Risk of HCC Warrants Careful Surveillance in People With Primary Biliary Cholangitis

It is unclear what role treatment plays in affecting hepatocellular carcinoma (HCC) risk, the authors found.

People with primary biliary cholangitis (PBC) and cirrhosis should be aggressively screened for hepatocellular carcinoma (HCC), using twice-annual liver screening, according to a new report in Clinics in Liver Disease.

The authors wrote about the latest evidence related to the risks and outcomes of HCC in people with PBC. They said such cases warrant vigilance.

PBC is an autoimmune condition that affects the biliary epithelial cells, leading to a range of symptoms and severity, the authors noted. Some patients experience no symptoms, others develop cirrhosis, and some develop end-stage liver disease.

Another common complication of PBC, however, is HCC.

“Advanced fibrosis is the most important risk factor for the development of HCC, but there are other reports showing the development of HCC in PBC without evidence of advanced disease,” the investigators wrote.

They said autoimmune liver disease has been linked with an increased risk of developing HCC, but they said that risk is typically lower than the risk conferred by other liver diseases. Among autoimmune diseases, PBC appears to be associated with the greatest HCC risk. Among the research they cite, one study found people with PBC had a odds ratio (OR) of developing HCC of 31.33 (95% CI, 23.63-41.56) compared with primary sclerosing cholangitis (OR, 4.42; 95% CI, 2.06-9.45).

Although PBC cannot be cured at present, the investigators said treatment with ursodeoxycholic acid (UDCA) can delay progression to cirrhosis, and cirrhosis in PBC puts patients at a higher risk of developing HCC. However, there have been several studies looking at how UDCA itself affects the risk of HCC, and those studies have so far been inconclusive, the authors said.

Apparent risk factors for the development of HCC in people with PBC include age, the male sex, and comorbidities such as diabetes, previous viral infections, and alcohol consumption, they reported. They noted that even though PBC is more common in women than in men, studies indicate that women with PBC cirrhosis are less likely than men to develop HCC.

“The possible protective effect of estrogen against hepatocellular cancer through inhibiting cytokine and interleukin-6 has been proposed,” the investigators wrote.

What is clear, however, is that HCC is associated with a high risk of death. The 5-year survival rate among people with HCC and PBC is just 50%, significantly lower than the 75% HCC survival rate among people with other chronic liver diseases, the authors said. The best chance of survival for patients is liver transplant, they added.

At present, the authors added, cirrhosis is the only indication for which all scientific societies recommend HCC screening. They said cirrhosis in PBC warrants screening every 6 months given the high risks associated with HCC, and they added that more studies are needed to better understand the ways in which treatment response for PBC might affect the risk of developing HCC.


Sy AM, Ferreira RD, John BV. Hepatocellular carcinoma in primary biliary cholangitis. Clin Liver Dis. 2022;26(4):691-704. doi:10.1016/j.cld.2022.06.011

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