Albert C. Y. Chan

Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation.

BACKGROUND & AIMS We investigated the efficacy of entecavir, a cyclopentyl guanosine nucleoside analogue, as monoprophylaxis in patients with chronic hepatitis B who received a liver transplant. METHODS We studied data from 80 consecutive patients who received a liver transplant (47 from living donors and 33 from deceased donors) for hepatitis B-related disease and entecavir monotherapy as prophylaxis. None of the patients received hepatitis B immunoglobulin. Indications for transplant included decompensation from cirrhosis (27.5%), acute-on-chronic hepatitis B (47.5%), and hepatocellular carcinoma (25%). The median follow-up time was 26 months (range, 5-40 months). Before transplant, 33 patients were not on antiviral therapy and 47 were on oral therapy (18 had received less than 3 months of treatment). RESULTS At the time of transplant, the median log HBV DNA level was 3.5 copies/mL (range, 1.54-8.81); 21 patients (26%) had undetectable levels of HBV DNA. The cumulative rate of hepatitis B surface antigen (HBsAg) loss was 86% and 91% after 1 and 2 years, respectively. Ten patients had reappearance of HBsAg. Eighteen patients (22.5%) were HBsAg positive at the time of their last examination; 17 of these had undetectable levels of HBV DNA, and the remaining patient had a low level of HBV DNA (217 copies/mL). There was no evidence of mutations at sites that confer resistance to entecavir among patients who were HBsAg positive. CONCLUSIONS Although only 26% of patients had complete viral suppression at the time of transplant, 91% lost HBsAg, with 98.8% achieving undetectable levels of HBV DNA. A hepatitis B immunoglobulin-free regimen of entecavir monotherapy is effective after liver transplantation for chronic hepatitis B.

Impact of Antiviral Therapy on the Survival of Patients After Major Hepatectomy for Hepatitis B Virus–Related Hepatocellular Carcinoma

OBJECTIVES To assess whether commencement of antiviral therapy after hepatectomy improves the prognosis of hepatocellular carcinoma (HCC) in preoperatively antiviral-naive patients with chronic hepatitis B virus (HBV) infection. DESIGN Retrospective analysis of a prospectively collected database. SETTING University teaching hospital. MAIN OUTCOME MEASURES Disease-free and overall survival rates. RESULTS One hundred thirty-six patients received major hepatectomy for HBV-related HCC from September 1, 2003, through December 31, 2007. Among them, 42 patients received antiviral therapy (treatment group) after hepatectomy, whereas 94 did not (control group). Patient demographics, preoperative liver function, tumor characteristics, and liver function at the time of tumor recurrence were comparable between the 2 groups. Disease-free and overall survival rates were significantly prolonged in the treatment group. The 1-, 3-, and 5-year overall survival rates in the treatment group were 88.1%, 79.1%, and 71.2%, respectively; in the control group, 76.5%, 47.5%, and 43.5%, respectively (P = .005). The 1-, 3-, and 5-year disease-free survival rates in the treatment group were 66.5%, 51.4%, and 51.4%, respectively; in the control group, 48.9%, 33.8%, and 33.8%, respectively (P = .05). Subgroup analysis stratified against tumor stage and major vascular invasion showed that posthepatectomy antiviral treatment conferred a significant survival benefit in stages I and II tumors or HCCs without major venous invasion. CONCLUSIONS Antiviral therapy improves the prognosis of HBV-related HCC. It should be considered after hepatectomy for HBV-related HCC, especially in early-stage tumors.

Knowledge sharing and social media

Knowledge sharing gains a lot of attention from academics and practitioners.We extended an interpersonal relationship model for knowledge sharing.Factors had significant, direct and indirect effects on knowledge sharing.Altruism was found to have significant moderating effect.The proposed extended model explained 64.9% of the observed variance. Social media, such as Facebook and Twitter, have become extremely popular. Facebook, for example, has more than a billion registered users and thousands of millions of units of information are shared every day, including short phrases, articles, photos, and audio and video clips. However, only a tiny proportion of these sharing units trigger any type of knowledge exchange that is ultimately beneficial to the users. This study draws on the theory of belonging and the intrinsic motivation of altruism to explore the factors contributing to knowledge sharing behavior. Using a survey of 299 high school students applying for university after the release of the public examination results, we find that perceived online attachment motivation (β=0.31, p<0.001) and perceived online relationship commitment (β=0.49, p<0.001) have positive, direct, and significant effects on online knowledge sharing (R2 0.568). Moreover, when introduced into the model, altruism has a direct and significant effect on online knowledge sharing (β=0.46, p<0.001) and the total variance explained by the extended model increases to 64.9%. The implications of the findings are discussed.

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.

Changing paradigm in the management of hepatocellular carcinoma improves the survival benefit of early detection by screening.

Objective:To evaluate the impact of improved surgical management of hepatocellular carcinoma (HCC) on the survival of patients with screened HCC. Summary Background Data:It is unclear whether the advent of new treatment modalities such as liver transplantation and radiofrequency ablation (RFA) in recent years have improved the long-term survival in patients with HCC detected by screening. Methods:A prospective database of 1366 patients with known chronic hepatitis B or C virus infection diagnosed with HCC either by screening or symptomatic presentation from January 1991 to December 2004 was reviewed. The long-term survival of HCC patients in the screened and symptomatic groups was compared. The management and survival of patients in two 7-year periods (1991–1997 vs. 1998–2004) were further compared. Results:Long-term survival was significantly better in the screened group than in the symptomatic group (median survival 61.9 vs. 11.5 months, P < 0.001). The proportion of patients with curative treatment increased from 50.5% in the first period to 67.8% in the second period in the screened group, but there was no significant change in the symptomatic group. Improved long-term survival was observed in patients with HCC detected by screening and treated in the second period compared with the first period (median survival 68.5 vs. 38.7 months, P = 0.022), but no significant improvement was observed for symptomatic patients. Conclusion:Survival of patients with HCC detected by screening has improved in recent years due to increased chance of curative treatment with the advent of liver transplantation and RFA.

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.

Treatment strategy for recurrent hepatocellular carcinoma: salvage transplantation, repeated resection or radiofrequency ablation?

The objective of this study was to evaluate the efficacy of salvage liver transplantation (SLT), repeated hepatic resection (RR), and repeated radiofrequency ablation (rRFA) for patients with postoperative tumor recurrence. The optimal treatment strategy for patients with recurrent hepatocellular carcinoma (HCC) remains unclear. From January 1993 to September 2009, 532 patients underwent either hepatic resection or radiofrequency ablation (RFA) for HCC within the Milan criteria. In all, 219 patients experienced intrahepatic recurrence, and 87 were selected for SLT (n=19), RR (n=24), or rRFA (n=44). Their clinicopathological data were reviewed, and their survival outcomes were assessed with Kaplan‐Meier methods. Seventy‐four of 220 patients (33.6%) developed recurrent HCC within the Milan criteria. The median Model for End‐Stage Liver Disease (MELD) scores for SLT, RR, and rRFA were 10.7, 7.2, and 8.3, respectively (P<0.001). The 1‐, 3‐, and 5‐year tumor‐free survival rates were 68.4%, 57.9%, and 57.9%, respectively, for SLT; 69.7%, 49.3%, and 49.3%, respectively, for RR; and 40.0%, 19.8%, and 10.6%, respectively, for rRFA (P=0.001). For recurrent HCC within the Milan criteria, the 1‐, 3‐, and 5‐year tumor‐free survival rates for SLT were all 60%; the corresponding rates were 70.2%, 48.0%, and 48.0% for RR and 41.0%, 20.3%, and 10.9% for RFA (P=0.004). After adjustments of the MELD score, the 5‐year survival rates for SLT, RR, and rRFA were 50.0%, 48.0%, and 11.4%, respectively (P=0.003). A subgroup analysis showed that SLT and RR led to comparable survival outcomes, but both treatments led to significantly better survival outcomes than rRFA (P<0.001). In conclusion, SLT is an efficacious treatment for patients with recurrent HCC and should be considered when RR is not feasible. Liver Transpl 19:411–419, 2013.

Can positron emission tomography with the dual tracers [11C]acetate and [18F]fludeoxyglucose predict microvascular invasion in hepatocellular carcinoma?

Microvascular invasion is a poor prognostic indicator of the recurrence of hepatocellular carcinoma (HCC) after surgical treatment. Positron emission tomography (PET) with [18F]fludeoxyglucose ([18F]FDG) as a tracer has been employed to predict the prognosis before surgery for various kinds of tumors, but it has not been found to be sensitive enough for HCC. Thus, [11C]acetate has been adopted as an additional tracer. This study was designed to evaluate the ability of dual‐tracer PET ([18F]FDG and [11C]acetate) to predict microvascular invasion before liver resection or transplantation. Fifty‐eight HCC patients who were preoperatively examined with whole‐body dual‐tracer PET were studied. Twenty‐five patients were [18F]FDG‐positive, and 56 were [11C]acetate‐positive. The sensitivity of [18F]FDG in detecting primary HCC was 43%, and the sensitivity of [11C]acetate was 93%. Twenty‐nine patients had HCC with microvascular invasion according to the final pathological examination. The sensitivity, specificity, positive predictive value, and negative predictive value of [18F]FDG PET in predicting microvascular invasion were 55.2%, 69%, 64%, and 60.6%, respectively; the corresponding rates for [11C]acetate PET were 93.1%, 0%, 48.2%, and 0%. The factors associated with HCC recurrence, which included multifocal involvement, a large tumor size, microsatellite lesions, poor HCC differentiation, and an advanced stage of disease, were analyzed and compared with positive PET results. A tumor size greater than 5 cm was significantly associated with positive [18F]FDG PET results; [11C]acetate was not associated with poor prognostic indicators. Preoperative [18F]FDG PET may predict microvascular invasion. The addition of [11C]acetate improves the overall sensitivity of PET, but it has no incremental value in predicting microvascular invasion. Liver Transpl 17:1218–1225, 2011.

Bile duct anastomotic stricture after adult-to-adult right lobe living donor liver transplantation.

Duct‐to‐duct anastomosis (DDA) and hepaticojejunostomy (HJ) are options for biliary reconstruction in patients undergoing adult‐to‐adult right lobe living donor liver transplantation (ARLDLT), after which biliary anastomotic stricture (BAS) is common as a complication. The risk factors for BAS are not clearly defined. We aimed to determine the rate of post‐ARLDLT BAS in our center and its associated factors. In 265 ARLDLT recipients, 55 (20.8%) developed postoperative BAS. The diagnosis was based on clinical, biochemical, histological, and radiological results. The BAS rates were 21.4% (43/201) for recipients undergoing DDA during transplantation, 18.9% (10/53) for recipients undergoing HJ, and 18.2% (2/11) for recipients undergoing both procedures. BAS and non‐BAS patients had comparable demographics. The number of graft bile duct openings (P = 0.516) and the size of the grafts smallest bile duct (5 versus 5 mm, P = 0.4) were not significantly different between BAS and non‐BAS patients. Univariate analysis showed that the factors associated with postoperative BAS were the recipient warm ischemia time (55 versus 51 minutes, P = 0.026), graft cold ischemia time (120 versus 108 minutes, P = 0.046), stent use (21.8% versus 7.1%, P = 0.001), postoperative acute cellular rejection (29.1% versus 11.0%, P = 0.001), and University of Wisconsin solution use (21.8% versus 7.1%, P = 0.001). Multivariate analysis showed that the cold ischemia time (odds ratio = 1.012, 95% confidence interval = 1.002‐1.023, P = 0.014) and acute rejection (odds ratio = 3.180, 95% confidence interval = 1.606‐6.853, P = 0.002) were significant factors. The graft survival rates of BAS and non‐BAS patients were comparable. One patient required retransplantation for secondary biliary cirrhosis. In conclusion, BAS remains common after ARLDLT regardless of DDA or HJ. The graft cold ischemia time and postoperative acute cellular rejection are significantly associated with postoperative BAS. Liver Transpl 17:47–52, 2011.

Pure laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma in 110 patients with liver cirrhosis: a propensity analysis at a single center

Objective: To investigate the long-term outcomes of pure laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma (HCC) with background cirrhosis. Background: Laparoscopic hepatectomy has been gaining popularity, but has not been widely accepted, because published data were gathered from small numbers of patients. Methods: Data of patients diagnosed with HCC and cirrhosis treated by hepatectomy were reviewed. The outcomes of pure laparoscopic hepatectomy were compared with those of open hepatectomy. Propensity score matching of patients in a ratio of 1:3 was conducted. Results: There were 110 patients and 330 patients in the laparoscopic group and the open group, respectively. The laparoscopic group had less blood loss (150 vs 400 mL; P < 0.001), shorter operation time (185 vs 255 minutes; P < 0.001), and shorter hospital stay (4vs 7 days; P < 0.001). The median overall survival was 136 months in the laparoscopic group and 120 months in the open group. The 1, 3, and 5-year overall survival rates were 98.9%, 89.8%, and 83.7%, respectively, in the laparoscopic group, and 94%, 79.3%, and 67.4%, respectively, in the open group (P = 0.033). The median disease-free survival was 66.37 months in the laparoscopic group and 52.4 months in the open group. The 1, 3, and 5-year disease-free survival rates were 87.7%, 65.8%, and 52.2%, respectively, in the laparoscopic group, and 75.2%, 56.3%, and 47.9%, respectively, in the open group (P = 0.141). Conclusions: Pure laparoscopic hepatectomy for HCC can be carried out safely with favorable short-term and long-term outcomes even in cirrhotic patients at high-volume liver cancer centers.