int. 2011;31:507–515.CrossRefPubMed
8.
go back to reference Verma S, Bonacini M, Govindarajan S, et al. More advanced hepatic fibrosis in Hispanics with chronic hepatitis C infection: role of patient demographics, hepatic necroinflammation, and steatosis. Am J Gastroenterol. 2006;101:1817–1823.CrossRefPubMed Verma S, Bonacini M, Govindarajan S, et al. More advanced hepatic fibrosis in Hispanics with chronic hepatitis C infection: role of patient demographics, hepatic necroinflammation, and steatosis. Am J Gastroenterol. 2006;101:1817–1823.CrossRefPubMed
9.
go back to reference Huang YW, Yang SS, Fu SC, et al. Increased risk of cirrhosis and its decompensation in chronic hepatitis C patients with new-onset diabetes: a nationwide cohort study. Hepatology. 2014;60:807–814.CrossRefPubMed Huang YW, Yang SS, Fu SC, et al. Increased risk of cirrhosis and its decompensation in chronic hepatitis C patients with new-onset diabetes: a nationwide cohort study. Hepatology. 2014;60:807–814.CrossRefPubMed
10.
go back to reference Nieminen U, Arkkila PE, Kärkkäinen P, et al. Effect of steatosis and inflammation on liver fibrosis in chronic hepatitis C. Liver Int. 2009;29:153–158.CrossRefPubMed Nieminen U, Arkkila PE, Kärkkäinen P, et al. Effect of steatosis and inflammation on liver fibrosis in chronic hepatitis C. Liver Int. 2009;29:153–158.CrossRefPubMed
11.
go back to reference Ortiz V, Berenguer M, Rayon JM, et al. Contribution of obesity to hepatitis C-related fibrosis progression. Am J Gastroenterol. 2002;97:2408–2414.CrossRefPubMed Ortiz V, Berenguer M, Rayon JM, et al. Contribution of obesity to hepatitis C-related fibrosis progression. Am J Gastroenterol. 2002;97:2408–2414.CrossRefPubMed
12.
go back to reference Patel K, Thompson AJ, Chuang WL, et al. Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients. J Gastroenterol Hepatol. 2011;26:1182–1188.CrossRefPubMed Patel K, Thompson AJ, Chuang WL, et al. Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients. J Gastroenterol Hepatol. 2011;26:1182–1188.CrossRefPubMed
13.
go back to reference Alsatie M, Kwo PY, Gingerich JR, et al. A multivariable model of clinical variables predicts advanced fibrosis in chronic hepatitis C. J Clin Gastroenterol. 2007;41:416–421.CrossRefPubMed Alsatie M, Kwo PY, Gingerich JR, et al. A multivariable model of clinical variables predicts advanced fibrosis in chronic hepatitis C. J Clin Gastroenterol. 2007;41:416–421.CrossRefPubMed
14.
go back to reference Cross TJ, Quaglia A, Hughes S, et al. The impact of hepatic steatosis on the natural history of chronic hepatitis C infection. J Viral Hepat. 2009;16:492–499.CrossRefPubMed Cross TJ, Quaglia A, Hughes S, et al. The impact of hepatic steatosis on the natural history of chronic hepatitis C infection. J Viral Hepat. 2009;16:492–499.CrossRefPubMed
15.
go back to reference Castéra L, Hézode C, Roudot-Thoraval F, 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.PubMedCentralCrossRefPubMed Castéra L, Hézode C, Roudot-Thoraval F, 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.PubMedCentralCrossRefPubMed
16.
go back to reference Lo Iacono O, Venezia G, Petta S, et al. The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2007;5:1181–1191.CrossRef Lo Iacono O, Venezia G, Petta S, et al. The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2007;5:1181–1191.CrossRef
17.
go back to reference Hu KQ, Kyulo NL, 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.CrossRefPubMed Hu KQ, Kyulo NL, 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.CrossRefPubMed
18.
go back to reference Fartoux L, Poujol-Robert A, Guéchot J, et al. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut. 2005;54:1003–1008.PubMedCentralCrossRefPubMed Fartoux L, Poujol-Robert A, Guéchot J, et al. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut. 2005;54:1003–1008.PubMedCentralCrossRefPubMed
19.
go back to reference Moucari R, Ripault MP, Martinot-Peignoux M, et al. Insulin resistance and geographical origin: major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4. Gut. 2009;58:1662–1669.CrossRefPubMed Moucari R, Ripault MP, Martinot-Peignoux M, et al. Insulin resistance and geographical origin: major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4. Gut. 2009;58:1662–1669.CrossRefPubMed
20.
go back to reference Muzzi A, Leandro G, Rubbia-Brandt L, et al. Insulin resistance is associated with liver fibrosis in non-diabetic chronic hepatitis C patients. J Hepatol. 2005;42:41–46.CrossRefPubMed Muzzi A, Leandro G, Rubbia-Brandt L, et al. Insulin resistance is associated with liver fibrosis in non-diabetic chronic hepatitis C patients. J Hepatol. 2005;42:41–46.CrossRefPubMed
21.
22.
go back to reference Ong JP, Younossi ZM, Speer C, et al. Chronic hepatitis C and superimposed nonalcoholic fatty liver disease. Liver. 2001;21:266–271.CrossRefPubMed Ong JP, Younossi ZM, Speer C, et al. Chronic hepatitis C and superimposed nonalcoholic fatty liver disease. Liver. 2001;21:266–271.CrossRefPubMed
23.
go back to reference Petta S, Cammà C, Di Marco V, et al. Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. Am J Gastroenterol. 2008;103:1136–1144.CrossRefPubMed Petta S, Cammà C, Di Marco V, et al. Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. Am J Gastroenterol. 2008;103:1136–1144.CrossRefPubMed
24.
go back to reference Bhat G, Baba CS, Pandey A, et al. Insulin resistance and metabolic syndrome in nonobese Indian patients with non-alcoholic fatty liver disease. Trop Gastroenterol. 2013;34:18–24.CrossRefPubMed Bhat G, Baba CS, Pandey A, et al. Insulin resistance and metabolic syndrome in nonobese Indian patients with non-alcoholic fatty liver disease. Trop Gastroenterol. 2013;34:18–24.CrossRefPubMed
25.
go back to reference Fan JG. Epidemiology of alcoholic and nonalcoholic fatty liver disease in China. J Gastroenterol Hepatol. 2013;28:11–17.CrossRefPubMed Fan JG. Epidemiology of alcoholic and nonalcoholic fatty liver disease in China. J Gastroenterol Hepatol. 2013;28:11–17.CrossRefPubMed
26.
go back to reference Hassan K, Bhalla V, El Regal ME, et al. Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic. World J Gastroenterol. 2014;20:12082–12101.PubMedCentralCrossRefPubMed Hassan K, Bhalla V, El Regal ME, et al. Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic. World J Gastroenterol. 2014;20:12082–12101.PubMedCentralCrossRefPubMed
27.
go back to reference Wong RJ, Chou C, Sinha SR, et al. Ethnic disparities in the association of body mass index with the risk of hypertension and diabetes. J Community Health. 2014;39:437–445.CrossRefPubMed Wong RJ, Chou C, Sinha SR, et al. Ethnic disparities in the association of body mass index with the risk of hypertension and diabetes. J Community Health. 2014;39:437–445.CrossRefPubMed
28.
go back to reference Wiese M, Fischer J, Löbermann M, East German HCV Study Group, et al. Evaluation of liver disease progression in the German hepatitis C virus (1b)-contaminated anti-D cohort at 35 years after infection. Hepatology. 2014;59:49–57.CrossRefPubMed Wiese M, Fischer J, Löbermann M, East German HCV Study Group, et al. Evaluation of liver disease progression in the German hepatitis C virus (1b)-contaminated anti-D cohort at 35 years after infection. Hepatology. 2014;59:49–57.CrossRefPubMed
29.
go back to reference Shah SR, Patel K, Marcellin P, et al. Steatosis is an independent predictor of relapse following rapid virologic response in patients with HCV genotype 3. Clin Gastroenterol Hepatol. 2011;9:688–693.PubMedCentralCrossRefPubMed Shah SR, Patel K, Marcellin P, et al. Steatosis is an independent predictor of relapse following rapid virologic response in patients with HCV genotype 3. Clin Gastroenterol Hepatol. 2011;9:688–693.PubMedCentralCrossRefPubMed
30.
go back to reference Goossens N, Negro F. Is genotype 3 of the hepatitis C virus the new villain? Hepatology. 2014;59:2403–2412.CrossRefPubMed Goossens N, Negro F. Is genotype 3 of the hepatitis C virus the new villain? Hepatology. 2014;59:2403–2412.CrossRefPubMed
31.
go back to reference Nkontchou G, Ziol M, Aout M, et al. HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J Viral Hepat. 2011;18:e516–e522.CrossRefPubMed Nkontchou G, Ziol M, Aout M, et al. HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J Viral Hepat. 2011;18:e516–e522.CrossRefPubMed
32.
go back to reference Khan A, Tanaka Y, Azam Z, et al. Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan. J Med Virol. 2009;81:1189–1197.CrossRefPubMed Khan A, Tanaka Y, Azam Z, et al. Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan. J Med Virol. 2009;81:1189–1197.CrossRefPubMed
33.
go back to reference Lonardo A, Adinolfi LE, Restivo L, et al. Pathogenesis and significance of hepatitis C virus steatosis: an update on survival strategy of a successful pathogen. World J Gastroenterol. 2014;20:7089–7103.PubMedCentralCrossRefPubMed Lonardo A, Adinolfi LE, Restivo L, et al. Pathogenesis and significance of hepatitis C virus steatosis: an update on survival strategy of a successful pathogen. World J Gastroenterol. 2014;20:7089–7103.PubMedCentralCrossRefPubMed
34.
go back to reference Zampino R, Marrone A, Restivo L, et al. Chronic HCV infection and inflammation: clinical impact on hepatic and extra-hepatic manifestations. World J Hepatol. 2013;5:528–540.PubMedCentralPubMed Zampino R, Marrone A, Restivo L, et al. Chronic HCV infection and inflammation: clinical impact on hepatic and extra-hepatic manifestations. World J Hepatol. 2013;5:528–540.PubMedCentralPubMed
35.
go back to reference Jha DK, Mittal A, Gupta SP, et al. Association of type II diabetes mellitus with hepatocellular carcinoma occurrence—a case control study from Kathmandu Valley. Asian Pac J Cancer Prev. 2012;13:5097–5099.CrossRefPubMed Jha DK, Mittal A, Gupta SP, et al. Association of type II diabetes mellitus with hepatocellular carcinoma occurrence—a case control study from Kathmandu Valley. Asian Pac J Cancer Prev. 2012;13:5097–5099.CrossRefPubMed
36.
go back to reference Memon MS, Arain ZI, Naz F, et al. Prevalence of type 2 diabetes mellitus in hepatitis C virus infected population: a Southeast Asian study. J Diabetes Res. 2013;2013:539361. Memon MS, Arain ZI, Naz F, et al. Prevalence of type 2 diabetes mellitus in hepatitis C virus infected population: a Southeast Asian study. J Diabetes Res. 2013;2013:539361.
Metadata
Title
Concurrent Obesity, Diabetes, and Steatosis Increase Risk of Advanced Fibrosis Among HCV Patients: A Systematic Review
Authors
Harleen K. Dyal
Maria Aguilar
Taft Bhuket
Benny Liu
Edward W. Holt
Sharon Torres
Ramsey Cheung
Robert J. Wong
Publication date
01-09-2015
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 9/2015
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3760-3

Other articles of this Issue 9/2015

Digestive Diseases and Sciences 9/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.