Occult Hepatocellular Carcinoma Associated With Transjugular Intrahepatic Portosystemic Shunts in Liver Transplant Recipients

Abstract

Transplant eligibility for hepatocellular carcinoma (HCC) is determined by the imaging identification of tumor burden within the Milan criteria. Transjugular intrahepatic portosystemic shunt(s) (TIPS) reduce portal hypertension but may impact HCC visualization. It was hypothesized that the presence of pretransplant TIPS would correlate with occult HCC and reduced survival. A single-center, retrospective, case control study was performed among liver transplant recipients with HCC (2000-2017). The primary endpoint was occult disease on explant pathology. Backward stepwise logistic regression was performed. The secondary endpoints disease-free survival (DFS) and overall survival (OS) were evaluated with Kaplan-Meier curves and Cox regression analysis. Of 640 patients, 40 had TIPS and more frequently exhibited occult disease (80.0% versus 43.1%; P < 0.001; odds ratio [OR], 4.16; P < 0.001). Portal vein thrombosis (PVT) similarly correlated with occult disease (OR, 1.97; P = 0.02). Explant tumor burden was equivalent between TIPS subgroups; accordingly, TIPS status was not independently associated with reduced DFS or OS. However, exceeding the Milan criteria was associated with reduced DFS (hazard ratio, 3.21; P = 0.001), and TIPS status in patients with a single suspected lesion (n = 316) independently correlated with explant tumor burdens beyond these criteria (OR, 13.47; P = 0.001). TIPS on pretransplant imaging are associated with occult HCC on explant pathology. Comparable occult disease findings in patients with PVT suggest that the mechanism may involve altered hepatic perfusion, obscuring imaging diagnosis. TIPS are not independently associated with reduced DFS or OS but are associated with exceeding the Milan criteria for patients with a single suspected lesion. The presence of TIPS may necessitate a higher index of suspicion for occult HCC.

No Foul Play for Transjugular Intrahepatic Portosystemic Shunts in Liver Transplantation for Hepatocellular Carcinoma

“…Previous studies have shown no difference in stage of HCC at initial diagnosis (4) or response to treatment (5) between patients with and without TIPS. Notably, while Krumeich et al (1) demonstrate more occult HCC at explant, and more understaging among those with a presumed single lesion before LT, no independent association between TIPS and recurrence-free or overall survival after LT was demonstrated. We have similarly investigated this at our own institution.…”

“…Transjugular intrahepatic portosystemic shunt (TIPS) can be placed to treat or prevent complications of portal hypertension in patients with cirrhosis, yet little is known about the effects of TIPS placement on diagnosis or liver transplantation (LT) outcomes in patients with hepatocellular carcinoma (HCC). We read with interest the recent retrospective analysis from Krumeich et al (1) suggesting that the presence of TIPS may alter radiographic HCC visualization, leading to understaging and underdiagnosis of HCC-or occult disease-prior to LT. Previous studies have suggested in vivo alteration of hepatic parenchymal blood flow, increased arterial perfusion, and decreased portal venous perfusion in patients with cirrhosis implanted with TIPS (2,3) as potential contributory mechanisms to Krumeich et al's recently published findings.…”

“…An important factor that could explain the lack of association is size of occult lesions. In the study by Krumeich and colleagues, (1) the total summed diameter of lesions on explant was 10 mm greater than that on pre-LT imaging, and additional small lesions are unlikely to result in adverse outcomes. In conclusion, the many benefits of minimizing portal hypertensive complications through TIPS likely outweigh any negative effects from underdiagnosis in patients with HCC.…”

TIPS in Patients With Hepatocellular Carcinoma: Is There an Indication?

“…6 To note, contrary to previous retrospective studies in which most of the included patients were Child-Pugh C within the TIPS cohort, which might explain the higher incidence of HCC observed, a recent series on 640 liver explants did not observe higher HCC occurrence, but more occult HCC, underlying the need to adapt imaging surveillance for HCC after TIPS placement. 7 Finally, even if we acknowledge the fact that specific data are lacking, we think that TIPS recommendations should also address patients with HCC, especially if of peripheral localization, in case of AVB or as a bridge to curative HCC treatments or downstaging.…”

Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management

“…[90] Further series showed a similar incidence of primary liver cancer in patients with and without TIPS. [91,92] Moreover, a recent series of 640 liver explants in patients transplanted for HCC did not outline higher HCC occurrence but more occult HCC in patients who underwent TIPS, [93] underlying the need to adapt imaging surveillance for HCC after TIPS placement. Interestingly, TIPS placement was also associated with an improvement in liver function in patients with ascites and allowed them to access locoregional treatment.…”