Liver cancer declines seen after anti-HCV drugs added to PBS

Medicines

By Geir O'Rourke

15 Nov 2023

Hepatitis C-related hepatocellular carcinoma rates in Australia have almost halved since the broadening of access to direct-acting antiviral therapy, demonstrating the role virus elimination could play in reducing cancer risk, researchers say.

Sydney gastroenterologists and hepatologists set out to evaluate the temporal change in hepatocellular carcinoma (HCC) aetiology and characteristics using data from 1370 patients admitted to public hospitals in NSW between 2008 and 2021.

The median age of patients was 65 and the majority were male (79%), while just over one-third of patients had HCC detected through surveillance.

The most common HCC aetiologies were hepatitis C virus (HCV, 35%), alcohol-related liver disease (ARLD, 33%), nonalcoholic fatty liver disease / nonalcoholic steatohepatitis (NAFLD/NASH, 25%) and hepatitis B virus (HBV, 22%).

At diagnosis, 20% of patients did not have cirrhosis, 26% had experienced at least one episode of decompensation and 47% were diagnosed at an early stage.

Findings published in Internal Medicine Journal [link here] showed the annual number of patients diagnosed with HCC steadily increased from 53 in 2008 to 146 in 2019, followed by a sharp decline after 2019 to 106 in 2020 and 73 in 2021.

Similarly, the proportion of HCV-related HCC increased from 2008, reaching a peak of 44% and stabilising over the five year period from 2011-2016, before a significant decline over the next five years to 25% in 2021 (odds ratio [OR] 0.53).

The decline coincided with HCV direct-acting antivirals (DAA) being added to the PBS in March 2016, replacing interferon-based therapies as first-line treatment.

The proportion of patients with HCV-related HCC achieving sustained virologic response due to treatment increased from 10% before 2016 to 42% after 2016.

The researchers noted that 39% of patients with HCV and HCC had ARLD as a comorbidity, leading them to suggest that alcohol use should be monitored in patients with HCV so as to not compromise the benefits of DAA treatment.

Among the other aetiologies, the proportion of NAFLD/NASH HCC increased from 13% during 2008-2009 to 19% in 2016 (OR per annum, 1.05).

While the trend was not statistically significant, the researchers said similar findings elsewhere, together with data from the study, suggested NAFLD/NASH was an emerging HCC risk factor in multiple countries, including Australia.

The proportion of HBV HCC decreased from 22% in 2008–2009 to 14% in 2016 (OR per annum, 0.95), while ARLD HCC remained stable (OR per annum, 1.04).

Other findings included increases in the proportion of HCC diagnosed at an early stage from 41% in 2008–2009 to 56% in 2020–2021 (OR per annum, 1.05) and the proportion of patients receiving potentially curative HCC management from 29% in 2008–2009 to 41% in 2020–2021 (OR per annum, 1.06).

The authors said the decrease in total HCC cases after 2019 might be related to COVID-19-related delays in diagnosis and treatment, while the decrease of HCV HCC cases since 2017 might be the result of a rapid scale-up in DAA treatment.

“It was estimated that about 70% of people with HCV-related cirrhosis received DAA treatment by the end of 2017,” said the authors, led by Kirby Institute, UNSW.

“Our findings are consistent with another study demonstrating significant changes in the trend of decompensated cirrhosis and HCC diagnosis and mortality among people with HCV in NSW after access to DAA therapy.”

However they stressed considering 30% of HCC cases during 2017-2021 were still HCV-related and results of a meta-analysis demonstrated that HCV cure did not completely eliminate HCC risk, patients still required post-treatment surveillance.

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