Circulating microRNAs may predict HCC risk in patients with HCV

New data indicate that circulating microRNAs may increased risk for hepatocellular carcinoma among patients with chronic hepatitis C-related cirrhosis and a sustained virologic response.

“Hepatocellular carcinoma represents the fourth leading cause of cancer death, with an increasing incidence around the world and HCV remains the second leading cause of HCC worldwide,” Massimo Levrero, MD, from the University of Rome La Sapienza, Italy, said during The Liver Meeting Digital Experience. “Successful antiviral therapy in HCV cirrhotic patients has been associated with the prevention of clinical decompensation and reduction, but not an elimination, of the risk for HCC. New diagnostic biomarkers for risk stratification and early diagnosis are urgently needed to increase the access to curative therapeutic options.”

To explore these potential biomarkers, Levrero and colleagues conducted a retrospective analysis circulating microRNAs in 565 patients with HCV-related cirrhosis who were treated with direct-acting antiviral agents (DAAs). The study population included 12 patients with cirrhosis who were treated with DAA reach SVR and developed HCC. Sera samples were collected before DAA treatment and at HCC diagnosis. The study also included a case-control cohort of 12 patients treated with DAA who did not develop HCC during a comparable follow-up period after SVR. For these patients, sera samples were taken before DAA and at SVR.

Results from a principal component analysis of the circulating microRNA profiles of the four sera sample groups showed that patients with HCV cirrhosis reaching SVR after DAA treatment who develop HCC cluster tightly together and are well separated from patients with HCV cirrhosis who did not develop HCC after DAA treatment and SVR, according to Levrero.

Of 46 circulating microRNAs detected in all patients with HCV cirrhosis and SVR, including those who did an did not develop HCC, the researchers identified five circulating microRNAs in patients who developed HCC after DAA treatment and SVR that were not found in patients with SVR who did not develop HCC. These five microRNAs may serve as candidate biomarkers for HCC diagnosis in patients treated with DAA, Levrero noted.

Additionally, of 53 circulating microRNAs detected in pretreatment samples from patients who did and did not develop HCC, 26 circulating microRNAs were detected in patients who developed HCC after DAA treatment and SVR but not in patients who did not develop HCC.

“These 26 circulating microRNAs are obviously good candidate biomarkers for HCC risk in DAA-treated patients,” Levrero said.

Notably, five of these 26 circulating microRNAs shared multiple target transcripts and these target transcripts cluster around the p53 signaling pathway and the EZH2-dependent transcription, according to Levrero.

Additional analysis indicated that HCV eradication has an effect on circulating microRNAs, with a further reduction in circulating microRNAs occurring with HCC development.

“In summary, we showed that HCV eradication has a strong impact on circulating microRNAs and we identified potential candidate circulating microRNAs for HCC diagnosis and, more importantly, HCC prediction in HCV cirrhosis patients treated successfully with DAA. The relevant candidate circulating microRNAs are currently being validated in an independent large prospective cohort,” Levrero said.