S5618 Vanishing Act: Spontaneous Regression of HCC After Starting HCV Treatment and Emergent TIPS Placement

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Chronic liver diseases like hepatitis C virus (HCV) and cirrhosis are risk factors for developing HCC due to accelerated hepatic fibrosis. Although rare, spontaneous regression of HCC has been reported. We present a case of HCC regression in a patient with HCV/alcohol-associated cirrhosis following emergent transjugular intrahepatic portosystemic shunt (TIPS) placement for esophageal variceal bleed and initiation of direct acting antiviral (DAAs) for chronic HCV infection. Case Description/Methods: A 71-year-old man with a history of hypertension, HCV/alcohol-related cirrhosis with ascites requiring biweekly large volume paracentesis, esophageal varices, and 4.6 cm segment V HCC diagnosed December 2024 was referred for liver transplant evaluation. In January 2025, he was started on sofosbuvir/velpatasvir daily given his significantly decompensated disease. He was hospitalized the following month with variceal bleeding. Endoscopic therapy was unsuccessful, and he subsequently required emergent TIPS. In March, he underwent a repeat MRI abdomen as part of his transplant evaluation, and his HCC appeared non-viable despite not yet undergoing any locoregional therapy. In May, he underwent orthotopic liver transplant. His explant demonstrated HCC with tumor necrosis and <5% viable tumor that was about 0.5 cm in aggregate. Discussion: This patient’s HCC regression following HCV treatment initiation and TIPS is likely related to portal pressure reduction and reduction of HCV burden. Achieving sustained virologic response (SVR) with DAA therapy significantly reduces liver inflammation and halts fibrogenesis. There have been documented cases of HCC regression after DAA-induced SVR, including a patient with extrahepatic metastases who experienced tumor regression post-SVR despite prior failure of systemic therapy. TIPS is often used to manage complications of portal hypertension like variceal bleeding and refractory ascites. Emerging data suggest that TIPS may create a less permissive environment for HCC given reduced blood flow to the lesion, which may contribute to improved survival and reduced HCC progression. While spontaneous regression of HCC is rare, HCV treatment and TIPS-induced hepatic recompensation may contribute to spontaneous regression in patients like ours. Further investigation is needed to better understand the effects of these management strategies on HCC.