Sc Chan

Living donor versus deceased donor liver transplantation for early irresectable hepatocellular carcinoma

Hypothetical studies that favour living donor liver transplantation (LDLT) for early hepatocellular carcinoma (HCC) assumed a comparable outcome after LDLT and deceased donor liver transplantation (DDLT). The aim of this study was to compare the outcome after LDLT with that after DDLT, and to identify factors that might account for any differences.

The role and limitation of living donor liver transplantation for hepatocellular carcinoma

Liver transplantation for hepatocellular carcinoma (HCC) is restricted by the scarcity of cadaver grafts. Living donor liver transplantation (LDLT) may potentially increase the applicability but its role and limitation are not clear. We studied the outcome of a cohort of 51 patients with unresectable HCC who were accepted on list for both options of deceased donor liver transplantation (DDLT) and LDLT. Twenty‐five of 51 (49%) patients had voluntary living donors (group 1) and 26 did not (group 2). Patients in group 1 were younger, and more often had a MELD score more than 20 or blood group other than O. Twenty‐one patients of group 1 underwent LDLT after a median waiting time of 24 days (range, 2–126 days), but 4 did not because the donors were not suitable (HBsAg‐positive, 2; ABO‐incompatible, 1; liver dysfunction, 1). Of the 30 patients who remained on list, only 6 underwent DDLT after a median waiting time of 344 days (range, 22–1359 days, P < .005). Nineteen died before transplantation and 2 were alive but taken off the list because of disease progression (drop‐out rate, 70%). One patient was alive on list and 2 had undergone transplantation outside Hong Kong. The 1‐, 2‐, 3‐, and 4‐year intention‐to‐treat survival rates were 88%, 76%, 66%, and 66%, respectively, for group 1 and 72%, 46%, 38%, and 31%, respectively, for group 2 (relative risk of death for group 1, 0.35; 95% CI, 0.14 to 0.90; P = .029). In conclusion, although complicated factors such as donor voluntarism and selection criteria limit the role of LDLT for HCC, LDLT allows more patients to undergo early transplantation and results in a better outcome. (Liver Transpl 2004;10:440–447.)

Safety of duct-to-duct biliary reconstruction in right-lobe live-donor liver transplantation without biliary drainage

Background. Duct-to-duct biliary reconstruction is frequently used in right-lobe live-donor liver transplantation (RLDLT), and routine biliary drainage has been recommended. The aim of the present study was to evaluate the safety and operative outcomes of duct-to-duct biliary reconstruction after RLDLT without biliary drainage. Methods. The study comprised 41 RLDLT recipients who had duct-to-duct biliary reconstruction. During donor and recipient operations, precautions were taken to preserve blood supply to the bile duct. Biliary anastomosis was performed with fine Prolene sutures without stents or drainage tubes. The operative outcomes were prospectively evaluated. Results. The median postoperative intensive care unit and hospital stay were 3 days (range, 1–47 days) and 19 days (range, 8–114 days), respectively. There was no hospital mortality. At a median follow-up of 13.3 months (range, 4.0–26.8 months), the graft and patient survival rates were 95% and 98%, respectively. Three (7%) patients had biliary leakage. These three patients and the other seven patients developed late biliary stricture. The overall biliary complication rate was 24%. On multivariate analysis, preoperative Model for End-Stage Liver Disease (MELD) score of greater than or equal to 35 was the risk factor associated with biliary complication (P =0.032; risk ratio, 4.58). Conclusions. Duct-to-duct anastomosis without biliary drainage is safe in RLDLT. Patients with a high preoperative MELD score were associated with an increased incidence of biliary complications. Further studies are required to investigate the hemodynamic changes and modulation of blood flow of liver grafts in patients with chronic liver disease, which may significantly affect the incidence of biliary complications.

Oral Nucleoside/Nucleotide Analogs Without Hepatitis B Immune Globulin After Liver Transplantation for Hepatitis B

OBJECTIVES:The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone.METHODS:A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up.RESULTS:Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients.CONCLUSIONS:Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.

Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria.

There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment.

Efficacy of a Pre‐S Containing Vaccine in Patients Receiving Lamivudine Prophylaxis after Liver Transplantation for Chronic Hepatitis B

Lamivudine monoprophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants and second generation recombinant HBV vaccine is not effective. We studied the efficacy of two courses each of three double‐doses (20 ug) of third‐generation recombinant pre‐S containing vaccine (Sci‐B‐Vac™) in 20 patients on lamivudine prophylaxis at a median of 637 days (range, 390–2666 days) after transplantation. At enrollment, all patients were seronegative for HBsAg, anti‐HBs and HBVDNA (by qPCR). Lamivudine (100 mg/day) was continued throughout the study. Five patients (25%) responded to the first course and five additional patients responded after the second course (overall response rate 50%). The response rate was 88% in patients younger than 50 years old and 25% in older patients (p = 0.02). The median peak anti‐HBs titer was 153 mIU/mL with six responders having a titer >100 mIU/mL and seven sustained >6 months. Among seven previous nonresponders to second generation recombinant vaccine, three (44%) responded. At the end of the study, all patients remained seronegative for HBsAg. In conclusion, Sci‐B‐Vac™ is effective in about 50% of patients receiving lamividine prophylaxis and may prevent recurrence due to escape mutants.

Correlation of Liver Stiffness and Histological Features in Healthy Persons and in Patients With Occult Hepatitis B, Chronic Active Hepatitis B, or Hepatitis B Cirrhosis

OBJECTIVES:Liver stiffness measurement using transient elastography has become a popular tool to assess liver fibrosis. The aim of this study was to determine liver stiffness values and histological features in healthy subjects and in patients with chronic hepatitis B (CHB).METHODS:A total of 157 people were included (28 healthy subjects and 18 patients with occult hepatitis B infection, 102 with active CHB, and 9 with end-stage hepatitis B cirrhosis). Histology and liver stiffness measurements were obtained from all patients.RESULTS:The median liver stiffness in healthy subjects and in occult hepatitis B, active hepatitis B, and end-stage cirrhosis patients was 4.6, 4.2, 8.7, and 33.8 kPa, respectively. In healthy subjects and in patients with occult hepatitis B infection, none had significant fibrosis on histology, and all had liver stiffness <7.2 kPa. In patients with active CHB, 32 (31%) had liver stiffness >11.0 kPa, but only four (12%) had cirrhosis on histology. Using liver stiffness to predict cirrhosis in this group had a sensitivity of 100%, a specificity of 69%, a positive predictive value of 10%, and a negative predictive value of 100%. All nine patients with end-stage liver cirrhosis had liver stiffness >11.0 kPa. The overall area under the ROC curve (AUROC) for diagnosing cirrhosis using a cutoff of 11.3 kPa was 0.89.CONCLUSIONS:Liver stiffness measurement has an overall good diagnostic accuracy with excellent negative predictive value. However, in active CHB with elevated alanine aminotransferase (ALT) levels, the positive predictive value for diagnosing cirrhosis is poor, and further studies are needed to optimize the use of transient elastography in this important group.

Alleviating the Burden of Small-for-Size Graft in Right Liver Living Donor Liver Transplantation Through Accumulation of Experience

The issue of small‐for‐size graft (SFSG) containing the middle hepatic vein in right liver living donor liver transplantation from 1996 to 2008 (n = 320) was studied. Characteristics of donors, grafts and recipients were comparable between Era I (first 50 cases) and Era II (next 270 cases) except that the median model for end‐stage liver disease (MELD) score was higher in Era I (29 vs. 24; p = 0.024). The median graft to standard liver volume ratio (G/SLV) in Era I was 49.0% (range, 32.8–86.2%), versus 49.3% (range, 28.4–89.4%) in Era II (p = 0.498). Hospital mortality rate, the study endpoint, dropped from 16.0% (8/50) in Era I to 2.2% (6/270) in Era II (p = 0.000). Univariate analysis showed that MELD score (p = 0.002), pretransplant hepatorenal syndrome (p = 0.000) and Era I (p = 0.000) were significant in hospital mortality. Logistic regression analysis showed that only Era I (relative risk 9.758; 95% confidence interval, 2.885–33.002; p = 0.000) was significant. In Era I, G/SLV<40% had a relative risk of 7.8 (95% confidence interval, 1.225–49.677; p = 0.030). The hospital mortality rates for G/SLV<40% were 50% (3/6) and 1.9% (1/52) in Era I and II respectively. In conclusion, through accumulation of experience, SFSG became less important as a factor in hospital mortality.

Post-transplant endothelial progenitor cell mobilization via CXCL10/CXCR3 signaling promotes liver tumor growth

BACKGROUND & AIMS Patients with hepatocellular carcinoma (HCC) receiving living donor liver transplantation appear to possess significantly higher tumor recurrence than the recipients receiving deceased donor liver transplantation. The underlying mechanism for HCC recurrence after transplantation remains unclear. Here, we aim to investigate the impact of small-for-size liver graft injury on HCC recurrence after transplantation. METHODS The correlation between tumor recurrence, liver graft injury, CXCL10 expression and endothelial progenitor cell (EPC) mobilization was studied in 115 liver transplant recipients and rat orthotopic liver transplantation (OLT) models. The direct role of CXCL10/CXCR3 signaling on EPC mobilization was investigated in CXCL10(-/-) mice and CXCR3(-/-) mice. The role of EPCs on tumor growth and angiogenesis was further investigated in an orthotopic liver tumor model. RESULTS Clinically, patients with small-for-size liver grafts (<60% of standard liver weight, SLW) had significantly higher HCC recurrence (p=0.04), accompanied by more circulating EPCs and higher early-phase intragraft and plasma CXCL10 levels, than the recipients with large grafts (≥60% of SLW), which were further validated in rat OLT models. Circulatory EPC mobilization was reduced after liver injury both in CXCL10(-/-) mice and CXCR3(-/-) mice in comparison to wild-type controls. CXCL10 recruited EPCs in dose-dependent and CXCR3-dependent manners in vitro. Early-phase EPC/CXCL10 injection enhanced orthotopic liver tumor growth, angiogenesis and metastasis in nude mice. CONCLUSIONS Post-transplant enhanced CXCL10/CXCR3 signaling in small-for-size liver grafts directly induced EPC mobilization, differentiation and neovessel formation, which further promotes tumor growth. Targeting CXCL10/CXCR3 signaling may attenuate early-phase liver graft injury and prevent late-phase tumor recurrence/metastasis after transplantation.

The right may not be always right: Biliary anatomy contraindicates right lobe live donor liver transplantation

A 56-year-old woman presented with acute-onchronic hepatitis B liver failure and was put on a high-urgency list for liver transplantation. She was cared for in the intensive care unit and rapidly lapsed into a coma because of hepatic encephalopathy. She had endotracheal intubation and was supported with mechanical ventilation. Her brother, 40 years old, volunteered to be the liver donor after detailed counseling. The preoperative donor evaluation including independent psychological assessment to confirm true volunta-