Successful conversion therapy for advanced hepatocellular carcinoma with biliary tumor thrombus and bilateral lobe involvement: A case report

Abstract

BACKGROUND

Bilateral multilobular hepatocellular carcinoma (HCC) complicated by HCC-derived biliary tumor thrombus is classified as an advanced-stage disease. Owing to the heavy tumor burden, obstructive jaundice, and other issues, the prognosis with conventional treatment is extremely poor, and most patients lose the opportunity for radical resection. The advent of immune-combined targeted conversion therapy has brought new hope for such patients.

CASE SUMMARY

A 36-year-old man with ≥ 10-year history of hepatitis B was admitted for upper abdominal distension and pain. Imaging demonstrated bilateral multifocal HCC with a left HCC-derived biliary tumor thrombus (Chinese Liver Cancer stage IIIa, Barcelona Clinic Liver Cancer stage C), obstructive jaundice, and cirrhosis. The tumor was initially considered unresectable. The patient received conversion therapy with camrelizumab, apatinib mesylate, and radiofrequency ablation. After five cycles, both the tumors and thrombus regressed, and tumor marker levels decreased markedly. The response was assessed as partial response according to mRECIST 1.1 criteria. Liver function improved from Child-Pugh class B to class A, allowing radical surgical resection with negative margins. Postoperative maintenance therapy was administered for 1 year. No recurrence was detected during follow-up.

CONCLUSION

For advanced bilateral multi-lobular HCC complicated by HCC-derived biliary tumor thrombus, immune-targeted therapy combined with local ablation reduces tumor burden, eliminates thrombus, converts unresectable disease to resectable status, and achieves effective short-term disease control.

Key Words: Hepatocellular carcinoma; Hepatocellular carcinoma-derived biliary tumor thrombus; Conversion therapy; Immunotherapy; Targeted therapy; Case report

Core Tip: For advanced bilateral multilobular hepatocellular carcinoma (HCC) with HCC-derived biliary tumor thrombus, conversion therapy using camrelizumab (immunotherapy) combined with apatinib mesylate (targeted therapy) and hepatic radiofrequency ablation successfully reduced tumor burden and eliminated the biliary tumor thrombus, enabling radical surgical resection. This approach resulted in short-term disease-free survival (6 months after surgery) with preserved normal liver function.

INTRODUCTION

Hepatocellular carcinoma (HCC) represents a major global public health concern, characterized by high mortality and poor prognosis. While the global burden of HCC remains substantial, China bears a disproportionately large share of this burden, highlighting the need for focused clinical attention. As documented by the 2023 China Cancer Registry Annual Report, China accounts for approximately 42.4% of newly diagnosed HCC cases and 41.7% of HCC-related deaths worldwide, far exceeding any other nation. Chronic hepatitis B virus (HBV) infection remains the predominant etiological factor, responsible for over 80% of HCC cases in China[1]. These findings underscore the critical need for tailored therapeutic approaches to address this region-specific public health challenge.

Notably, clinical practice in China has witnessed a rising incidence of HCC among younger populations, a trend closely linked to chronic HBV infection. This occurs despite the Standards for Diagnosis and Treatment of Primary Hepatic Carcinoma (2024 Edition) classifying males over 40 years as the primary high-risk group[1]. Prolonged chronic HBV infection can drive a pathological cascade from hepatic fibrosis to cirrhosis, laying the pathophysiological foundation for HCC development—a causal link validated by robust epidemiological evidence.

Among HCC subtypes, bilateral multi-lobular HCC complicated by HCC-derived biliary tumor thrombus represents a particularly challenging clinical scenario. Diffuse intrahepatic tumor dissemination, biliary obstruction-induced jaundice, and impaired liver function often render these patients ineligible for curative resection. For patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) stage C disease, the 5-year survival rates remain below 10% with conventional therapies, highlighting the poor prognosis associated with this condition.

In recent years, breakthroughs in systemic therapy—specifically the combination of immune checkpoint inhibitors and anti-angiogenic agents—have reshaped the treatment paradigm for advanced HCC. The phase III CARES-310 trial demonstrated that first-line camrelizumab plus apatinib achieved an objective response rate (ORR) of 25.4% and a median overall survival of 22.1 months for unresectable/metastatic HCC[2], while the TRIPLET regimen (camrelizumab + apatinib + hepatic arterial infusion chemotherapy) further increased the ORR to 77.1% and the conversion resection rate to 17.1%[3], offering curative potential for patients previously considered untreatable.

Nevertheless, clinical data on multidisciplinary conversion therapy for young patients with HBV-associated bilateral multi-lobular HCC complicated by HCC-derived biliary tumor thrombus remain scarce. Unlike previously reported cases of advanced HCC conversion therapy, this case involves a young HBV-infected patient (36-years-old) with bilateral multi-lobular HCC and HCC-derived biliary tumor thrombus who was treated with a sequential regimen of “biliary drainage - camrelizumab + low-dose apatinib - radiofrequency ablation”—a strategy that balances efficacy and safety, as the use of low-dose apatinib reduces treatment-related adverse events while achieving complete regression of the biliary tumor thrombus. Herein, we report this case to provide practical insights for managing similarly complex HCC cases.

CASE PRESENTATION

Chief complaints

A 36-year-old man was admitted with a 1-week history of upper abdominal distension and pain.

History of present illness

One week before admission, the patient developed upper abdominal distension and pain without any identifiable triggers. The symptoms were intermittent; worsened after meals; and were accompanied by nausea, fatigue, scleral icterus, darkened reddish-brown urine, and pale stools. The patient visited a local hospital, where an abdominal non-contrast computed tomography (CT) scan revealed findings suggestive of a hepatic neoplasm. He was subsequently referred to our institution for further diagnosis and management.

History of past illness

The patient had a known history of hepatitis B infection but had not received regular treatment. Upon admission, he was diagnosed with chronic active hepatitis B. Oral antiviral therapy with entecavir (0.5 mg/day) was initiated, and HBV DNA levels were monitored every 3 months. After 3 months of treatment, the viral load decreased to < 100 IU/mL.

Personal and family history

The patient had no significant past medical history and denied any relevant family history.

Physical examination

Physical examination revealed mild tenderness in the hepatic region, while the remaining findings were unremarkable.

Laboratory examinations

Blood tests revealed an elevated alpha-fetoprotein (AFP) level of 230.00 ng/mL (reference range: < 7 ng/mL) and a markedly increased carbohydrate antigen 19-9 (CA19-9) level of 481.00 U/mL (reference range: < 27 ng/mL). Hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B e antigen were all positive. The HBV DNA level was 2.81 × 10⁴ IU/mL. Bilirubin-related parameters were as follows: Total bilirubin 35 μmol/L (reference range: < 21 μmol/L), direct bilirubin 22 μmol/L, indirect bilirubin 13 μmol/L, alkaline phosphatase 380 U/L, γ-glutamyl transpeptidase 420 U/L. Liver function indicators showed albumin to be 32 g/L and a prothrombin time of 14.2 seconds. All other laboratory parameters were within the normal range.

Imaging examinations

Contrast-enhanced abdominal magnetic resonance imaging (MRI) revealed multiple nodules and masses in the liver, with the largest measuring 46 mm × 37 mm and located in the right hepatic lobe near the hepatic dome (Figure 1A). Strip-like abnormal signal shadows were observed in the intrahepatic bile ducts of the left hepatic lobe, accompanied by dilatation of the intrahepatic bile duct. These findings were suggestive of HCC-derived biliary tumor thrombus (Figure 1B).

Figure 1 Contrast-enhanced magnetic resonance imaging and histopathological findings of the patient. A: Arterial phase image showing a hyperintense lesion on T1-weighted imaging (T1WI) before treatment; B: Arterial phase image showing reduced enhancement of the lesion on T1WI after treatment; C: Preoperative hematoxylin and eosin (H&E) staining (× 100); D: Venous phase image showing a hypointense lesion on T1WI, indicating a hepatocellular carcinoma (HCC)-derived biliary tumor thrombus before treatment; E: Venous phase image showing complete disappearance of the HCC-derived biliary tumor thrombus after treatment; F: Postoperative H&E staining (× 100).

FINAL DIAGNOSIS

On January 10, 2025, the patient underwent ultrasound-guided liver biopsy. Sampling sites included the 46 mm × 37 mm lesion in the right hepatic lobe and the suspected biliary tumor thrombus area in the left hepatic duct. Histopathological examination revealed nests of HCC cells with significant nuclear atypia, consistent with moderately differentiated HCC. Tumor cell infiltration was identified in the tissue of the left hepatic duct, confirming the diagnosis of HCC-derived biliary tumor thrombus. No cellular features suggestive of intrahepatic cholangiocarcinoma were observed, ruling out the diagnosis of combined hepatocellular-cholangiocarcinoma (Figure 1C). No complications such as bleeding or biliary leakage occurred after the biopsy.

To avoid diagnostic ambiguity, the term “HCC-derived biliary tumor thrombus” is used throughout this manuscript, as intrahepatic cholangiocarcinoma was pathologically ruled out. Based on the biopsy and imaging findings, the patient was diagnosed with advanced-stage HCC (BCLC stage C), with liver function classified as Child-Pugh class B.

TREATMENT

Based on the patient’s diagnosis of HCC (China National Liver Cancer Collaboration Network stage IIIa; BCLC stage C) complicated by HCC-derived biliary tumor thrombus and obstructive jaundice, a multidisciplinary oncology team formulated a stepwise treatment regimen. As imaging indicated obstructive jaundice caused by intrahepatic HCC-derived biliary tumor thrombus, and the tumor burden was too extensive for immediate surgical resection, the patient first underwent digital subtraction angiography combined with color Doppler ultrasound-guided percutaneous transhepatic cholangiography and percutaneous transhepatic biliary external drainage in the interventional radiology suite on January 6, 2025. One week after the procedure, the total bilirubin level decreased to 28 μmol/L, and further declined to 19 μmol/L (within the normal range) 2 weeks later, with alleviation of obstructive jaundice symptoms. Considering the patient’s advanced disease stage and the multicentric nature of the tumors, and with reference to current conversion therapy strategies for HCC, immunotherapy combined with targeted therapy was recommended to reduce tumor size and suppress tumor activity. After obtaining informed consent from the patient, treatment was initiated on January 13, 2025, consisting of oral apatinib mesylate (250 mg/day) and intravenous camrelizumab (200 mg every 3 weeks). Tumor markers were monitored every two treatment cycles; by the 3^rd cycle, AFP had decreased to 186 ng/mL and CA19-9 to 124 U/mL, indicating an early therapeutic response. Following four cycles of systemic therapy, imaging showed faint enhancement in some small nodules of the right hepatic lobe, accompanied by a 61.5% decrease in AFP levels.

On May 8, 2025, the patient underwent CT-guided radiofrequency ablation for three active nodules (each < 1.5 cm in diameter) in this region, with the ablation margin extending 0.5 cm beyond the lesion margins. The procedure lasted 30 minutes, and no postoperative complications, such as fever or bleeding, were observed. The rationale for selecting this timing of ablation was threefold: (1) Prior treatment had reduced tumor activity, enabling precise eradication of residual lesions while minimizing damage to normal hepatic tissue; (2) Immunotherapy combined with targeted therapy may alter the vascular supply pattern of tumors, thereby enhancing the rate of coagulative necrosis in ablated lesions[4]; and (3) Ablation-induced tumor cell necrosis releases tumor-associated antigens, which can enhance the “abscopal effect” of immunotherapy[5].

After five cycles of treatment, follow-up contrast-enhanced abdominal MRI demonstrated partial shrinkage of the intrahepatic tumors, with the largest lesion in the left hepatic lobe measuring approximately 41 mm × 43 mm (Figure 1D). The previously identified HCC-derived biliary tumor thrombus in the left hepatic lobe had disappeared (Figure 1E). The detailed baseline and post-treatment characteristics of the target lesions are summarized in Table 1. Following multidisciplinary team evaluation, the regimen was deemed effective and the patient was deemed eligible for surgical resection based on the following criteria: (1) Tumors were confined to the left hepatic lobe and the previously ablated area of the right hepatic lobe; (2) HCC-derived biliary tumor thrombus had fully resolved, with relief of biliary obstruction; (3) Liver function had improved to Child-Pugh class A; (4) No distant metastasis or surgical contraindications were identified; and (5) Eastern Cooperative Oncology Group performance status was 0. After excluding surgical contraindications, the patient underwent laparoscopic left hemihepatectomy and cholecystectomy under general anesthesia on June 12, 2025.

Table 1 Baseline and post-treatment characteristics of target lesions.

Assessment time	Target lesion location	Maximum lesion size (mm)	AFP level (ng/mL)	CA19-9 level (U/mL)	Liver function grade
Baseline (Jan 2025)	Right hepatic lobe, near hepatic dome	46 × 37	230.00	481.00	Child-Pugh B
After 5 cycles (Jun 2025)	Left hepatic lobe	41 × 43	86.00	7.71	Child-Pugh A

Target lesions were defined as the largest measurable lesions in each hepatic lobe, according to the mRECIST 11 criteria. AFP: Alpha-fetoprotein; CA19-9: Carbohydrate antigen 19-9.

Postoperative pathological examination revealed no definite residual HCC lesions in the left hepatic lobe (Figure 1F). The patient recovered uneventfully without postoperative complications. To consolidate the therapeutic effect, postoperative maintenance therapy with apatinib mesylate combined with camrelizumab was continued.

OUTCOME AND FOLLOW-UP

Postoperatively, the patient underwent contrast-enhanced abdominal MRI, tumor marker detection (AFP and CA19-9), and liver and renal function tests every 3 months. As of December 2025 (6 months after surgery), no evidence of tumor recurrence or metastasis was detected, and liver and renal function remained at Child-Pugh class A. This 6-month follow-up represents a short-term outcome; the long-term prognosis remains to be evaluated, as the 1-year recurrence risk after resection for advanced HCC is approximately 40%-50%. Follow-up was ongoing at the time of writing this report.

DISCUSSION

This young patient with bilateral multifocal HCC successfully achieved eligibility for radical surgical resection following a multimodal conversion therapy regimen. This case not only validates the feasibility and efficacy of conversion therapy for advanced HCC but also sheds light on the synergistic mechanisms underlying multimodal combination strategies, offering valuable clinical insights for managing complex HCC subtypes.

The conversion efficacy of camrelizumab combined with apatinib stems from their synergistic effects in regulating the tumor microenvironment[6]. Camrelizumab relieves immune suppression by blocking the PD-1/PD-L1 pathway[7], while apatinib inhibits tumor angiogenesis via vascular endothelial growth factor receptor-2 (commonly known as VEGFR-2) targeting[8]. Notably, apatinib was administered at a reduced dose (250 mg/day, 50% of the standard dose) to balance efficacy and safety, aligning with prior studies demonstrating a comparable ORR to that of standard-dose regimens but with fewer treatment-related adverse events.

The sequential model of “systemic therapy - local ablation - systemic therapy” is particularly suitable for multifocal HCC. In this case, radiofrequency ablation was performed after four cycles of systemic therapy, guided by a 61.5% reduction in AFP levels and partial tumor shrinkage. This timing minimized damage to normal hepatic tissue while maximizing the eradication of residual lesions. No progression was observed in the right hepatic lobe nodules after ablation, further confirming the rationality and effectiveness of this sequential strategy.

The following discussion proposes potential mechanisms underlying the regression of HCC-derived biliary tumor thrombus, although direct evidence (e.g., pre- and post-treatment thrombus biopsy) was not available, and the hypotheses remain exploratory. Apatinib-induced inhibition of the VEGF/VEGFR signaling pathway may suppress thrombus neovascularization, thereby leading to ischemic necrosis. Meanwhile, camrelizumab-activated immune effector cells may infiltrate the thrombus via the bile duct wall[9]. Additionally, preoperative biliary drainage reduced the total bilirubin level to < 30 μmol/L, thereby avoiding hyperbilirubinemia-induced immune suppression and optimizing hepatic functional reserve for subsequent therapy.

Five cycles of conversion therapy were administered to achieve optimal tumor response, aligning with the current clinical consensus that recommends response evaluation after 3-6 cycles[1].

This case report has inherent limitations, including the potential bias associated with a single-case design and the lack of dynamic genetic testing to elucidate potential drug resistance mechanisms. Future research should focus on multicenter prospective studies to validate the efficacy of this multimodal conversion strategy.

CONCLUSION

For patients with advanced bilateral multifocal HCC complicated by HCC-derived biliary tumor thrombus, a conversion strategy consisting of camrelizumab combined with low-dose apatinib followed by sequential radiofrequency ablation may achieve tumor downstaging and regression of HCC-derived biliary tumor thrombus through mechanistic synergy, significantly increasing the likelihood of radical surgical resection. Throughout treatment, it is essential to adhere to the principles of early response evaluation, individualized dosing, and timing optimization, with particular attention to viral control and functional liver protection in young patients. This multimodal conversion model provides important practical references for the individualized treatment of complex HCC, although its long-term benefits require further validation in large-scale prospective studies.