In the latest medical research, experts explore the potential and efficacy of immune checkpoint inhibitors in the treatment of advanced hepatocellular carcinoma prior to liver transplantation. Although liver transplantation is a curative approach, first-line systemic therapies, especially emerging immunotherapies, have demonstrated the potential to prolong survival. However, clinical data on the use of these therapies prior to transplantation are limited. By documenting three case studies in detail, the course of treatment with atezolizumab + bevacizumab or ipilimumab + nivolumab and its clinical outcomes before receiving liver transplantation was demonstrated. The results show that these treatments not only help to control the tumor burden, but also have no negative impact on organ function after transplantation, thus providing an important clinical basis for future treatment strategies. suggests that immune checkpoint inhibitors may serve as pre-transplant bridging therapies under appropriate clinical conditions.
For localized intrahepatic hepatocellular carcinoma, liver transplantation is the ultimate curative treatment. The Milan criteria are primarily used to evaluate transplant indications, and their prediction is that the risk of recurrence is low in patients with a single tumor less than 5 cm or up to three tumors less than 3 cm and no macrovascular invasion. Patients with hepatocellular carcinoma beyond the Milan criteria can be downstaged with locoregional and systemic treatments, while patients who meet the Milan criteria can receive the same treatment to control the disease and wait for organ transplantation.
Case 1
Basic Information:
A 68-year-old man was diagnosed with compensated cirrhosis due to new onset of jaundice and ascites.
Disease History and Diagnosis:
The patient was diagnosed with decompensated cirrhosis, presenting with new jaundice and ascites.
Magnetic resonance imaging revealed multiple lesions in the right lobe of the liver, up to 2.5 cm maximum, consistent with hepatocellular carcinoma.
The patient has a long history of alcohol use and has active hepatitis C virus infection at the time of diagnosis.
Treatment & Treatment:
The patient was successfully treated with sofosbuvir and vepatasvir for hepatitis C.
Over the next year, MRI showed that the lesion had grown in size and five new lesions had appeared.
His liver function deteriorated further, his ascites did not respond well to diuretic therapy, and he required biweekly ascites aspiration.
Given that the patient had an ECOG status of 0, an AFP of 3, and a Child-Pugh grade of B, the patient was started on systemic therapy with atezolizumab and bevacizumab.
Treatment Effect and Progress:
After 7 cycles of immunotherapy and the change of diuretics from amlodipine to spironolactone, the patient's liver function improved significantly and the ascites was controlled.
He did not experience any immune-related side effects while receiving immunotherapy.
Despite the increased total tumor burden on imaging, patients were considered suitable for locally controlled Y90 radiation therapy due to resolution of ascites.
Liver Transplant and Outcomes:
After the patient was injected with glass microspheres into the largest lesion in the liver, the tumor recurred within one year.
He then underwent a liver transplant.
After the transplant, the patient did not experience any postoperative complications, had good liver function since transplantation, and showed no signs of rejection or failure.
Case 2
Basic Information:
A 58-year-old man was treated for recurrent hepatocellular carcinoma due to hepatitis C.
Disease History and Diagnosis:
The patient initially underwent left lobe partial resection and antiviral therapy for hepatitis C infection and hepatocellular carcinoma.
Surveillance ultrasound six years later revealed hypoechoic lesions in the left lobe of the liver.
Magnetic resonance imaging confirmed hepatocellular carcinoma recurrence and found at least 9 lesions, the largest of which was 2.2 cm in diameter.
Treatment & Treatment:
Initial exposure to atezolizumab and bevacizumab was unable to continue due to program closure, and patients subsequently participated in a clinical trial of nivolumab and ipilimumab.
The patient had an ECOG status of 0, an AFP of 8, and a Child-Pugh grade of A.
The patient received four cycles of nivolumab and ipilimumab combination therapy, and then adjusted to single-agent nivolumab therapy due to adverse effects, and then underwent three more cycles.
Adverse effects and management:
While receiving immunotherapy, the patient develops hypothyroidism and central adrenal insufficiency, requiring daily administration of levothyroxine and hydrocortisone.
The condition remained stable throughout the treatment period, with no new lesions or enlargement of existing lesions.
Liver Transplant and Outcomes:
The patient received a last dose of nivolumab treatment two days prior to transplantation.
The transplant was done with the liver of a hepatitis C-positive donor, and the patient was also tested positive for hepatitis B core antibody at the time of transplantation.
After transplantation, the patient was treated for hepatitis B and C with excellent liver function and no acute liver failure, thrombosis, or rejection.
Case 3
Basic Information:
37 years old, male.
Disease History and Diagnosis:
Cirrhosis due to hepatitis B progresses to hepatocellular carcinoma.
The initial diagnosis was early-stage hepatocellular carcinoma, and the tumor was located in the second segment of the liver with a diameter of 1.4 cm.
The patient underwent open partial hepatectomy and gallbladder resection, and the tumor margin was found to be positive after surgery, and repair surgery was required.
Treatment & Treatment:
MRI and PET six months after surgery showed a new 3.75 cm mass in the fifth segment of the liver.
While waiting for a liver transplant, patients were started on immunotherapy with atezolizumab and bevacizumab through the Access to Charity Program.
He has an ECOG status of 0, an AFP of 2143 and a Child-Pugh grade of B.
Patients received a total of 6 courses of immunotherapy with no adverse events.
Treatment Effect and Progress:
Follow-up MRI showed tumor size shrunk from 3.5 cm × 3.2 cm × 3.3 cm to 1.9 cm × 2.2 cm × 1.9 cm.
The patient was further treated with directed stereoradiotherapy with a total dose of 50 Gy in 5 treatments.
Seven days after completing the last dose of immunotherapy, the patient underwent a liver transplant.
Liver Transplant and Outcomes:
Eighteen months after transplantation, the patient's liver function remained good without acute liver failure, thrombosis, or rejection.
summary
These three cases demonstrate a new immunotherapy regimen as a bridging therapy for liver transplantation. Cases 1 and 2 did not meet the Milan criteria prior to systemic therapy and were therefore not eligible for liver transplantation. Conversely, Case 3 met the Milan criteria for liver transplantation prior to treatment. Despite showing differences in the effect of tumor burden, all three cases demonstrated minimal complications and good transplant outcomes after transplantation, with no problems associated with wound healing identified. Despite the presence of autoimmune-mediated endocrine lesions requiring long-term management in case 2, immunotherapy was shown to be safe overall, suggesting that the use of immune checkpoint inhibitors prior to transplantation is feasible.
bibliography
Ohm H, Khwaja R, Karachiwala H. Immunotherapy before liver transplant in unresectable hepatocellular carcinoma: a case report. J Gastrointest Oncol. 2023; 14(6):2644-2649. doi:10.21037/jgo-23-634
Source: International Hepatobiliary Information