Hepatocellular carcinoma with obstructive jaundice: Biliary drainage and multimodal therapy

Abstract

Obstructive jaundice is an uncommon manifestation of hepatocellular carcinoma (HCC), reported in 1%-12% of patients, and must be distinguished from jaundice caused by diffuse hepatic failure. This narrative review evaluates HCC with an imaging-supported mechanical obstructive component caused by bile duct tumor thrombus, extrinsic compression, intraductal growth, or hemobilia. HCC-specific studies use heterogeneous definitions of successful drainage, including bilirubin reductions of > 30% or ≥ 50% and absolute thresholds below 2-3 mg/dL. Retrospective series suggest that endoscopic or percutaneous drainage can relieve cholestasis and permit reassessment for surgery, transarterial chemoembolization, radiotherapy, or systemic treatment in selected patients. However, comparisons between patients who did and did not receive subsequent therapy are strongly confounded by liver function, performance status, tumor burden, and drainage response. Direct evidence is greatest for drainage followed by transarterial chemoembolization; evidence for hepatic arterial infusion chemotherapy, radiotherapy, immune checkpoint inhibitor regimens, and liver transplantation remains limited to small retrospective series, case reports, or extrapolation from broader HCC populations. We propose an evidence-calibrated multidisciplinary framework that prioritizes confirmation of mechanical obstruction, individualized drainage, clinical reassessment, and explicit recognition of evidentiary uncertainty.

Key Words: Hepatocellular carcinoma; Obstructive jaundice; Bile duct tumor thrombus; Biliary drainage; Transarterial chemoembolization; Hepatic arterial infusion chemotherapy; Immunotherapy; Multidisciplinary management

Core Tip: Patients with hepatocellular carcinoma-related jaundice should first be evaluated for a mechanical obstructive component rather than assumed to have irreversible liver failure. Endoscopic or percutaneous drainage may relieve cholestasis and allow treatment reassessment, but response definitions vary and apparent survival advantages are vulnerable to selection bias. Transarterial chemoembolization has the largest direct post-drainage evidence base; hepatic arterial infusion chemotherapy, radiotherapy, systemic therapy, and transplantation are supported mainly by small retrospective studies, case reports, or extrapolation. Drainage modality and subsequent treatment should be individualized by a multidisciplinary team, with clinical trials preferred whenever feasible.

INTRODUCTION

Primary liver cancer is a leading cause of cancer incidence and mortality worldwide, accounting for approximately 900000 new cases and 830000 deaths annually[1]. Hepatocellular carcinoma (HCC) constitutes approximately 75%-85% of primary liver cancers and remains a major cause of cancer-related death in Asia, sub-Saharan Africa, and increasingly in Western countries[1,2].

Jaundice is a presenting feature in 5%-44% of patients with HCC[3]. This broad range reflects the diverse etiologies: Underlying cirrhosis with parenchymal dysfunction, massive tumor replacement of hepatic parenchyma, or direct biliary obstruction from tumor invasion. True obstructive jaundice (OJ) caused by bile duct tumor thrombus (BDTT), hilar lymphadenopathy, or intraductal tumor growth is relatively uncommon, with an estimated incidence of 1%-12% in large series[3-5].

OJ in HCC has historically been considered a preterminal event. An et al[5] reported a median overall survival of 4.1 months among 247 patients with bile duct invasion (BDI), the majority having Barcelona Clinic Liver Cancer staging system stage C disease. Jiang et al[6] found that biliary tract invasion with OJ was an independent predictor of poor survival in unresectable HCC, with a median overall survival of 5.7 months compared with 14.2 months in patients without BTI.

Eligibility criteria based on hyperbilirubinemia and impaired hepatic function have generally excluded these patients from prospective trials and, in some centers, from active antitumor therapy. Retrospective series report longer survival among patients who achieve a clinical drainage response and subsequently receive tumor-directed treatment; however, these comparisons are highly vulnerable to selection bias because treatment recipients usually have better hepatic reserve, performance status, tumor burden, and bilirubin recovery[7,8].

SCOPE AND TARGET POPULATION

This review addresses adults with HCC and an imaging-supported mechanical biliary obstruction, including BDTT, extrinsic compression, intraductal tumor growth, or hemobilia. Jaundice attributable solely to diffuse parenchymal failure is outside the principal scope. Because drainage response is an outcome rather than a pretreatment diagnosis, we distinguish patients with a potentially drainable obstruction from those who subsequently achieve study-defined clinical success.

LITERATURE SEARCH AND EVIDENCE APPRAISAL

Structured searches of PubMed and Europe PMC were updated through July 22, 2023 to July 23, 2026. Search concepts combined ‘hepatocellular carcinoma’ or ‘HCC’ with ‘obstructive jaundice’, ‘bile duct invasion’, or ‘bile duct tumor thrombus’, and with ‘biliary drainage’, ‘ERCP’, ‘endoscopic drainage’, ‘PTBD’, ‘PTCD’, ‘stent’, ‘TACE’, ‘HAIC’, ‘systemic therapy’, ‘radiotherapy’, ‘resection’, or ‘transplantation’. English-language original studies, reviews, and guidelines directly relevant to diagnosis or management were considered; modality-specific case reports were retained only when higher-level direct evidence was unavailable. Reports of non-HCC obstruction, post-transplant or purely iatrogenic strictures, and studies without relevant diagnostic, treatment, or outcome information were excluded. Reference lists were hand-searched. Because this is a narrative review, no pooled effect estimate or formal risk-of-bias synthesis was undertaken. Evidence is described as direct retrospective cohort evidence, small-series or case-report evidence, or extrapolation from broader HCC populations rather than as a formal guideline grade.

MECHANISMS AND CLASSIFICATION OF OJ IN HCC

Mechanisms of biliary obstruction

OJ in HCC can arise through several distinct mechanisms: (1) BDTT: Direct extension of HCC into the bile duct lumen is the most common mechanism. Macroscopic BDTT is found in 0.5%-9.1% of surgical or autopsy series, although microscopic BDI is detectable in up to 29% of autopsy specimens[9]; (2) Extrinsic compression by the primary tumor or metastatic lymph nodes at the porta hepatis[3]; (3) Intraductal polypoid growth. Rarely, HCC presents as an intrabiliary mass without a demonstrable vascular component; and (4) Hemobilia. Tumor bleeding into the biliary tree, either spontaneous or iatrogenic, may cause obstructive blood clots[10]. These mechanisms are illustrated schematically in Figure 1.

Figure 1 Mechanisms of obstructive jaundice in hepatocellular carcinoma. A: Bile duct tumor thrombus extends into the duct lumen; B: Extrinsic compression by the tumor or a hilar lymph node; C: Intraductal polypoid tumor growth; D: Hemobilia with obstructing blood clot. The schematic is not to scale. BDTT: Bile duct tumor thrombus; CBD: Common bile duct; CHD: Common hepatic duct; HCC: Hepatocellular carcinoma; LHD: Left hepatic duct; LN: Lymph node; RHD: Right hepatic duct.

Classification of BDTT

Several classification systems have been proposed, as summarized in Table 1. Anatomic systems such as the Satoh classification describe the level and continuity of BDTT, whereas Zhou et al[11] proposed a resectability-oriented four-type framework: Microscopic BDTT (type I), resectable primary or recurrent HCC with BDTT (type II), BDTT without an obvious intrahepatic HCC mass (type III), and BDTT associated with unresectable intrahepatic or extrahepatic disease (type IV). The proposal was derived from a seven-patient institutional series and a literature review; therefore, it may help organize clinical reasoning but requires external validation before prognostic or treatment decisions are based on it. Selected definitions are summarized in Table 1.

Table 1 Selected classification systems for bile duct tumor thrombus in hepatocellular carcinoma.

Classification	Type	Definition	Interpretive use
Satoh	1	BDTT in a first-order hepatic duct branch without reaching the right-left duct confluence	Anatomically limited intraductal extension
Satoh	2	BDTT extending across the right-left hepatic duct confluence	Hilar involvement
Satoh	3	BDTT separated from the primary HCC and growing in the common bile duct	Detached/distal intraductal disease
Zhou et al[11]	I	Microscopic BDTT	Detected pathologically
Zhou et al[11]	II	Resectable primary or recurrent HCC with BDTT	Resectability-oriented category
Zhou et al[11]	III	BDTT without an obvious intrahepatic HCC mass	High diagnostic-mimic risk
Zhou et al[11]	IV	BDTT with unresectable intrahepatic or extrahepatic HCC	Systemic/non-surgical disease context
Zhou et al[11]	a/b	Subclassified by presence/absence of extrahepatic bile duct wall invasion	Proposed surgical-pathology modifier

Zhou et al’s proposal[11] has not been prospectively validated. BDTT: Bile duct tumor thrombus; HCC: Hepatocellular carcinoma.

DIAGNOSTIC WORKUP AND DIFFERENTIATION FROM CHOLANGIOCARCINOMA

Imaging

Contrast-enhanced computed tomography and magnetic resonance imaging with magnetic resonance cholangiopancreatography are the primary imaging modalities. Typical HCC features (arterial hyperenhancement with portal venous or delayed-phase washout) should be sought, as these are highly specific for HCC[12,13].

Differentiation from hilar cholangiocarcinoma

HCC with BDTT can mimic hilar cholangiocarcinoma (CCA). An associated parenchymal mass with arterial hyperenhancement and washout favors HCC, whereas progressive delayed enhancement and irregular bile duct wall thickening favor CCA[13,14]. Alpha-fetoprotein may support HCC and carbohydrate antigen 19-9 may support CCA, but neither marker is diagnostic and cholangitis can elevate carbohydrate antigen 19-9. Cholangioscopy may show a smooth, yellow-white polypoid intraductal lesion in HCC with BDTT[15]. When tissue is required, morphology integrated with a panel of hepatocellular and biliary immunohistochemical markers is preferable to reliance on a single marker.

Serum bilirubin profiling

A conjugated hyperbilirubinemia with alkaline phosphatase and gamma-glutamyl transferase elevations disproportionate to aminotransferases supports cholestasis but does not by itself establish a mechanical obstruction. No direct-to-total bilirubin cutoff has been validated specifically for HCC with cirrhosis. Biochemical findings should therefore be integrated with bile duct dilation, contrast-enhanced imaging, magnetic resonance cholangiopancreatography, and the clinical context. Retrospective drainage studies have used heterogeneous response definitions, including bilirubin reductions of > 30% or ≥ 50% over 2-4 weeks and absolute thresholds below 2-3 mg/dL[4,16-21]. A post-drainage decline quantifies clinical response; it should not be presented as retrospective proof of the pretreatment jaundice mechanism.

BILIARY DRAINAGE AND REASSESSMENT FOR ANTITUMOR THERAPY

Biliary drainage can palliate pruritus or cholangitis and may permit reassessment for tumor-directed therapy. No universal definition of successful drainage exists in HCC-related OJ. Published cohorts have used relative bilirubin reductions, absolute bilirubin thresholds, symptom improvement, or combinations of these outcomes (Table 2). Values below 2-3 mg/dL or two times the upper limit of normal frequently reflect trial or treatment eligibility boundaries rather than a prospectively validated safety threshold for the post-drainage population.

Table 2 Source-verified clinical outcomes in selected hepatocellular carcinoma-specific biliary drainage studies.

Ref.	Cohort and drainage	Clinical response definition	Verified drainage results	Key findings
Lee et al[4], 2002	Retrospective; 22 patients; PTBD	> 50% reduction in total bilirubin within 4 weeks	Good response: 13/22 (59.1%)	Lower baseline bilirubin favored response; survival was not reported in the verified abstract
Hong et al[23], 2008	Retrospective; 15 patients, 19 sessions; percutaneous SEMS	≥ 30% decrease in total bilirubin or total bilirubin < 2 mg/dL	Technical: 15/15 (100.0%); clinical: 11/15 (73.3%)	Major complications: 2/19 sessions (10.5%); mean stent patency: 149.8 days (range: 12-790 days)
Cho et al[19], 2011	Retrospective; 68 patients; ERBD or PTBD	> 30% decrease in total bilirubin within 4 weeks	Effective drainage: 51.5% (numerator not stated in the verified abstract)	Additional HCC treatment was more frequent after effective drainage; mean survival: 247 days vs 44 days
Choi et al[24], 2012	Retrospective; 60 patients; ERBD 29, PTBD 31	Study-defined successful drainage	ERBD: 22/29 (75.9%); PTBD: 15/31 (48.4%)	Median patency: 82 days vs 37 days; median survival after successful vs unsuccessful drainage: 143 days vs 38 days
Choi et al[7], 2013	Retrospective; 60 patients; ERBD or PTBD	Study-defined successful drainage	Successful drainage: 39/60 (65.0%)	TACE was given to 17/39 responders; median survival: 410 days vs 77 days for TACE vs conservative care, with major selection bias
Lu et al[22], 2013	Retrospective; 16 patients; PTBD with external/internal drainage or covered stent	Improvement in clinical symptoms and quality of life	Technical: 16/16 (100.0%); symptom/quality-of-life improvement: 12/16 (75.0%)	Immediate biliary hemorrhage: 5/16; hemorrhage with infection: 3/16; median survival: 199.5 days (mean: 203.7 days)
Choi et al[25], 2013	Retrospective ITT; 111 patients; attempted endoscopic drainage	Study-defined favorable response	Favorable response: 46/111 (41.4%); cannulation failed in 5/111	Further HCC treatment: 40/46 responders (87.0%); median survival: 8.7 months vs 1.3 months for responders vs nonresponders
Sugiyama et al[20], 2014	Retrospective; 36 patients; endoscopic stenting	≥ 50% reduction in total bilirubin	Technical: 36/36 (100.0%); clinical: 27/36 (75.0%)	No early complications; late complications: 13/36 (36.1%); median patency: 43 days; median survival: 150 days vs 22 days
Chung et al[17], 2015	Retrospective; 96 patients; SEMS 36, plastic stent 60	Study-defined successful drainage	SEMS: 25/36 (69.4%); plastic: 39/60 (65.0%)	Adverse events: 6/36 (16.7%) vs 13/60 (21.7%); median patency: 60 days vs 68 days; median survival: 48 days vs 123 days
Woo et al[18], 2017	Retrospective; 74 patients, 76 attempted procedures; endoscopic drainage	Total bilirubin < 3 mg/dL	Technical: 70/76 (92.1%); clinical: 25/70 (35.7%)	Post-drainage HCC treatment was associated with survival; median survival: 28 days overall. An internally inconsistent re-aggravation percentage was not reproduced
Matsumi et al[16], 2021	Multicenter retrospective; 107 patients; endoscopic drainage	≥ 30% reduction in jaundice after technical success; cholangitis resolution when applicable	Technical: 105/107 (98.1%); clinical: 85/105 (81.0%)	ERC-related complications: 3/107 (2.8%); 41/107 received HCC treatment after EBD; median survival: 5.0 months vs 0.93 months
Wang et al[21], 2022	Multicenter retrospective; 138 patients; PTBD	At 4 weeks: Any total bilirubin decrease or nadir < 5, < 3, or < 2 mg/dL as separate endpoints	No single pooled clinical-success rate was reported	Internal prediction-model study restricted to HBV-related cirrhosis; external validation is required
Tachi et al[26], 2025	Retrospective; 10 patients, 14 attempts, 11 evaluable procedures; EUS-HGS	Improved cholangitis or ≥ 50% reduction in total bilirubin within 4 weeks	Technical: 13/14 (92.9%); clinical: 10/11 (90.9%); ≥ 50% reduction by 2 weeks: 8/11 (72.7%)	Mild adverse events: 3/11 (27.3%); no bleeding; survival was not reported

Percentages were recalculated to one decimal place when numerators and denominators were available. Between-study response rates are not directly comparable because definitions, anatomy, hepatic reserve, and denominators differed. PTBD: Percutaneous transhepatic biliary drainage; SEMS: Self-expandable metal stent; ERBD: Endoscopic retrograde biliary drainage; HCC: Hepatocellular carcinoma; TACE: Transarterial chemoembolization; ITT: Intention-to-treat; ERC: Endoscopic retrograde cholangiography; EBD: Endoscopic biliary drainage; HBV: Hepatitis B virus; EUS-HGS: Endoscopic ultrasound-guided hepaticogastrostomy.

Endoscopic retrograde biliary drainage

Endoscopic retrograde biliary drainage (ERBD) is commonly used when transpapillary access is feasible. It avoids an external catheter but carries risks of pancreatitis, bleeding, stent occlusion, cholangitis, and duodenobiliary reflux. Existing HCC-specific comparative data do not support a universal preference for a metal or plastic stent; expected survival, obstruction anatomy, anticipated reintervention, and local expertise should guide device selection.

Technical and clinical outcomes: In a multicenter retrospective study of 107 patients, Matsumi et al[16] reported technical success in 105 of 107 patients (98.1%) and clinical success in 85 of 105 technically successful procedures (81.0%). Endoscopic retrograde cholangiography-related complications occurred in 3 patients (2.8%), and Child-Pugh class C was associated with clinical failure.

Metal vs plastic stents: Chung et al[17] compared self-expandable metal stents with plastic stents in 96 patients. Successful drainage (69.4% vs 65.0%), adverse events (16.7% vs 21.7%), and median patency (60 days vs 68 days) did not differ significantly. The study therefore did not establish self-expandable metal stents superiority; the longer survival observed in the plastic-stent group was also susceptible to treatment-selection bias.

Predictors of successful drainage: Across retrospective ERBD cohorts, preserved hepatic reserve, lower baseline bilirubin, absence of ascites, intrahepatic bile duct dilation, normal or near-normal prothrombin time, and absence of portal vein thrombosis were associated with a greater probability of clinical response[18-20]. These predictors should support, not replace, individualized assessment.

Percutaneous transhepatic biliary drainage

Percutaneous transhepatic biliary drainage (PTBD) remains an essential option for complex hilar obstruction, failed or impossible endoscopic access, altered anatomy, or a need for selective lobar drainage[21,22]. It also provides a percutaneous route for catheter exchange or stent placement. However, HCC-specific evidence does not establish universally higher success than ERBD, and the risks of bleeding, bile leak, catheter dislodgement, infection, and patient burden should be weighed against anatomical and procedural advantages.

Efficacy: Lee et al[4] reported a > 50% bilirubin reduction within 4 weeks in 13 of 22 PTBD-treated patients (59.1%). In a later multicenter cohort of 138 patients, Wang et al[21] developed endpoint-specific prediction models incorporating variables such as the Model for End-Stage Liver Disease score, platelet count, portal vein thrombosis, international normalized ratio, cholinesterase, and prealbumin; the models were internally evaluated but require external validation.

Complications: In a 15-patient series of percutaneously placed metallic stents, technical success was 15 of 15 (100.0%), clinical success was 11 of 15 (73.3%), and major complications occurred in 2 of 19 sessions (10.5%)[23]. These small, selected series do not justify a single complication-rate estimate for all patients with HCC-related OJ.

Choosing the drainage approach

The choice among ERBD, PTBD, and emerging endoscopic ultrasound-guided drainage should be highly individualized. In one retrospective 60-patient comparison, successful drainage was reported in 22 of 29 ERBD procedures (75.9%) and 15 of 31 PTBD procedures (48.4%), although multivariable analysis was only marginally significant and anatomical selection was likely[24]. A separate 111-patient endoscopic cohort reported a favorable response in 46 patients (41.4%), of whom 40 received further HCC treatment[25]. Endoscopic ultrasound-guided hepaticogastrostomy achieved technical success in 13 of 14 procedures and clinical success in 10 of 11 evaluable procedures in a 10-patient Japanese series, but this approach remains limited to expert centers and small-sample evidence[26]. A dedicated summary of drainage outcomes is provided in Table 2.

LOCOREGIONAL THERAPY AFTER BILIARY DRAINAGE

Once cholangitis is controlled, drainage patency is confirmed, and hepatic reserve is reassessed, tumor-directed therapy may be considered without avoidable delay. The timing and dose should remain individualized because no prospective study has defined an optimal bilirubin trajectory or waiting period.

Transarterial chemoembolization

Transarterial chemoembolization (TACE) is among the most frequently reported locoregional approaches after drainage for HCC with OJ in the available literature.

Outcomes: Choi et al[7] studied 60 patients who underwent ERBD or PTBD; drainage was successful in 39, and 17 of these patients received subsequent TACE. Median survival was 410 days in the TACE group and 77 days among successfully drained patients managed conservatively. Suh et al[8] reported a 1-year overall survival of 32% among patients receiving HCC treatment and 0% among those receiving supportive care. These comparisons are strongly confounded. In a 2024 multicenter study of 64 treated patients with BDI and OJ, apparent overall and progression-free survival advantages associated with drainage were no longer significant after propensity score matching[27], directly illustrating the influence of selection. In a separate post-drainage B1-type BDI cohort, propensity-matched drug-eluting bead-TACE was associated with longer time to progression and a higher response rate than conventional TACE, but overall survival did not differ[28]. The TEMP score was developed in 267 post-drainage TACE recipients using a training and an internal validation set[29]; independent external validation is still needed. Collectively, these retrospective studies support clinical equipoise rather than a causal claim that TACE itself accounts for the observed survival differences.

Technical considerations: Superselective catheterization is generally favored to limit non-target embolization and ischemic injury, but this technical principle is derived from broader HCC and vascular-invasion experience rather than comparative trials in the OJ subgroup[30].

Complications: Biliary instrumentation can increase bacterial contamination and may increase post-TACE abscess risk in susceptible patients. An all-comers multicenter series reported 23 abscesses after 6984 TAE/TACE procedures (0.33% per procedure)[31], but it does not establish a specific rate for HCC with OJ. Antibiotic selection and other preventive measures should therefore be individualized according to prior sphincterotomy, stenting, biliary-enteric communication, local protocols, and patient risk rather than presented as a universally validated regimen.

Hepatic arterial infusion chemotherapy

The role of hepatic arterial infusion chemotherapy (HAIC) in patients with HCC and OJ after biliary drainage remains insufficiently characterized. Direct evidence is largely confined to case reports and small retrospective series, and no prospective study has specifically evaluated HAIC in this population.

Rationale: FOLFOX-based HAIC improved overall survival over TACE in a randomized trial of 315 patients with large unresectable HCC[32]. That trial did not provide direct evidence for patients with active OJ after biliary drainage, so its results cannot be assumed to apply unchanged to this subgroup.

Available evidence: Direct HAIC evidence remains limited. Zhang et al[33] reported a single patient with advanced HCC, portal vein tumor thrombus, and OJ in whom PTBD was not feasible; reduced-dose HAIC was followed by lenvatinib and camrelizumab. This case is hypothesis-generating and cannot establish efficacy, safety, or a bilirubin threshold. A separate 141-patient retrospective comparison concerned percutaneous transhepatic cholangial drainage followed by TACE vs apatinib, not HAIC, and is therefore discussed only as indirect evidence for post-drainage treatment selection[34].

Radiation therapy

Proton beam therapy: Iizumi et al[35] treated 15 patients with HCC and BDI using proton beam therapy; the 2-year local control and overall survival rates were 93.3% and 58.7%, respectively. Because the cohort was small and not restricted to drainage-responsive OJ, applicability to the target population remains uncertain. A larger phase II proton study included HCC and intrahepatic CCA but did not report an OJ-specific subgroup[36].

Stereotactic body radiation therapy: Evidence for stereotactic body radiation therapy in patients with BDTT and clinically significant OJ is too sparse to support a general recommendation. Its use should be restricted to individualized multidisciplinary assessment, with particular attention to central biliary toxicity.

SYSTEMIC THERAPY AFTER BILIRUBIN IMPROVEMENT

Systemic treatment after drainage is an extrapolation rather than an evidence-based standard for HCC-related OJ. Common clinical considerations include substantial bilirubin improvement, adequate hepatic reserve (usually Child-Pugh A and only exceptionally selected Child-Pugh B), controlled cholangitis, documented drainage patency, adequate hematologic and renal function, and management of high-risk varices or active bleeding. These are pragmatic safety considerations, not validated eligibility criteria for this subgroup. Immune-related hepatitis or cholangitis may also be difficult to distinguish from infectious cholangitis or recurrent obstruction.

Tyrosine kinase inhibitors

Sorafenib: Tanaka et al[37] compared 10 patients with BDI and 165 without BDI who received sorafenib. Median overall survival was 14.1 months and 14.8 months, respectively (P = 0.780), while 5 of 10 patients with BDI experienced biliary complications that were managed endoscopically. The very small exposed group precludes firm conclusions about efficacy.

Lenvatinib: No dedicated cohort has established lenvatinib efficacy in HCC with active OJ. Published evidence is limited to case reports, including a report of lenvatinib-associated duodenal ulceration at the ampulla causing secondary OJ[38].

Immune checkpoint inhibitor-based combinations

Landmark immune checkpoint inhibitor trials required preserved hepatic function and did not report outcomes for a defined HCC-OJ subgroup[39-42]. Patients with clinically significant hyperbilirubinemia or uncontrolled biliary infection would generally not have met trial eligibility. Recommendations for ICI-based therapy after drainage are therefore extrapolated from populations without active biliary obstruction.

Atezolizumab plus bevacizumab or durvalumab plus tremelimumab may be considered only after individualized safety assessment and adequate hepatic recovery, but direct OJ-specific evidence is absent. Sintilimab plus a bevacizumab biosimilar was evaluated in ORIENT-32, which required bilirubin within protocol limits and likewise did not establish efficacy in active OJ[43].

Practical concerns include recurrent stent-related cholangitis, differentiation of immune-mediated toxicity from obstruction or infection, and upper gastrointestinal bleeding risk with bevacizumab-containing therapy. A sustained bilirubin decline may inform reassessment, but no universal dose-adjustment algorithm has been prospectively validated.

Locoregional therapy combined with targeted agents and immunotherapy

TACE or HAIC combined with a tyrosine kinase inhibitor and an anti-programmed death receptor 1/programmed death ligand 1 antibody has shown activity in broader advanced-HCC cohorts[44,45]. These studies either excluded marked hepatic dysfunction or did not report an OJ subgroup; consequently, combination therapy should not be presented as established treatment for post-drainage OJ. The evidence-calibrated management pathway is summarized in Figure 2. The extension of these approaches to patients with OJ after biliary drainage is an area of active investigation, but prospective data are needed before definitive recommendations can be made.

Figure 2 Evidence-calibrated multidisciplinary framework for hepatocellular carcinoma with obstructive jaundice. Management begins by confirming a mechanical obstructive component and excluding jaundice caused solely by diffuse hepatic failure. Drainage modality is selected according to anatomy and expertise. Treatment after drainage depends on clinical response, hepatic reserve, tumor extent, and patient goals. Evidence labels are descriptive rather than formal guideline grades. HCC: Hepatocellular carcinoma; CT: Computed tomography; MRI: Magnetic resonance imaging; MRCP: Magnetic resonance cholangiopancreatography; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; PTBD: Percutaneous transhepatic biliary drainage; ERBD: Endoscopic retrograde biliary drainage; ERCP: Endoscopic retrograde cholangiopancreatography; EUS: Endoscopic ultrasound; ALBI: Albumin-bilirubin; ULN: Upper limit of normal; MDT: Multidisciplinary team; PVTT: Portal vein tumor thrombus; OJ: Obstructive jaundice; TACE: Transarterial chemoembolization; HAIC: Hepatic arterial infusion chemotherapy; RT: Radiation therapy.

SURGERY AND TRANSPLANTATION IN SELECTED PATIENTS

Hepatic resection with bile duct thrombectomy

Surgical resection is an option for resectable HCC with BDTT in patients with adequate future liver remnant and preserved hepatic function. OJ alone should not preclude surgical evaluation.

Outcomes: A Korea-Japan multicenter study included 257 surgically treated patients with macroscopic BDTT; 244 underwent curative surgery, operative mortality was 5.1%, and 5-year overall survival was 43.6%[46]. In a separate 138-patient multicenter cohort undergoing hepatectomy with preservation of the extrahepatic bile duct, median overall survival was 28.6 months and 5-year overall survival was 33.5%[47]. Both studies were retrospective and highly selected.

Surgical technique: In a 120-patient multicenter retrospective study, a thrombus-first operative sequence was associated with longer overall survival than a tumor-first sequence (42.7 months vs 23.6 months), but the nonrandomized design does not establish a causal advantage[48]. Indocyanine-green fluorescence navigation has been described for identifying the BDTT tip, but evidence is limited to case-report experience[49].

Liver transplantation

Liver transplantation for HCC with BDTT is not a standard indication and remains supported by very limited, center-specific retrospective evidence. Any consideration should occur only within an experienced transplant program after rigorous assessment of tumor biology, vascular invasion, extrahepatic disease, treatment response, and allocation policy.

Lee et al[50] reported a single-center series comprising 16 patients with BDTT, 45 with portal vein tumor thrombus, and 11 with both. In the BDTT group, 1-, 2-, and 3-year disease-free survival was 66.7%, 53.3%, and 46.7%, and overall survival was 81.3%, 62.5%, and 48.2%, respectively. Common bile duct involvement was absent, and outcomes did not differ statistically from the portal-vein-thrombus group. The small, retrospectively selected cohort cannot establish BDTT as a transplant indication or define generalizable selection criteria.

PROPOSED MULTIDISCIPLINARY TREATMENT ALGORITHM

Figure 2 presents a stepwise framework intended to support multidisciplinary discussion rather than function as a prescriptive guideline.

Step 1 - initial assessment: Contrast-enhanced computed tomography or magnetic resonance imaging with magnetic resonance cholangiopancreatography, serum bilirubin, liver function tests, alpha-fetoprotein, performance status, and tumor staging. ERBD may be considered for accessible distal or mid-duct obstruction, whereas PTBD may be favored for complex hilar disease, failed endoscopic retrograde cholangiopancreatography, or altered anatomy; endoscopic ultrasound-guided drainage is an expert-center option when standard routes are unsuitable. The response assessment should integrate symptoms, infection control, drainage patency, bilirubin trajectory, hepatic reserve, and performance status. Bilirubin < 2-3 mg/dL or < 2 × the upper limit of normal may be an ideal treatment-eligibility target, but a sustained decline with preserved hepatic reserve may support carefully dose-modified therapy in selected patients.

Step 2 - restaging and treatment assignment: Treatment categories and their evidence limitations are summarized in Table 3. When bilirubin fails to improve, clinicians should reassess catheter or stent position, undrained segments, infection, progressive tumor, and the contribution of irreversible hepatic failure. Drainage optimization, infection control, symptom palliation, best supportive care, and later reassessment are all explicit options.

Table 3 Potential treatment approaches after biliary drainage in hepatocellular carcinoma with obstructive jaundice.

Disease setting	Potential approach after successful drainage	Evidence basis and limitation
Resectable disease with adequate hepatic reserve	Hepatectomy with thrombectomy and selective bile duct resection when required for complete resection	Retrospective surgical cohorts; strong selection by anatomy, hepatic reserve, and tumor stage
Unresectable, intrahepatic-predominant disease	TACE in selected patients; HAIC or focal radiotherapy only after case-specific multidisciplinary review or in trials	TACE: Retrospective HCC-OJ cohorts; HAIC/radiotherapy: Small series, case reports, or extrapolation
Advanced disease with PVTT or extrahepatic spread	Systemic therapy only after adequate hepatic recovery and infection control; clinical trial preferred	No direct prospective OJ evidence; recommendations extrapolated from broader HCC trials
Transplant consideration	Exceptionally selected, center-specific assessment; not a standard indication	Small single-center retrospective series; no validated general selection criteria
Inadequate drainage response or progressive hepatic failure	Drainage optimization, infection control, symptom palliation, best supportive care, and reassessment	Clinical-practice framework; no comparative prospective evidence

TACE: Transarterial chemoembolization; HAIC: Hepatic arterial infusion chemotherapy; HCC: Hepatocellular carcinoma; OJ: Obstructive jaundice; PVTT: Portal vein tumor thrombus.

Step 3 - surveillance: Surveillance should be tailored to the treatment delivered and the patient’s clinical status, with monitoring for recurrent cholangitis, stent or catheter dysfunction, hepatic decompensation, and tumor progression. No HCC-OJ-specific evidence supports a single fixed laboratory or imaging interval.

PROGNOSTIC FACTORS AND EVIDENCE GAPS

Key prognostic factors

Across retrospective cohorts, study-defined drainage success, preserved liver function, lower bilirubin, absence of portal vein thrombosis, lower tumor burden, and eligibility for subsequent HCC treatment were associated with longer survival[5-8,16,18-20,25]. These variables are interdependent; the association between later treatment and survival should not be interpreted as proof of treatment causality.

Evidence gaps

Critical gaps include the absence of prospective trials dedicated to HCC-related OJ; heterogeneous definitions of drainage success; confounding by hepatic reserve and treatment selection; little direct evidence for HAIC, systemic therapy, stereotactic radiotherapy, or transplantation; no validated post-drainage bilirubin threshold; and sparse quality-of-life and patient-reported outcome data.

FUTURE DIRECTIONS

Prospective clinical trials

Prospective registries and pragmatic trials should use standardized definitions of mechanical obstruction, drainage success, cholangitis, time zero, hepatic reserve, treatment eligibility, and patient-reported outcomes. Designs should separate the effect of drainage response from the effect of subsequent tumor-directed treatment.

HAIC-based multimodal therapy

HAIC-based strategies warrant study only after prospective safety criteria are defined for patients with recent obstruction, biliary instrumentation, and impaired hepatic function. Existing broader-HCC efficacy data and isolated case reports do not justify routine use in HCC-OJ.

Molecular characterization

The molecular determinants of BDI remain poorly defined. Translational studies should distinguish conventional HCC with BDTT from combined hepatocellular-CCA and should avoid inferring a biliary genotype from morphology alone.

Advanced endoscopic techniques

Peroral cholangioscopy and endoscopic ultrasound-guided biliary drainage may improve diagnosis or provide alternative drainage in selected cases. The current HCC-specific evidence consists largely of case reports and a small endoscopic ultrasound-guided hepaticogastrostomy series[15,26]; comparative studies are needed before routine adoption.

CONCLUSION

HCC with imaging-confirmed mechanical OJ should not automatically be equated with irreversible hepatic failure. ERBD, PTBD, or selected expert-center alternatives may palliate cholestasis and permit clinical reassessment, but modality choice must be individualized. Study-defined drainage response and receipt of subsequent HCC treatment are associated with longer survival in retrospective cohorts, yet substantial selection bias limits causal interpretation.

TACE has the largest direct post-drainage evidence base, while HAIC, radiotherapy, systemic therapy, and transplantation remain supported mainly by small retrospective studies, case reports, or extrapolation. The proposed algorithm is therefore a hypothesis-generating multidisciplinary framework rather than an evidence-based guideline. Prospective studies with standardized response definitions and explicit bias control are required.