Successfully clearing the hepatitis C virus is a major medical milestone — but it does not fully close the door on liver cancer. A large-scale, long-term cohort study led by researchers at National Taiwan University Hospital (NTUH) has found that patients who eliminate the virus through direct-acting antiviral (DAA) therapy but still have metabolic dysfunction-associated steatotic liver disease (MASLD) face a significantly elevated risk of developing hepatocellular carcinoma (HCC) over time.
The findings were published in Gut, one of the world's leading peer-reviewed gastroenterology journals.
About the Research Team
Thestudy was led by Dr. Chang Yu-ping (張鈺屏) of NTUH Hsin-Chu Branch and Dr. Chen Yun-chu (陳韻竹) of NTUH's Department of Internal Medicine. Overall direction was provided by NTUH Vice Superintendent Prof. Kao Jia-horng (高嘉宏) and Prof. Liu Chen-hua (劉振驊) of the hospital's Hepatitis Research Center.
Why Clearing the Virus Is No Longer the Whole Story
The introduction of DAA therapy transformed hepatitis C treatment. More than 95% of patients can now achieve a sustained virologic response — meaning the virus is undetectable in the blood — through a short course of oral medication. That achievement cuts overall HCC risk by roughly 80%.
Yet a meaningful proportion of patients still develop liver cancer during long-term follow-up. This study set out to understand why, and to identify which post-treatment patients remain most vulnerable.
MASLD: The Residual Risk Factor
The research team found that MASLD — a form of fatty liver disease driven by metabolic dysfunction such as obesity, insulin resistance, and abnormal lipid levels — is a key driver of persistent cancer risk after viral clearance. Patients who had successfully eradicated the hepatitis C virus but still had MASLD faced approximately twice the risk of developing HCC compared to those without fatty liver disease. This finding builds on work the same team published earlier in 2025 in the *Journal of Hepatology*.
The current study goes a step further by identifying which MASLD patients face the greatest danger. Within the MASLD group, two factors roughly doubled liver cancer risk again:
- Severe hepatic steatosi (significant fat accumulation in the liver, as opposed to mild steatosis)
- Diabetes or prediabetes (impaired glucose metabolism, compared to patients with normoglycemia)
The researchers conclude that metabolic dysfunction continues to drive hepatocarcinogenesis — the biological process through which liver cancer develops — even after the underlying viral infection is resolved.
Implications for Post-Treatment Care
NTUH said the findings carry significant implications for how clinicians worldwide approach long-term surveillance of hepatitis C patients after treatment.
Rather than treating viral clearance as the finish line, the study calls for a more nuanced risk-stratification framework — one that weighs metabolic health alongside virological status. Patients with MASLD, particularly those with severe hepatic steatosis or abnormal blood glucose, warrant closer monitoring for HCC development.
The hospital also emphasized that the residual cancer risk is not fixed. Actively managing fatty liver and blood sugar levels — through lifestyle interventions such as weight control and dietary changes, combined with appropriate medical treatment — may meaningfully reduce the likelihood of liver cancer after viral cure.
MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease): The current international consensus term for fatty liver disease driven by metabolic factors such as obesity, insulin resistance, and dyslipidemia. It replaced the older term NAFLD (non-alcoholic fatty liver disease) in clinical guidelines in 2023.
- DAA (Direct-Acting Antiviral) therapy: A class of oral antiviral drugs that target specific proteins in the hepatitis C virus life cycle, enabling high cure rates with minimal side effects.
- Hepatocellular carcinoma (HCC): The most common form of primary liver cancer, accounting for the vast majority of liver cancer diagnoses globally.
- Sustained virologic response (SVR): The standard measure of hepatitis C cure, defined as undetectable viral levels in the blood 12 weeks after completing treatment.
- Hepatocarcinogenesis: The biological process by which normal liver cells undergo genetic and cellular changes that lead to the development of liver cancer.
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