The Association between Fatty Liver Disease and Hepatocellular Carcinoma


US GASTROENTEROLOGY & HEPATOLOGY REVIEW


55


Table 1: Cohort Studies Examining the Association between Non-alcoholic Fatty Liver Disease/Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma Reference Author


Year Timing Country Data Source


Population-based Cohort Studies of NAFLD/NAS 9


Sanyal A Follow-up


Number Exposed


2010 retro US


18 million persons in insurance 2002–2008 database (2002–2008)


7 11 10 Ong JP 2008 pros US Adams LA 2005 pros US Younossi Z 2010 pros US


NHANES III cohort study (1988–2000)


8.7 years Rochester Epidemiology Project 7.6 years


NHANES III cohort study (1988–2000)


160 months Number Unexposed HCC Mortality/Incidence in


Exposed NAFLD/NASH Cohort versus in Unexposed


729,018 ≥1 NAFLD claim; 145 HCC-HCV+only and 38% of HCC due to


3,562 HCC-NAFLD/NASH 44,060 randomly selected NAFLD/NASH versus 22% HCV; (with no other risk factor) cohort controls without HCC


817 NAFLD 435 NAFLD 25 HCC deaths,


10,468 other liver disease negative


6% liver-related deaths NAFLD versus 1% in OLD


Minnesota population Cumulative mortality = 1 mortality rates 3,579 non-HCC/


58 liver-related deaths non-liver-related deaths CI 3.21–41.67 for overall in 15,866 cohort


in 15,866 cohort


Clinic-based Cohort Studies of Patients with NAFLD/NASH and No Cirrhosis 17


Soderberg C 13 2009 retro Sweden single hospital Dam-Larsen S 2009 retro Denmark single-center biopsy registry


Clinic-based Cohorts of Patients with Cirrhosis Possibly NASH-related 14


Hui JM 15 12 16 Kojima H 2003 pros 2006 retro Japan Ascha MS 2010 pros US Ratziu V 2002 retro France


liver-related mortality with NAFLD


21 years 67 NAFLD, 51 NASH


20.7 years NAFLD, 170 NAFLD 12.8 years AFLD


Australia single medical center


consecutive cirrhosis registry single-center


inpatient registry


single liver transplant clinic registry single hospital


3.2 years 195 NASH-C 40.5 months 27 CC 315 HCV-C 122 HCV-C 60 months 5.7 years 23 CC-NASH 24 CC 30 HCV, 10 ALD 247 AFLD


Cumulative mortality = 2 (9%) NR NAFLD, 3 (13%) NASH versus 2 (15%) HCV, 0 (0%) ALD


Cumulative mortality = 0 (0%) N/A NAFLD versus 1 (1%) AFLD


46 HCV-C 72 HCV-C or HBV-C


Cumulative incidence = 0 (0%) N/A CC-NASH versus 3 (7%) HCV-C


Cumulative mortality = 9 (46%) NR CC versus 53 (74%) HCV-C/HBV-C Cumulative incidence = 13% NASH-C versus 3% HCV-C


Cumulative incidence = 8 (30%) NS 8 Yatsuji S


Natural History Cohorts 18


2009 retro Japan single medical center 41.1–74.5 months 54 NASH-C


age-/gender-matched CC obese, 0 (0%) CC-lean versus 18 (21%) HCV-C matched CC-obese, 4 (11%) HCV-C matched CC-lean Cumulative incidence = 11% NASH-C versus 31% HCV-C


60 HCV-C Ekstedt M 2006 retro Sweden single-county hospital 13.7 years 71 NASH, 58 NAFLD N/A 0.03 NR


NASH-C and 1 CC versus NR NR HCC; HR = 11.56, 95%


NR


Cumulative incidence = 2.7% NAFLD/NASH versus 2.3% HCV+


Cumulative mortality = NR HCC, <0.001 NR p-value


0.19


Cumulative mortality = 2 (3%) N/A NAFLD, 1 (1%) NASH; cumulative survival = 1 (33%) NAFLD, 0 (0%) NASH


19 Hashimoto E 2009 pros Japan


single-center biopsy proven NAFLD


40.3 months 382 NASH advanced fibrosis N/A


Cumulative incidence = 7.6% (5-yr)


N/A


AFLD = alcoholic fatty liver disease; ALD = alcohol-related liver disease; C = cirrhosis; CC = cryptogenic cirrhosis; CI = confidence interval; HBV = hepatitis B virus; HCC = hepatocellular carcinoma; HCV = hepatitis C virus; HR = hazard ratio; OLD = other liver disease; N/A = not applicable; NAFLD = non-alcoholic fatty liver disease; NASH = non-alcoholic steatohepatitis; NHANES = National Health and Nutrition Examination Survey; NR = not reported; NS = not significant; pros = prospective; retro = retrospective.


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