Hepatic cancer stem cell marker granulin-epithelin precursor and β-catenin expression associate with recurrence in hepatocellular carcinoma

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Management of recurrent hepatocellular carcinoma after liver transplant – a single center experience

Background: Hepatocellular carcinoma (HCC) recurs in 10-60% of patients after liver transplantation and carries very dismal prognosis. Optimal management of this condition has yet to be defined. Patients and Methods: All adult patients with HCC within the UCSF (University of California, San Francisco) criteria who underwent liver transplantation at Queen Mary Hospital during the period from July 1995 to September 2013 were reviewed. Two hundred and fifty-two patients were included in the analysis. They were divided into three groups for comparison: with intrahepatic recurrence (IR), with multiple or extrahepatic recurrence (MR), with no recurrence (NR). Results: HCC recurrence occurred in 35 (13.9%) patients, 3 with IR and 32 with MR. Patients in the IR and MR groups had a younger age (51 vs. 51 vs. 56 years; p=0.007), a higher pretransplant serum α-fetoprotein level (27 vs. 97.5 vs. 18 ng/mL; p=0.005), more tumor nodules (4 vs. 2 vs. 1; p=0.003) and a higher incidence of lymphovascular permeation (33% vs. 59% vs. 27%; p=0.001) than patients in the NR group. More patients in the IR and MR groups had tumors beyond the UCSF criteria on histopathology (67% vs. 56% vs. 17%) when compared with the NR group. Treatments for IR included hepatectomy, radiofrequency ablation and transarterial chemoembolization. One patient with IR remained alive 3 years after last treatment. Overall survival in the IR group was longer than that in the MR group (59 vs. 30.4 months; p<0.001). Time from transplant to recurrence was similar between the two groups (23.1 vs. 12 months; p=0.141). Conclusions: Recurrence of HCC after liver transplantation is not uncommon. Aggressive surgical treatment may prolong survival in patients with IR only. Prognosis for patients with MR is dismal. Effective systemic therapy is urgently needed.published_or_final_versio

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

PURPOSE: Microvascular 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. METHODS: Adult 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. RESULTS: There 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 (n = 4) or microvascular (n = 21) 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%, p < 0.0001). Overall survivals were compromised by multiple tumors [odds ratio (OR) 1.902, confidence interval (CI) 1.374-2.633, p = 0.0001], vascular invasion (OR 2.678, CI 1.952-3.674, p < 0.0001), blood transfusion (OR 2.046, CI 1.337-3.131, p = 0.001), and being beyond the up-to-7 criteria (OR 1.457, CI 1.041-2.037, p = 0.028). LT was a favorable factor for survival (OR 0.243, CI 0.130-0.454, p < 0.0001). CONCLUSION: Primary LT for HCC with microvascular invasion and within the up-to-7 criteria doubled the chance of cure as compared with LR.published_or_final_versio

Does hepatitis B seroconversion affect survival outcome in patients with hepatitis B related hepatocellular carcinoma?

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Use of liver stiffness measurement for liver resection surgery: correlation with indocyanine green clearance testing and post-operative outcome

Background:Liver stiffness measurement (LSM) using transient elastography has recently become available for the assessment of liver fibrosis. Whether LSM can predict the functional liver reserve in patients undergoing liver resection is not certain.Aim:To correlate liver stiffness measurement (LSM) with indocyanine green (ICG) clearance test and liver biochemistry, and to determine its usefulness in predicting postoperative outcomes in patients undergoing liver resection.Patients and Methods:Transient elastography and ICG clearance test were performed pre-operatively in 44 patients with hepatocellular carcinoma. The LSM and ICG retention rate at 15 minutes (R15) were correlated with pre-operative factors and post-operative outcomes.Results:There was significant correlation between ICG R15 and LSM. In patients with LSM ≥11 kPa vs <11 kPa, there was significantly higher ICG R15 (17.1% vs 10.0% respectively, p = 0.025). For patients with ICG R15≥10% compared to those <10%, there was significantly higher LSM (12.0 vs 7.6 kPa respectively, p = 0.015). Twenty-eight patients proceeded to resection. There was a significant correlation between LSM and the peak INR after liver resection (r = 0.426, p = 0.024). There was a significant correlation between ICG R15 and the post-operative peak AST level (r = -0.414, p = 0.029) and peak ALT level (r = -0.568, p = 0.002). The operative time was a significant independent factor associated with post-operative complications and peak INR.Conclusion:LSM correlated well with ICG R15 in patients undergoing liver resection, and predicted early post-operative complications. Addition of LSM to ICG R15 testing may provide better prognostic information for patients undergoing resection. © 2013 Fung et al.published_or_final_versio

Granulin-epithelin precursor interacts with 78-kDa glucose-regulated protein in hepatocellular carcinoma

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Long-term outcomes of entecavir monotherapy after liver transplantation for hepatitis B: 5 years data

Oral Abstract Session: HEPATITIS B/C: no. O-55BACKGROUND: Previous study has shown that entecavir monotherapy is effective and safe to prevent hepatitis B (HBV) recurrence after liver transplantation (LT) but long-term data is lacking. The aim of the current study is to review the long-term results of entecavir monotherapy in HBV patients after LT ...postprin

New insights after the first 1000 liver transplantations at The University of Hong Kong

Background/objective: One thousand liver transplantations have been performed at the only liver transplant center in Hong Kong over a period of 22 years, which covered the formative period of living donor liver transplantation. These 1000 transplantations, which marked the journey of liver transplantation from development to maturation at the center, should be educational. This research was to study the experience and to reflect on the importance of technical innovations and case selection. Methods: The first 1000 liver transplantations were studied. Key technical innovations and surgical therapeutics were described. Recipient survival including hospital mortality was analyzed. Recipient survival comparison was made for deceased donor liver transplantation and living donor liver transplantation indicated by hepatocellular carcinoma and other diseases. Results: Among the 1000 transplantations, 418 used deceased donor grafts and 582 used living donor grafts. With the accumulation of experience, hospital mortality improved to < 2% in the past 2 years. In the treatment of diseases other than hepatocellular carcinoma, living donor liver transplantation was superior to deceased donor liver transplantation, with a 10-year recipient survival around 90%. Conclusion: Transplant outcomes have been improving consistently over the series, with a very low hospital mortality and a predictably high long-term survival. © 2015

A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio