James Y. Y. Fung

11C-Acetate and 18F-FDG PET/CT for Clinical Staging and Selection of Patients with Hepatocellular Carcinoma for Liver Transplantation on the Basis of Milan Criteria: Surgeon’s Perspective

The success of liver transplantation (LT) for hepatocellular carcinoma (HCC) is enhanced by careful patient selection on the basis of the Milan criteria. The criteria are traditionally assessed by contrast CT, which is known to be affected by structural or architectural changes in cirrhotic livers. We aimed to compare dual-tracer (11C-acetate and 18F-FDG) PET/CT with contrast CT for patient selection on the basis of the Milan criteria. Methods: Patients who had HCC and had undergone both preoperative dual-tracer PET/CT and contrast CT within a 1-mo interval were retrospectively studied. They then underwent either LT (n = 22) or partial hepatectomy (PH) (n = 21; HCC of ≤ 8 cm). Imaging data were compared with data from postoperative pathologic analysis for accuracy in assessment of parameters specified by the Milan criteria (tumor size and extent, vascular invasion, and metastasis), TNM staging, and patient selection for LT. Results: Dual-tracer PET/CT performed equally well in both LT and PH groups for HCC detection (94.1% vs. 95.8%) and TNM staging (90.9% vs. 90.5%). Contrast CT performed reasonably well in the LT group but not in the PH group for HCC detection (67.6% vs. 37.5%) and TNM staging (54.5% vs. 28.6%). In the LT group, the sensitivity and specificity of contrast CT for patient selection on the basis of the Milan criteria were 43.8% and 66.7%, respectively (comparable to values in the literature); the sensitivity and specificity of dual-tracer PET/CT were 93.8% and 100%, respectively (both Ps < 0.05). From the surgeon’s perspective, we tended to perform transplantation for patients with higher diagnostic certainty (stricter CT criteria) because of a shortage of donor grafts. Patients who were not transplant candidates usually underwent up-front hepatectomy without the benefit of reassessment contrast CT, resulting in lower accuracies for the PH group. The overall sensitivity (96.8%) and specificity (91.7%) of dual-tracer PET/CT for patient selection for LT were significantly higher than those of contrast CT (41.9% and 33.0%, respectively) (both Ps < 0.05). Sources of error for contrast CT were related to cirrhosis or previous treatment and included difficulty in differentiating cirrhotic nodules from HCC (39%) and estimation of tumor size (14%). Overstaging of vascular invasion (4.6%) and extrahepatic metastases (4.6%) was infrequent. The rate of false-negative results of dual-tracer PET/CT was 4.7%. Conclusion: Dual-tracer PET/CT was significantly less affected by cirrhotic changes than contrast CT for HCC staging and patient selection for LT on the basis of the Milan criteria. The inclusion of dual-tracer PET/CT in pretransplant workup may warrant serious consideration.

High-intensity focused ultrasound ablation: An effective bridging therapy for hepatocellular carcinoma patients

AIMnTo analyze whether high-intensity focused ultrasound (HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma (HCC).nnnMETHODSnFrom January 2007 to December 2010, 49 consecutive HCC patients were listed for liver transplantation (UCSF criteria). The median waiting time for transplantation was 9.5 mo. Twenty-nine patients received transarterial chemoembolization (TACE) as a bringing therapy and 16 patients received no treatment before transplantation. Five patients received HIFU ablation as a bridging therapy. Another five patients with the same tumor staging (within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison. Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores, tumor size and number, and cause of cirrhosis.nnnRESULTSnThe HIFU group and TACE group showed no difference in terms of tumor size and tumor number. One patient in the HIFU group and no patient in the TACE group had gross ascites. The median hospital stay was 1 d (range, 1-21 d) in the TACE group and two days (range, 1-9 d) in the HIFU group (P < 0.000). No HIFU-related complication occurred. In the HIFU group, nine patients (90%) had complete response and one patient (10%) had partial response to the treatment. In the TACE group, only one patient (3%) had response to the treatment while 14 patients (48%) had stable disease and 14 patients (48%) had progressive disease (P = 0.00). Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list (P = 0.559).nnnCONCLUSIONnHIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis. It may reduce the drop-out rate of liver transplant candidate.

Survival advantage of primary liver transplantation for hepatocellular carcinoma within the up-to-7 criteria with microvascular invasion

PurposeMicrovascular invasion of hepatocellular carcinoma (HCC) is considered a poor prognostic factor of liver resection (LR) and liver transplantation (LT), but its significance for lesions within the up-to-7 criteria is unclear. This study investigated the survival benefit of primary LT against LR for HCC with microvascular invasion and within the up-to-7 criteria.MethodsAdult patients who underwent LR or LT as the primary treatment for HCC were included for study. Patients with prior local ablation, neoadjuvant systemic chemotherapy, targeted therapy, positive resection margin, or metastatic spread were excluded.ResultsThere were 471 LR patients and 95 LT recipients (70 with living donor, 25 with deceased donor). Seventy-seven (81.1%) LT recipients had HCC within the up-to-7 criteria. Twenty-five (26.3%) LT recipients had HCC with either macrovascular (nxa0=xa04) or microvascular (nxa0=xa021) invasion. The 5-year survival rate was 85.7% for LT recipients with HCC within the up-to-7 criteria, unaffected by the presence or absence of vascular invasion (88.2 vs. 85.1%). The rate was comparable with that of LR patients with HCC without vascular invasion (81.2%, p 0.227), but far superior to that of LR patients with lesions with vascular invasion (50.0%, pxa0<xa00.0001). Overall survivals were compromised by multiple tumors [odds ratio (OR) 1.902, confidence interval (CI) 1.374–2.633, pxa0=xa00.0001], vascular invasion (OR 2.678, CI 1.952–3.674, pxa0<xa00.0001), blood transfusion (OR 2.046, CI 1.337–3.131, pxa0=xa00.001), and being beyond the up-to-7 criteria (OR 1.457, CI 1.041–2.037, pxa0=xa00.028). LT was a favorable factor for survival (OR 0.243, CI 0.130–0.454, pxa0<xa00.0001).ConclusionPrimary LT for HCC with microvascular invasion and within the up-to-7 criteria doubled the chance of cure as compared with LR.

Pilot study of high‐intensity focused ultrasound ablation as a bridging therapy for hepatocellular carcinoma patients wait‐listed for liver transplantation

The objective of this study was to investigate the outcomes of high‐intensity focused ultrasound (HIFU) ablation as a bridging therapy for patients with hepatocellular carcinoma (HCC) who had been wait‐listed for deceased donor liver transplantation (DDLT). Adult patients with unresectable and unablatable HCCs within the University of California San Francisco criteria who had been wait‐listed for DDLT were screened for their suitability for HIFU ablation as a bridging therapy if they were not suitable for transarterial chemoembolization (TACE). Treatment outcomes for patients receiving HIFU ablation, TACE, and best medical treatment (BMT) were compared. Fifty‐one patients were included in the analysis. Before the introduction of HIFU ablation, only 39.2% of the patients had received bridging therapy (TACE only, nu2009=u200920). With HIFU ablation in use, the rate increased dramatically to 80.4% (TACEu2009+u2009HIFU, nu2009=u200941). The overall dropout rate was 51% (nu2009=u200926). Patients in the BMT group had a significantly higher dropout rate (Pu2009=u20090.03) and significantly poorer liver function as reflected by higher Model for End‐Stage Liver Disease scores and higher Child‐Pugh grading. Clinically relevant ascites was found in 5 patients in the HIFU group and 2 patients in the BMT group, but none was found in the TACE group (Pu2009=u20090.01 and Pu2009=u20090.03, respectively). The TACE and HIFU groups had comparable percentages of tumor necrosis in excised livers (Pu2009=u20090.35), and both were significantly higher than that in the BMT group (Pu2009=u20090.01 and Pu2009=u20090.02, respectively). In conclusion, HIFU ablation was safe even for HCC patients with Child‐Pugh C disease. Its adoption increased the percentage of patients receiving bridging therapy from 39.2% to 80.4%. A randomized controlled trial for further validation of its efficacy is warranted. Liver Transpl 20:912–921, 2014.

Outcomes of living donor liver transplantation for patients with preoperative type 1 hepatorenal syndrome and acute hepatic decompensation.

This study investigated the outcomes of living donor liver transplantation (LDLT) for patients with preoperative type 1 hepatorenal syndrome (HRS) and acute hepatic decompensation. Prospectively collected data for 104 patients who had fulminant hepatic failure, acute decompensation of cirrhosis, or an acute flare of chronic hepatitis B were analyzed. Thirty‐three patients (31.7%) had HRS (the HRS group), and 71 patients (68.3%) did not (the non‐HRS group). The median follow‐up period was 60 months. The HRS group had significantly more preoperative intensive care unit (ICU) admissions (84.8% versus 60.6%, P = 0.01), worse preoperative blood test results (creatinine, 248 versus 88 μmol/L, P < 0.001; total bilirubin, 630 versus 555 μmol/L, P = 0.001), more hemodialysis (48.5% versus 0%, P < 0.001), more blood transfusions (9 versus 4 U, P < 0.001), longer postoperative ICU stays (8 versus 4 days, P < 0.001), worse postoperative blood test results (creatinine at 1 year, 108 versus 96 μmol/L, P = 0.006), and poorer overall survival (P < 0.001). In a multivariate analysis, only HRS was associated with poorer overall survival (hazard ratio = 8.592, 95% confidence interval = 1.782‐41.431, P = 0.007). In conclusion, HRS patients had worse postoperative renal function and overall survival than non‐HRS patients. However, their 5‐year overall survival rate was still nearly 80%, which is satisfactory. Therefore, LDLT can be considered for patients who have acute hepatic decompensation with or without HRS. Liver Transpl, 2012.

Report from a Viral Hepatitis Policy Forum on implementing the WHO Framework for Global Action on viral hepatitis in North Asia

BACKGROUND & AIMSnThe World Health Organisation (WHO) Prevention & Control of Viral Hepatitis Infection: Framework for Global Action offers a global vision for the prevention and control of viral hepatitis. In October 2012, the Coalition to Eradicate Viral Hepatitis in Asia Pacific (CEVHAP) organised the North Asia Workshop on Viral Hepatitis in Taipei to discuss how to implement the WHO Framework in the North Asia region. This paper presents outcomes from this workshop.nnnMETHODSnTwenty-eight representatives from local liver associations, patient organisations, and centres of excellence in Hong Kong, Japan, Korea, and Taiwan participated in the workshop.nnnFINDINGSnPriority areas for action were described along the four axes of the WHO Framework: (1) awareness, advocacy and resources; (2) evidence and data; (3) prevention of transmission; and (4) screening and treatment. Priorities included: axis 1: greater public and professional awareness, particularly among primary care physicians and local advocacy networks. Axis 2: better economic data and identifying barriers to screening and treatment uptake. Axis 3: monitoring of vaccination outcomes and targeted harm reduction strategies. Axis 4: strengthening links between hospitals and primary care providers, and secure funding of screening and treatment, including for hepatocellular carcinoma.nnnCONCLUSIONSnThe WHO Framework provides an opportunity to develop comprehensive and cohesive policies in North Asia and the broader region. A partnership between clinical specialists, primary care physicians, policy makers, and people with or at risk of viral hepatitis is essential in shaping future policies.

Survival outcomes of right-lobe living donor liver transplantation for patients with high Model for End-stage Liver Disease scores.

BACKGROUNDnControversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a high MELD score would result in inferior outcomes of right-lobe LDLT.nnnMETHODSnAmong 411 consecutive patients who received right-lobe LDLT at our center, 143 were included in this study. The patients were divided into two groups according to their MELD scores: a high-score group (MELD score ≥25; n=75) and a low-score group (MELD score <25; n=68). Their demographic data and perioperative conditions were compared. Univariable and multivariable analyses were performed to identify risk factors affecting patient survival.nnnRESULTSnIn the high-score group, more patients required preoperative intensive care unit admission (49.3% vs 2.9%; P<0.001), mechanical ventilation (21.3% vs 0%; P<0.001), or hemodialysis (13.3% vs 0%; P=0.005); the waiting time before LDLT was shorter (4 vs 66 days; P<0.001); more blood was transfused during operation (7 vs 2 units; P<0.001); patients stayed longer in the intensive care unit (6 vs 3 days; P<0.001) and hospital (21 vs 15 days; P=0.015) after transplantation; more patients developed early postoperative complications (69.3% vs 50.0%; P=0.018); and values of postoperative peak blood parameters were higher. However, the two groups had comparable hospital mortality. Graft survival and patient overall survival at one year (94.7% vs 95.6%; 95.9% vs 96.9%), three years (91.9% vs 92.6%; 93.2% vs 95.3%), and five years (90.2% vs 90.2%; 93.2% vs 95.3%) were also similar between the groups.nnnCONCLUSIONSnAlthough the high-score group had significantly more early postoperative complications, the two groups had comparable hospital mortality and similar satisfactory rates of graft survival and patient overall survival. Therefore, a high MELD score should not be a contraindication to right-lobe LDLT if donor risk and recipient benefit are taken into full account.

Excellent outcomes of liver transplantation using severely steatotic grafts from brain‐dead donors

Liver grafts with macrovesicular steatosis of >60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain‐dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosisu2009>60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosisu2009>60%), and 354 patients had grafts with ≤60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; Pu2009=u20090.03). Median Model for End‐Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (Pu2009=u20090.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30‐day mortality (0/19 [0%] versus 11/354 [3.1%]; Pu2009=u20090.93) were also similar between groups. No patient developed PNF. The 1‐year and 3‐year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (Pu2009=u20090.55). The use of severely steatotic liver grafts from low‐risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation. Liver Transpl 22:226‐236, 2016.

Increasing the recipient benefit/donor risk ratio by lowering the graft size requirement for living donor liver transplantation

In living donor liver transplantation (LDLT), a right liver graft is larger than a left liver graft and hence leads to better recipient survival. However, in comparison with donor left hepatectomy, donor right hepatectomy carries a higher donor risk. We estimated the expansion of the applicability of left liver living donor liver transplantation (LLDLT) by lowering the graft weight (GW)/standard liver volume (SLV) ratio in increments of 5%. Consecutive LDLT cases were included in this study. The results of computed tomography volumetry provided the graft volume measurements, and the GW was derived from the graft volume with the conversion factor of 1.19 mL/g. We tried to estimate how many more times LLDLT would have been feasible if the GW/SLV requirement had been lowered to 40%, 35%, 30%, or 25%. In all, 361 consecutive donor‐recipient pairs underwent LDLT. Right liver living donor liver transplantation (RLDLT) accounted for 95% of the LDLT cases. Most recipients were male (74.2%), and most donors were female (60.4%). The median GW/SLV ratio was 46% (47% for RLDLT and 37% for LLDLT, P < 0.001). Two of the 218 female donors donated the left liver, and 12 of the 93 female recipients received a left liver. In 147 of the 173 cases (85%) when the donor was female and the recipient was male, the GW/SLV ratio did not reach 30%. LLDLT could have been performed more often than 5% of the time if a lower GW/SLV requirement had been adopted. With GW/SLV ratios ≥ 40%, ≥ 35%, ≥ 30%, and ≥ 25%, the proportion of LLDLT cases would have risen from 5% to 5.8%, 12.5%, 29.1%, and 62.3%, respectively. LLDLT could have been performed approximately twice as often with every 5% reduction of the GW/SLV requirement. In conclusion, lowering the graft size requirement could improve the applicability of LLDLT and hence reduce donor risk. Liver Transpl, 2012.

Prevention of recurrent hepatitis B infection after liver transplantation.

BACKGROUNDnRecurrence of hepatitis B virus (HBV) infection after liver transplantation can lead to graft loss and a reduction in long-term survival. The purpose of this review is to summarize the current therapeutic options for preventing HBV recurrence in liver transplant recipients.nnnDATA SOURCESnUp to January 2013, studies that were published in MEDLINE and EMBASE on prevention of HBV recurrence after liver transplantation were reviewed.nnnRESULTSnThere have been remarkable advancements in the past two decades on the prevention of HBV recurrence after liver transplantation, from the discovery of hepatitis B immune globulin (HBIG) and lamivudine monotherapy to the combination therapy using HBIG and lamivudine. With the development of newer and stronger antiviral agents, the need for life-long HBIG is doubtful. With their low resistance profile, oral antiviral prophylaxis using these new agents alone is sufficient and is associated with excellent outcome.nnnCONCLUSIONSnRestoration of host HBV immunity with adoptive immunity transfer and vaccination may represent the ultimate strategy to withdraw prophylactic treatment and to achieve a drug free regimen against HBV recurrence after liver transplantation.