The Association between Fatty Liver Disease and Hepatocellular Carcinoma
Table 3: Clinical Features Associated with Hepatocellular Carcinoma-Non-alcoholic Fatty Liver Disease/ Non-alcoholic Steatohepatitis in Case Series and Case Reports
Reference
36 46 30 39
Author Hessheimer Year 2010 2009
Number of HCC Cases
2
Takuma 2010 11 Chagas
7 Kawada 2009 6
45 Smith 2009 1 33 40 35 47
Guzman 2008 3 Maeda
2008
Hashizume 2007 Tsutsumi
2007
3 9 2
34 Hai 2006 2 37
Ichikawa 2006 2
38 Ikeda 2006 1 32
Cuadrado 2005 2
43 Sato 2005 1 28 29
Bencheqroun 2004
41 Mori 2004 1 42
44, 48 2002/2004 6 1 Bullock 2004 2 Orikasa 2001 1
49 Zen 2001 1 31
Cotrim 2000 1 Shimada/Yoshioka
Male (%)
100 45 57 50 0
33 67 67 50
100 50
100 100 100 100 100 100 0 0
100 50
Age (Years)
55, 89 67–83
63 ± 13
73 (median) 70
45–70 52–68
71.5 (median) 46, 58 65, 72 60, 66 69
69, 74 64 68
64, 74 76 67 72 66
56–72
HCC = hepatocellular carcinoma; NAFLD = non-alcoholic fatty liver disease; NASH = non-alcoholic steatohepatitis; NR = not reported. *One hyperglycemia, borderline diabetes mellitus; **One of two cases.
cryptogenic cirrhosis or documented NASH-related cirrhosis reported high HCC incidence that was generally the same as, or lower than, that of HCV-related cirrhosis (see Table 1).
Clinic- or Hospital-based Cohort Studies without a Comparison Group
These studies may be useful in providing estimates of absolute risk for HCC in the examined cohorts, but cannot provide relative risk estimates. Two natural history cohort studies without a comparison group were identified (see Table 1).18,19
two NAFLD (3%) and one cohorts, respectively.8,12,13,15 This substantial variability in diabetes and In a Swedish cohort study of consecutive
patients with alcoholic fatty liver disease and NAFLD seen at a single hospital during 1976–1987, and later linked to the Swedish National Registry of Patients and mortality data,18
While cardiovascular disease was the leading cause of death in the Swedish NAFLD/NASH cohort, HCC was the leading cause of death in the Japanese NASH cohort.
NASH (1%) case ultimately developed and died from HCC during the mean 13.7-year follow-up period. In the second study, a 118-member Japanese cohort with NASH-related severe fibrosis at baseline, cumulative five-year HCC incidence was 7.6%, with a total of 12 HCC-related deaths during the study period (10% cumulative HCC mortality).19
obesity prevalence rates is likely to be predominantly attributable to methodological differences, e.g., underlying target population, database diagnostic codes versus direct measurement. However, in spite of this substantial inter-study variability, within each individual cohort study diabetes prevalence was uniformly greater in the NASH/NAFLD cohorts compared with the respective control cohorts with other chronic liver diseases. Similarly, obesity prevalence was significantly greater in all NASH/NAFLD cohorts. These findings support the NAFLD/NASH diagnosis of patients at risk in these studies because these patients were more likely to have diabetes and obesity than controls.
Case-control and Cross-sectional Studies Several studies compared prevalence of diabetes and obesity between HCC cases ascribed to NASH or cryptogenic cirrhosis and groups of HCC due to other causes (see Table 2).22–25
The reported diabetes prevalence
Most of the longitudinal studies shown in Table 1 also reported on diabetes and obesity prevalence (data not shown in the Table). The reported diabetes prevalence rates among these 11 studies ranged between 6 and 88% and between 4 and 33% in the NAFLD/NASH and other liver disease cohorts, respectively.7–9,11–13,16,18,19
Obesity prevalence
was reported in five studies, with rates ranging between 35 and 73% and between 20 and 55% in NASH/NAFLD and other liver disease
US GASTROENTEROLOGY & HEPATOLOGY REVIEW
in the NAFLD/NASH-presumed HCC case groups, or with cryptogenic cirrhosis-related HCC, ranged between 47 and 80%, while reported diabetes prevalence in the comparable control groups ranged between 8 and 44%. Reported obesity prevalence in the NAFLD/NASH-related or cryptogenic cirrhosis-related HCC cases ranged between 41 and 60% compared with between 6 and 25% in HCC controls (see Table 2). However, in all four studies, diabetes, as well as obesity, was significantly more frequent in NAFLD/NASH or cryptogenic cirrhosis cases compared with their respective other liver disease controls. In the single study that specifically compared obesity between cases and controls both prior to and after cirrhosis developed, significant excess risk was observed only with pre-cirrhosis obesity (odds ratio [OR] pre-cirrhosis obesity=6.34, 95% CI 1.6–24.2).23
57
Liver Cirrhosis (%)/ Diabetes (%)/ Obesity (%)
100/100/100 37/55/55 86/78/100 0/50/33.3 0/NR/100 0/67*/67
100/NR/NR 67/78/67
100/NR/NR 50/100/100 0/0/50
100/100/100 100/100/100 0/100/100 0/0/100 0/0/100
100/100/100 100/100/0 100/100/0
100/100/100 100/50/50
√**
Biopsy-confirmed NAFLD/NASH Prior to HCC Diagnosis?
√ √ √
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