Long-term effect of sustained virological response on hepatocellular carcinoma in patients with hepatitis C in Canada.
Evidence is limited on hepatocellular carcinoma (HCC) risk after sustained virological response (SVR) to interferon-based treatment of hepatitis C virus (HCV) infection. We evaluated the effect of SVR on the risk of HCC and estimated its incidence in post-SVR HCV patients from a large population-based Canadian cohort.



The British Columbia Hepatitis Testers Cohort includes individuals tested for HCV between 1990-2013 linked with data on their medical visits, hospitalizations, cancers, prescription drugs and mortality. Patients receiving interferon-based HCV treatments were followed from the end of treatment to HCC diagnosis, death or December 31, 2012. We examined HCC risk among those who did and did not achieve SVR using multivariable proportional hazard models with the Fine and Gray modification for competing risks.



Of 8147 individuals who received HCV treatment and were eligible for analysis, 4663 (57%) achieved SVR and 3484 (43%) did not. Each group was followed for a median of 5.6years (range: 0.5-12.9) for an HCC incidence rate of 1.1/1000 person-years (PY) among the SVR and 7.2/1000 PY among the no SVR group. The HCC incidence rate was higher among those with cirrhosis (SVR: 6.4, no SVR: 21.0/1000 PY). In the multivariable model, SVR was associated with a lower HCC risk (subdistribution hazard ratio [SHR]=0.20, 95% CI: 0.13-0.3), while cirrhosis (SHR=2.61, 95% CI: 1.68-4.04), age ⩾50years, being male and genotype 3 infection were associated with a higher HCC risk. Among those who achieved SVR, cirrhosis, age ⩾50years and being male were associated with a higher HCC risk.



SVR after interferon-based treatment substantially reduces but does not eliminate HCC risk, which is markedly higher among those with cirrhosis and age ⩾50years at treatment initiation. Treatment of patients at an advanced fibrosis stage with new highly effective drugs will warrant continued surveillance for HCC post-SVR.



We assessed the effect of successful hepatitis C treatment with older interferon-based treatment on the occurrence of liver cancer (hepatocellular carcinoma) and found that successful treatment prevents liver cancer. However, more people with cirrhosis and older age continued to develop liver cancer after successful treatment. Thus, treatment with new drugs among those with cirrhosis will require continued monitoring for liver cancer.
British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. Electronic address: naveed.janjua@bccdc.ca.
Naveed Z
NZ
Janjua
British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Mei
M
Chong
British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Margot
M
Kuo
British Columbia Cancer Agency, Vancouver, BC, Canada.
Ryan
R
Woods
British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
Jason
J
Wong
Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Eric M
EM
Yoshida
Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Morris
M
Sherman
British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
Zahid A
ZA
Butt
British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
Hasina
H
Samji
British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Darrel
D
Cook
British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Amanda
A
Yu
British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Maria
M
Alvarez
British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
Mark
M
Tyndall
British Columbia Centre for Disease Control, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Mel
M
Krajden
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use; D001955:British Columbia / Q000453:epidemiology; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D015994:Incidence; D007372:Interferons / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000072230:Sustained Virologic Response
D000998:Antiviral Agents; D007372:Interferons
BC Hepatitis Testers Cohort; Canada; Hepatitis C; Hepatocellular carcinoma; Interferon; North America; Population based; Proportional hazard models