The spread of cancer from the bowel to the liver – metastasis – is more likely to occur in people with chronic hepatitis B infection, a Chinese study published in Clinical Infectious Diseases has found. Active replication of the hepatitis B virus appears to promote metastases – the development of new tumours away from the site of an original tumour.
However, the researchers also found that where active replication was not taking place, a greater degree of liver fibrosis or the presence of cirrhosis of the liver reduced the likelihood of developing a secondary tumour in the liver, suggesting that fibrosis may be protective against metastases.
Hepatitis B virus is widespread in Asia. Approximately 7% of Chinese people were estimated to have chronic hepatitis B infection in 2006. Several countries in East Asia have also observed sharp increases in colorectal, or bowel, cancer. A total of 376,000 new cases were diagnosed in China in 2015. Metastasis of colorectal cancer to other sites, most frequently the liver, is a strong predictor of poor survival after diagnosis and up to 25% of people with colorectal cancer have already suffered metastasis to the liver by the time they are diagnosed.
Investigators at Shangdong Cancer Hospital and Qingdao University Hospital carried out a retrospective study of all cases of colorectal cancer diagnosed at two of the largest hospitals in Shangdong province between 2010 and 2016. (Shangdong is China’s second most populous province and lies on the coast between Shanghai and Beijing.)
They identified 4033 new cases in whom hepatitis B virus (HBV) status had been recorded (HBV serology formed part of the routine tests for all people diagnosed with bowel cancer). Liver tumours were confirmed by imaging and pathological report after surgery, or by biopsy in cases where surgery had not taken place.
Six per cent of the cohort had chronic HBV infection (hepatitis B surface antigen detectable (HBsAg) for greater than six months).
Of the 4033 cases of colorectal cancer, 364 had confirmed metastases at the time of colorectal cancer diagnosis: 38 out of 244 people who were HBsAg-positive had metastasis to the liver compared to 326 out of 3789 people without HBsAg. The prevalence of metastases was higher in people with chronic HBV infection, 15.5% vs 8.6%, p < 0.001).
A multivariate analysis showed that HBsAg was the strongest predictor of liver metastasis at the time of diagnosis (HR: 2.317, 95% CI 1.4-3.8). CEA and CA19-9 were also significant cancer-related predictors; ALT, AST and GGT were also significant liver-related factors, but all these factors had only a modest predictive value. Tumour stage was the only other strong predictor (HR: 2.1, 95% CI 1.2-3.7) of liver metastasis.
Lung metastases were significantly less common in people with HBsAg (0.82 vs 2.98%, p = 0.049).
Looking only at those with HBsAg, the investigators found that people without metastases had significantly higher FIB-4 and APRI scores than people who were diagnosed with liver metastases (p = 0.045), indicating that cirrhosis reduced the risk of liver metastases.
The investigators say that further research is needed in prospective studies, but they also point out that the findings have more immediate implications, such as the need for more intensive screening in people with hepatitis B, saying “An awareness of hepatitis B status and the extent of liver disease in patients may help physicians define the risk for the development of [colorectal-liver metastases] and may ultimately influence the treatment of both [colorectal cancer] and chronic hepatitis B in select populations.” They also draw attention to the “poor awareness of and education surrounding chronic hepatitis B, despite the fact that CHB is still endemic in China.”
As well as having clinical implications, the findings also have implications for understanding the burden of disease caused by hepatitis B; apart from causing primary liver cancer, hepatitis B is also implicated in reducing survival in colorectal cancer, emphasising the case for wider treatment of hepatitis B.