Everolimus-based immunosuppression in liver transplant recipients: a single-centre experience

Purpose

Everolimus, a mammalian target of rapamycin inhibitor, has been shown to reduce growth factor-mediated cell proliferation, but data regarding its effectiveness and impact on renal function and recurrence of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients are limited.

Methods

We evaluated LT recipients with a calcineurin inhibitor (CNI)-based immunosuppression regimen in whom everolimus treatment was initiated. The changes in laboratory data, including glomerular filtration rate (GFR), compared to the baseline (i.e. the day of everolimus conversion), were assessed.

Results

Totally, 44 consecutive patients (32 men, age 55 ± 7 years) were commenced on everolimus [indications: renal dysfunction post-LT (16 patients, group 1); prevention of HCC recurrence (21 patients) or others (7 patients), group 2] at 6 months (range 1–206) post-LT. After 48 (range 12–76) months, all patients were alive without any rejection episodes. Compared to group 2 patients, group 1 patients had significantly greater improvement in renal function (DGFR: 12 ± 5 vs. ?0.4 ± 0.2 ml/min, p = 0.02). GFR at baseline (OR 0.08, p = 0.002) and the combination of everolimus + MMF (OR 0.14, p = 0.024) were the factors independently associated with improvement in renal function. Finally, HCC recurrence was observed less frequently in the everolimus group of patients (n = 21) compared to the CNI-historical control group (n = 22) with HCC before LT [0/21 (0 %) vs. 4/22 (18.5 %), log rank p = 0.055), although the two groups of recipients had similar baseline characteristics and follow-up.

Conclusions

Everolimus is effective and is associated with low rates of HCC recurrence and improvement of renal function in LT recipients.     

Value of Highly Sensitive Fucosylated Fraction of Alpha-Fetoprotein for Prediction of Hepatocellular Carcinoma Recurrence After Curative Treatment

Background

The fucosylated fraction of alpha-fetoprotein (AFP-L3) has been used as a diagnostic marker for hepatocellular carcinoma (HCC). Recently, a highly sensitive immunoassay using an on-chip electrokinetic reaction and separation by affinity electrophoresis (micro-total analysis system; μTAS) has been developed.

Aim

The aim of this study was to investigate the relationship between changes in the serum AFP-L3 level measured by μTAS assay and recurrence of HCC after curative treatment.

Methods

A total of 414 HCC patients who met the Milan criteria and underwent hepatectomy or radiofrequency ablation were investigated prospectively for the relationship between HCC recurrence and values of tumor markers.

Results

There were significant differences in recurrence-free survival between groups with and without AFP-L3 elevation measured before and after treatment (p = 0.024 and p = 0.001 for before and after treatment, respectively). Multivariate analysis revealed that AFP-L3 status (p = 0.002) measured 1 month after treatment was a significant independent predictor of HCC recurrence after curative treatment.

Conclusions

Elevation of the serum AFP-L3 level before treatment is a predictor of HCC recurrence, and sustained elevation of the AFP-L3 level after treatment is an indicator of HCC recurrence. Repeated measurement of μTAS AFP-L3 should be performed for surveillance of HCC recurrence after curative treatment.     

United States Women Receive More Curative Treatment for Hepatocellular Carcinoma Than Men

Background

Previous database studies have found gender disparities favoring men in rates of liver transplantation, which resolve in cohorts examining only patients with hepatocellular carcinoma (HCC).

Aims

Our study aims to use two large, multicenter United States (US) databases to assess for gender disparity in HCC treatment regardless of transplant listing status.

Methods

We performed a retrospective database analysis of inpatient admission data from the University Health Consortium (UHC) and the Nationwide Inpatient Sample (NIS), over a 9- and 10-year period, respectively. Adults with a primary discharge diagnosis of HCC, identified using the International Classification of Diseases 9th Edition (ICD-9) code, were included. Series of univariate and multivariate analyses were performed to examine gender disparities in metastasis, liver decompensation, treatment type, and inpatient mortality after controlling for other possible predictors.

Results

We included 26,054 discharges from the NIS database and 25,671 patients from the UHC database in the analysis. Women with HCC appear to present less often with decompensated liver disease (OR = 0.79, p < 0.001). Furthermore they are more likely to receive invasive HCC treatment, with significantly higher rates of resection across race and diagnoses (OR = 1.34 and 1.44, p < 0.001). Univariate analyses show that US women have lower unadjusted rates of transplant; however, the disparity resolves after controlling for other clinical and demographic factors.

Conclusions

US women more often receive invasive treatment for HCC (especially resection) than US men with no observed disparity in transplantation rates when adjusted for pre-treatment variables.     

Non-Adherence and Graft Failure in Adult Liver Transplant Recipients

Background

Non-adherence to medical therapy after liver transplantation is confounded by different methods of measurement.

Aims

(1) To compare the performance of three different methods of measuring non-adherence: (a) biochemical (standard deviation [SD] tacrolimus levels), (b) clinician report, (c) self-report. (2) To identify pre-transplant predictors of post-transplant non-adherence. (3) To evaluate whether SD tacrolimus is an accurate predictor of graft outcomes.

Methods

In this retrospective cohort study, charts of adult recipients of a liver transplant 2003–2009 (sample A, n = 444) were reviewed to determine pre-transplant predictors of non-adherence and clinician report of non-adherence. SD tacrolimus levels were measured between 6 and 18 months post-transplant. A subset of sample A (n = 122) completed a survey on non-adherence. The three methods were compared using linear and logistic regression. Multivariable analysis was used to investigate pre-transplant predictors of non-adherence. In sample B (transplant recipients 1995–2003, n = 544) Cox regression was used to determine the relationship between SD immunosuppressant level and graft failure.

Results

Non-adherence was found in 22–62 % of subjects, with the highest rates indicated by self-report. Clinician report of non-adherence was associated with both self-report and SD tacrolimus. On multivariable analysis, unemployment at time of listing and chart evidence of pre-transplant non-adherence were significant predictors of higher SD of tacrolimus. History of substance abuse and pre-transplant chart evidence of non-adherence were also significant independent predictors of post-transplant chart evidence of non-adherence. Drug variability in the immediate post-transplant setting was independently associated with graft failure over time (hazard ratio 1.005 per unit increase in standard deviation, p = 0.04).

Conclusions

Non-adherence among liver transplant recipients is a common problem associated with increased risk of graft failure. SD tacrolimus can be used to measure non-adherent behavior and perhaps target patients for behavioral interventions.     

A non-smooth tumor margin in the hepatobiliary phase of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging predicts microscopic portal vein invasion, intrahepatic metastasis, and early recurrence after hepatectomy in patients with hepatocellular carcinoma

Background

The value of the hepatobiliary phase of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC) has not been evaluated in detail.

Methods

Between 2008 and 2009, 61 patients with HCC within the Milan criteria underwent Gd-EOB-DTPA-enhanced MRI and hepatectomy. The tumor margin was determined preoperatively based on hepatobiliary phase images. Microscopic portal vein invasion (MPVI), intrahepatic metastasis (IM), and recurrence of HCC within 1 year after hepatectomy were evaluated in 24 patients with non-smooth margins at the periphery of the tumor and 37 patients with smooth margins.

Results

The number of patients with MPVI and IM of HCC was significantly higher among those with non-smooth margins (42 and 38%, respectively) than among those with smooth margins (3%; p = 0.0002 and 5%; p = 0.0042, respectively). A non-smooth margin was identified as a significant predictor of MPVI (odds ratio 18.814, p = 0.024) and IM (odds ratio 6.498, p = 0.036) of HCC on multivariate analysis. Furthermore, a non-smooth margin was identified as a significant predictor of recurrence within 1 year after hepatectomy (odds ratio 4.306, p = 0.04) on multivariate analysis.

Conclusions

A non-smooth tumor margin in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is useful to predict MPVI, IM, and early recurrence of HCC after hepatectomy.     

Familial clustering of hepatocellular carcinoma in HBsAg-positive patients in the United States

Purpose

The impact of familial clustering of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected persons in a low HBV endemic area was investigated.

Methods

Four hundred thirteen HBsAg-positive patients, 173 with HCC and 240 without HCC, were subgrouped into those with or without a family history of HCC and analyzed for risk factors associated with HCC development. In families with HCC clustering, the ages of HCC onset in parents and siblings were compared.

Results

Forty-four of 173 (25.4 %) HCC patients, all of Asian descent, had 82 other blood relatives with HCC. Of these, 69 (84.1 %) were first-degree relatives. Compared to HCC patients without HCC family history, male HCC patients with family history developed HCC at a younger age than either their mothers or fathers with HCC (45.2 ± 10.3 years vs. 63.0 ± 6.8 years, p < 0.001 and 41.2 ± 14.8 years vs. 60.5 ± 5.5 years, p = 0.001, respectively); however, this was not observed in female HCC patients. In mothers of index HCC cases, 22/26 (84.6 %) tested were HBsAg positive and 14 (63.6 %) had HCC; in fathers, 11/21 (52.4 %) tested were HBsAg positive and 10 (90.9 %) had HCC. By multivariate analysis, independent risk factors for HCC development included family history (OR = 2.58, p = 0.05), male gender (OR = 3.23, p = 0.03), cirrhosis (OR = 2.4, p = 0.04), Child-Pugh classification (OR = 7.62, p = 0.004), AFP per log₁₀ increase (OR = 1.68, p = 0.01), precore mutation (OR = 3.77, p = 0.003), and basal core promoter mutation (OR = 8.33, p < 0.001).

Conclusions

HBsAg-positive male HCC patients presented at a younger age than their parents with HCC. In adult patients with an HCC family history, HCC surveillance should begin at the time of the initial clinic encounter.     

Liver transplantation for hepatocellular carcinoma: the Baylor experience

Background

Liver transplantation (LTX) is indicated in selected patients with hepatocellular carcinoma (HCC) and cirrhosis.

Methods

We compared the outcome of LTX for patients with and without HCC in 5-year time periods between 1987 and 2007 to reflect the implementation of the Milan tumor selection criteria in 1997 and of the model for end-stage liver disease (MELD) score-based liver allocation in 2002.

Results

Of 2350 patients who underwent primary LTX, 330 had HCC. Five-year patient survival for HCC patients was 28.6% in 1987–1992 and 42.3% in 1992–1997, which was 41.4–31.4% lower than that in non-HCC patients (P < 0.0001). After 1997, 5-year survival was 76% for HCC patients, similar to the survival for non-HCC patients (P = 0.8784). Five-year tumor recurrence dropped from 52.9% (1987–1992) and 48.2% (1992–1997) to 11.4% (1997–2002) and 8.4% (2002–2007) (P < 0.0001). Multivariate analysis for tumor recurrence showed the following significant factors: tumor size >6 cm [hazard ratio (HR) 3.67], ≥5 nodules (HR 3.441), vascular invasion (HR 3.18), transplant in 1987–1992 (HR 6.772), and transplant in 1992–1997 (HR 3.059). MELD-based liver allocation reduced median waiting time for LTX for HCC versus non-HCC (35 vs. 111 days; P = 0.005) without compromise in patient outcome.

Conclusions

The results of LTX for HCC continue to improve and are equal to results in patients without HCC.     

Hepatic Preservation Injury: Severity of Hepatitis C Recurrence and Survival After Liver Transplantation

Background

Preservation injury in the HCV liver transplant population has been reported to correlate with poorer survival outcomes compared to preservation injury in the non-HCV liver transplant population. However, determinants of progression to cirrhosis in HCV infection remain poorly defined in this population.

Aim

This study aimed to determine if the presence and severity of preservation injury impact the acceleration of HCV recurrence and survival after liver transplant.

Methods

We retrospectively reviewed liver transplant HCV patients over a 10-year period. Biopsies from postoperative day 7 were assessed for preservation injury and 4- and 12-month biopsies were assessed for fibrosis. Patients with Ishak fibrosis >0.8 Units/year were considered rapid fibrosers.

Results

Our study group consisted of 255 patients. The mean age was 49.3 years old, 180 (70.6 %) were male, and 221 (86.7 %) were Caucasian. The incidence of preservation injury on the 7-day biopsy was 69.0 %. A strong correlation between postoperative peak AST within the first week and preservation injury was found. The overall prevalence of rapid fibrosers at 4 months, 1 and 2 years was 47.4, 75.2, and 58.9 %, respectively. The prevalence of rapid fibrosers at 4 months, 1 and 2 years between patients with or without preservation injury was not statistically significant (p = 0.39, p = 0.46, and p = 0.53, respectively). No differences were seen between patients with and without PI in terms of patient and graft survival.

Conclusion

In this study, the presence and severity of preservation injury were not associated with development of rapid HCV recurrence or worsening in survival.     

Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation

Background

High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is a strong risk factor of hepatocellular carcinoma (HCC) development, independent of hepatitis B e antigen, serum alanine aminotransferase level, and liver cirrhosis. We evaluated whether serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC treated with radiofrequency ablation (RFA).

Methods

The study population was 69 consecutive patients with HBV-related HCC treated locally completely with RFA between January 2000 and September 2007. The risk factors for HCC recurrence were analyzed based on laboratory data, including serum HBV DNA load, together with tumor size and number using univariate and multivariate proportional hazard regression analyses.

Results

HCC recurrence was observed in 42 of 69 patients during the median observation period of 1.5 years. Cumulative recurrence rates at 1, 3, and 5 years were 26.5, 57.8, and 74.3%, respectively. In univariate analysis, albumin (<3.5 g/dl), platelet count (<150 × 10³/mm³), prothrombin activity (PT) (<70%), Child-Pugh class B, serum HBV DNA load (>4.0 log10 copies/ml), and tumor number (>3) were associated with the recurrence at p ≤ 0.15. Multivariate Cox regression analysis with stepwise variable selection showed that the tumor number (risk ratio, 4.63; 95% CI, 1.50–14.25, P = 0.0076), low PT (3.39, 1.52–5.78, P = 0.0029), and high HBV DNA load (2.67, 1.16–6.14, P = 0.021) were independent risk factors for HCC recurrence.

Conclusion

Serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC after RFA.     

Diffusion-weighted imaging of hepatocellular carcinoma for predicting early recurrence and survival after hepatectomy

Purpose

The effectiveness of imaging (including apparent diffusion coefficient [ADC] of diffusion-weighted magnetic resonance imaging [DWI]) and laboratory variables for predicting early tumor recurrence and overall survival after surgery in hepatocellular carcinoma (HCC) patients are analyzed.

Methods

The present study included 116 consecutive patients with HCC who underwent partial hepatectomy. Patients were classified into two groups: patients with and without early recurrence (<1 year). Preoperative imaging variables (tumor number, size, shape, capsule, ADC, and venous invasion) and laboratory variables were evaluated to predict early recurrence using univariate and multivariate analyses. Overall survival was calculated using the Kaplan–Meier method.

Results

Twenty patients (17 %) developed early recurrence after surgery. Multivariate logistic regression analysis showed that tumor ADC (p = 0.0002), aspartate aminotransferase (p = 0.0121), and serum prothrombin time activity percentage (p = 0.0082) were statistically significant for predicting early recurrence. The optimal ADC cutoff value for predicting early recurrence obtained from receiver operating characteristic analysis was ≤0.898 × 10^?3 mm²/s. In patients with ADC ≤0.898 × 10^?3 mm²/s, the 3- and 5-year survival rates (77 and 56 %, respectively) were significantly decreased compared with those in patients with ADC >0.898 × 10^?3 mm²/s (97 and 97 %, respectively; p = 0.0015).

Conclusions

Low tumor ADC value by DWI was a risk factor for early postoperative HCC recurrence and was associated with lower patient survival rates.     

Fibrosis and AST to platelet ratio index predict post-operative prognosis for solitary small hepatitis B-related hepatocellular carcinoma

Purpose

Although advanced liver fibrosis is crucial in the development of hepatocellular carcinoma (HCC) for patients with chronic hepatitis B, whether it is associated with the recurrence of HCC after resection remains obscure. This study was aimed to compare the outcomes for patients with minimal or advanced fibrosis in solitary small hepatitis B virus (HBV)-related HCC.

Methods

This study enrolled 76 patients with small (<5 cm) solitary HBV-related HCC who underwent resection. The outcomes of patients with minimal and advanced fibrosis in non-tumor areas were compared. Serum markers were tested to assess the stage of hepatic fibrosis and to predict prognosis.

Results

Fourteen patients with an Ishak fibrosis score of 0 or 1 were defined as having minimal fibrosis; the remaining 62 patients were defined as having advanced fibrosis. During a follow-up period of 77.0 ± 50.7 months, 41 patients died. The overall survival rate was significantly higher (P = 0.018) and recurrence rate was lower (P = 0.018) for patients in the minimal fibrosis group. Aspartate aminotransferase–platelet ratio index (APRI) exhibited the most reliable discriminative ability for predicting advanced fibrosis. The overall survival rate was significantly higher (P = 0.003) and recurrence rate was lower (P = 0.005) for patients with an APRI of 0.47 or less.

Conclusions

For patients with solitary small HBV-related HCC who underwent resection, minimal fibrosis is associated with a lower incidence of recurrence and with better survival. APRI could serve as a reliable marker for assessing hepatic fibrosis and predicting survival.     

Intravenous Interferon Administered During Liver Transplantation Is Not Effective in Preventing Hepatitis C Reinfection

Background

Post-transplant hepatitis C is a major challenge after liver transplantation (LT). Antiviral therapy is associated with lower efficacy in the post-transplant setting.

Aims

The purpose of this study was to determine the safety and effect of intravenous interferon (IFN) during the anhepatic phase of LT on hepatitis C viral load.

Methods

Fifteen consecutive subjects undergoing liver transplant for hepatitis C cirrhosis were enrolled in the study, ten of which received study drug and five subjects served as controls. Cases received weight-based ribavirin and subcutaneous IFN at time of incision followed by intravenous IFN at the start of the anhepatic phase. Adverse events and viral levels were recorded. Repeated measures ANOVA was employed to test for differences over time, between the groups, and time by group interaction.

Results

All subjects had genotype 1 virus. Hepatitis C viral load was lower at week 4 in cases compared to controls (769,004 ± 924,082 IU/ml and 2,329,896 ± 3,731,749 IU/ml, respectively), but did not reach statistical significance (p = 0.50). Three subjects developed adverse events related to IFN including pulmonary edema, rejection, and neutropenia.

Conclusions

Intravenous IFN administered during the anhepatic phase of liver transplant did not prevent graft reinfection and was associated with manageable adverse events. This regimen could be further studied if direct acting antiviral agents alone are insufficient for treating post-transplant hepatitis C.     

Impact of Anti-Thymocyte Globulin During Immunosuppression Induction in Patients with Hepatitis C After Liver Transplantation

Background

Induction immunosuppression with anti-thymocyte globulin (ATG) provides potential benefits after liver transplantation (LT). However, its use in patients with LT and hepatitis C (HCV) is controversial.

Aim

To evaluate the 1- and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression (IPI) after LT.

Methods

A total of 49 patients undergoing their first LT for HCV were randomized to receive ATG during IPI. Patient survival and HCV recurrence were determined at 1 and 2 years. The frequency of acute cellular rejection (ACR), infections, and neoplasms was also evaluated.

Results

Twenty-six patients were randomized to receive ATG (Arm-1) and 23 to standard induction therapy (Arm-2). Those given ATG had lower HCV recurrence (26.9 vs 73.9 %, p = 0.001). The 1- and 2-year patient survival rates were similar for both arms (p = 0.33). Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 (p = 0.562). There was a greater proportion of fungal infections in Arm-1 (19.2 vs 0 %, p = 0.032).

Conclusions

ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT. This, however, did not affect the 1- and 2-year survival and the frequency of ACR, infections, or neoplasms.     

Radiofrequency-Assisted Versus Clamp-Crushing Parenchyma Transection in Cirrhotic Patients with Hepatocellular Carcinoma: A Randomized Clinical Trial

Background

Surgical resection remains the optimal therapy for cirrhotic patients with hepatocellular carcinoma (HCC) that are not suitable for liver transplantation (LT). Recently, various innovative techniques for liver resection have been developed.

Aim

The aim of the study was to compare radiofrequency-assisted parenchyma transection (RF-PT) with the traditional clamp-crushing (CC) technique to explore the preferred therapy in cirrhotic patients with HCC.

Methods

From January 2009 to December 2010, 75 cirrhotic patients with HCC who underwent hepatectomy were randomized to RF-PT (group 1, n = 38) or CC-PT (group 2, n = 37) groups. The primary endpoint was intraoperative blood loss. The secondary endpoints included hepatic transection time, total operating time, postoperative morbidity, mortality, length of intensive care unit and hospital stays, and liver function.

Results

The characteristics of the two patient groups were closely matched. The Pringle maneuver was not used in RF-PT patients. The blood loss of the RF-PT group, total or during transection, was significantly lower than that of the CC-PT group (385 vs. 545 ml, p = 0.001; 105 vs. 260 ml, p = 0.000, respectively). Compared with CC-PT patients, the morbidity of the RF-PT group was lower though not statistically significant (28.9 vs. 38.8 %, p = 0.197). One death occurred in the RF-PT group 12 days postoperative due to a large area cerebral embolism.

Conclusion

RF-PT is a safe and feasible surgical resection method for patients with cirrhosis and concomitant HCC. In addition, RF-PT results in lower blood loss and lower morbidity than the CC technique during liver resection.     

Clinicopathologic study on complications of orthotopic liver transplantation in 54 patients with chronic hepatitis B viral infection

Objective

To study the complication incidence of 54 patients with chronic HBV infection following orthotopic liver transplantation (OLT) and risk factors associated with HBV recurrence and hepatocellular carcinoma (HCC) recurrence or metastasis post-OLT.

Methods

The light-microscopic appearance of hepatic allograft biopsies in 54 patients with chronic HBV infection following OLT was examined. The related clinical data were analyzed. The incidence and occurrence time of post-OLT complications were studied. Furthermore, the relationship between hepatitis B virus recurrence and acute rejection and the relationship among HCC recurrence/metastasis, acute rejection, tumor diameter, and portal vein invasion were particularly studied.

Results

Frequent complications of patients with chronic HBV infection following OLT were acute rejection [38 (70.4 %); occurrence time: 5–365 days], chronic rejection [1 (1.9 %); occurrence time: 10.7 months], bile duct complications [24 (44.4 %);occurrence time: 7–940 days], HBV recurrence [7 (13.0 %); occurrence time: 1–540 days], HCV infection [3 (5.6 %); occurrence time: 60 days, 60 days, 33 months], CMV infection [8 (14.8 %); occurrence time: 67–90 days], and HCC recurrence or metastasis [17 (31.5 %); occurrence time: 2–41 months]. At the end of 1 year post-OLT, 95 % of patients with post-hepatitis B cirrhosis were alive. At the end of 3 years post-OLT, 85 % of patients with post-hepatitis B cirrhosis were alive. However, at the end of 1 year post-OLT, 67.6 % of patients with post-hepatitis B HCC were alive. At the end of 3 years post-OLT, 50 % of patients with post-hepatitis B HCC were alive. The number of acute rejection episodes in patients with recurrent HBV infection and in those without recurrent HBV infection was 0.86 ± 1.46 times/patient and 1.07 ± 0.90 times/patient, respectively (p > 0.05); the number of moderate acute rejection episodes (RAI score ≥4) in patients with recurrent HBV infection and in those without recurrent HBV infection was 0.29 ± 0.49 times/patient and 0.50 ± 0.63 times/patient (p > 0.05). Incidence of patients with ≥3 episodes of acute rejection in patient with recurrent HBV infection and in those without recurrent HBV infection was 14.3 and 10.6 % (p > 0.05). Furthermore, the number of acute rejection episodes in patients with HCC recurrence or metastasis and in those without HCC recurrence or metastasis was 1.12 ± 0.93 times/patient and 1.06 ± 1.39 times/patient, respectively (p > 0.05). The number of moderate acute rejection episodes (RAI score ≥4) in patients with HCC recurrence or metastasis and in those without HCC recurrence or metastasis was 0.65 ± 0.79 times/patient and 0.65 ± 1.06 times/patient, respectively (p > 0.05). Incidence of patients with ≥3 episodes of acute rejection in patients with HCC recurrence or metastasis and in those without HCC recurrence or metastasis was 5.9 and 17.6 %, respectively (p > 0.05). The tumor diameter in patients with HCC recurrence or metastasis was 6.72 ± 3.40 cm; however, that in patients without HCC recurrence or metastasis was 3.55 ± 2.17 cm (p = 0.0047). The incidence of portal vein invasion in patients with HCC recurrence or metastasis and in those without HCC recurrence or metastasis was 68.75 and 33.3 %, respectively (p = 0.006).

Conclusion

There was no significant difference between HBV recurrence and acute rejection post-liver transplantation in patients with chronic HBV infection. There was no significant difference between HCC recurrence and acute rejection. The tumor diameter in patients with HCC recurrence or metastasis was significantly greater than that in patients with no HCC recurrence or metastasis. Portal vein invasion was significantly more frequent in patients with HCC recurrence or metastasis than in those with no HCC recurrence or metastasis.     

Primary Surgical Resection Versus Liver Transplantation for Transplant-Eligible Hepatocellular Carcinoma Patients

Background

Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.

Aim

The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.

Methods

The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.

Results

The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08–6.86).

Conclusion

Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.     

Hepatitis C viral load predicts tumor recurrence after curative resection of hepatocellular carcinoma regardless of the genotype of hepatitis C virus

Purpose

To clarify the prognostic impact of the hepatitis C virus (HCV) genotype after curative resection for hepatocellular carcinoma (HCC).

Methods

A total of 199 patients who underwent a curative hepatic resection for HCV-related HCC were reviewed. The clinical outcomes were compared between patients infected with HCV genotype 1b (n = 160) and those infected with other genotypes (n = 39).

Results

With a comparable median HCV viral load (6.0 vs. 5.8 log₁₀ IU/mL, p = 0.17), the 3-year recurrence-free survival (RFS) rates (25 vs. 20 %, p = 0.65) and the 5-year overall survival (OS) rates (72 vs. 65 %, p = 0.73) were similar between the two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log₁₀ IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40 mAu/mL (HR, 1.64) were independent predictors of tumor recurrence, while the HCV genotype was not a significant risk factor. When the population was stratified according to the HCV viral load, a significant difference was observed in the RFS rate for both genotype 1b (p = 0.003) and the other genotypes (p = 0.037) at HCV viral load of 5.3 log₁₀ IU/mL.

Conclusions

The HCV genotype does not affect the surgical outcomes of patients with HCC. A lower HCV viral load is advantageous regardless of the HCV genotype.     

XPC gene variants: a risk factor for recurrence of urothelial bladder carcinoma in patients on BCG immunotherapy

Purpose

To investigate the association between two Xeroderma pigmentosum group C polymorphism (XPC Lys939Gln and insertion/deletion PAT ?/+ in intron 9) and bladder cancer (BC) susceptibility.

Materials and methods

Genotyping was performed in 208 BC patients and 245 controls by PCR–RFLP method.

Results

XPC PAT +/+ genotype was associated with elevated risk of BC (p = 0.021, OR = 2.49). XPC Lys939Gln AC + CC genotype was significantly associated with risk in invasive stage of BC (p = 0.041, OR = 2.52). Haplotype analysis revealed that variant genotypes C of XPC Lys939Gln and + of PAT, C+ were significantly associated with risk of BC (p = 0.004, OR = 1.70). The CC genotype of Lys939Gln was associated with high risk for recurrence in BCG-treated patients (HR = 3.21, p = 0.036) thus, showing reduced recurrence-free survival (AC + CC/AA = 36/60 months; log rank p = 0.045).

Conclusion

Polymorphisms and haplotypes in XPC appear to influence susceptibility to BC risk. The variant C allele at Lys939Gln may be responsible for early recurrence in BCG-treated patients.     

Lipiodolized transarterial chemoembolization in hepatocellular carcinoma patients after curative resection

Purpose

To explore the effect of lipiodolized transarterial chemoembolization (lip-TACE) in hepatocellular carcinoma (HCC) patients at different risk of recurrence after curative resection.

Methods

One thousand nine hundred and twenty-four consecutive HCC patients who underwent curative resection were retrospectively analyzed. Patients who underwent resection only were classified into control group, while those received adjuvant lip-TACE were classified into intervention group. Patients were further stratified into 4 groups, that is, tumor ≤5 cm with low or high risk factors, as well as tumor >5 cm with low or high risk factors for recurrence. Tumor number and microscopic tumor thrombus were defined as risk factors for recurrence. The effect of adjuvant lip-TACE on early (<2 year) or late (≥2 year) recurrence was evaluated.

Results

There was no significant difference in recurrence curve between intervention group and control group in each stratum. Adjuvant lip-TACE showed an overall survival benefit in patients with tumor >5 cm and presenting high risk factors, mainly for those with time to recurrence (TTR) <2 years after operation. For them, the median survival was 17 months in the intervention group and 11 months in the control group (P = 0.010). For patients who were confirmed to be recurrence-free at 2 years after operation, it had the negative effect for survival (HR = 1.75, P = 0.004).

Conclusion

Adjuvant lip-TACE had no preventive effect on recurrence, but may be of benefit to detect early recurrence.     

Laparoscopic liver resection for treating recurrent hepatocellular carcinoma

Background

It is still unknown whether laparoscopic liver resection is suitable for recurrent hepatocellular carcinoma (HCC) after previous curative hepatic resection.

Method

The perioperative outcomes of 40 patients treated with second surgery for recurrent HCC by partial hepatectomy were studied retrospectively. The second surgery was performed under laparotomy in 20 patients (laparotomy group) and under laparoscopy in 20 patients (laparoscopy group).

Results

Intraoperative blood loss (p < 0.0001) and the incidence of postoperative complications (p = 0.0004) were lower in the laparoscopy group than in the laparotomy group. The incidence rates of surgical site infection and intractable ascites were significantly higher in the laparotomy group than in the laparoscopy group (p = 0.0202, p = 0.0436, respectively). The proportion of patients classified as Clavien grade IIIa was higher in the laparotomy group than in the laparoscopy group (p = 0.0033). The duration of the postoperative hospital stay was significantly shorter in the laparoscopy group than in the laparotomy group (p < 0.0001).

Conclusions

Postoperative morbidity has been decreased by the introduction of laparoscopic liver resection in patients with recurrent HCC after curative hepatic resection. As a result, the duration of the postoperative stay is shorter.