Risk of liver cancer persists even after HCV eradication


Although the risk of liver cancer decreases in patients infected with the hepatitis C virus (HCV) for whom the virus is cleared with direct-acting antiviral drugs (DAAs), these patients have not come out of the woods, and those without a sustained viral infection (SVR) have a significantly higher risk of developing hepatocellular carcinoma (HCC), according to the results of a large study.

Among patients with cirrhosis of the liver due to HCV infections treated at 30 centers in Italy, a large percentage had SVR after treatment with DAA drugs. Only a small percentage of this group subsequently developed HCC.

In contrast, not having an SVR was associated with a more than seven times higher risk of liver cancer, said Loreta A. Kondili, MD, PhD, of the Center for Global Health at Istituto Superiore di Sanità, Rome. , in Italy, during a conference presenting the results at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.

“Failure to achieve SVR after treatment with AAD is strongly associated with the likelihood of developing HCC. Older age, [HCV] genotype 3 and low platelet and albumin levels are independent factors in the development of HCC despite viral eradication, ”she said.

Cohort study

The results of the study come from the PITER cohort study, a prospective, multicenter observational study of a representative sample of patients with HCV.

Kondili and colleagues evaluated the medium and long-term effects of DAA treatment on HCC levels in patients with HCV-induced cirrhosis of the liver. Patients who had undergone a liver transplant or who had previously been diagnosed with HCC were excluded.

The investigators identified a total of 2214 patients treated with DAA, of which 149 (6.7%) developed de novo HCC after a median follow-up of 30 months.

In the total group, 2064 (93%) patients had SVR, of which 119 (5.8%) developed HCC. Of those patients who developed HCC, 80% were diagnosed with stage B or C disease according to the Barcelona Clinic’s liver cancer staging system.

For the remaining 150 patients who did not have SVR, 30 (20%) developed de novo HCC, a difference that resulted in an adjusted risk ratio (HRa) for HCC of 7.38 (P <.01>

The time between the end of DAA treatment and the diagnosis of HCC was shorter for patients who did not have SVR. For these patients, the 2-year CHC-free survival rate was 81%, compared to 98% for patients who had SVR (P <.001>

As reported by Kondili, among patients who achieved SVR, variables significantly associated with the risk of HCC included advanced age (aHR, 1.06), a platelet count above the baseline of 150,000 L (aHR , 2.43), albumin levels> 3.5 g / dL (aHR, 2.36) and diabetes (aHR, 1.53; all of these variables were significant by confidence intervals).

A total of 26% of these patients died during the follow-up period and 7.6% underwent a liver transplant.

Of the patients still alive at the end of the follow-up period, 38% had active HCC.

Long-term follow-up required

“It is useful to think of hepatitis C as a viral infection on the one hand [and] liver disease on the other, ”commented Raymond T. Chung, MD, director of the Hepatology and Liver Center and vice chief of gastroenterology at Massachusetts General Hospital, Boston, Massachusetts.

“In terms of elimination, we can eradicate the virus from most patients with almost 100% success with antivirals. the rest of their life without hepatitis C, ”he said.

Chung, who was not involved in the study, pointed out that despite clearing the virus, patients may still have severe liver fibrosis or cirrhosis. It is imperative that these patients are monitored for signs of cancer, he said.

“This is what is important in staging patients and in understanding the severity of their liver disease, because if there is advanced fibrosis, bridging fibrosis or cirrhosis, these are the patients who will require long-term cancer care. Their infectious disease is ruled out, but the liver disease persists, ”he said.

Chung also noted that the rates of liver cancer, decompensation and liver failure are higher in patients with untreated HCV than in patients whose HCV has been eradicated or suppressed with drug treatment. In addition, patients with untreated HCV are at greater risk of requiring a transplant than patients with treated HCV, and there is a residual cancer risk for patients who become HCV negative.

The study was funded by the Italian Ministry of Health. Kondili has financial relationships with Gilead Science and AbbVie. Chung did not report any relevant financial relationship.

The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD): Abstract 99. Presented November 14, 2021.

Award-winning medical journalist Neil Osterweil is a long-time and frequent contributor to Medscape.

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