Supplementary Table 2. Studies of interferon-based therapies against hepatitis C on primary prevention of hepatocellular carcinoma
A. Studies comparing HCC among IFN-treated versus untreated patients
Author, Year of
Publication
Location
HCC
Study Italy,
Group 19981
Argentina
Mazzella 19962
Italy
Study
Design
Retrospective
cohort
Prospective
cohort
Retrospective
cohort
Follow-up
(in years)
(treated v.
control)
3, overall
Total number of
patients; % with
cirrhosis
491; 100%
2.7 v. 2.8
285; 100%
4.0 v. 3.9
563; 9%
No. of patients with
HCC
IFNUntreated
treated
patients
21/232
48/259
(9.0%)
(18.5%)
5/193
9/92
(0.5%)
(9.8%)
28/419
19/144
(6.7%)
(13.2%)
Key results

Adjusted RRa: 0.5 (0.3-0.8)

Adjusted HRa: 0.3 (0.1-0.8)


Imai 19983
Japan
Nishiguchi 20014
Japan
RCT
9.2 v. 8.2
90; 100%
12/45
(26.7%)
33/45
(73.3%)


Serfaty 19985
France
Prospective
cohort
3.3, overall
103; 100%
2/59 (3.4%)
9/44
(20.4%)


Shiratori 20056
Japan
6.8, overall
345; 100%
France
3, overall
99; 100%
Adjusted RRa: 0.6 (0.2-1.7)
Japan
Retrospective
cohort
4.3, overall
2890; 12%
35/74
(47.3%)
9/52
(17.3%)
59/490
(12.0%)

Yoshida 19998
84/271
(31.0%)
5/47
(10.6%)
89/2400
(3.7%)

Valla 19987
Prospective
cohort
RCT
Adjusted HRa: 0.5 (0.3-1.0)
4-year cumulative incidence of HCC
(IFN v. no treatment): 6.6% v. 12.2%
Adjusted RRa: 0.3 (0.1-0.5)
10-year cumulative incidence of HCC
(IFN v. no treatment): 31% v. 72%
Adjusted HRa: 0.2 (0.03-0.8)
4-year cumulative incidence of HCC
(IFN v. no treatment): 4.4% v. 23%
Adjusted HRa: 0.6 (0.4-0.9)


Adjusted HRa: 0.5 (0.4-0.7)
Annual incidence of HCC (IFN v. no
treatment): 1.1 v. 3.2 per 100 p-y
B. Studies comparing HCC risk among patients who achieve sustained virologic response versus non-responders to IFN-based therapy
Author, Year of
Publication
Location
Study
Design
Bruno 20079
Italy
Retrospective
cohort
Cardoso 201010
France
Retrospective
cohort
Follow-up (in
years) (SVR
v. Nonresponders)
8.5 v. 7.6
Total number
of patients; %
with cirrhosis
883; 100%
3.5, overall
307; 61%
No. of patients with
HCC
SVR
Nonresponders
7/124
122/759

(5.6%)
(16.1%)

6/103
(5.8%)
40/204
(19.6%)


Key Results
Adjusted HRb: 0.4 (0.2-0.9)
Annual incidence of HCC (SVR v.
non-responders): 0.7 v. 2.1 per 100 p-y
Adjusted HRb: 0.3 (0.1-0.9)
Annual incidence of HCC (SVR v.
non-responders): 1.2 v. 5.8 per 100 p-y
Hung 201111
Japan
Kamawura 2010 Japan
12
Kramer
201013 United States
[abstract]
Morgan 201014
United States
5/73
(6.9%)
12/1081
(1.1%)
51/4292
(1.2%)
2/140
(1.4%)
11/59
(18.6%)
61/977
(6.2%)
432/10,276
(4.2%)
16/386
(8.5%)

Adjusted HRb: 0.2 (0.1-0.8)

Adjusted HRb: 0.1 (0.06-0.3)

Adjusted HRb: 0.3 (0.2-0.4)


1013; 15%
13/557
(2.3%)
21/152c
(13.8%)


6.6 v. 8.1
546; 100%
7/125
(5.6%)
76/405
(18.8%)


Retrospective
cohort
Retrospective
cohort
Retrospective
cohort
Prospective
cohort
3.1, overall
132; 100%
6.7, overall
2058; 0%
8.7, overall
14,568; 13%
6.6 v. 7.2
526; 35%
Prospective
cohort
3.6, overall
Veldt 200717
United States
Retrospective
cohort
2.1, overall
479; 100% with 3/142
advanced
fibrosis
32/337


Velosa 201118
Portugal
6.4, overall
140; 100%
Japan
4.3, overall
2400; 9%
20/91
(22.0%)
79/1611
(4.9%)

Yoshida 19998
Retrospective
cohort
Retrospective
cohort
Adjusted HRb: 0.2 (0.04-0.8)
7.5-year cumulative incidence of HCC
(SVR v. non-responders): 1.1% v.
8.8%
Adjusted HRc: 0.3 (0.1-0.6)
5-year cumulative incidence of HCC
(SVR v. non-responders): 3.1% v.
18.8%
Adjusted HRb: 0.2 (0.1-0.4)
10-year cumulative incidence of HCC
(SVR v. non-responders): 5.1% v.
21.8%
Adjusted HRb: 0.5 (0.1-1.7)
5-year cumulative incidence of HCC
(SVR v. non-responders): 9.2% v.
13.1%
Adjusted HRa: 0.1 (0.1-0.8)

Adjusted HRa: 0.3 (0.2-0.6)
Ogawa 201315
Van der
201216
Japan
Meer Europe/Canada Prospective
cohort
1/39
(2.6%)
10/789
(1.3%)
ausing
control as referent category; busing non-responders as referent category; cno-virologic responders [abbreviations: HCC-hepatocellular cancer; HR-hazard ratio; IFNinterferon; p-y-person-years; RCT-randomized controlled trial; RR-relative risk; SVR-sustained virologic response, i.e., absence of det HCV RNA at least 6 months after
discontinuing treatment]
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