Better risk stratification can help prioritize patients with hepatocellular carcinoma on the transplant waitlist who have higher risk disease.
For more than 20 years, early-stage hepatocellular carcinoma (HCC) has been an indication for liver transplantation. Given the heterogeneity of the group of patients with HCC, and the introduction of newer and more effective therapies, better risk stratification can help prioritize patients with HCC on the transplant waitlist, according to a report in Liver Transplantation.
Patients with HCC who are on the liver transplantation waitlist have varying degrees of waitlist dropout based on tumor characteristics and baseline liver function.
“In addition, changing demographics of liver disease, including the rising incidence of NASH [nonalcoholic steatohepatitis], effective antiviral therapy for hepatitis C virus, and earlier detection of HCC due to improved screening programs and awareness, may influence the overall survival benefit to liver transplantation,” the authors explained.
They analyzed adults listed for primary liver transplantation in the Organ Procurement and Transplantation Network database between January 2005 and June 2021. Patients included had received at least 1 approved HCC exception. They identified 4 eras based on major policy changes in liver allocation: 2005-2012 (era 1), 2013-2015 (era 2), 2016-2018 (era 3), and 2019-2021 (era 4).
There were 38,789 waitlist registrations. The median age in era 1 was 57 years, which increased to 63 years in era 4. During the time reviewed, the proportion of NASH listings grew from 5.5% to 21.9% and the listings with Child-Pugh class A increased from 38.4% to 51.9%.
The authors identified a low-risk group based on the following characteristics at listing: Model for End-Stage Liver Disease (MELD) < 15, Child-Pugh Class A, alpha fetoprotein (AFP) ≤ 20 mg/mL, and a single tumor 2-3 cm.
In 2005, the low-risk group was just 6.1% of the overall waitlist, but it grew to 18.6% in 2020. More than half of the patients with T2 HCC—defined as a solitary tumor with microvascular invasion or multiple tumors > 5 cm—qualified for the lowest-risk group in eras 3 and 4.
From 2005 to 2020, posttransplant survival improved and rates of recurrence declined. The 1-year patient survival in era 1 was 91.0% vs 94.9% in era 4. The 3-year survival was 81.1% in era 1 vs 88.1% in era 3 (last year for 3-year data). The 5-year survival was 74.7% in era 1 vs 81.6% in era 2 (last year for 5-year data). The posttransplant recurrence decreased from 12.5% in era 1 to 1.8% in era 4.
The authors noted the findings suggest better prioritization is needed for those who will “derive greater benefit from liver transplantation.” In addition, patients with low-risk disease should have a lower priority score and perhaps those who have a complete response to therapy should not receive any exception points. In comparison, patients with tumors > 3 cm, multifocal or recurrent HCC, or MELD-Na ≥ 15 are considered higher risk and should warrant higher priority on the waitlist.
“As newer and more effective medical therapies for HCC emerge, liver transplant with its attendant risks may not be the first-line option for patients with low-risk HCC and compensated liver disease, particularly those who are older and/or have more co-morbid conditions,” the authors concluded. “Our analysis suggests that better risk stratification and prioritization on the waitlist is possible and may help to optimize organ utility.”
Kwong AJ, Ghaziani TT, and Mehta N. Decreased urgency among liver transplant candidates with hepatocellular carcinoma in the United States. Liver Transpl. Published online November 22, 2021. doi:10.1002/lt.26373