An Analysis of Resection vs Transplantation for Early Hepatocellular Carcinoma: Defining the Optimal Therapy at a Single Institution

Background The reported survival after liver transplantation (OLT) for early hepatocellular carcinoma (HCC) is superior to the results of liver resection (LR), but few analyses have considered long waiting times and patient drop-offs due to tumor progression. Methods From 1995–2005, 347 patients with HCC were evaluated at our institution and underwent either LR (n = 174) or placed on the OLT waiting list (n = 173). Patients who only underwent ablation were not included. After eliminating patients with 1) incidental tumors after OLT, 2) tumors outside of Milan criteria, 3) preoperative vascular invasion prior to LR and 4) Child-Pugh Class C cirrhosis prior to OLT, 261 patients (LR = 121; OLT = 140) were included in this analysis. Results Median follow-up time was 35 months. Median waiting time for OLT was 7.7 months; during this time, 30 patients were taken off the waiting list. Overall survival (OS) from time of listing or LR was not different between the two groups; 1, 3, and 5 year OS after LR was 89%, 75%, and 56% compared with 90%, 70%, and 64% for OLT (P = .84). Only patients who waited <4 months for OLT (n = 67) had better survival than those who underwent LR (P = .05). Patients who waited longer that four months for OLT had a 2.5× higher risk of death in a Cox multivariate model [odds ratio (OR) 2.5; 95% confidence interval (CI): 1.3–5; P = .007]. Conclusion Unless waiting time is short (<4 months), the survival of patients with early HCC is similar between LR and LT. Presented at the 2006 Seventh International Hepato-Pancreato-Biliary Association, Edinburgh, Scotland, September 3–7, 2006.     

Management of Hepatocellular Carcinoma Recurrence After Liver Transplantation

Management of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT) is not well established. We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients. The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria, had an average follow-up of 60 months.

Results

The median time to recurrence was 23.4 months. Surgical resection of the recurrence was possible in 11 patients, but an R-0 resection was obtained in 8 patients. Four of these 8 patients developed another recurrence, with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence. The other 4 patients without recurrences, include 3 who are alive at 19, 31, and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence. The 3 patients with palliative resections developed recurrences. Twelve patients were rejected for surgery: 8 were treated symptomatically, 2 with systemic chemotherapy, and 2 with everolimus and sorafenib. This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months. Of 15 patients who died, 13 succumbed to HCC recurrence. The average survival from transplantation was 61.7 ± 37.5 and 48 ± 34.3 months for patients without and with recurrence, respectively (P < .001). The survival from the recurrence was significantly higher among patients with R-0 surgery: 32.3 ± 21.5 versus 11.9 ± 6.9 months (P = .006).

Conclusions

HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival. Few cases are amenable to R-0 resection, but when possible it was associated with a significantly increased survival, although with an high incidence of a new recurrence. There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression, which warrants randomized studies.     

Role of Transarterial Chemoembolization Before Liver Resection for Hepatocarcinoma

The aim of this study was to clarify whether chemoembolization (TACE) before liver resection (LR) can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve disease-free and overall survival. Eighty-nine patients with tumor-stage (TNM) I-II HCC were evaluated for LR. Patients were prospectively allocated to LR alone or TACE plus LR based on their place of residence. Twenty nonlocal patients (24%) were selected for LR, while 69 (77.5%) local patients were selected for TACE plus LR. Following TACE, the tumor stage could be confirmed in only 20 patients (29%) who then underwent LR. Operative mortality was 0%, but in the TACE-LR group, 3 patients died of liver failure between 2 and 5 months after surgery. Early recurrence (<24 months) was 59% for LR versus 20% for TACE plus LR (P < .05). Late recurrence was 18% for LR versus 10% for TACE plus LR (P = not significant [NS]). The overall recurrence rate was 76% for LR versus 30% for TACE plus LR (P < .02). Death due to HCC recurrence was 70% for LR versus 15% for TACE plus LR (P < .05). The overall 1- and 5-year survival rates did not differ significantly (71% to 38% for LR v 85% to 43% for TACE + LR; P = NS), whereas the difference in 1- and 5-year disease-free survival was highly significant (64% to 21% for LR v 82% to 57% for TACE + LR; P < .02). TACE was able to improve the HCC staging process and significantly reduce the incidence of early and overall HCC recurrence and related death after LR; it improved the disease-free interval, but not the overall survival, due to an increase in liver failure in the first 5 months. (Liver Transpl 2000;6:619-626.)     

Liver Resection in Transplanted Patients: A Single-Center Western Experience

Background

Liver resection (LR) in liver transplant (OLT) recipients, an extremely rare situation, who performed on 8 recipients.

Methods

This retrospective analysis of prospectively collected data concerned 8 (0.66%) 1198 LR cases among OLT performed from 1997 to 2011. We analyzed demographic data, surgical indications, and postoperative courses.

Results

The indications were resectable recurrent hepatocellular carcinomas (HCC, n = 3), persistent fistula from a posterior sectorial duct (n = 1), recurrent cholangitis due to anastomotic stricture on the posterior sectorial duct (n = l), hydatid cyst (n = l), left arterial hepatic thrombosis with secondary ischemic cholangitis (n = 1), and a large symptomatic biliary cyst (n = 1). The mean interval time to liver resection was 23.7 months (range, 5–47). LR included right hepatectomy (n = 1), right posterior hepatectomy (n = 1), left lobectomy (n = 4), pericystectomy (n = 1), or biliary fenestration (n = 1). Which there was no postoperative mortality, the global morbidity rate was 62% (5/8). The mean follow-up after LR was 92 months (range, 11–156). No patients required retransplantation. None of the 3 patients who underwent LR for HCC showed a recurrence.

Conclusions

LR in OLT recipients is safe, but associated with a high morbidity rate. This procedure can avoid retransplantation in highly selected patients, presenting a possible option particularly for transplanted patients with a resectable, recurrent HCC.     

Predictive Factors of Recurrence of Hepatocellular Carcinoma After Liver Transplantation: A Multivariate Analysis

We analyzed predictive risk factors for recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). We retrospectively analyzed the clinical data from 109 consecutive HCC patients who underwent OLT at our center from 1988 to 2007. We excluded all patients who died due to factors other than tumor recurrence within the first year (n = 24). The remaining 85 patients were enrolled in either a recurrence group (A; n = 19) or a nonrecurrence group (B; n = 66). Upon univariate analysis, the 2 groups were significantly different for 11 parameters. Group A included more females (P = .05), noncirrhotic liver recipients (P = .003), “up-to 7 status” patients (HCC with 7 as the sum of the size of the largest tumor [cm] and the number of tumors, P < .0001), patients exceeding Milan criteria (MC; P < .0001) or University of California San Francisco (UCSF) criteria (P < .0001), and OLT performed before 1999 (P = .003). Group A also showed a higher number of lesions (P = .035), a greater sum of diameters of the lesions (P < .0001), a major number of macrovascular (P < .0001) and microvascular invasions (P < .0001), and an increased number of G3-G4 grading (P = .006). Only microvascular invasion (P = .007) and exceeding UCSF criteria (P = .003) were independent risk factors for recurrence upon multivariate analysis. Patients with both these parameters are not candidates for OLT. Microvascular invasion is a good predictive parameter, but is impossible to detect preoperatively. New pre-OLT predictive risk factors are needed to achieve optimal results.     

Sequential versus contemporaneous portal and arterial reperfusion during liver transplantation

Although sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (OLT), contemporaneous portal and hepatic artery revascularization (CPAr) has been used to reduce arterial ischemia to the bile ducts. The aim of this study was to prospectively compare SPAr (group 1; n = 19) versus CPAr (group 2; n = 21) among 40 consecutive OLT from heart-beating donors. There were no differences in the demographics characteristics, Model for End-stage Liver Disease scores, indication for OLT and donor parameters between the groups. OLT was performed using the piggyback technique. The biliary anastomosis was performed in all cases by a duct-to-duct technique with a T-tube in 32% versus 29% of cases without a T tube (P = .83). In the CPAr group, the liver was reperfused simultaneously via the portal vein and hepatic artery. CPAr showed a longer warm ischemia (66 ± 8 vs 37 ± 7 minutes; P < .001), while SPAr had a longer arterial ischemia 103 ± 42 vs 66 ± 8 minutes (P = .0004). Recovery of graft function was similar. There was no primary nonfunction and delayed graft function occurred among 10% versus 9%. Liver function tests were similar between the two groups up to 90 days case of follow-up- One-year graft and patient survivals were, respectively, 89% and 95% versus 94% and 100% (P = .29). At a median follow-up of 13 ± 6 versus 14 ± 7 months, biliary complications included anastomotic stenoses in 15% versus 19% (P = .78) and intrahepatic non-anastomotic biliary strictures in 26% versus none (P = .01) for SPAr and CPAr, respectively. CPAr was safe and feasible, reducing the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts.     

Microwave thermal ablation for hepatocarcinoma: six liver transplantation cases

Surgical resection for malignant hepatic tumors, especially hepatocarcinoma (HCC), has been demonstrated to increase overall survival; however, the majority of patients are not suitable for resection. Radiofrequency ablation (RFA) is the most widely used modality for radical treatment of small HCC (<3 cm). It improves 5-year survival compared with standard chemotherapy and chemical ablation, allowing down-staging of unresectable hepatic masses. Microwave ablation (MWA) has been extensively applied in Asia and was recently introduced in the United States of America and Europe with excellent results, especially with regard to large unresectable HCC. Our single-center experience between May 2009 and October 2010 included application of MWA to 154 patients of median age ± standard deviation of 63.5 ± 8.5 years, 6 males, and 1 female, of mean Model for End-Stage Liver Disease (MELD) score (10.1 ± 3.8). The HCC included, hepatitis C virus (HCV)-related (n = 70; 45.5%); alcool (ETOH)-related (n = 42; 27%), hepatitis B virus (HBV)-related (n = 16; 10.5%); and cryptogenic cases (n = 26; 17%). The cases were performed for radical treatment down-staging for multifocal pathology or bridging liver transplantation to orthotopic (OLT) in selected patients with single nodules. A computed tomography (CT) scan was performed at 1 month after the surgical procedure to evalue responses to treatment. Among 6 selected patients who underwent OLT; 5 (83.3%) showed disease-free survival at one-year follow-up. The radical treatment achieved no intraoperative evidence of tumor spread or of pathological signs of active HCC among the explanted liver specimens. In conclusion, a MWA seemed to be a safe novel approach to treat HCC and could serve as a “bridge” to OLT and down-staging for patients with HCC.     

Liver Transplantation for Hepatocellular Carcinoma Within Milan Criteria in Patients With Model For End-Stage Liver Disease Score Below 15: The Impact of the Etiology of Cirrhosis on Long-Term Survival

Background

Liver transplantation (OLT) is the gold standard therapy for patients with cirrhosis complicated by hepatocellular carcinoma (HCC) within Milan Criteria (MC). We evaluated the impact of the etiology of the underlying liver disease on long-term outcomes of patients undergoing OLT for HCC within MC having a Model for End-stage Liver Disease (MELD) score < 15.

Methods

From November 2002 to December 2009, we performed 203 primary OLTs from brain-dead donors in recipients with HCC and cirrhosis with biochemical MELD scores below 15. We excluded 31 patients outside MC on the explant pathology of the native liver. The remaining 172 were divided into 3 groups according to the etiology of the underlying cirrhosis: hepatitis C virus-positive (HCV+; n = 78; 45%), hepatitis B virus-positive (HBV+; n = 65; 38%) and other indications (n = 29; 17%). The groups were compared for donor and recipient features, donor-recipient match, and transplant variables. The study endpoint was long-term patient survival.

Results

The groups were similar, except for a greater prevalence of hepatitis B core antibody-positive grafts in the HBV+ group and less frequent HCC bridging procedures in the other indications group. After a median follow-up of 72 months, HCC recurrence was observed in 8 (4.7%) patients (6 HCV+, 2 other indications), 5 of whom died. Overall 5-year patient survival of 82%, revealed significant differences among groups: 98.3% in HBV+, 67.1% in HCV+, and 85.8% in other indications (HBV+ vs other indications: P = .01; HBV+ vs HCV+: P = .0001; HCV+ vs other indications: P = NS). In the HCV+ group, recurrent HCV hepatitis was the most frequent cause of death. Upon multivariate analysis, HBV positivity in the recipient was an independent predictor of better patient survival (hazard ratio = 0.10, 95% confidence interval 0.02–0.64, P = .013).

Conclusions

Etiology of the underlying cirrhosis significantly influenced the long-term survival after OLT of patients with HCC within MC and MELD < 15. It should be taken into account in estimation of survival benefit.     

Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database

Background

Orthotopic liver transplantation (OLT) is the only treatment option for unresectable hepatoblastoma (HB) and hepatocellular carcinoma (HCC) in children. Aggregated outcomes of OLT for these hepatic malignancies have not been evaluated in the United Network for Organ Sharing national database.

Purpose

The purpose of this study was to evaluate graft and patient survival in pediatric OLT recipients with HB and HCC.

Methods

Data from the United Network for Organ Sharing Standard Transplant and Research Files were analyzed and included pediatric (<18 years) OLT recipients with HB or HCC from 1987 to 2004. The effects of diagnosis on pretransplant variables were evaluated using analysis of variance methods or χ² tests, as appropriate. Actuarial survival and effect of diagnosis on survival were determined using Kaplan-Meier methods and log-rank tests.

Results

Since 1987, 152 OLTs have been performed in 135 pediatric patients for HB and 43 OLTs in 41 pediatric patients for HCC. Respective 1-, 5-, and 10-year patient survival after OLT was 79%, 69%, and 66% for HB and 86%, 63%, and 58% for HCC (P = .73). The primary cause of death for both groups was metastatic or recurrent disease, accounting for 54% of deaths in the HB group and 86% in the HCC group (P = .338). Patients with hepatoblastoma were younger (mean age, 2.9 ± 2.5 vs 10.4 ± 4.8 years for the HCC group; P < .001) and more likely to receive a living donor organ (16% vs 4%, P = .03). A greater proportion of the patients with HB had previous abdominal surgery than patients with HCC (63% HB vs 37% HCC, P = .04). Pretransplant medical condition and transplant era were associated with graft and patient survival on univariate and multivariate analysis (all P < .05).

Conclusions

Orthotopic liver transplantation remains a viable option for pediatric patients with unresectable primary hepatic malignancies and results in good long-term survival. Pretransplant medical condition is an important predictor of outcome. Thus, in conjunction with better chemotherapy regimens, earlier evaluation for OLT in patients with unresectable HB and HCC may result in yet further improved long-term survival.     

Incisional Hernia Repair After Liver Transplantation: Role of the Mesh

Background

Patients undergoing orthotopic liver transplantation (OLT) show a high risk of developing an incisional hernia. The aim of this retrospective study was to establish the incidence and the factors influencing the outcomes of this complication.

Methods

We reviewed 450 consecutive OLT performed in 422 adult recipient between January 2000 and December 2005. Herniae were analysed with aspect to localization, classification, repair technique, and recurrence. All treated herniae were followed for a median of 50.5 months.

Results

Incisional herniae occurred in 36 patients (8.5%, Group 1). Their mean age OLT was 51.4 years with 94.4% male subjects. No significant difference was observed between affects and unaffected individuals for age, OLT indication, Child-Pugh score, albumin, comorbidities, operative time, transfusions, immunosuppressant regimen, and graft rejection episodes as well as for the incisional approach and hospital stay. Gender, body mass index (BMI), preoperative ascites, and pulmonary complications after OLT were significantly different (P < .01). Herniae were small (<5 cm; n = 12), medium (5-10 cm; n = 28), or large (> 10 cm; n = 2). Herniorrhaphy techniques included primary suture repair in 5 (13.9%) and mesh repair in 31 (86.1%) cases. In 3 patients with a primary repair and 1 patient with a mesh repair there were recurrences.

Conclusions

Preoperative ascites, gender, BMI, and pulmonary complications after OLT seemed to have significant influences on the formation of incisional herniae. Polypropylene mesh may be a first choice for the surgical treatment of there transplant recipients.     

Laparoscopic Approach for Down-Staging in Hepatocellular Carcinoma Patients Who Are Candidates for Liver Transplantation

Introduction

The aim of this study was to assess the impact of laparoscopic thermoablation (LTA) and laparoscopic resection (LR) as neoadjuvant therapy before orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC).

Methods

From June 2005 to November 2010, 50 consecutive patients affected by HCC with liver cirrhosis were treated with LTA under ultrasound guidance or LR. Of them, 10 patients (mean age, 58.3 ± 5.59 years; male:female, 8:2) underwent OLT. They were mostly Child-Pugh class A (80%).

Results

A LTA of 12 nodules was achieved in 7 patients and an LR of 3 HCC nodules in the other 3 subjects. The mean length of surgery was 163 minutes (range; 60–370). The mean hospital stay was 6.1 days. Transient mild postoperative liver failure was reported in 1 case. Complete tumor necrosis was observed in 10 thermoablated nodules (83.3%) via spiral computerized tomographic scan at 1 month after treatment; the resected patients showed absence of recurrence. All patients underwent OLT after a mean interval of 7 months. The histology of the native liver showed complete necrosis in 9/12 thermoablated nodules (75%); a recurrence at surgical site occurred in 1 patient in the resection group.

Conclusions

Laparoscopic ultrasound can be used in potential OLTs candidates to accurately stage HCC in advanced cirrhosis with minimal morbidity. LTA and LR proved to be safe and effective techniques for HCC patients, representing a valid “bridge” to OLT.     

Surgical Treatment of Hepatocellular Carcinoma beyond Milan Criteria. Results of Liver Resection, Salvage Transplantation, and Primary Liver Transplantation

Background There is no clear consensus regarding the best treatment strategy for patients with advanced hepatocellular carcinoma (HCC). Methods Patients with cirrhosis and HCC beyond Milan who had undergone liver resection (LR) or primary orthotopic liver transplantation (OLT) between November 1995 and December 2005 were included in this study. Pathological tumor staging was based on the American Liver Tumor Study Group modified Tumor-Node-Metastasis classification. Results A total of 23 HCC patients were primarily treated by means of LR, 5 of whom eventually underwent salvage OLT. An additional 32 patients underwent primary OLT. The overall actuarial survival rates at 3 and 5 years were 35% after LR, and 69% and 60%, respectively, after primary OLT. Recurrence-free survival at 5 years was significantly higher after OLT (65%) than after LR (26%). Of the patients who underwent LR, 11 (48%) experienced HCC recurrence only in the liver; 6 of these 11 presented with advanced HCC recurrence, poor medical status, or short disease-free intervals and were not considered for transplantation. Salvage OLT was performed in 5 patients with early stage recurrence (45% of patients with hepatic recurrence after LR and 22% of all patients who underwent LR). At a median of 18 months after salvage OLT, all 5 patients are alive, 4 are free of disease, and 1 developed HCC recurrence 16 months after salvage OLT. Conclusion For patients with HCC beyond Milan criteria, multimodality treatment—including LR, salvage OLT, and primary OLT—results in long-term survival in half of the patients. When indicated, LR can optimize the use of scarce donor organs by leaving OLT as a reserve option for early stage HCC recurrence.     

Sirolimus-Based Immunosuppression Therapy in Liver Transplantation for Patients With Hepatocellular Carcinoma Exceeding the Milan Criteria

Aim

Sirolimus (SRL) acts as a primary immunosuppressant or antitumor agent. The aim of the present study was to evaluate the influence of SRL on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) exceeding the Milan criteria.

Materials and Methods

We retrospectively examined 73 consecutive patients who underwent OLT for HCC exceeding the Milan criteria from March 2004 through December 2005. Among them, 27 patients were treated with SRL-based immunosuppressive protocols after OLT, and 46 patients by an FK506-based protocol. Statistical analysis was based on the intent-to-treat method.

Results

The 2 groups were comparable in all clinicopathologic parameters. The mean overall survival was 594 ± 35 days in the SRL group and 480 ± 42 days in the FK506 group (P = .011); the mean disease-free survival period was 519 ± 43 days in the SRL group and 477 ± 48 days in the FK506 group (P = .234). Multivariate analysis revealed Child's status (P = .004) and immunosuppressive protocol (P = .015) were the significant factors affecting overall survival. Only microvascular invasion (P = .004) was significantly associated with disease-free survival. Among 24 surviving patient in the SRL group, 2 patients had SRL discontinued for toxicity; 10 had SRL monotherapy immunosuppression.

Conclusion

The SRL-based immunosuppressive protocol improved the overall survival of patients after OLT for HCC exceeding the Milan criteria, probably by postponing recurrence and with better tolerability.     

Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma

BackgroundScarce data are available comparing outcomes of hepatic resection vs orthotopic liver transplantation (OLT) for localized hepatocellular carcinoma (HCC) patients both meeting and exceeding the Milan criteria. This study compared the clinical and oncological outcomes of patients undergoing hepatic resection vs transplantation localized HCC.MethodBetween January 2005 and February 2017, clinical and oncological outcomes of patients who underwent liver resection (n = 38) vs OLT (n = 28) for localized HCC were compared using a prospectively maintained database.ResultsA total of 66 patients (with a median age of 62) who met the study criteria were analyzed. Comparable postoperative complications (13.2% vs 28.6%, P = .45) and perioperative mortality rates (7.9% vs 10.7%, P = .2) were noted for the resection vs OLT groups. While Child-Pugh Class A patients were more prevalent in the resection group (78.9% vs 7.1%, P = .0001), the rate of patients who met the Milan criteria was higher in the OLT group (89.3% vs 34.25, P = .0001). Recurrence rates were 36.8% in the resection group and 3.6% in the OLT group at the end of the median follow-up period (32 vs 39 months, respectively). The HCC-related mortality rate was significantly higher in the resection group (39.5% vs 10.7%, P = .034).However, a subgroup analysis of patients who met the Milan criteria revealed similar rates of recurrence and HCC-related mortality (15.4% vs 8%, P = .63). Based on logistic regression analysis, number of tumors (P = .034, odds ratio: 2.1) and “resection”-type surgery (P = .008, odds ratio: 20.2) were independently associated with recurrence.ConclusionCompared to liver transplantation, hepatic resection for localized hepatocellular carcinoma is associated with a higher rate of recurrence and disease-related mortality.     

Hepatopulmonary Syndrome: Morbidity and Survival After Liver Transplantation

Hepatopulmonary Syndrome (HPS) is a triad of liver disease, intrapulmonary vascular dilatation (IPVD), and arterial deoxygenation. Orthotopic liver transplantation (OLT) constitutes the only effective treatment; however, adverse outcomes have been reported. The aim of this study was to evaluate the early morbidity and short- and long-term survival after OLT for patients with and without HPS. We studied 59 transplant recipients divided into 2 groups: with HPS (HPS group n = 25) and without HPS (control group, n = 34) before the OLT. IPVD was diagnosed using transthoracic contrast-enhanced echocardiography. Arterial deoxygenation was defined as PA-a,O₂ ≥ 15 mm Hg. The HPS and control groups were homogeneous regarding age (P = .36; 43.8 ± 12.2 vs 46.9 ± 13.5), gender (P = .47), male/female ratio (68%:32% and 78%:22%, respectively), and severity of liver disease. The PaO₂ was significantly lower (74.9 ± 12.1 vs 93 ± 6.4 mm Hg; P < .001) and the PA-a,O₂ was significantly higher in the HPS group (30.3 ± 10.6 vs 11.0 ± 7.0; P < .001). The percentage of severe (n = 3) and very severe (n = 1) hypoxemia was 16%. There were no significant differences between HPS and control groups regarding short- (68% vs 77%; P = .27) and long-term survival (60% vs 64%; P = .67) as well as among patients with mild, moderate, severe, or very severe HPS and the control group (P = .53). Also, intensive care unit (ICU) stay (7.0 vs 5.5; P = .41), duration of mechanical ventilation (38.0 vs 27.5; P = .43), reintubation rate (32.0% vs 23.5%; P = .45), and early postoperative complications (P = .72) were not different. In conclusion, there were no significant differences regarding the outcomes of OLT for patients with versus without HPS related to early morbidity or short- and long-term survival.     

Mycophenolate Mofetil Monotherapy in Patients Who Underwent Liver Transplantation for Hepatitis C Cirrhosis

Introduction

Mycophenolate mofetil (MMF) monotherapy has recently been proposed for liver transplant recipients with adverse events (nephrotoxicity, hypertension) related to calcineurin inhibitors. We analyzed the influence of MMF on the clinical course of recurrent hepatitis C.

Methods

Among 1038 patients who underwent liver transplantation (OLT) from April 1986 to October 2006, we analyzed 48 adult recipients (4.6%) whose diagnosis was hepatitis C virus (HCV) cirrhosis and who were converted from calcineurin inhibitors to MMF monotherapy.

Results

The 36 men and 12 women, had a mean age at OLT of 52.9 ± 7.2 years; the time elapsed from OLT to the onset of MMF monotherapy was 72.5 ± 47.6 months (range = 11-210). The mean follow-up after monotherapy was 19 ± 16.1 months (range = 2-67). Indications for conversion were: chronic renal dysfunction with HCV in 45 patients; HCV recurrence in two; and hypertension plus HCV recurrence in one subject. When the indication was renal dysfunction (excluding three patients who underwent hemodialysis), the mean creatinine values decreased significantly from baseline to 6 months of monotherapy from 1.63 ± 0.61 mg/dL to 1.51 ± 0.78 mg/dL (P < .03). The creatinine clearance only improved significantly from the baseline value of 56.6 ± 16.8 mL/min to the value at 3 months of monotherapy—63.6 ± 18.4 mL/min (P < .001). At the last outpatient visit, creatinine and creatinine clearances had not changed significantly. The mean diastolic blood pressure did improve significantly at the end of the study. The mean glucose levels decreased but not significantly at the last outpatient visit. Liver function tests did not change significantly after conversion to MMF monotherapy. The acute rejection rate was 8.3%, and adverse events related to MMF monotherapy were present in 9 patients (18.7%).

Conclusions

Conversion from calcineurin inhibitors to MMF monotherapy in patients who underwent OLT for HCV transiently improved renal function and hypertension. The acute rejection rate was low, and adverse events were usually well tolerated.     

Hepatocellular Carcinoma in Unrelated Viral Cirrhosis: Long-Term Results After Liver Transplantation

Introduction

Chronic viral hepatitis is considered to be the most significant risk factor for development of hepatocellular carcinoma (HCC). Nevertheless, about 5%-15% of HCC occur in noncirrhotic or virus-unrelated cirrhotic patients. The natural history of HCC in terms of incidence, clinical features, and tumor progression differs according to the underlying cancerogenic factors and differences in hepatocarcinogenetic pathways. Little is know about the relationship between HCC outcomes after liver transplantation (OLT) and the primary liver disease. We retrospectively analyzed the outcomes of patients transplanted due to HCC in settings of either virus—related or virus-unrelated cirrhosis.

Patients and Methods

From January 2000 to December 2007, 179 patients underwent OLT due to HCC: 157 (87.8%) affected by virus-related (group A) and 22 (12.2%) virus-unrelated cirrhosis (group B). We analyzed patient characteristics including demographics, tumor features, downstaging treatments, and recurrences.

Results

At a mean follow-up of 41.2 months, the 3- and 5-year overall long-term survivals between group A versus group B were 81% versus 75% and 85% versus 78.4% respectively (P = NS). The 3- and 5-year disease-free survivals between group A versus group B were 90.8% versus 89.6% and 85.6% versus 85.6%, respectively (P = NS). After OLT, HCC recurrences occurred in 14 group A (14/157, 8.9%) and 4 patients (4/22, 18.1%) group B subjects.

Discussion

Our data demonstrated that after OLT, HCC outcomes were not different between patients with virus-related or -unrelated cirrhosis. The direct oncogenetic role played by hepatitis B and C appear to not be associated with a greater risk to develop HCC recurrence.     

Downstaging prior to liver transplantation for hepatocellular carcinoma: advisable but at the price of an increased risk of cancer recurrence – a retrospective study

The use of downstaging prior to liver transplantation for hepatocellular carcinoma (HCC) still needs refinement. This study included patients with HCC listed for transplantation according to the Total Tumour Volume (TTV) ≤115 cm³ and alpha fetoprotein (AFP) ≤400 ng/ml criteria, with and without previous downstaging. Overall, 455 patients were listed, and 286 transplanted. Post‐transplant follow‐up was 38.5 ± 1.7 months. Patients downstaged to TTV115/AFP400 (n = 29) demonstrated similar disease‐free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 (n = 257). Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Among patients downstaged to Milan, those originally beyond TTV115/AFP400 (n = 27) had similar outcomes as those originally beyond Milan, but within TTV115/AFP400 (n = 53). However, the likelihood of being within Milan at transplant was lower for patients with more advanced original HCCs (P < 0.0001). Overall, despite an expected increase in post‐transplant HCC recurrence, similar survivals can be achieved with and without downstaging, using the TTV115/AFP400 transplantation criteria, and including patients with advanced original HCCs. Downstaging should continue to be performed.     

Salvage living donor liver transplantation versus repeat liver resection for patients with recurrent hepatocellular carcinoma and Child-Pugh class A liver cirrhosis: A propensity score-matched comparison

Following curative liver resection (LR), resectable tumor recurrence in patients with preserved liver function leads to deciding between a repeat LR and a salvage liver transplantation (LT), if a donor’s liver is available. This retrospective study compared survival outcomes and recurrence pattern following salvage living donor LT (LDLT) and repeat LR in patients with recurrent hepatocellular carcinoma (HCC). We reviewed the medical records of patients who underwent repeat LR (n = 163) or LDLT (n = 84) for recurrent HCC following curative resections, between January 2005 and December 2017 at a single institution. A 1:1 propensity score matching led to 42 patients per group. Disease-specific and recurrence-free survival were significantly better in the salvage LDLT group than in the repeat LR group (p = .042; HR = 2.40; 95% CI, 0.69–6.00 and p < .001; HR = 4.23; 95% CI, 2.05–8.71, respectively). Despite significant differences in recurrence patterns between the two groups (p = .019), the patient death rates, after recurrence, were similar for both groups (p = .760). This study indicates that salvage LDLT is superior to repeat LR for treating patients with transplantable, intrahepatic HCC recurrence, even in patients with Child-Pugh class A liver cirrhosis.     

Orthotopic Liver Transplantation for Hepatocellular Carcinoma: A Thirteen-Year Single-Center Experience

Background

When restrictive selection criteria are applied orthotopic liver transplantation (OLT) is the most efficient option for the treatment of hepatocellular carcinoma (HCC) in terms of survival and recurrence rate. Nevertheless, tumor recurrence may occur in 3.5%-21% of recipients, with a consequent negative impact on prognosis. The aim of this study was to analyze the long-term survival and tumor recurrence rate among a cohort of liver transplant recipients with HCC.

Methods

During the period 1994-2007, 130 HCC patients, including 111 males with a mean overall age of 57.8 ± 7.1 years (range, 38-70), underwent cadaveric donor-OLT. The etiology of liver disease was alcoholic cirrhosis in 66 patients (50.8%) and viral infection in 52 patients (40%). Baseline alpha fetoprotein values were 53.4 ± 280.9 ng/mL (range, 1-2593). Median interval between inclusion date and transplantation was 179.5 days.

Results

After a median follow-up of 40.8 months, 93 recipients (71.5%) were alive. Tumor recurrence was detected in 11 patients (8.5%). Neoplasm recurrence sites were as follows: liver graft (45.4%), bone (36.4%), lymphoadenopathies (27.3%), adrenal glands (27.3%), and lung (27.3%). Overall survival rates at 1, 3, 5, and 10 years were 85.1%, 78.3%, 70.1%, and 57%, respectively. After examination of the explanted liver, Milan criteria were surpassed in 32 recipients (24.6%). Nevertheless, no differences in survival were observed according to fulfilment or not of Milan criteria (log-rank test, P > .05). Hepatitis C virus (HCV) infection, female gender, and tumor recurrence were associated with a worse survival rate (log-rank test, < .05).

Conclusions

OLT is an effective option for the treatment of HCC with good long-term survival and low recurrence rates. In this series, survival was not affected by findings of poor prognostic factors in the explanted liver.