Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter Study.

BACKGROUND: Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented. METHODS: In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint was failure rate by month 6, defined as serum anti-HBs of 100 IU/L or less or HBV reinfection despite serum anti-HBs greater than 100 IU/L. RESULTS: Of 49 patients treated, 47 (95.9%) continued treatment until month 6. All patients achieved administration by a caregiver or self-injection by week 14. No treatment failures occurred. Mean anti-HBs declined progressively to month 6, plateauing at a protective titer of approximately 290 IU/L. All patients tested for HBV DNA remained negative (45/45). Only 1 adverse event (mild injection site hematoma) was assessed as treatment-related. CONCLUSIONS: Introduction of subcutaneous HBIg administration by week 3 posttransplantation, combined with HBV virostatic prophylaxis, is effective and convenient for preventing HBV recurrence.

Value of transient elastography measured with FibroScan in predicting the outcome of hepatic resection for hepatocellular carcinoma.

OBJECTIVE: : To evaluate the efficacy of preoperative liver stiffness (LS) measurement in predicting postoperative liver failure (PLF) after hepatectomy for hepatocellular carcinoma (HCC). BACKGROUND: : Hepatectomy for HCC in cirrhosis is affected by the risk of PLF, which is not completely predictable with common biochemical tests. Transient elastography with FibroScan is used to calculate the degree of LS, and it may be applicable to patients scheduled for hepatectomy to estimate perioperative complications. METHODS: : Ninety-two patients undergoing hepatectomy for HCC were prospectively evaluated with preoperative FibroScan. Accuracy of LS measurement in predicting PLF, the presence of cirrhosis, and the presence of clinical signs of portal hypertension (PH) were assessed using receiver operating characteristic (ROC) analysis. RESULTS: : In 2 patients, LS measurement could not be performed because of obesity; consequently, 90 patients were suitable for the study. Perioperative mortality was 2.2% (2 patients); PLF occurred in 28.9% of patients (26 patients). ROC analysis identified patients with LS value higher than or equal to 15.7 kPa as being at higher risk of PLF [area under the curve (AUC) = 0.865, 95% confidence interval: 0.776-0.928; sensitivity = 96.1%; specificity = 68.7%; positive predictive value = 55.6%; negative predictive value = 97.8%; positive likelihood ratio = 3.08; negative likelihood ratio = 0.056; P < 0.001]. Patients with LS value lower than 14.8 kPa had no PLF. LS value higher than 12.6 kPa and higher than 19.6 kPa was correlated with the presence of cirrhosis (AUC = 0.880; P < 0.001), and of PH (AUC = 0.786; P < 0.001), respectively. Multivariate analysis showed that low preoperative serum sodium levels (P = 0.012), histological cirrhosis (P = 0.024), and elevated LS (P = 0.005) were independent predictors of PLF. CONCLUSIONS: : LS measured with FibroScan is a valid tool for prediction of PLF in patients undergoing hepatectomy for HCC.

Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: a meta-regression approach.

BACKGROUND: The optimal margin width and its influence on outcomes after hepatic resection for colorectal liver metastases is still controversial: a meta-analysis was conducted to analyze the impact of subcentimeter margin width on patient and disease-free survival after resection. METHODS: A systematic search was performed, covering the last decade, following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Relative risks (RRs) for patient and disease-free survival (DFS) were calculated after resection in relationship to a margin width >1 cm (R0 > 1 cm) and between 1 mm and 1 cm (R0 < 1 cm) using the DerSimonian and Laird random-effects model. Meta-regression was applied for covariate adjustment. RESULTS: Eleven observational studies were identified involving 2823 patients. Overall, 59.1% of patients were R0 < 1 cm and 40.9% were R0 > 1 cm. Meta-analysis showed that compared with patients with margins R0 > 1 cm, a R0 < 1 cm margin lead to decreased 1-, 3-, and 5-year DFS with a RR of 1.17 (95% confidence interval [CI] 1.07-1.27), 1.38 (95% CI 1.16-1.65), and 1.55 (95% CI 1.25-1.91), respectively, but patient survival was obviously affected (P > .05 in all cases). Patients with margins of R0 < 1 cm differ from those with R0 > 1 cm for greater proportions of multiple metastases (RR 1.43; 95% CI 0.25-1.61) and synchronous bowel disease (RR 1.42; 95% CI 0.8-1.92). Meta-regression showed that these two covariates had a significant impact on DFS but not on patient survival. CONCLUSION: A resection margin width >1 cm is desirable even if patient survival is at best only slightly affected by subcentimeter margin as a consequence of a decreased DFS. The presence of multiple metastases and synchronous bowel neoplasm represent potential study selection biases that significantly decrease DFS; well-conducted, matched analyses consequently are essential to clarify the issue.

Relationship between hepatic haemodynamics assessed by Doppler ultrasound and liver stiffness.

AIM: We tested the relationship between hepatic haemodynamics assessed by Doppler ultrasonography and liver stiffness assessed by Transient Elastography in hepatitis C related chronic liver disease. METHODS: Three liver Doppler ultrasound parameters (hepatic artery resistance index, splenic artery resistance index and waveform pattern in hepatic veins) and liver stiffness measured by Transient Elastography were analysed in one hundred consecutive patients affected by hepatitis C related chronic liver disease. RESULTS: Hepatic and splenic arteries resistance indexes correlate significantly (p<0.0001 for both) with liver stiffness. A hepatic artery resistance index cut-off value of 0.64 provided sensitivity and specificity respectively of 84.4% and 69.1% for predicting liver stiffness ≤or >13 kPa, whereas a splenic artery resistance index cut-off value of 0.56 provided sensitivity and specificity respectively of 81.3% and 48.5%. The coincidental finding of both resistance indexes above the respective cut-off values showed a good accuracy in identifying patients with liver stiffness values >13 kPa (accuracy=78%, +LR=2.90, -LR=0.31). A significant difference in liver stiffness values was evident between patients with triphasic and bi- or monophasic waveform pattern (p=0.005). CONCLUSIONS: Hepatic and splenic arteries resistance indexes and the hepatic veins waveform pattern assessed by Doppler ultrasound may provide information similar to that of Transient Elastography in hepatitis C related chronic liver disease.

Safety of hepatic resection for colorectal metastases in the era of neo-adjuvant chemotherapy.

PURPOSE: The relationship between neo-adjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases and post-operative morbidity still has to be clarified. METHODS: Data from 242 patients undergoing hepatectomy for colorectal liver metastases, judged resectable at first observation, were reviewed and their clinical outcome was related to neo-adjuvant chemotherapy (125 patients). Selection biases were outlined and properly handled by means of propensity score analysis. RESULTS: Post-operative death was 1.2% and morbidity 40.9%. Pre-operative chemotherapy was only apparently related to higher morbidity (P = 0.021): multivariate analysis identified extension of hepatectomy and intra-operative blood loss as independent prognostic variables (P < 0.05). Patients receiving and not receiving neo-adjuvant chemotherapy were significantly different for several covariates, including extension of hepatectomy (P = 0.049). After propensity score adjustment, 94 patients were identified as having similar covariate distribution (standardized differences <|0.1|) except for neo-adjuvant treatment (47 patients for each group). In this matched sample, mortality was similar and post-operative complications were only slightly higher (hazard ratio = 1.38) in treated patients. A significantly higher need for fluid replacement was only observed in patients receiving neo-adjuvant chemotherapy (P = 0.038). CONCLUSIONS: Neo-adjuvant chemotherapy showed a limited role in determining post-operative morbidity after hepatic resection and did not modify mortality.

Effectiveness and cost-effectiveness of peri-operative versus post-operative chemotherapy for resectable colorectal liver metastases.

BACKGROUND: The role of neo-adjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases is currently a matter of debate. The aim of the present study was to analyse life-expectancy, quality adjusted life-expectancy and cost-effectiveness of the two chemotherapeutic strategies. METHODS: A Markov decision model was developed, on the basis of parameters derived from an extensive literature search of the last ten years, to compare outcomes of peri-operative versus post-operative chemotherapy. RESULTS: Life-expectancy observed for peri-operative chemotherapy was 54.56months and 52.62months with post-operative chemotherapy only; the quality-adjusted life-expectancy with peri-operative chemotherapy was 39.33 quality-adjusted life-months (QALMs) and 37.84 QALMs with post-operative chemotherapy. Peri-operative chemotherapy results in an increase in total costs of 1180€ over ten years and in an incremental cost-effectiveness ratio (ICER) of 791.9€/QALM. The model was more sensitive to the expected 3-year recurrence-free survival (RFS) and cost of hepatic resection: with respect to an expected 3-year RFS⩽25% the peri-operative approach was more cost-effective than post-operative strategy but differences in average cost-effectiveness were small. The relationship between ICER and cost of hepatic resection was inverse because the higher the cost of hepatic resection, the higher the cost saving due to patients becoming unresectable during neo-adjuvant therapy. CONCLUSIONS: In the treatment of resectable colorectal liver metastases, the addition of neo-adjuvant chemotherapy could be cost-effective because it makes it possible to avoid hepatic resection in patients who do not respond to the neo-adjuvant approach; however, the life-expectancy of the two strategies is very similar.

Anatomic variations of intrahepatic bile ducts in a European series and meta-analysis of the literature.

BACKGROUND: Accurate knowledge of biliary anatomy and its variants is essential to ensure successful hepatic surgery; however, data from European countries are lacking. METHODS: Two hundred cholangiograms obtained from patients submitted to whole liver transplantation were reviewed; donors' characteristics were related to the prevalence of typical biliary anatomy and its variants. A comprehensive literature search was performed with MEDLINE and EMBASE from 1980 to 2010 to investigate whether geographical origin could be related to biliary abnormalities. RESULTS: Typical biliary anatomy was observed in 64.5% of cases, but female donors more frequently presented an anatomic variation; typical anatomy was present in 55.0% of females and in 74.0% of males (P = 0.005). Twenty-two reports were identified by the literature search with a total of 7,559 cases, including the present series; heterogeneity was low (Q = 14.60; I2 < 5.0%) after exclusion of three outlier reports. Prevalence of typical biliary anatomy was similar in Europeans and Americans (∼60%); a slightly higher prevalence was observed in Asiatics (∼65%). CONCLUSIONS: Anatomic variants seem to be more frequent in females, probably as a consequence of different embryologic development. Available data suggest that typical biliary anatomy can be more frequent in Asiatics, but an accurate means of classification is essential to making comparison realistic.

Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (<5 cm) hepatocellular carcinomas.

UNLABELLED: Transarterial chemoembolization (TACE) is commonly used as a bridge therapy for patients awaiting liver transplantation (LT) and for downstaging patients initially not meeting the Milan criteria. The primary aim of this study was to analyze whether a difference exists between selective/superselective and lobar TACE in determining tumor necrosis by a pathological analysis of the whole lesion at the time of LT. The secondary aim was to investigate the relationship between the tumor size and the capacity of TACE to induce necrosis. Data were extracted from a prospective database of 67 consecutive patients who underwent LT for hepatocellular carcinoma and cirrhosis from 2003 to 2009 and were treated exclusively with TACE as a bridging (n = 53) or downstaging therapy (n = 14). We identified 122 nodules; 53.3% were treated with selective/superselective TACE. The mean histological necrosis level was 64.7%; complete tumor necrosis was obtained in 42.6% of the nodules. In comparison with lobar TACE, selective/superselective TACE led to significantly higher mean levels of necrosis (75.1% versus 52.8%, P = 0.002) and a higher rate of complete necrosis (53.8% versus 29.8%, P = 0.013). A significant direct relationship was observed between the tumor diameter and the mean tumor necrosis level (59.6% for lesions < 2 cm, 68.4% for lesions of 2.1-3 cm, and 76.2% for lesions > 3 cm). Histological necrosis was maximal for tumors > 3 cm: 91.8% after selective/superselective TACE and 66.5% after lobar procedures. Independent predictors of complete tumor necrosis were selective/superselective TACE (P = 0.049) and the treatment of single nodules (P = 0.008). Repeat sessions were more frequently needed for nodules treated with lobar TACE (31.6% versus 59.3%, P = 0.049). CONCLUSION: Selective/superselective TACE was more successful than lobar procedures in achieving complete histological necrosis, and TACE was more effective in 3- to 5-cm tumors than in smaller ones.