Projected Mitigation of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B in the Gray Zone and the Immune-Tolerant Phase in the United States.

Purpose: Based on current practice guidelines, there are a substantial number of individuals who do not meet criteria for chronic hepatitis B (CHB) treatment eligibility but may be at risk of developing HCC. We sought to determine the estimated number of untreated patients with CHB in the Gray Zone or immune-tolerant phase who would develop HCC.

Methods: US epidemiologic data were obtained from the US Department of HHS. The literature was reviewed for studies that analyzed the distribution of phases of CHB patients including the Gray Zone and studies that determined the cumulative incidence of HCC over a set period unique to both the Gray Zone and the immune-tolerant phase populations. We modeled the projected number of patients in each group who would develop HCC in a period of 5 and 10 years.

Results: There are about 880,000 to 1.89 million people living with CHB in the US. Based on our model, we estimated 1224-4146 patients and 6662-22,574 patients will likely develop HCC in 5 years and 10 years, respectively, if left untreated in the high viral load and normal liver enzyme Gray Zone. An estimated 356-1537 patients and 873-3774 patients will develop HCC in 5 years and 10 years, respectively, if left untreated in the immune-tolerant phase of CHB. Among patients who develop cirrhosis in the Gray Zone, approximately, 1615-5471 patients will develop HCC.

Conclusion: Current guidelines do not recommend hepatitis B antiviral therapy in patients in the Gray Zone and the immune-tolerant phase. Patients who fall into these categories are still at risk for HCC. By the numbers, the projected number of patients to develop HCC among these populations is in the order of thousands. Future guidelines should explore increasing treatment eligibility for potential mitigation of HCC burden in the US.