Individuals living with hepatitis C (HCV) and cirrhosis who are treated with direct-acting antivirals (DAAs) do not face a higher risk of developing liver cancer when compared with untreated individuals, according to a study presented at the Liver Meeting 2016, in Boston. Developing hepatocellular carcinoma (HCC), the most common form of liver cancer, either during or after being treated with DAAs, was associated with more advanced HCV disease or treatment failure, the study found.
For background, using current DAAs to treat chronic HCV is standard of care, particularly in patients with advanced liver disease or decompensated cirrhosis. However, there has been conflicting data on the risk of developing HCC during or after treatment with DAAs, with some reports suggesting significant recurrence or new incidences of HCC. Therefore, the researchers set out to assess the incidence of new HCC in individuals living with HCV who had advanced liver disease but no history of HCC when treated with DAAs.
The study, which was presented by Antonietta Romano, M.D., followed 3,075 HCV patients with cirrhosis in Italy from January 2015 to June 2016. The researchers gathered data prospectively from a web-based network that had recorded data and outcomes of all HCV patients treated with DAAs across 24 sites in northeast Italy since January 2015. Patients who had a history of HCC, had received a liver transplant before starting DAAs or had less than four weeks of follow-up after starting DAAs were excluded from the study.
The study participants were treated with different DAA regimens according to the EASL (European Association for the Study of the Liver) guidelines and AISF (Italian Association for the Study of the Liver) guidelines. Prior to treatment, imaging tests ruled out any existing HCC. During or after treatment, HCC was identified and confirmed by at least two independent imaging techniques and/or with biopsy.
About 63% of the study participants were male, and 37% were female -- all with a mean age of 58. Almost 56% had never been on HCV treatment before.
About 27.7% of the study had stage F3 (severe) fibrosis. A little over 72% had cirrhosis (65.3% with Child-Pugh class A and 7% with Child-Pugh class B). Comorbidities were somewhat common, with 11.2% having diabetes, 14.8% having cardiovascular disease and 5.3% being obese.
In terms of genotypes:
- Genotype 1a was found in 19.1% of participants.
- Genotype 1b was found in 43% of participants.
- Genotype 2 was found in 12.7% of participants.
- Genotype 3 was found in 17% of participants.
- Genotype 4 was found in 7.7% of participants.
- Genotype 5 was found in 0.4% of participants.
The DAA regimens were also varied:
- Sofosbuvir (Sovaldi) + ribavirin for 12-24 weeks in 18.3% of participants.
- Sofosbuvir + simeprevir (Olysio) with or without ribavirin for 12 weeks in 10.1% of participants.
- Ledipasvir/sofosbuvir (Harvoni) with or without ribavirin for 12-24 weeks in 33.8% of participants.
- Sofosbuvir + daclatasvir (Daklinza) with or without ribavirin for 12-24 weeks in 14.6% of participants.
- Ombitasvir/paritaprevir/Ritonavir (Technivie) or dasabuvir/ombitasvir/paritaprevir/ritonavir (Viekira Pak) with or without ribavirin for 12-24 weeks in 23.1% of participants.
Rates of cure, otherwise known as SVR12 (sustained virologic response 12 weeks after ending therapy), varied based on liver disease stage. About 97.2% of those with F3 fibrosis achieved SVR12, while 92.7% of those with cirrhosis (Child A) and 80% of those with cirrhosis (Child B) achieved SVR12.
The researchers found that during the study period 41 participants had developed HCC for an HCC incidence rate of 1.64%. This incidence rate differed by liver disease stage. For those with F3 fibrosis, the incidence was 0.23%. For those with cirrhosis (Child A), the incidence rate was 1.64%. And, for those with cirrhosis (Child B), the incidence rate was 2.92%. The difference between all three groups was statistically significant (P = .05), while the difference between the two cirrhosis groups was not (P = .259).
The overall HCC incidence rate found in this group was lower than historical incidence rates found in untreated individuals living with HCV in the same region, the researchers noted, with Romano highlighting that 2.8% and 3.9% were past incidence rates.
Further analyzing the data, the researchers found that HCC risk was associated with elevated liver enzymes and low platelet count, but not with other factors, including gender, age, HCV genotype and DAA regimen. Notably, the best predictor of HCC risk was APRI score, which measures liver scarring. Those with an APRI score below 2.5 had an HCC incidence rate of 1.52, while those with an APRI score greater than or equal to 2.5 had an incidence rate of 3.27 (P = .02).
"The results of this study, while confirming that DAAs treatment doesn't increase the overall risk of HCC, indicate that there is no pharmacological prevention of HCC even with successful antiviral therapy, at least during the first six to 12 months after initiation of treatment[,]" said lead study author Alfredo Alberti, M.D., according to the study press release. "Therefore, it is mandatory that patients treated with DAAs with advanced liver disease should continue to be monitored for HCC," Alberti concluded.