Treatment with direct-acting antiviral (DAA) therapy did not increase the risk of developing hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection, according to a prospective study presented at the 2016 AASLD Liver Meeting.
In the study, a total of 3075 patients with HCV infection were followed after the initiation of DAA therapy. After 300 days of follow-up, 1.64% of patients had developed carcinoma, and after 18 months of follow-up cancer had developed in 2.5% of the patients. These rates compared favorably with patients with HCV infection who did not receive DAAs. In this historical comparators, 2.8% to 3.9% of patients with untreated HCV developed HCC.
“Patients with hepatitis C who take direct-acting antiviral medication are at no higher risk for developing liver cancer than those who do not take the medication,” said lead investigator Alfredo Alberti, MD, of the University of Padua, Padua, Italy. “There were few patients out of 3000 that developed hepatic cancer. From these results, there is no reason to change the current way you treat patients.” He added that “this is the natural history of the cancer” and mimics the population not on DAA medication.
Data for the study were collected using a web-based network, which included data from patients treated at 24 clinical centers located in the Veneto region of North-East Italy. Patients were prospectively monitored between January 2015 and June 2016, and those previously diagnosed with cancer were excluded from the study.
In the study, 3381 HCV-infected patients with F3 or F4 fibrosis who were treated with DAAs were screened for the study. Overall, 306 patients were excluded: 111 had a history of HCC, 154 received a liver transplant before receiving DAAs, and 41 had a liver transplant within 4 weeks of starting DAAs. Patients were treated with different combinations of DAAs, according to international guidelines. The most common DAA regimen used was sofosbuvir plus ledipasvir with or without ribavirin for 12 to 24 weeks (33.8%).
The mean age of patients was 58.1 years. The most frequent genotype of HCV was 1a/b (62.1%). The majority of patients had F4 cirrhosis, and a minority had severe fibrosis (F3, 27.7%). Cirrhosis was Child-Pugh (CP) score A (65.3%) and B (7%). Comorbidities were identified in approximately a third of the population, including cardiovascular disease (14.8%), diabetes (11.2%), and obesity (5.3%).
The incidence of HCC increased with cirrhosis grade, with fewer patients getting cancer with F3 fibrosis. Overall, 0.23% of patients in the F3 group developed HCC, versus 1.64% and 2.92% in the CP A and B arms, respectively. For both groups combined, the incidence rate was 1.93% for all patients with cirrhosis.
“Patients with cirrhosis taking DAA therapy should be carefully assessed for any tumor and monitored for tumor development,” Alberti reinforced.
In a univariate analysis of cirrhotic patients, AST to Platelet Ratio Index (APRI) predicted a higher HCC incidence rate (P
= .02). The incidence was 1.52% in those with an APRI score <2.5 compared with 3.27% for those with a score ≥2.5. It was found that HCC risk increase by 10% for each 1 point increase in APRI.
In relation to the virological response, the sustained viral response (SVR) was 97.2% in patients with fibrosis F3, 92.7% in patients with Child-Pugh A cirrhosis, and 80% in those with Child Pugh B cirrhosis. In the univariate analysis, those who failed to achieve SVR had a higher likelihood of developing HCC (8.38%) compared to those who responded to DAA therapy (1.55%).
In looking at the patterns of HCC development, 48.8% of patients had a single cancerous nodule, 12.2% of patients had 2 or 3 nodules, and 39% had more than 3 nodules or an infiltrative HCC. Portal thrombosis and extrahepatic metastasis were noted for 12.2% and 9.7% of patients, respectively.
When looking at these patterns in conjunction with SVR, it was found that a response to DAA greatly impacted the number of detected nodules. Those who did not respond were more likely to have >3 nodules (53.8%) compared with patients who responded (33.3%). Additionally, the time from initiation of therapy impacted morphologic patterns. When cancer was detected within 6 months of initating DAA therapy, it was more likely to be detected in >3 nodules. After 6 months, a single nodule was more likely.
“Further studies are needed to clarify these issues and identify predictive markers,” said Alberti. “Meanwhile patients treated with DAAs with advanced liver disease should continue to be closely monitored for HCC.”
Romano A, Piovesan S, Anastassopoulos G, et al. Incidence and pattern of "de novo" hepatocellular carcinoma in HCV patients treated with oral DAAs. Presented at: AASLD Liver Cancer Meeting; Boston, Massachusetts, November 11-15, 2016. Abstract 19.
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