Liver Cancer Rare After HCV Therapy

— But some patients develop aggressive form of the disease

MedicalToday

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BOSTON -- For patients with advanced liver disease owing to hepatitis C (HCV), treatment with direct-acting antiviral agents did not increase the risk of hepatocellular carcinoma, a researcher said here.

The risk of liver cancer in the first year after such therapy was pretty much the same as it is in untreated patients, according to , of the University of Padua in Italy.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • For patients with advanced liver disease owing to hepatitis C, treatment with direct-acting antiviral agents did not increase the risk of hepatocellular carcinoma.
  • Note that the rare patients who developed cancer after HCV treatment were more likely to have an aggressive form of the disease.

On the other hand, the rare patients who developed cancer after HCV treatment were more likely to have an aggressive form of the disease, Alberti told reporters at the American Association for the Study of Liver Diseases (AASLD) annual meeting.

The findings, from a large prospective cohort of patients in northern Italy, should help to settle what has been a "controversial and confusing issue," Alberti said, with small studies yielding conflicting results on the issue.

Analysis of outcomes in 3,075 patients after a median of 300 days of follow-up, Alberti said, showed that liver cancer after therapy was associated with more advanced disease and treatment failure. But the rate of cancer was 1.64% per patient-year, he said, roughly similar to the rates found in previous studies in untreated and cirrhotic patients -- 2.8% and 3.9% a year, respectively.

Indeed, although effective treatment of HCV is expected to reduce the burden of liver cancer over the long term, it's probably too much to expect a benefit quickly, commented of Massachusetts General Hospital in Boston, who was not part of the study but who moderated an AASLD media briefing.

Some patients with advanced liver disease are likely to have very early cancers that would not show up on screening, Chung told , and it's "overambitious" to expect even a successful HCV cure to do much about that.

"We cannot return the patients to sender," he said. "Their infectious disease problem is gone, but their liver damage remains."

What is intriguing about the study, he said, is that about half the patients who did develop cancer had a more aggressive form than is usually seen. The implication is that, for patients with advanced liver disease, clinicians have to be extraordinarily vigilant after HCV treatment to nip any cancer in the bud.

"We cannot let up in this group of patients," he said.

But Chung cautioned that the findings are not a reason to hold back treatment in patients with advanced disease; instead clinicians simply have to monitor them very carefully after the completion of the HCV therapy.

Alberti reported on a prospective analysis of all patients with advanced liver disease -- defined as F3 fibrosis or cirrhosis -- treated with direct-acting agents (DAAs) in the region of Venice from January 2015 to July 2016.

Of the more than 3,300 patients, 27.7% had F3 fibrosis, 65.3% had Child-Pugh cirrhosis, and 7% had Child-Pugh B cirrhosis. Patients with a history of liver cancer were excluded, as were those with a transplant before starting DAAs.

Most patients did well on the HCV therapy -- cure rates were 97% in patients with fibrosis F3, 92% in patients with Child-Pugh A cirrhosis, and 80% in patients with Child-Pugh B disease -- but 41 of the 3,075 patients developed liver cancer.

And the liver cancer rates rose with the seriousness of the illness, from 0.23% per patient-year for those with F3 fibrosis, to 1.64% per patient-year for Child-Pugh A, and to 2.92% per patient-year for Child-Pugh B.

Incidence was also higher if the treatment did not succeed -- 8.38% per patient-year, compared with 1.55%, Alberti said.

An unexpected finding, he said, was that half of the patients developed the usual single-node tumor, while the remainder developed more diffuse -- and unusually aggressive -- disease, Alberti said.

The findings "should not shake the confidence of physicians and patients in the tremendous advantages of hepatitis C therapy," Alberti said, but patients should be "carefully assessed" to find any occult liver cancer that may exist so it can be treated before beginning HCV therapy.

Researchers should now turn their attention to the mechanisms involved and potential markers that might identify patients at greatest risk -- a risk that he told probably varies according to the phase of the treatment.

Disclosures

Alberti disclosed relationships with Gilead, AbbVie, and Bristol-Myers.

Chung disclosed relationships with AbbVie, Gilead, Merck, Bristol-Myers Squibb, and Mass Biologics.

Primary Source

American Association for the Study of Liver Diseases

Romano A, et al "Incidence and pattern of 'de novo' hepatocellular carcinoma in HCV patients treated with oral DAAs" AASLD 2016; Abstract 19.