World Congress at ACG2017

Simultaneous Plenary Session 4A: Liver

57 - Lack of Evidence for Increased Rates of Hepatocellular Carcinoma Following Treatment With Direct Acting Antivirals: A Systematic Review and Meta-Analysis

Wednesday, October 18
9:10 AM - 9:20 AM
Location: Valencia Ballroom BC (Level 4)



Category: Liver       

Stephanie Rutledge, MBBCh, BAO, MRCPI, Hui Zheng, PhD, Darrick K. Li, MD, PhD, Raymond T. Chung, MD
Massachusetts General Hospital, Boston, MA
Introduction: Hepatitis C (HCV) is one of the leading causes of hepatocellular carcinoma (HCC) in the United States. Once cirrhosis is established, HCC occurs at a rate of 1-5% annually in persons with untreated HCV. Achieving sustained virologic response (SVR) after treatment with interferon (IFN) reduces the risk to 0.5-1% annually. Several studies have reported unexpectedly high rates of HCC after treatment with direct acting antivirals (DAA). The aim of our study is to compare rates of de novo and recurrent HCC in DAA- and IFN-treated populations.

Methods: A literature search was conducted using ScienceDirect, Ovid®, Web of Science and MEDLINE through May 2017. Studies were included if they measured rates of de novo or recurrent HCC (following curative treatment) in persons treated with HCV therapy.

Results: We included a total of 22 studies (n=23,874) and 18 studies (n=12,650) measuring the incidence of de novo HCC after treatment with IFN and DAA therapy, respectively. We included 8 studies (n=189) and 14 studies (n=1056) evaluating HCC recurrence rates after IFN and DAA therapy, respectively. Overall, DAA-treated patients had higher incident cirrhosis compared to IFN-treated patients (76% vs 33%, p=0.003), and among cirrhotics, Child-Pugh stage B/C disease was more frequent in the DAA-treated group (23% vs 3%, p=0.004). Mean platelet count was lower in the DAA group (129x109/L vs 152x109/L), as was mean albumin (3.9g/dL vs 4.1g/dL). Mean age was higher in the DAA group (62 vs 52 yrs; p=0.004) as was the prevalence of diabetes (23% vs 12.5%; p=0.04). Mean follow-up was longer in the IFN group: 5.5 vs 1.1 yr.

Using the random effects method, the incidence rate of de novo HCC was calculated at 5.86/100py (95% CI 0.85, 13.08) in the DAA group and 1.22/100py (0.16, 3.06) in the IFN-treated SVR group. The rate of HCC recurrence was 25.34/100py (6.52, 48.70) in the DAA group and 20.04/100py (2.58, 45.21) in the IFN SVR group. In untreated persons, the rate of HCC recurrence was 29.21/100py (5.23, 63.62), similar to the recurrence rate in IFN-treated patients who did not achieve SVR (28.70/100py; 2.19, 71.57).

Discussion: We did not find clear evidence of increased rates of de novo HCC or recurrence in DAA-treated compared with IFN-treated patients. Compared to those treated with IFN, older patients with additional pre-existing risk factors for HCC development were treated with DAA. This imbalance would appear to explain the higher numerical incidence of de novo HCC among DAA-treated patients.

Supported by Industry Grant: No


Citation: . LACK OF EVIDENCE FOR INCREASED RATES OF HEPATOCELLULAR CARCINOMA FOLLOWING TREATMENT WITH DIRECT ACTING ANTIVIRALS: A SYSTEMATIC REVIEW AND META-ANALYSIS. Program No. 57. World Congress of Gastroenterology at ACG2017 Meeting Abstracts. Orlando, FL: American College of Gastroenterology.

Stephanie Rutledge

Massachussetts General Hospital
Boston, Massachusetts

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