Misdiagnosis of hepatocellular carcinoma in patients receiving no local‐regional therapy prior to liver transplant: An analysis of the Organ Procurement and Transplantation Network explant pathology form

Patients with T1 hepatocellular carcinoma (HCC) are not eligible for Model for End Stage Liver Disease (MELD) exception for liver transplant (LT) in part due to a high rate of misdiagnosis (no HCC on explant). The likelihood of misdiagnosis for T2 HCC and factors associated with misdiagnosis are unknown. We analyzed the Organ Procurement and Transplantation Network database including 5664 adults who underwent LT from 2012 to 2015 with MELD exception for T2 HCC, and searched for no evidence of HCC in the explant pathology file. We focused on those (n = 324) receiving no local‐regional therapy (LRT) to evaluate the probability of no HCC found in explant. Median waiting time was short at 1.7 months, and 35 (11%) had no HCC on explant. On multivariable logistic regression, factors associated with no HCC on explant were age <50 (OR: 17.3, P < .001), non‐HCV (OR: 5.4, P = .001), and alpha‐fetoprotein <10 (OR: 2.9, P = .04). Tumor size and number were not different between groups. The proportion of misdiagnosis did not change significantly after implementation of Liver Imaging Reporting and Data System (LI‐RADS) for HCC diagnosis. Conclusion: The rate of misdiagnosis was 11% among T2 HCC patients who underwent LT without receiving LRT prior to LT and did not change significantly after implementation of LI‐RADS. More efforts are needed to eliminate unnecessary LT for patients without HCC.     

The prognosis and treatment outcomes of patients with recurrent hepatocellular carcinoma after liver transplantation

Liver transplantation (LT) is performed in patients with hepatocellular carcinoma (HCC), but recurrent HCC after LT remains a problem. We retrospectively reviewed the data from 63 patients with recurrent HCC who underwent LT at a single institution between September 1996 and March 2011 to determine the prognosis of patients with recurrent HCC after LT. A survival analysis was performed with the preoperative data, histological findings, patterns of recurrence, and treatment methods. Univariate and multivariate analyses were performed to determine the factors associated with early (<1 yr) cancer‐related death. The independent prognostic factors, according to the multivariate analysis, were recurrence within six months (hazards ratio [HR] = 4.557, p = 0.021) and initial multiple‐organ involvement (HR = 5.494, p = 0.015). The survival rates of patients differed according to the treatment type. The combined treatment with local and systemic treatment resulted in increased survival even in patients with HCC recurrences involving multiple organs.     

Liver Transplantation for Malignant Diseases: Selection andPattern of Recurrence

Liver transplantation (LT) for malignant tumors should be accepted if, with adequate case selection, long-term results are similar to those in patients transplanted for benign diseases. The aim of the present study was to reexamine selection criteria for LT in malignant diseases with particular emphasis on hepatocellular carcinoma (HCC) in cirrhosis. One hundred-three of 369 patients transplanted in our unit had HCC in cirrhosis (28%), 15 of which were incidental tumors, and 234 patients underwent LT for non-cholestatic cirrhosis. Pretransplant arterial chemoembolization(TACE) was performed in 36 cases (41%) of known HCC. Only early,well-delimited tumors in advanced cirrhosis with no extrahepatic disease were accepted for LT. Hepatocellular carcinoma characteristics included mean tumor size (3.1 cm), multiple (59%), bilobular involvement (31%), and vascular invasion (9.2%). Postoperative mortality was 4%. Median follow-up was 67.5 months. Tumor recurrence rate was 14.5%, 33% (5/15) in incidental tumors and 11.4% (10/88) in known HCC and by tumor stage (pTNM): 7.7% (1/13) in stage I, 16.7%(5/30) in stage II, 15% (3/20) in stage III, and 17% (6/35) in stage IV. Mean time for recurrence was 20.6 months. Tumoral vascular invasion, tumor differentiation, and satellite tumors were significant factors for tumor recurrence in univariate analysis, whereas tumor vascular invasion was the only significant factor for tumor recurrence in multivariate analysis. Actuarial survival rates at 1, 3, and 5 years were 81%, 66%, 58%, respectively, in patients with HCC and were similar to those of cirrhotic patients 76%, 67%, 63%, respectively.In conclusion, patients with early HCC in cirrhosis are good candidates for LT; results are similar when compared with those of cirrhotic patients without tumor. Liver transplantation for other malignancies is admitted only in fibrolamellar hepatoma, hepatoblastoma, epithelioid hemangioendothelioma without extrahepatic disease, and in metastases from carcinoid tumors.     

Hepatocellular carcinoma in Child's A cirrhosis: a retrospective analysis of matched pairs following liver transplantation vs. liver resection according to the intention‐to‐treat principle

This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Child's A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Child's A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre‐treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention‐to‐treat principle resulted in a better five‐yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five‐yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five‐yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Child's A cirrhosis.     

Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database

Researchers in a recent multicenter study developed and validated a novel prognostic index, Risk Estimation of Tumor Recurrence After Transplant (RETREAT), which incorporates α‐fetoprotein (AFP) at liver transplantation (LT), microvascular invasion, and the sum of the largest viable tumor and number of tumors on explant. We now aim to evaluate RETREAT in the United Network for Organ Sharing (UNOS) database in patients with hepatocellular carcinoma (HCC) who meet Milan criteria by imaging and underwent LT between 2012 and ‐2014. On explantation (n = 3276), 13% had microvascular invasion, 30% had no viable tumor, and 15% exceeded Milan criteria. Post‐LT survival at 3 years decreased with increasing RETREAT score: 91% for a score of 0, 80% for a score of 3, and 58% for a score ≥5 (P < .001). Post‐LT HCC recurrence probability within 3 years increased from 1.6% with RETREAT score of 0% to 29% for a score ≥5 (P < .001). Increasing RETREAT score was also associated with a shorter time to HCC recurrence. RETREAT was superior to Milan criteria (explant) in predicting HCC recurrence by the net reclassification index (P < .001). This study validates the prognostic power of RETREAT, which may help standardize post‐LT surveillance, provide a framework for tumor staging and risk stratification, and select candidates for adjuvant therapies.     

Sorafenib treatment is save and may affect survival of recurrent hepatocellular carcinoma after liver transplantation

Introduction

Recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) is a rare but challenging condition. In most cases, the recurrent tumor is presented with extrahepatic spread. Therefore, systemic treatment with sorafenib has to be assessed. Because of a plethora of possible drug interactions, e.g., with immunosuppressant or anti-infective therapy, safety and feasibility of sorafenib treatment requires special attention.

Materials and methods

We retrospectively analyzed 18 patients who suffered from recurrent advanced HCC after LT between January 2002 and December 2010 at the University Hospital Heidelberg regarding safety of sorafenib treatment and survival.

Results

Results showed that 8 patients were eligible for treatment with sorafenib showing a median time to progression (TTP) of 4.5 months and an overall survival of 9 months. Most common side effects were grades I and II diarrhea and hand–foot syndrome (HFS) which could be managed by sorafenib dose reduction. No grade III or IV adverse events (AEs) were noticed. No patient had to discontinue treatment due to AEs. The ten patients not amenable for sorafenib treatment, due to initial poor performance status or its deterioration after first line treatment, were treated with surgical resection (n?=?3), locoregional therapies (n?=?1), or palliative radiation therapy (n?=?1). They showed a median overall survival of 2.3 months.

Conclusion

Sorafenib may represent a therapeutic option for recurrent HCC after LT with manageable side effects. The clinical benefit of sorafenib in this setting is promising but needs to be confirmed in a prospective randomized trial.     

Liver transplant for hepatocellular carcinoma in the United States: Evolving trends over the last three decades

Hepatitis C virus infection has been the most common etiology in HCC‐related liver transplantation (LT). Since 2014, direct‐acting antivirals (DAAs) have dramatically improved HCV cure. We aimed to study the changing pattern of etiologies and impact in outcome in HCC‐related LT according to HCV treatment‐era through retrospective analysis of the Scientific Registry of Transplant Recipients (SRTR) database (1987‐2017). A total of 27 855 HCC‐related liver transplants were performed (median age 59 years, 77% male). In the DAA era (2014‐2017) there has been a 14.6% decrease in LT for HCV‐related HCC; however, HCV remains the most common etiology in 50% of cases. In the same era, there has been a 50% increase in LT for NAFLD‐related HCC. Overall survival was significantly worse for HCV‐related HCC compared to NAFLD‐related HCC during pre‐DAA era (2002‐2013; P = .031), but these differences disappeared in the DAA era. In addition, HCV patients had a significant improvement in survival when comparing the DAA era with IFN era (P < .001). Independent predictors of survival were significantly different in the pre‐DAA era (HCV, AFP, diabetes) than in the DAA era (tumor size). HCV‐related HCC continues to be the main indication for LT in the DAA era, but patients’ survival has significantly improved and is comparable to that of NAFLD‐related HCC.     

Physical frailty after liver transplantation

Frailty is prevalent in liver transplant candidates, but little is known of what happens to frailty after liver transplantation. We analyzed data for 214 adult liver transplant recipients who had ≥1 frailty assessment using the Liver Frailty Index (LFI) at 3‐ (n = 178), 6‐ (n = 139), or 12‐ (n = 107) months posttransplant (higher values=more frail). “Frail” and “robust” were defined as LFI ≥4.5 and <3.2. Median pre–liver transplant LFI was 3.7, and was worse at 3 months (3.9; P = .02), similar at 6 months (3.7; P = .07), and improved at 12 months (3.4; P < .001). The percentage who were robust pre‐ and 3‐, 6‐, and 12‐months posttransplant were 25%, 14%, 28%, and 37%; the percentage frail were 21%, 21%, 10%, and 7%. In univariable analysis, each 0.1 pretransplant LFI point more frail was associated with a decreased odds of being robust at 3‐ (odds ratio [OR] 0.75), 6‐ (OR 0.77), and 12‐months (OR 0.90) posttransplant (P ≤ .001), which did not change substantially with multivariable adjustment. In conclusion, frailty worsens 3 months posttransplant and improves modestly by 12 months, but fewer than 2 of 5 patients achieve robustness. Pretransplant LFI was a potent predictor of posttransplant robustness. Aggressive interventions aimed at preventing frailty pretransplant are urgently needed to maximize physical health after liver transplantation.     

The association of pretransplant ferritin level with waiting list and post‐transplant survival. Does ferritin actually predict outcome?

Recent data suggest an association of serum ferritin (SF) with waiting list (WL) and postliver transplant (LT) outcomes. To assess the predictive capacity of SF on pre‐ and post‐LT outcomes, and to identify whether recipient or donor liver siderosis is associated with post‐LT survival; a retrospective analysis of 1079 patients assessed for first LT, 2000–2007 was performed. Iron deposition in the liver tissue was assessed using a semi‐quantitative grading system. Median age was 54 (18–82) years and 67% were male. Seventeen per cent had hepatocellular carcinoma (HCC). Median Model for End‐stage Liver Disease MELD score was 14 (6–40), ferritin was 174 μg/l (4–4597) with 36.5% had a SF ≥ μg/l. Age (OR = 1.028) and MELD score (OR = 1.158) were independently associated with WL mortality (P < 0.001), whilst SF was not (P = NS). Age (OR = 1.018), HCC (OR = 1.542) and cold ischemia time (CIT) ≥ 10 h (OR = 1.418) were independently associated with post‐LT survival (P < 0.05). Explant siderosis grade <2 was seen in 376 (71.7%) patients. Patients with explant siderosis grade ≥2 had inferior 12‐month post‐LT survival (P = 0.030). Presence of graft siderosis (15.8% of patients) was not associated with survival. In conclusion, we found a limited role for SF as a prognostic indicator for pre‐ or post‐transplant survival.     

Related Factors of Hepatocellular Carcinoma Recurrence Associated With Hyperglycemia After Liver Transplantation

BackgroundRecurrence of hepatocellular carcinoma (HCC) is the main factor affecting the prognosis of patients with HCC undergoing liver transplantation (LT). In this study, we investigated the influencing factors of tumor recurrence and survival after LT for HCC, especially the long-term correlation with elevated fasting blood glucose (FBG).MethodsClinical data from 165 patients with HCC after LT in the General Hospital of Southern Theater Command of PLA between January 2013 and December 2016 were retrospectively analyzed. Disease-free survival (DFS) and overall survival (OS) rates, demographic characteristics, tumor characteristics, and surgical and postoperative data were evaluated.ResultsAmong 165 patients, 144 completed over 60 months of follow-up; the median follow-up period was more than 36 months. DFS rates were 76.97%, 51.52%, and 34.73% for 1, 3, and 5 years, respectively. The OS rate for 5 years was 40.28%. Independent risk factors for 1-year DFS were maximum tumor diameter >5 cm, age <49 years, and platelet transfusion. Independent risk factors for 3- and 5-year DFS were maximum tumor diameter >5 cm, capsular invasion, and FBG ≥6.1 mmol/L. Independent risk factors for OS were maximum tumor diameter >5 cm, capsular invasion, and FBG ≥6.1 mmol/L.ConclusionElevated FBG after LT for HCC may promote medium- to long-term tumor recurrence and affect OS. Age <49 years, platelet transfusion, maximum tumor diameter, capsular invasion, and microvascular invasion in patients with HCC also impact survival and tumor recurrence after LT.     

Outcome comparison of liver transplantation for hepatitis A‐related versus hepatitis B‐related acute liver failure in adult recipients

Hepatitis A virus (HAV) can cause acute liver failure (ALF). This study compares outcomes between liver transplantation (LT) for HAV‐related ALF (HAV‐ALF) and LT for hepatitis B virus (HBV)‐related ALF (HBV‐ALF). Of 3616 adult LTs performed between January 2005 and December 2014, we performed LT for HAV‐ALF recipients (n = 29) and LT for HBV‐ALF recipients (n = 34). HAV‐ALF group included 18 males and 11 females with mean age of 33.1 years. Graft survival rates in HAV‐ALF and HBV‐ALF were 65.5% and 88.0% (1 year) and 65.5% and 84.0% (5 years) (P = .048). Patient survival rates in HAV‐ALF and HBV‐ALF were 69.0% and 88.0% (1 year) and 69.0% and 84.0% (5 years) (P = .09). Multivariate analyses demonstrated that acute pancreatitis and HAV recurrence were independent risk factors of graft and patient survival. Post‐transplant outcome was poorer in patients with HAV‐ALF than in those with HBV‐ALF. This weakens LT's appropriateness in HAV‐ALF patients with pancreatitis. HAV recurrence after LT for HAV‐ALF is common and often fatal; thus, HAV recurrence should be monitored vigilantly, beginning early post‐transplant.     

Efficacy and Safety of Combination Therapy With Everolimus and Sorafenib for Recurrence of Hepatocellular Carcinoma After Liver Transplantation

Background

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice.

Methods

This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug.

Results

Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%).

Conclusions

Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival.     

Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review

Calcineurin inhibitors (CNIs) have been associated in a dose‐dependent fashion with an increased risk of post‐transplant hepatocellular carcinoma (HCC) recurrence. The mammalian target of rapamycin inhibitors (mTORi) (sirolimus/everolimus) might represent an alternative immunosuppressive regimen with antineoplastic effect. In the present systematic review, the association between mTORi and HCC recurrence after liver transplantation (LT) was evaluated and compared against that of CNIs‐treated patients. In total, 3666 HCC liver transplant recipients from 42 studies met the inclusion criteria. Patients under CNIs developed HCC recurrence significantly more frequently, compared with patients under mTORi (448/3227 or 13.8% vs. 35/439 or 8%, P < 0.001), although patients treated with CNIs had a higher proportion of HCC within Milan criteria (74% vs. 69%) and lower rates of microvascular invasion, compared with mTORi‐treated patients (22% vs. 44%) (P < 0.05). Patients on everolimus had significantly lower recurrence rates of HCC, compared with those on sirolimus or CNIs (4.1% vs. 10.5% vs. 13.8%, respectively, P < 0.05), but everolimus‐treated recipients had shorter follow‐up period (13 vs. 30 vs. 43.2 months, respectively) and more frequently been transplanted for HCC within Milan criteria (84% vs. 60.5% vs. 74%, respectively, P < 0.05). Our findings favor the use of mTORi instead of CNIs to control HCC recurrence after LT, but comparative studies with longer follow‐up are needed for final conclusions.     

Recurrence of Hepatitis D Virus in Liver Transplant Recipients With Hepatitis B and D Virus–Related Chronic Liver Disease

PurposeData on recurrence of hepatitis D virus (HDV) and its long-term impact on liver transplant (LT) are limited. In this study, we investigated the incidence of hepatitis B virus (HBV) and the long-term effect of postoperative HDV recurrence HDV coinfection in our liver transplant patients.Patients and MethodsBetween 2004 and 2018, all patients with LT because of HBV (n = 361; 37.3%) were reviewed, and those with HBV and HDV coinfection (n = 104; 30% of all HBV patients) were enrolled in our study. All patients received post-transplant combination therapy with nucleos(t)ide analogue and antihepatitis B immunoglobulins. Breakthrough infection was defined as reemergence of HBV DNA or hepatitis B surface antigen during postoperative treatment. In case of recurrence, another oral nucleos(t)ide analogue was added and antihepatitis B immunoglobulins were stopped.ResultsDuring the study period, the frequency of HDV (+) was decreased (41% to 14%). Median follow-up time was 82 months (range, 1-274 months). Post LT survival and HBV recurrence were 97% (n = 15) and 13.4%, respectively. Only 15 patients (14%) developed breakthrough infection. There was no predictive factor for recurrent HDV infection, including demographics data and concomitant hepatocellular carcinoma (P = .73). Mortality was similar between patients with and without recurrence (2.2% vs 7.1%, P = .35)ConclusionsPatients who received transplants for hepatitis B and D virus cirrhosis had favorable prognosis and good long-term results despite recurrent infection. Close follow-up of patients and effective postoperative viral suppression with appropriate medications seems to be favorable for both prevention and management of recurrence and provides comparable outcome with patients without recurrence.     

Impact of locoregional therapy and alpha‐fetoprotein on outcomes in transplantation for liver cancer: a UNOS Region 6 pooled analysis

Liver transplantation (LT) provides optimal long‐term disease‐free survival for hepatocellular carcinoma (HCC). High pre‐LT alpha‐fetoprotein (AFP) has been associated with HCC recurrence, but it is unclear whether a drop in AFP or locoregional therapy impacts survival/recurrence after LT. LT‐recipients transplanted for HCC in three centers (UNOS Region 6) were reviewed (2006–2009) for demographics, tumor characteristics, locoregional therapy, AFP, recurrence, and survival. Among 211 LT recipients (mean age 56.4 yr, 83% male, mean MELD 12.2), 94% met Milan criteria and 61% received locoregional therapy. Mean disease‐free survival (DFS) was 1549.7 d, and 84% are currently alive. Factors affecting DFS included recurrence (RR, 0.074; 95% CI, 0.038–0.14), normal peak AFP (29.6, 95% CI, 2.96–296.3), peak AFP >400 (RR, 0.15; 95% CI, 0.03–0.73) and AFP at LT >400 (RR, 15.5; 95% CI, 2.4–100.5). Twenty‐one patients had recurrence and were more likely beyond Milan criteria (5/23(21%) vs. 8/220 (4%), p = 0.0038), with peak AFP >400 and AFP at LT >400 (p = 0.001). Locoregional therapy did not affect mean DFS (1458.0 vs. 1603.8 d, p = 0.05) or recurrence (12.5% vs. 6%). Predictors of recurrence were similar to previous studies, including high AFP and tumor outside Milan criteria. While locoregional therapy itself did not affect DFS/recurrence, a decrease in AFP pre‐transplant appears to positively influence outcomes in those who received locoregional therapy.     

The long‐term efficacy of nucleos(t)ide analog plus a year of low‐dose HBIG to prevent HBV recurrence post‐liver transplantation

Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long‐term nucleos(t)ide analog in combination with one yr of low‐dose HBIG. One hundred and fifty‐two adults with HBV‐related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long‐term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow‐up post‐transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long‐term follow‐up, demonstrates that short course of low‐dose HBIG (without anti‐HBs monitoring) combined with the use of long‐term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.     

Progression of Alphafetoprotein Before Liver Transplantation for Hepatocellular Carcinoma in Cirrhotic Patients: A Critical Factor

Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty‐three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, ‘progression’ of AFP was defined by >15 μg/L per month before LT. A total of 127 (83%) were transplanted under and 26(16%) over this threshold. After 45 months of follow‐up (median), 5‐year overall survival (OS) and recurrence free‐survival (RFS) were 72% and 69%, respectively. Five‐year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP >15 μg/L per month and preoperative nodules >3 were associated with decreased OS. Progression group and age >60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor >30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP >15 μg/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness.     

New nucleos(t)ide analogue monoprophylaxis after cessation of hepatitis B immunoglobulin is effective against hepatitis B recurrence

New nucleos(t)ide agents (NAs) [entecavir (ETV) and tenofovir (TDF)] have made hepatitis B immunoglobulin (HBIG)‐sparing protocols an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). Twenty‐eight patients transplanted for HBV cirrhosis in our centre were prospectively evaluated. After LT, each patient received HBIG (1000 IU IM/day for 7 days and then monthly for 6 months) plus ETV or TDF and then continued with ETV or TDF monoprophylaxis. All patients had undetectable HBV DNA at the time of LT, and they were followed up with laboratory tests including glomerular filtration rate (GFR) after LT. All patients (11 under ETV and 17 under TDF) remained HBsAg/HBV DNA negative during the follow‐up period [median: 21 (range 9–43) months]. GFR was not different between TDF and ETV groups of patients at 6 and 12 months and last follow‐up (P value >0.05 for all comparisons). The two groups of patients were similar regarding their ratio of maximum rate of tubular phosphate reabsorption to the GFR (TmP/GFR). In conclusion, in this prospective study, we showed for the first time that maintenance therapy with ETV or TDF monoprophylaxis after 6 months of low‐dose HBIG plus ETV or TDF after LT is highly effective and safe.     

TACE联合射频消融及索拉非尼治疗巨块型肝细胞癌的回顾性研究

目的:评估经导管肝动脉栓塞化疗(TACE)联合射频消融及索拉非尼在巨块型肝细胞癌治疗中的安全性及疗效。方法:回顾分析2012年1月至2017年12月于中山大学附属第三医院诊治的36例肝细胞癌(直径5～7 cm)患者资料,其中男性33例,女性3例,年龄范围32.0～76.0岁,平均51.8岁。所有患者均接受TACE联合射...     

Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience

The safety and efficacy of an IFN‐free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV‐DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg‐IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg‐IFN/RBV in 12 (16.2%) patients. Resistance‐associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty‐one (82.4%) patients completed the 24‐week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no‐SVR. By excluding the patients with either a history of SMV‐based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV‐DCV was favorable, with a high SVR rate.