Non-Invasive Tests Predict Liver Cancer Risk in Hepatitis C Patients After SVR

A new study found transient elastography and the fibrosis-4 index offer acceptable predictive performance for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) who have achieved a sustained viral response (SVR).¹

“These findings highlight the substantial role of non-invasive surrogates in identifying patients at increased risk of HCC development after SVR, emphasizing their utility in clinical practice for guiding surveillance strategies after SVR,” wrote investigators, led by Han Ah Lee, from the department of internal medicine at Chung-Ang University Hospital, in Korea.

Even after achieving a sustained viral response following antiviral therapy for HCV, individuals with advanced liver fibrosis and cirrhosis may still develop hepatocellular carcinoma. In fact, 8.2 – 12.0% of people in South Korea and 34% of people in the US who have HCV develop liver cancer.^2,3 To assess the predictive performance of transient elastography and the fibrosis-4 index in forecasting HCC development after SVR, investigators conducted a meta-analysis.¹

The investigators searched PubMed, MEDLINE, EMBASE, and the Cochrane Library, selecting 27 studies for inclusion. Among these, 9 studies focused on transient elastography, 15 on the fibrosis-4 index, and 3 evaluated both methods.

Of the included studies, 11 were single-center, and 16 were multicenter. Most studies originated from Asia (n = 17), with the remaining from non-Asian regions (n = 10).

In total, the meta-analysis examined 169,911 participants with HCV who achieved SVR following antiviral therapy. The mean age of the participants was 54.1 years. The mean liver stiffness measured with transient elastography was 7.1 kPa and with fibrosis-4 index it was 1.86.

Investigators evaluated the predictive performances of transient elastography and fibrosis 4-index using the area under the curve (AUC). Before treatment, the pooled predictive AUC of transient elastography was 0.73, with a sensitivity of 65.7% and specificity of 69.5%.

The pooled risk ratio of pre-treatment transient elastography for HCC development after SVR was 3.88 (95% confidence interval [CI], 2.21 – 18.16). However, with a cut-off of 9.2 – 13 kPa, the predictive performance improved, showing a pooled AUC of 0.79, sensitivity of 75.1%, and specificity of 71.7%. The pooled risk ratio at this cutoff was 4.56 (95% CI, 3.05–6.81).

For the fibrosis 4-index, the pre-treatment pooled predictive AUC was 0.72, with a sensitivity of 73.4% and a specificity of 60.5%. It has a pooled risk ratio of 2.30 (95% CI: 1.64–3.10) for hepatocellular carcinoma development after sustained viral response. With a cut-off of 3.35, the pooled predictive AUC was 0.73 and the pooled risk ratio was 2.45 (95% CI, 1.68 – 3.13).

The team identified optimal cut-off values for predicting HCC after SVR: 12.6 kPa for transient elastography measured before treatment and 11.2 kPa for transient elastography measured after SVR.

“The identification of optimal cut-off values for TE and FIB-4 enhances the precision of risk stratification, enabling clinicians to tailor surveillance and management strategies more effectively,” investigators wrote. “The study findings support the use of simple, specific cut-off values, thereby enhancing the clinical utility of TE and FIB-4 in HCC surveillance after achieving SVR.”

Investigators added that using cut-off values improves patient care and enhances the healthcare system more efficiently by focusing on patients most at risk.

Despite these findings, investigators said the results were limited by the reliance of retrospective studies, which introduces bias and limits causal inference, and significant heterogeneity in study design and patient characteristics, affecting the generalizability of findings. Additionally, the lack of standardized cut-off values and variability in follow-up duration complicate the applicability of the results, with further prospective studies needed to refine risk stratification and validate findings.

“…this systematic review and meta-analysis reinforces the importance of TE and FIB-4 in predicting the risk of HCC development after SVR in patients with HCV,” investigators wrote. “These tools can guide the implementation of targeted surveillance strategies by identifying patients at an increased risk of HCC after SVR, ultimately facilitating the early detection and management of HCC. Future research for prospective validation of optimal cut-off values and the integration of non-invasive surrogates into clinical practice guidelines for HCC surveillance in patients with HCV who achieved SVR are needed.”

References

1. ^{Lee HA, Kim MN, Lee HA, et al. Non-invasive prediction of post-sustained virological response HCC in HCV: A systematic review and meta-analysis. Clin Mol Hepatol. Published online August 12, 2024. doi:10.3350/cmh.2024.0262}
2. ^{Yoon JS, Lee HA, Kim HY, Sinn DH, Lee DH, Hong SK, Cho JY, et al. Hepatocellular Carcinoma in Korea: an Analysis of the 2015 Korean Nationwide Cancer Registry. J Liver Cancer 2021;21:58-68. 2.}
3. ^{Karim MA, Singal AG, Kum HC, Lee YT, Park S, Rich NE, Noureddin M, et al. Clinical Characteristics and Outcomes of Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in the United States. Clin Gastroenterol Hepatol 2023;21:670-680.e618.}