Hepatocellular carcinoma radiation segmentectomy treatment intensification prior to liver transplantation increases rates of complete pathologic necrosis: an explant analysis of 75 tumors.

PURPOSE: To verify the correlation between yttrium-90 glass microsphere radiation segmentectomy treatment intensification of hepatocellular carcinoma (HCC) and complete pathologic necrosis (CPN) at liver transplantation. METHODS: A retrospective, single center, analysis of patients with HCC who received radiation segmentectomy prior to liver transplantation from 2016 to 2021 was performed. The tumor treatment intensification cohort (n = 38) was prescribed radiation segmentectomy as per response recommendations identified in a previously published baseline cohort study (n = 37). Treatment intensification and baseline cohort treatment parameters were compared for rates of CPN. Both cohorts were then combined for an overall analysis of treatment parameter correlation with CPN. RESULTS: Sixty-three patients with a combined 75 tumors were analyzed. Specific activity, dose, and treatment activity were significantly higher in the treatment intensification cohort (all p < 0.01), while particles per cubic centimeter of treated liver were not. CPN was achieved in 76% (n = 29) of tumors in the treatment intensification cohort compared to 49% (n = 18) in the baseline cohort (p = 0.013). The combined cohort CPN rate was 63% (n = 47). ROC analysis showed that specific activity ≥ 327 Bq (AUC 0.75, p < 0.001), dose ≥ 446 Gy (AUC 0.69, p = 0.005), and treatment activity ≥ 2.55 Gbq (AUC 0.71, p = 0.002) were predictive of CPN. Multivariate logistic regression demonstrated that a specific activity ≥ 327 Bq was the sole independent predictor of CPN (p = 0.013). CONCLUSION: Radiation segmentectomy treatment intensification for patients with HCC prior to liver transplantation increases rates of CPN. While dose strongly correlated with pathologic response, specific activity was the most significant independent radiation segmentectomy treatment parameter associated with CPN.

Radiation Segmentectomy for the Treatment of Solitary Hepatocellular Carcinoma: Outcomes Compared with Those of Surgical Resection.

PURPOSE: To investigate the outcomes of radiation segmentectomy (RS) versus standard-of-care surgical resection (SR). MATERIALS AND METHODS: A multisite, retrospective analysis of treatment-naïve patients who underwent either RS or SR was performed. The inclusion criteria were solitary hepatocellular carcinoma ≤8 cm in size, Eastern Cooperative Oncology Cohort performance status of 0-1, and absence of macrovascular invasion or extrahepatic disease. Target tumor and overall progression, time to progression (TTP), and overall survival rates were assessed. Outcomes were censored for liver transplantation. RESULTS: A total of 123 patients were included (RS, 57; SR, 66). Tumor size, Child-Pugh class, albumin-bilirubin score, platelet count, and fibrosis stage were significantly different between cohorts (P ≤ .01). Major adverse events (AEs), defined as grade ≥3 per the Clavien-Dindo classification, occurred in 0 patients in the RS cohort vs 13 (20%) patients in the SR cohort (P < .001). Target tumor progression occurred in 3 (5%) patients who underwent RS and 5 (8%) patients who underwent SR. Overall progression occurred in 19 (33%) patients who underwent RS and 21 (32%) patients who underwent SR. The median overall TTP was 21.9 and 29.4 months after RS and SR, respectively (95% confidence interval [CI], 15.5-28.2 and 18.5-40.3, respectively; P = .03). Overall TTP subgroup analyses showed no difference between treatment cohorts with fibrosis stages 3-4 (P = .26) and a platelet count of <150 × 109/L (P = .29). The overall progression hazard ratio for RS versus SR was not significant per the multivariate Cox regression analysis (1.16; 95% CI, 0.51-2.63; P = .71). The median overall survival was not reached for either of the cohorts. Propensity scores were calculated but were too dissimilar for analysis. CONCLUSIONS: RS and SR were performed in different patient populations, which limits comparison. RS approached SR outcomes, with a lower incidence of major AEs, in patients who were not eligible for hepatectomy.

Focal Nodular Hyperplasia and Focal Nodular Hyperplasia-like Lesions.

Focal nodular hyperplasia (FNH) is a benign lesion occurring in a background of normal liver. FNH is seen most commonly in young women and can often be accurately diagnosed at imaging, including CT, MRI, or contrast-enhanced US. In the normal liver, FNH frequently must be differentiated from hepatocellular adenoma, which although benign, is managed differently because of the risks of hemorrhage and malignant transformation. When lesions that are histologically identical to FNH occur in a background of abnormal liver, they are termed FNH-like lesions. These lesions can be a source of diagnostic confusion and must be differentiated from malignancies. Radiologists' familiarity with the imaging appearance of FNH-like lesions and knowledge of the conditions that predispose a patient to their formation are critical to minimizing the risks of unnecessary intervention for these lesions, which are rarely symptomatic and carry no risk for malignant transformation. FNH is thought to form secondary to an underlying vascular disturbance, a theory supported by the predilection for formation of FNH-like lesions in patients with a variety of hepatic vascular abnormalities. These include abnormalities of hepatic outflow such as Budd-Chiari syndrome, abnormalities of hepatic inflow such as congenital absence of the portal vein, and hepatic microvascular disturbances, such as those that occur after exposure to certain chemotherapeutic agents. Familiarity with the imaging appearances of these varied conditions and knowledge of their association with formation of FNH-like lesions allow radiologists to identify with confidence these benign lesions that require no intervention. Online supplemental material is available for this article. ©RSNA, 2022.

Promoting Surgical Resection through Future Liver Remnant Hypertrophy.

An inadequate future liver remnant (FLR) can preclude curative-intent surgical resection for patients with primary or secondary hepatic malignancies. For patients with normal baseline liver function and without risk factors, an FLR of 20% is needed to maintain postsurgical hepatic function. However, the FLR requirement is higher for patients who are exposed to systemic chemotherapy (FLR, >30%) or have cirrhosis (FLR, >40%). Interventional radiologic and surgical methods to achieve FLR hypertrophy are evolving, including portal vein ligation, portal vein embolization, radiation lobectomy, hepatic venous deprivation, and associating liver partition and portal vein ligation for staged hepatectomy. Each technique offers particular advantages and disadvantages. Knowledge of these procedures can help clinicians to choose the suitable technique for each patient. The authors review the techniques used to develop FLR hypertrophy, focusing on technical considerations, outcomes, and the advantages and disadvantages of each approach. Online supplemental material is available for this article. ©RSNA, 2022.

Prospective evaluation of lymphatic embolization as part of the treatment in dogs with presumptive idiopathic chylothorax.

OBJECTIVE: To describe the embolization technique and short-term clinical outcome in dogs undergoing lymphatic embolization (LE) as part of treatment for presumptive idiopathic chylothorax (IC). Additionally, to document findings in computed tomography lymphangiography (CTLa) following embolization. STUDY DESIGN: Prospective case series. ANIMALS: Eight client-owned dogs. METHODS: Dogs underwent CTLa followed by thoracic duct ligation (TDL), pericardiectomy (PC) and LE. A mixture of 3:1 lipiodol: n-butyl cyanoacrylate embolic solution was injected through a catheterized mesenteric lymphatic vessel via limited abdominal approach using intraoperative fluoroscopy. CTLa was scheduled for 12 weeks postoperatively, and long-term follow-up was obtained via telephone contact. RESULTS: LE was technically successful in six of the eight dogs; and clinically successful in five of the six dogs. In the unsuccessful dog, a diagnosis of lymphangiosarcoma was determined, and the owners elected for euthanasia. Five dogs who underwent successful LE underwent CTLa at 12 weeks. Complete resolution of pleural effusion occurred in three dogs and scant pleural effusion in two dogs. A robust lymphatic embolus preventing antegrade continuation of radiocontrast was documented in all five dogs. Five of the six dogs that underwent LE, were alive and clinically normal at 358-960 days postoperatively. CONCLUSIONS: LE is a feasible part of treatment for dogs with IC. Additionally, a robust lymphatic embolus and lack of radiocontrast flow past the embolus was documented at 12 weeks following surgery. CLINICAL SIGNIFICANCE: LE has the potential to reduce surgical failure by reducing efferent lymphatic chyle flow, occluding missed lymphatic branches and preventing the development of collateral branches.

Natural History of Incidental Enhancing Nodules on Cone-Beam Computed Tomography during Transarterial Therapy of Hepatocellular Carcinoma.

PURPOSE: To evaluate the natural history of incidental enhancing nodules (IENs) on contrast-enhanced cone-beam computed tomography (CT) during transarterial treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: A single-center retrospective analysis of 100 patients with HCC who underwent contrast-enhanced cone-beam CT prior to transarterial treatment from August 2015 to June 2019 was performed. Inclusion criteria were patients with segmental distribution sublobar HCC, contrast-enhanced cone-beam CT of the target lesion and nontarget liver parenchyma, and follow-up cross-sectional imaging. Patients with IENs ≥3 mm that did not meet imaging criteria for HCC were analyzed. Exclusion criteria included biphenotypic tumors and IEN present inside the treated area of the liver. RESULTS: Fifty-six patients demonstrated 154 IENs on contrast-enhanced cone-beam CT, of which 13 IENs (8.5%) progressed to HCC. The mean primary tumor size was 29 mm (range: 10.2-189 mm). Ten patients had ≥4 IENs, and 46 patients had 1-3 IENs. The mean IEN size was 6.8 mm (range: 3.0-16.3 mm). The median follow-up interval after contrast-enhanced cone-beam CT was 282 days (interquartile range: 143-522). Increased alpha-fetoprotein before treatment (≥15.5 ng/mL, P = .035), having ≥4 IENs (P = .020), and hepatitis C virus (P = .015) were significantly correlated with IEN progression to HCC. No statistically significant differences were identified in baseline neutrophil-to-lymphocyte ratio, targeted HCC characteristics (size, macrovascular invasion, infiltrative pattern, enhancement pattern, and satellite lesions), and IEN size between those with IEN progression to HCC and those without. CONCLUSIONS: Most IENs of ≥3 mm on contrast-enhanced cone-beam CT in patients with segmental distribution sublobar HCC do not progress to HCC. Patients with segmental distribution sublobar HCC with ≥4 IENs, alpha-fetoprotein elevation (≥15.5 ng/mL), or hepatitis C virus have an increased risk of IEN progression to HCC.

Percutaneous direct pancreatic duct intervention in management of pancreatic fistulas: a primary treatment or temporizing therapy to prepare for elective surgery.

BACKGROUND: This study evaluates preliminary results of image-guided percutaneous direct pancreatic duct intervention in the management of pancreatic fistula after surgery or pancreatitis when initially ineligible for surgical or endoscopic therapy. METHODS: Between 2001 and 2018 the medical records of all patients that underwent percutaneous pancreatic duct intervention for radiographically confirmed pancreatic fistula initially ineligible for surgical or endoscopic repair were reviewed for demographics, clinical history, procedure details, adverse events, procedure related imaging and laboratory results, ability to directly catheterized the main pancreatic duct, and whether desired clinical objectives were met. RESULTS: In 10 of 11patients (6 male and 5 female with mean age 60.5, range 39-89) percutaneous pancreatic duct cannulation was possible. The 10 duct interventions included direct ductal suction drainage in 7, percutaneous duct closure in 3 and stent placement in 1. Pancreatic fistulas closed in 7 of 10, 2 were temporized until elective surgery, and 1 palliated until death from malignancy. The single patient with failed duct cannulation resolved the fistula with prolonged catheter drainage of the peri-pancreatic cavity. There were no major adverse events related to intervention. CONCLUSION: In patients with pancreatic fistulas initially ineligible for endoscopic therapy or elective surgery, direct percutaneous pancreatic duct interventions are possible, can achieve improvement without major morbidity or mortality, and can improve and maintain the medical condition of patients in preparation for definitive surgery.

Transarterial Yttrium-90 Radioembolization of Hepatocellular Carcinoma Perfused by the Cystic Artery: Multi-institutional Feasibility Study.

PURPOSE: To assess the safety and efficacy of transarterial yttrium-90 radioembolization via the cystic artery for patients with hepatocellular carcinoma (HCC) adjacent to the gallbladder with cystic artery supply. MATERIALS AND METHODS: This retrospective study included 17 patients treated at 4 institutions. Patients with HCC perfused by the cystic artery who received ablative-dose radioembolization were included. Median tumor size was 3.8 cm (range, 2.0-8.8 cm). Fourteen patients (82%) had Child-Pugh class A cirrhosis and 3 (18%) had class B cirrhosis. Adverse events, tumor response, and time to progression were analyzed. RESULTS: Median dose to the tissue perfused by the cystic artery was 340 Gy (range, 200-720 Gy). There were no occurrences of acute cholecystitis warranting invasive intervention. Four patients (24%) experienced transient right upper quadrant pain, with symptom resolution within 3 mo. Six patients (35%) exhibited gallbladder wall edema on follow-up imaging. Two (12%) and 0 grade 3/4 increases in alkaline phosphatase and bilirubin were observed, respectively. Follow-up imaging demonstrated complete response in 13 target tumors (76%) and partial response in 4 (24%). There were no cases of target tumor progression during a median follow-up of 9 mo (range, 3-72 mo). CONCLUSIONS: Direct infusion of 90Y microspheres via the cystic artery appears to have an acceptable safety profile, without resulting in acute cholecystitis warranting invasive intervention. In selected patients with HCC in whom other treatments may be contraindicated and the tumor is supplied via the cystic artery, treatment with selective ablative radioembolization can be considered.

Increasing Yttrium-90 Dose Conformality Using Proximal Radioembolization Enabled by Distal Angiosomal Truncation for the Treatment of Hepatic Malignancy.

PURPOSE: To evaluate safety and feasibility of improving radiation dose conformality via proximal radioembolization enabled by distal angiosomal truncation where selective administration was not practical. MATERIALS AND METHODS: Hepatic malignancies treated via angiosomal truncation between January 2017 and March 2019 were retrospectively evaluated. Thirty-three patients (8 women, 25 men; mean age, 62.2 y; range, 36-78 y) underwent 39 treatments. Of treatments, 74.3% (n = 29) were for hepatocellular carcinomas, 10.2% (n = 4) were for cholangiocarcinomas, and 15.4% (n = 6) were for metastatic tumors (1 colorectal adenocarcinoma, 1 pancreatic adenocarcinoma, 3 melanomas, and 1 endometroid carcinoma). Truncation was achieved using temporary embolic devices including a microvascular plug, detachable coil, gelatin slurry, and balloon microcatheter, after which proximal radioembolization was performed. Range of treatment activity was 0.47-5.75 GBq. Technetium-99m macroaggregated albumin and bremsstrahlung single photon emission computed tomography (CT)/CT threshold analysis was conducted to delineate and compare distribution of activity within the treatment angiosome before and after radioembolization. RESULTS: Dosimetric analysis of 14 patients demonstrated a significant reduction in nontarget liver radiation exposure at 5, 20, and 40% thresholds (P = .002, P = .001, and P = .008, respectively). There were no grade 3 or higher adverse events. There was no significant change in Albumin-Bilirubin grade and Eastern Cooperative Oncology Group Performance Status (P = .09 and P = .74) before and 3 months after the procedure. Truncated arteries were patent on subsequent angiography in 11 cases and on MR angiography or CT angiography in 38 of 39 cases. CONCLUSIONS: Proximal radioembolization enabled by distal angiosomal truncation is safe and decreases nontarget parenchymal radioembolization dose in cases not amenable to selective administration.

Laparoscopic access to the liver and application of laparoscopic microwave ablation in 2 dogs with liver neoplasia.

OBJECTIVE: To determine laparoscopic accessibility of liver lobes and access to the hilus and describe laparoscopic microwave ablation (LMWA) in 2 dogs with hepatic neoplasia. STUDY DESIGN: Experimental/descriptive case series. SAMPLE POPULATION: Six canine cadavers and 2 clinical dogs. METHODS: Cadavers in dorsal recumbency underwent laparoscopic assessment of the liver. A 17 gauge MWA probe was inserted to create an ablation zone at the most proximal aspect of the hilus. The distance from the center of each ablation zone to the most proximal aspect of the corresponding hilus was determined. Two dogs with hepatic neoplasia underwent LMWA. RESULTS: All lobes of the canine liver were accessible via laparoscopy. The median (interquartile range) distances from the ablation zones to the hilus for the caudate process, left lateral, left middle, quadrate, right lateral, and right middle lobes were 2.2 (1.2-2.6), 2.1 (1-4.4), 1.5 (1.4-3.7), 2, 1, 2.5 (1-4.1) cm, respectively. Histopathologic diagnoses treated by LMWA included metastatic hemangiosarcoma and primary hepatocellular carcinoma. Laparoscopic microwave ablation was technically feasible, and no complications from the procedure resulted. CONCLUSION: Laparoscopic access to the hilus of each liver lobe is possible via a ventrodorsal approach provided reverse Trendelenburg and lateral rotation is used, especially for the right lateral lobe. Laparoscopic microwave ablation is feasible in some dogs with hepatic neoplasia. The indications for and efficacy of LMWA for hepatic neoplasia in dogs requires additional investigation. CLINICAL SIGNIFICANCE: Laparoscopic access to all liver lobes and MWA of some neoplastic lesions is feasible in a canine pilot study.

Safety of Radioembolization in the Setting of Angiographically Apparent Arterioportal Shunting.

PURPOSE: To retrospectively analyze adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization in the setting of angiographically apparent arterioportal shunts (APSs). MATERIALS AND METHODS: Thirty-two patients with HCC underwent radioembolization with APSs from January 2011 to September 2016, totaling 34 administrations using resin (6) and glass (28) microspheres. APSs were graded angiographically as segmental (9), ipsilobar (15), contralobar (7), or main portal (2), according to portal perfusion. Tumors were categorized as solitary (9), multifocal (7), or infiltrative (16). Both unilobar (25) and bilobar (7) disease was treated. Child Pugh Score was A (22), B (10), or C (2), with a median Model for End-Stage Liver Disease (MELD)/Na-MELD of 8/8.5. Median procedure dose was 132.6 Gy. AEs were graded using Combined Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: CTCAE grade ≥3 AEs were observed in 22% of patients. Barcelona Clinic Liver Cancer (BCLC) C patients with nonsegmental shunts who received lobar administrations had a grade ≥3 AE rate of 38% compared with the remaining cohort, which was 12% (P = .076). No events were reported in patients with segmental shunts (P = .023). Imaging analysis revealed mRECIST complete response (17), partial response (13), stable disease (3), and progressive disease (1). Overall survival at 6 months and 12 months was 72% and 57%, respectively. CONCLUSIONS: Radioembolization in the setting of APS may have a higher AE profile than reported literature when BCLC-C patients with nonsegmental shunts receive lobar administrations. Segmental shunts are generally well tolerated.

Outcomes of cellophane banding or percutaneous transvenous coil embolization of canine intrahepatic portosystemic shunts.

OBJECTIVE: To compare clinical outcomes of dogs with congenital intrahepatic portosystemic shunts (CIHPSS) treated with cellophane banding (CB) or percutaneous transvenous coil embolization (PTCE). STUDY DESIGN: Dual-institutional retrospective study. ANIMALS: Fifty-eight dogs with CIHPSS (2001-2016). METHODS: Medical records of dogs undergoing CB or PTCE for CIHPSS were reviewed for signalment, body weight, hematologic values, shunt location, attenuation technique, procedure time, duration of hospitalization, complications, date of follow-up, and cause of death if applicable. RESULTS: Thirty-one dogs underwent CB, and 27 dogs underwent PTCE. No differences were detected between groups for gender, preoperative packed cell volume, albumin, cholesterol, or bile acids. Body weight was greater in dogs treated via PTCE. Shunts differed in location because dogs undergoing CB were diagnosed with more left divisional shunts compared with PTCE dogs. Procedural duration of CB and PTCE did not differ. Dogs treated with CB sustained more minor postoperative complications and were hospitalized longer than dogs treated with PTCE. The 1-year and 2-year survival rates were 89% for the CB group and 87% and 80% for the PTCE group, respectively. The proportion surviving at 5 years was 75% and 80% for CB dogs and PTCE dogs, respectively. CONCLUSION: CB and PTCE are associated with similar short-term and intermediate-term survival. PTCE is a minimally invasive alternative to CB via celiotomy. However, CB allows concurrent abdominal procedures requiring the same approach.

High-volume hydrodissection for abdominally based free flaps: Preliminary results.

INTRODUCTION: A novel method of high-volume hydrodissection that provides both subfascial and intramuscular perforator dissection of deep inferior epigastric perforators has been safely demonstrated in animals. This manuscript demonstrates our preliminary results when translating this technique to humans. METHODS: A retrospective review was performed of all free-flap breast reconstructions utilizing the high-volume hydrodissection technique performed by the senior author (DS) at the University of Florida Medical Center from January 2014 to June 2015. RESULTS: Twenty-one patients underwent 31 free-flap breast reconstructions during the study period utilizing the high-volume hydrodissection technique. No patients were lost to follow-up which averaged 8.2 months. Complications included 1 partial flap necrosis (<10%), 1 breast hematoma, 1 abdominal bulge, 2 flaps with minimal fat necrosis (<5%), and 1 abdominal wall cellulitis. CONCLUSION: High-volume hydrodissection is a safe technique to facilitate dissection of abdominally based free flaps for breast reconstruction. © 2015 Wiley Periodicals, Inc. Microsurgery 37:307-311, 2017.

Video-assisted microwave ablation for the treatment of a metastatic lung lesion in a dog with appendicular osteosarcoma and hypertrophic osteopathy.

OBJECTIVE: To describe video-assisted microwave ablation (VAMA) for the treatment of a metastatic lung lesion secondary to right forelimb osteosarcoma in a dog. STUDY DESIGN: Case report. ANIMALS: A 10-year-old female spayed mixed breed dog with a metastatic lung lesion secondary to appendicular osteosarcoma. METHODS: An osteosarcoma of the right distal scapula and proximal humerus that was suspected to be a radiation-induced osteosarcoma was treated with limb amputation and carboplatin chemotherapy. The patient developed pulmonary metastatic lesions and hypertrophic osteopathy (HO). VAMA of a metastatic lesion in the right caudal lung lobe was performed 227 days after amputation. The procedure was performed without complication. RESULTS: Follow-up information with the referring veterinarian 40 days after VAMA indicated that the patient was stable and that the clinical signs of HO had resolved. Thoracic radiographs taken by the referring veterinarian (RDVM) at monthly intervals showed that the previously treated metastatic lesion was stable. At 134 days from VAMA, the patient presented to the RDVM for lethargy and dyspnea and was transferred to an emergency clinic. The patient arrested and died 136 days from the VAMA procedure while hospitalized. A postmortem was not performed. CONCLUSION: VAMA for pulmonary metastatic lesions is technically feasible and allows for the treatment of symptoms associated with HO and minimally invasive management of pulmonary metastases in the case reported.

Transportal Radioembolization as Salvage Hepatocellular Carcinoma Therapy to Maintain Liver Transplant Candidacy.

A 53-year-old woman with chronic hepatitis B and multifocal hepatocellular carcinoma was unable to receive transarterial radioembolization and had disease progression despite multiple chemoembolizations and systemic chemotherapy. Transportal radioembolization (TPRE) to maintain transplant candidacy was performed. Two lesions (1.7 cm, 1.4 cm) were treated with a single session of TPRE. Imaging performed at 4 months after TPRE demonstrated complete response in one lesion and stable disease in the other. This case illustrates TPRE as a salvage therapy for hepatocellular carcinoma in select patients.

Radiation Segmentectomy for the Treatment of Hepatocellular Carcinoma: A Practical Review of Evidence.

Radiation segmentectomy is a versatile, safe, and effective ablative therapy for early-stage hepatocellular carcinoma. Advances in radiation segmentectomy patient selection, procedural technique, and dosimetry have positioned this modality as a curative-intent and guideline-supported treatment for patients with solitary HCC. This review describes key radiation segmentectomy concepts and summarizes the existing literary knowledgebase.

Abscopal downstaging of intermediate stage hepatocellular via combination cryoablation and immunotherapy with complete pathologic response.

The abscopal effect is a rare phenomenon characterized by disease regression in distant sites after tumoral locoregional therapy. Locoregional therapy, such as cryoablation, can induce an antitumor immunological response, potentially improving outcomes in cancer patients receiving immunotherapy. This report describes a patient with multifocal hepatocellular carcinoma who progressed through multiple locoregional therapies, was initially unresponsive to immunotherapy, and later achieved rapid and sustained disease regression with a combination cryoablation and immunotherapy. A 5-year sustained complete tumor response successfully bridged to liver transplantation.