Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma with obstructive jaundice: A case report and review of literature

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a major type of liver cancer worldwide. In advanced stages, portal vein tumor thrombosis (PVTT) and jaundice are common, whereas obstructive jaundice (OJ) is relatively rare. Both conditions markedly reduce survival and increase therapeutic complexity. Recently, hepatic artery infusion chemotherapy (HAIC) in combination with targeted immunotherapy has shown promise for advanced HCC.

CASE SUMMARY

We report a 47-year-old male with advanced HCC complicated by PVTT and OJ, who was admitted with marked jaundice of the skin and sclera. Imaging revealed a large hepatic mass (14.5 cm × 11.3 cm) in the right lobe with associated portal vein tumor thrombus. The tertiary bile duct was only mildly dilated, making percutaneous transhepatic cholangiography drainage infeasible. The patient underwent reduced-dose HAIC, which resulted in significant tumor shrinkage and marked reduction in serum bilirubin. This improvement enabled sequential treatment with lenvatinib and camrelizumab. After six cycles, both liver function and alpha-fetoprotein levels improved. The patient achieved a progression-free survival of 20 months and an overall survival of 29 months.

CONCLUSION

HAIC can treat high-bilirubin HCC with PVTT and OJ, allowing for subsequent targeted immunotherapy.

Key Words: Hepatocellular carcinoma; Obstructive jaundice; Hepatic artery perfusion chemotherapy; Portal vein tumor thrombosis; Case report

Core Tip: Hepatocellular carcinoma with portal vein tumor thrombosis (PVTT) and obstructive jaundice is rare and generally carries a poor prognosis. In this case, hepatic artery infusion chemotherapy (HAIC) followed by targeted immunotherapy achieved significant tumor shrinkage, improved bilirubin levels, and regression of PVTT. The patient attained 20 months of progression-free survival and 29 months of overall survival, indicating that HAIC conversion therapy followed by targeted immunotherapy may provide an effective option when biliary drainage is not feasible.

INTRODUCTION

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. In advanced stages, portal vein tumor thrombosis (PVTT) and jaundice are common, whereas obstructive jaundice (OJ) is relatively rare[1-3]. Approximately 19%-40% of patients with HCC present with jaundice at diagnosis, primarily due to hepatic dysfunction resulting from extensive parenchymal damage caused by underlying cirrhosis or large tumors[4]. OJ induced by HCC is rare and carries a poor prognosis, occurring in only 1%-12% of patients, typically due to tumor compression or intrabiliary tumor thrombus[5]. The development of OJ is often accompanied by hepatic failure, which greatly increases treatment difficulty and significantly shortens overall survival (OS)[6,7]. Studies have shown that patients with HCC complicated by OJ have markedly shorter OS compared with those without jaundice, with untreated patients surviving only 1.5-3 months[8-10]. Even with conventional treatments such as percutaneous transhepatic cholangiography drainage (PTCD), outcomes remain unsatisfactory, as jaundice often persists or worsens, further aggravating hepatic dysfunction[11]. Although transarterial chemoembolization (TACE) remains the standard palliative treatment for advanced HCC[12-14], hepatic artery infusion chemotherapy (HAIC) combined with systemic therapies such as targeted immunotherapy has emerged as a promising treatment option in the recent years[15], especially for advanced HCC complicated by PVTT[16-18]. Compared with conventional TACE, HAIC delivers chemotherapeutic agents more directly to the tumor’s blood supply, significantly increasing local drug concentration, thereby enhancing the tumor cell killing effect[19]. Studies have shown that HAIC can effectively improve bilirubin levels in patients with HCC complicated by PVTT and OJ, creating favorable conditions for subsequent therapies[20]. Its efficacy mainly depends on the chemosensitivity of the tumor and the short-term retention of chemotherapy agents within the tumor microenvironment[21], significantly prolonging progression-free survival and OS[22]. Additionally, the combination of tyrosine kinase inhibitors and programmed cell death-1 (PD-1) inhibitors has shown synergistic effects, modulating the immune microenvironment and enhancing immune cell function[23]. Therefore, the combination of HAIC with tyrosine kinase inhibitors and PD-1 inhibitors, known as targeted immunotherapy, has shown superior outcomes compared with HAIC monotherapy[24,25].

We report a case of giant HCC measuring 14.5 cm × 11.3 cm, complicated by PVTT and OJ. This report focuses on the application of HAIC combined with targeted immunotherapy as an effective treatment for the patient who could not undergo biliary drainage to relieve jaundice. After hepatoprotective treatment, the patient’s bilirubin levels continued to rise. Therefore, we chose HAIC to reduce tumor burden and alleviate jaundice, creating favorable conditions for subsequent targeted immunotherapy. After reduced-dose HAIC treatment, the patient’s jaundice symptoms significantly improved. The patient then received five cycles of full-dose HAIC combined with lenvatinib and camrelizumab therapy. However, due to esophageal-gastric variceal rupture and variceal bleeding, the patient underwent transjugular intrahepatic portosystemic shunt (TIPS). As the tumor progressed, the patient received one session of TACE, after which the targeted immunotherapy was adjusted to bevacizumab combined with sintilimab. When the condition further deteriorated, regorafenib was started as second-line treatment.

CASE PRESENTATION

Chief complaints

A 47-year-old male was admitted with progressive jaundice of the skin and sclera for one week.

History of present illness

The patient reported dark urine and progressive yellowing of the skin and sclera for 1 week, without abdominal pain, distension, nausea, vomiting, chills, or fever. Abdominal ultrasonography at our hospital revealed a hepatic space-occupying lesion, prompting admission for further evaluation.

History of past illness

The patient had a history of hepatitis B but had not received regular antiviral treatment.

Personal and family history

The patient reported a history of alcohol consumption for over 20 years, approximately 100 mL per day, and a smoking history for more than 20 years, with a daily consumption of one pack. However, there is no known family history of liver disease or malignant tumors.

Physical examination

Severe jaundice of the skin and sclera was noted; and no other abnormalities were detected.

Laboratory examinations

The detailed laboratory test results are summarized in Table 1. Other parameters were within normal ranges.

Table 1 Laboratory examination results on admission.

Blood tests	Result	Normal
AFP (ng/mL)	1658	< 7
HBV DNA (IU/mL)	5.374 × 103	< 1.0 × 102
TBIL (μmol/L)	140	< 26
DBIL (μmol/L)	128.7	0-8
ALB (g/L)	26.1	40-55
ALT (U/L)	135	< 50
AST (U/L)	188	< 40
GGT (U/L)	132	10-60

AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; TBIL: Total bilirubin; DBIL: Direct bilirubin; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase.

Imaging examinations

Computed tomography (CT) scan revealed a 14.5 cm × 11.3 cm diffuse mass in the right hepatic lobe (Figure 1A and B), with invasion of the right branch of the portal vein and formation of a tumor thrombus in the right portal vein (Figure1C). In addition, intrahepatic bile duct dilation was observed (Figure 1D). CT also suggested liver atrophy, splenomegaly, and irregular liver margins, with prominent signs of cirrhosis. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) showed a 10.2 cm × 8.8 cm × 7.8 cm lesion in the right lobe, accompanied by multiple intrahepatic metastases and portal vein tumor thrombus (Figure 1E-G).

Figure 1 Imaging features of the patient. A: Arterial phase computed tomography (CT) shows marked enhancement in the right hepatic lobe (orange arrow); B: Portal venous phase CT shows hypointensity in the right hepatic lobe (orange arrow); C: Portal venous phase CT demonstrates visualization of the left branch of the portal vein, but absence of the right branch (orange arrow), suggesting portal vein tumor thrombus; D: Intrahepatic bile duct dilatation is observed (orange arrow), indicating obstructive jaundice; E: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) in the arterial phase demonstrates significant tumor enhancement (orange arrow); F: MRI in the portal/venous phase shows marked hypointensity (washout) of the tumor (orange arrow); G: MRI in the hepatobiliary phase shows marked hypointensity of the tumor due to no contrast uptake (orange arrow).

FINAL DIAGNOSIS

According to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer, and based on the typical imaging features of HCC on CT and MRI, and the significantly elevated alpha-fetoprotein (AFP) level, the patient was diagnosed with advanced HCC (Barcelona clinic liver cancer stage C, Child-Pugh class B) without the need for pathological diagnosis.

TREATMENT

In advanced HCC with PVTT and OJ, standard management typically involves PTCD to relieve jaundice prior to TACE combined with targeted immunotherapy[26]. In this case, the tertiary bile duct was only mildly dilated, precluding PTCD drainage[27]. Therefore, hepatoprotective therapy was initially administered. The specific liver protection regimen included 930 mg polyene phosphatidylcholine, administered intravenously twice daily; 250 mg ursodeoxycholic acid capsules, taken orally three times a day; and 2400 mg reduced glutathione, administered intravenously once daily. After four days, bilirubin levels continued to rise [total bilirubin (TBIL): 209.3 μmol/L; direct bilirubin (DBIL): 175.1 μmol/L], indicating treatment failure. HAIC was then initiated using a reduced-dose regimen (one-third lower than standard): Hepatic arterial infusion of oxaliplatin 85 mg/m², intravenous leucovorin calcium 400 mg/m², and 5-fluorouracil 400 mg/m², followed by continuous hepatic arterial infusion of 5-fluorouracil 2400 mg/m² over 46 hours. Additionally, liver protective and antiviral therapy was continued.

Treatment process

HAIC: After the first cycle of HAIC, bilirubin levels improved slightly (TBIL: 51.5 μmol/L; DBIL: 43.95 μmol/L). CT imaging showed tumor reduction from 14.5 cm × 11.3 cm to 10.5 cm × 9.0 cm (Figure 2A). Once bilirubin improved, full-dose HAIC was resumed. After six cycles, tumor size further reduced to 7.1 cm × 6.5 cm (Figure 2B). No intrahepatic bile duct dilation was noted (Figure 2C), and PVTT markedly regressed (Figure 2D). Bilirubin levels improved (TBIL: 31.6 μmol/L), and AFP decreased to 27.6 ng/mL. Serial laboratory results are summarized in Table 2. Both bilirubin and AFP levels significantly decreased compared to baseline, suggesting a positive therapeutic effect. However, a slight increase in AFP was observed in the later stages of treatment, which may indicate liver damage or disease progression. Both aspartate aminotransferase and alanine aminotransferase levels showed a significant increase after the first HAIC cycle but gradually decreased and stabilized in subsequent cycles. This suggests that while HAIC treatment may cause short-term liver function impairment, liver function can gradually recover as the tumor burden decreases. Initially, albumin (ALB) levels were low, consistent with liver dysfunction in cirrhotic patients. Although ALB levels fluctuated during treatment, they remained relatively stable, indicating that the synthetic function of the liver was somewhat preserved although some degree of damage persisted.

Figure 2 Computed tomography changes after hepatic artery infusion chemotherapy treatment. A: Tumor shrinkage after one cycle of hepatic artery infusion chemotherapy (HAIC) (orange arrow); B: After six cycles of HAIC combined with lipiodol embolization (orange arrow); C: No bile duct dilatation after six cycles (orange arrow); D: Portal vein tumor thrombus decreased in size after six cycles (orange arrow); E: Tumor progression with new intrahepatic lesions after 20 months (orange arrow); F: Good lipiodol deposition after transarterial chemoembolization (orange arrow); G: Tumor progression with new lesions after 28 months, with portal vein tumor thrombus in the right branch and bile duct obstruction (blue arrow); H: Pulmonary metastases (orange arrow).

Table 2 Laboratory test results of each cycle during hepatic artery infusion chemotherapy treatment.

Blood tests	Normal	Baseline	After HAIC treatment
			Cycle 1	Cycle 2	Cycle 3	Cycle 4	Cycle 5	Cycle 6
TBIL (μmol/L)	0-26	209.3	51.5	39.8	29.3	35	29.2	31.6
DBIL (μmol/L)	0-8	175.1	43.95	29.1	16.02	15.24	13.4	15.55
ALT (U/L)	9-50	108	587	172	76	58	56	47
AST (U/L)	15-40	326	688	220	96	75	75	66
GGT (U/L)	10-60	207	182	117	76	63	54	60
ALB (g/L)	40-55	33.1	28.8	32.3	20.6	18.2	31	31.9
AFP (ng/mL)	0-7	1658	455.4	17.1	20.6	18.2	18.8	27.6

HAIC: Hepatic artery infusion chemotherapy; AFP: Alpha-fetoprotein; TBIL: Total bilirubin; DBIL: Direct bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; ALB: Albumin.

Combined targeted immunotherapy: One week after HAIC, when bilirubin normalized, lenvatinib (8 mg daily) plus camrelizumab (200 mg every 3 weeks) was initiated. AFP, liver function, and imaging were monitored regularly.

Complications and management: After 12 months, due to the progression of the patient’s cirrhosis and the presence of PVTT, portal pressure significantly increased, leading to gradual worsening of esophageal and gastric varices, which ultimately ruptured and caused bleeding. While this bleeding event is uncommon, it is a frequent complication in patients with advanced liver cancer complicated by PVTT. The rupture of esophageal and gastric varices is severe and carries a high risk of fatal bleeding. Consequently, the decision was made to perform a TIPS procedure to alleviate portal pressure as TIPS is a well-established intervention that creates an artificial shunt between the portal vein and hepatic vein, helping to relieve portal hypertension, control bleeding, and create favorable conditions for subsequent treatment. At 20 months, disease progression was observed (Figure 2E), and TACE was performed (Figure 2F). Targeted immunotherapy was switched to bevacizumab (400 mg every 3 weeks, intravenous injection) plus sintilimab (200 mg every 3 weeks, intravenous injection). At 28 months, tumor recurrence with lung metastases was detected (Figure 2G and H), and second-line therapy with regorafenib (160 mg daily for 21 days, followed by 7 days off, in a 28-day cycle) was initiated. The patient ultimately succumbed to hepatic and respiratory failure at 29 months.

OUTCOME AND FOLLOW-UP

Through HAIC, TACE, and sequential targeted immunotherapy, the patient achieved significant tumor shrinkage and marked bilirubin reduction, with a progression-free survival of 20 months and an OS of 29 months.

DISCUSSION

Patients with HCC complicated by PVTT and OJ generally have a much shorter OS than those without jaundice; untreated patients typically survive only 1.5-3 months. PTCD often helps relieve jaundice, enabling subsequent antitumor therapy. For patients unresponsive to PTCD, HAIC can reduce tumor burden and alleviate jaundice, thereby making combined immunotherapy a viable therapeutic option.

In the present case, we reported a patient with HCC complicated by PVTT and OJ, in whom biliary drainage was not feasible. The patient initially could not undergo systemic antitumor therapy due to severe jaundice. While HAIC combined with targeted immunotherapy has been shown to be effective for advanced HCC, it carries risks such as hepatic failure, particularly in patients with severely impaired liver function[28]. Therefore, we initiated treatment with a reduced-dose HAIC regimen. Following the first cycle, both tumor size and bilirubin levels decreased significantly, creating favorable conditions for subsequent targeted immunotherapy. This case highlights the potential of HAIC combined with targeted immunotherapy in treating advanced HCC with PVTT and OJ. Nonetheless, several challenges during treatment require careful consideration[29]. Patients may experience worsening jaundice or even liver failure following locoregional chemotherapy, as well as tumor recurrence or new metastases. Furthermore, the potential adverse effects of targeted immunotherapy must be monitored closely[30]. With disease progression, pulmonary metastases may occur, necessitating treatment adjustments and the use of second-line agents such as regorafenib. In addition, TIPS may be required in cases complicated by esophageal or gastric variceal bleeding. Overall, this case not only demonstrates the efficacy of HAIC combined with immunotherapy in the management of HCC with PVTT and OJ, but also provides valuable clinical insights. Future studies should aim to optimize HAIC-based combination regimens, evaluate the effectiveness of different therapeutic combinations, and address treatment-related complications.

CONCLUSION

This case highlights the clinical significance of managing HCC complicated by PVTT and OJ. It demonstrates that when PTCD is not feasible for jaundice relief, HAIC can effectively treat diffuse primary liver cancer. HAIC not only reduces tumor burden and alleviates jaundice but also creates favorable conditions for subsequent targeted immunotherapy, ultimately prolonging survival[31]. The concept of combining locoregional and systemic therapies has gained recognition, potentially shifting treatment approaches and improving response rates[32]. A real-world study showed that the combination of HAIC and targeted immunotherapy achieved an objective response rate of 76.7% and a disease control rate of 92.2%, providing a feasible treatment option for advanced liver cancer[33]. While this therapeutic strategy has shown significant efficacy in this case, further research in larger patient populations is needed to validate its effectiveness and long-term outcomes for broader application.

ACKNOWLEDGEMENTS

We thank the patient and his family for their cooperation, and the medical staff in the Department of Minimally Invasive Interventional Radiology of Guilin People’s Hospital for their help during treatment and follow-up.