Secondary Liver Transplantation Research Articles

Benefits of Laparoscopy for Liver Resection Are Seen at the Time of Secondary Liver Transplantation

Benefits of Laparoscopy for Liver Resection Are Seen at the Time of Secondary Liver Transplantation

Continuous Renal Replacement Therapy in Pediatric Patients With Acute Kidney Injury After Liver Transplantation.

ObjectiveThis study aimed to explore the clinical application of continuous renal replacement therapy (CRRT) in pediatric patients with acute kidney injury (AKI) after liver transplantation.MethodsPediatric patients who underwent liver transplantation were retrospectively investigated. Those who developed AKI within 1 year after the surgery were included and divided into a CRRT group and a non-CRRT group. The perioperative conditions and postoperative complications of the two groups were compared along with the prognoses of the groups to analyze the high-risk factors of the postoperative CRRT.Results189 (36.91%) patients developed AKI within 1 year after the liver transplantation surgery. There were 18 patients in the CRRT group and 171 in the non-CRRT group. The differences in the preoperative conditions were not statistically significant between the two groups. Compared with the non-CRRT group, patients in the CRRT group had significantly longer transplantation times, higher volumes of intraoperative hemorrhage, and increased incidence of postoperative unscheduled surgery, postoperative primary nonfunction of the transplanted liver, secondary liver transplantation, hepatic artery occlusion, and intestinal fistula (P < 0.05). Moreover, the proportion of patients in AKI stage 3 is higher in the CRRT group (83.33%) than that in the non-CRRT group (11.11%), P < 0.001. The median time to initiate CRRT was 10 days postoperatively, the median number of CRRT treatments per patient was 2 times, the average duration of each CRRT treatment was 10.1 h, and the average rate of the decrease in blood creatinine per treatment was 25.6%. Results of multivariate logistic regression analysis showed that AKI stage 3 [OR=40.000, 95%CI (10.598, 150.969), P = 0.016], postoperative unscheduled surgery [OR=6.269, 95%CI (3.051, 26.379), P = 0.007], and hepatic artery occlusion [OR = 17.682, 95%CI (1.707, 40.843), P = 0.001] were recognized as risk factors for postoperative AKI with CRRT therapy. The one- and two-year survival rates were 72.22% and 72.22% in the CRRT group, respectively; and 97.08% and 96.49% in the non-CRRT group, accordingly. There were statistically significant differences in the one- and two-year survival rates between the two groups (P < 0.001).ConclusionThe incidence of AKI after liver transplantation in pediatric patients was high. Patients with AKI stage 3, hepatic artery occlusion, and underwent unscheduled surgery postoperatively were with a high likelihood of receiving CRRT, which was related to a lower one- and two-year survival rates. CRRT effectively improved the one- and two-year survival rates.

The Impact of Time Interval between Hepatic Resection and Liver Transplantation on Clinical Outcome in Patients with Hepatocellular Carcinoma.

Simple SummaryRecurrence of disease or worsening of liver function after hepatic resection (HR) for hepatocellular carcinoma (HCC) may require secondary liver transplantation (SLT). However, a history of HR is supposed to increase the surgical complexity of LT. This is one of the largest series of SLT and it demonstrates that among all the features analyzed regarding the prior HR, only time interval between HR and SLT was an independent predictor of severe complications after SLT. In particular, an increasing probability of severe complications was observed in those patients who were transplanted close (<15 months) to the HR. There was no significant association between HCC-related death and the time between HR and SLT at the multivariable competing risks regression model. Furthermore, these results remained inside the benchmark values recently reported for LT, confirming that tertiary referral centers with consistent experience in HPB surgery and LT may have benefits in both fields.Hepatic resection (HR) for hepatocellular carcinoma (HCC) may require secondary liver transplantation (SLT). However, a previous HR is supposed to worsen post-SLT outcomes. Data of patients treated by SLT between 2000 and 2018 at two tertiary referral centers were analyzed. The primary outcome of the study was to analyze the impact of HR on post-LT complications. A Comprehensive Complication Index ≥ 29.6 was chosen as cutoff. The secondary outcome was HCC-related death by means of competing-risk regression analysis. In the study period, 140 patients were included. Patients were transplanted in a median of 23 months after HR (IQR 14–41). Among all the features analyzed regarding the prior HR, only time interval between HR and SLT (time HR-SLT) was an independent predictor of severe complications after LT (OR = 0.98, p < 0.001). According to fractional polynomial regression, the probability of severe complications increased up to 15 months after HR (43%), then slowly decreased over time (OR = 0.88, p < 0.001). There was no significant association between HCC-related death and time HR-SLT at the multivariable competing risks regression model (SHR, 1.06; 95% CI: 0.69–1.62, p = 0.796). This study showed that time HR-SLT was key in predicting complications after LT, without affecting HCC-related death.

LIVER TRANSPLANTATION FOR BILE DUCT INJURY AFTER CHOLECYSTECTOMY

Bile duct injury is a life-threatening complication that requires proper management to prevent the onset of negative outcomes. Patients may experience repeated episodes of cholangitis, secondary biliary cirrhosis, end-stage liver disease and death. To report a single center experience in iatrogenic secondary liver transplantation after cholecystectomy and review the literature. This was a retrospective single center study. Of the 1662 liver transplantation realized, 10 (0.60 %) were secondary to iatrogenic bile ducts injuries due cholecystectomies. Medical records of these patients were reviewed in this study. Nine of 10 patients were women; the median time in waiting list and between cholecystectomy and inclusion in waiting list was of 222 days and of 139.9 months, respectively. Cholecystectomy was performed by open approach in eight (80%) cases and by laparoscopic approach in two (20%) cases. The patients underwent an average of 3.5 surgeries and procedures before liver transplantation. Biliary reconstruction was realized with a Roux-en-Y hepaticojejunostomy in nine (90%) cases. Mean operative time was 447.2 minutes and the median red blood cell transfusion was 3.4 units per patient. Mortality in the first month was of 30%. Although the liver transplantation is an extreme treatment for an initially benign disease, it has its well-defined indications in treatment of bile duct injuries after cholecystectomy, either in acute or chronic scenario.

Complications in patients surviving over ten years after liver transplantation

Objective To analyze the complicationsin patients surviving over ten years after liver transplantation. Methods Total 397 patients underwent liver transplantation from May 2000 to May 2008 at Department of Hepatobiliary Surgery, Peking University People′s Hospital, among whom 217 patients survived for ≥10years; after 12 cases with incomplete data were excluded, 205 cases were enrolled in the study. The complications of patients after liver transplantation were analyzed. Results The survival rate of patients over 10 years after liver transplantation was 51.6% (205/397). In 205 patients surviving ≥10years after liver transplantation, the incidence of de novo neoplasms was 3.9% (n=8); the prevalence of hyperuricemia,obesity,hyperlipidemia, metabolic syndrome, hypertension, and diabetes was 54.1% (n=111), 52.2% (n=107), 48.3% (n=99), 46.8% (n=96), 42.9% (n=88), and 18.5% (n=38), respectively. The recurrence rate of hepatitis B and the incidence of newly infected hepatitis B were 2.0% (n=4) and 1.0% (n=2), respectively. The incidence of cardiovascular and cerebrovascular events, renal insufficiency and biliary complications were 2.0% (n=4), 4.9% (n=10) and 12.2% (n=25), respectively. Fourteen patients dies 10 years after liver transplantation, the causes of death were cancer (n=4), biliary complications (n=4), recurrence of hepatitis B (n=2), cardio-cerebrovascular disease (n=2), renal insufficiency (n=1), and secondary liver transplantation (n=1). Conclusion Liver transplantation may prolong survival of patients with terminal liver diseases. The neoplasms, metabolic diseases, cardiovascular and cerebrovascular diseases, hepatitis B recurrence and chronic renal damage would affect the long-term survival of patients after liver transplantation. Key words: Liver transplantation; End stage liver disease; Survival analysis

High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12\xa0months after resection

BackgroundHepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection. Early recurrence is driven by synchronous microscopic intrahepatic metastases. The predictive value of histological parameters is discussed controversially and adjuvant therapy is not established. The aim of this study was to identify patients at high risk for early intrahepatic recurrence by expression profiling of selected micro RNAs.MethodsIn 52 patients undergoing HCC resection between 2011 and 2014, liver and tumor tissue was collected during surgery. Twelve patients with incomplete data regarding HCC recurrence, secondary liver transplantation, or perioperative death were excluded, leaving 40 patients with early recurrence <12 months (R+) or without recurrence for >24 months (R-) to compare grading, T, L, V, and R status. If tissue quality permitted, micro RNAs were measured in HCC and liver tissue.ResultsTen women and 30 men (64.0 ± 10.2 years) were analyzed. R+ occurred in 29 patients 6.2 ± 4.5 months after resection. Surveillance of R- was 26.2 ± 5.2 months. High intratumoral expression of miR-135a was associated with high risk of recurrence (HR = 4.2, p = 0.024, time to recurrence 8.8 ± 2.0 vs. 24.8 ± 4.4 months in patients with low miR-135a expression). As expected, T3 status was correlated with early recurrence, while other histological parameters and expression of miR-21, miR-122, and miR-125a did not.ConclusionsWe show a significant association between high expression of miR-135a and early HCC recurrence. Therefore, high intratumoral miR-135a expression might serve as a novel biomarker to identify patients urgently requiring adjuvant therapy post resection.

Sofosbuvir and Ribavirin for Treatment of Compensated Recurrent Hepatitis C Virus Infection After Liver Transplantation

Interferon alfa-based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplantation HCV infection. In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplantation. All patients received 24 weeks of sofosbuvir 400 mg daily and ribavirin starting at 400 mg daily, which was adjusted according to creatinine clearance and hemoglobin values. The primary end point was sustained virologic response 12 weeks after treatment. Of the 40 patients enrolled and treated, 78% were male, 85% were white, 83% had HCV genotype 1, 40% had cirrhosis (based on biopsy), and 88% had been previously treated with interferon. Sustained virologic response 12 weeks after treatment was achieved by 28 of 40 patients (70%; 90% confidence interval: 56%-82%). Relapse accounted for all cases of virologic failure. No patients had detectable viral resistance during or after treatment. The most common adverse events were fatigue (30%), diarrhea (28%), and headache (25%). In addition, 20% of the subjects experienced anemia. Two patients discontinued study treatment because of adverse events, which were considered unrelated to study treatment. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported. Sofosbuvir and ribavirin combination therapy for 24 weeks is an effective and well-tolerated interferon-free treatment for post-transplantation HCV infection. EudraCT, Number: 2012-002417-19; ClinicalTrials.gov, Number: NCT01687270.

NTBC treatment in tyrosinaemia type I: Long‐term outcome in French patients

We describe a retrospective study of long-term outcome of 46 patients treated and regularly followed in France with 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) for tyrosinaemia type I. Most had initial good response with normalization of liver function and metabolic parameters. Only one infant had no response to treatment and required liver transplantation. Among the 45 long-term treated patients, three underwent secondary liver transplantation: one for cirrhosis and two because of hepatocellular carcinoma. One of the latter died of transplantation complications, so that the overall survival rate was 97.5%. However, 17 of 45 showed persistent abnormal liver imaging (heterogeneous liver) and 6 had cirrhosis. Furthermore, 15 had persistently elevated levels of alpha-fetoprotein, highlighting the question of the persistent risk of carcinoma. Quality of life was usually good but compliance problems were frequent, mainly regarding the low phenylalanine-tyrosine diet. Few adverse effects were observed. A main concern was the high frequency of cognitive impairment causing schooling problems, which may be related to persistent chronic hypertyrosinaemia. In conclusion, this series confirms that NTBC treatment has clearly improved the vital prognosis and quality of life of tyrosinaemia type I patients but that many late complications persist. Long-term studies are necessary to determine whether this drug may prevent or only delay liver complications, andto survey the possible risks of the drug. A more restricted diet could be necessary to prevent the neurological impact of the disease.

The recurrence of hepatitis C virus after liver transplantation

The main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C. Authors present the results of liver transplantations performed due to HCV infection. The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report. Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recurrence within 1 year, compared to those who had a late one. In case of an early HCV-recurrence the Knodell-score was significantly higher in the 6 months posttransplant biopsy than that of in case of late viral recurrence, however, less fibrosis was observed in early recurrence. An early HCV recurrence can be expected in case of an older donor, with a marginal or fatty liver graft transplanted with a higher transfusion need and having an acute rejection treated with steroid bolus in the postoperative period. The protocol of the postoperative antiviral treatment differs from the average: the so-called "stop-rule" cannot be applied, since less then 10% of the recipients are expected to turn to HCV-PCR-negative due to the immunosuppression. The combined interferon + ribavirin treatment is maintained in spite of RNA-positive state, further, a second or third course of treatment might also be applied. The prolonged and--in case if necessary--repeated antiviral treatment prevents fibrosis, and therefore rate of retransplantation need. The better is the general state of the patient the results of a secondary liver transplantation are better as well. MELD-score can help to set the exact timing for a re-OLT.

Prophylaxis and management of ischemic-type biliary lesion after orthotopic liver transplantation

To investigate the cause, prophylaxis, and management of ischemic-type biliary lesion (ITBL) after orthotopic liver transplantation. The clinical data of 212 operations of orthotopic liver transplantation on 209 patients, 184 males and 25 females, aged 44.5 (18-69), including 3 patients undergoing secondary liver transplantation, between February 1999 and August 2004 were reviewed retrospectively. ITBL occurred in 14 patients (6.6%), among whom 5 had biliary lesions of hepatic bifurcation, 3 had intrahepatic biliary lesions, and 6 had multiple extrahepatic and intrahepatic biliary lesions. The incidence rate of ITBL among the recipients of liver in cold storage for more than 10 hours, with donor-recipient ABO blood type incompatibility, with postoperative hepatic arterial lesions, and with hepatitis B related hepatic failure as the primary disease were 9.8% (10/102), 22.2% (2/9), 40% (2/5), and 14.6% (7/48) respectively. The 14 patients with ITBL were managed with conservative treatment, endoscopy, Roux-en-Y anastomosis, or re-transplantation. Seven of the 14 patients were cured, the condition of 5 patients was improved, and 1 patient died with a mortality of 7.1% (1/14). The incidence of ITBL-related graft loss was 23% (3/14). It is crucial to avoid too long preservation time of donor liver and donor-recipient ABO blood type incompatibility, and timely management of postoperative hepatic arterial lesions so as to prevent ITBL. Proper treatment for ITBL should be chosen according to the specific conditions of the lesion of biliary duct tree.

Resection prior to liver transplantation for hepatocellular carcinoma: a strategy of optimizing the role of resection and transplantation in cirrhotic patients with preserved liver function.

Objective To evaluate the feasibility and postoperative course of liver transplantation (LT) in cirrhotic patients who underwent liver resection prior to LT for HCC. Summary Background Data Although LT provides longer survival than liver resection for treatment of small HCCs, donor shortage and long LT wait time may argue against LT. The feasibility and survival following LT after hepatic resection have not been previously examined. Methods Between 1991 and 2001, among 107 patients who underwent LT for HCC, 88 met Mazzafero's criteria upon pathologic analysis of the explant. Of these, 70 underwent primary liver transplantation (PLT) and 18 liver resection prior to secondary liver transplantation (SLT) for recurrence (n = 11), deterioration of liver function (n = 4), or high risk for recurrence (n = 3). Perioperative and postoperative factors and long-term survival were compared. Results Comparison of PLT and SLT groups at the time of LT revealed similar median age (53 vs. 55 years), sex, and etiology of liver disease (alcohol/viral B/C/other). In the SLT group, the mean time between liver resection and listing for LT was 20 months (range 1-84 months). Overall time on LT waiting list of the two groups was similar (3 vs. 5 months). Pathologic analysis after LT revealed similar tumor size (2.2 vs. 2.3 cm) and number (1.6 vs. 1.7). Perioperative and postoperative courses were not different in terms of operative time (551 vs. 530 minutes), blood loss (1191 vs. 1282 mL), transfusion (3 vs. 2 units), ICU (9 vs. 10 days) or hospital stay (32 vs. 31 days), morbidity (51% vs. 56%) or 30-day mortality (5.7% vs. 5.6%). During a median follow-up of 32 months (3 to 158 months), 3 patients recurred after PLT and one after SLT. After transplantation, 3- and 5-year overall survivals were not different between groups (82 vs. 82% and 59 vs. 61%). Conclusions In selected patients, liver resection prior to transplantation does not increase the morbidity or impair long-term survival following LT. Therefore, liver resection prior to transplantation can be integrated in the treatment strategy for HCC. (Ann Surg 2003;238:885–893.) (Liver Transpl 2004;10:813–815.)

Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy?

To assess the viability of a strategy of primary resection with secondary liver transplantation (LT) for hepatocellular carcinoma (HCC) on cirrhosis. LT is the optimal treatment of HCC with cirrhosis. Owing to organ shortage, liver resection is considered as a reasonable first-line treatment of patients with small HCC and good liver function, with secondary LT as a perspective in case of recurrence. The viability of such strategy, positively explored in theoretical models, is not documented in clinical practice. Among 358 consecutive patients with HCC on cirrhosis treated by liver resection (n = 163; 98 of whom were transplantable) or transplantation (n = 195), the feasibility and outcome of secondary transplantation was evaluated in a 2-step fashion. First, secondary LT for tumor recurrence after resection (n = 17) was compared with primary LT (n = 195), to assess the risk and the outcome of secondary LT in patients who effectively succeeded to be treated by this approach. Second, primary resection in transplantable patients (n = 98) was compared with that of primary LT (n = 195) on an intention-to-treat basis, to assess the outcome of each treatment strategy and to determine the proportion of resected patients likely to be switched for secondary LT. Transplantability of resected patients was retrospectively determined according to selection criteria of LT for HCC. Operative mortality (< or =2 months) of secondary LT was significantly higher than that of primary LT (28.6% versus 2.1%; P = 0.0008) as was intraoperative bleeding (mean transfused blood units, 20.7 versus 10.5; P = 0.0001). Tumor recurrence occurred more frequently after secondary than after primary LT (54% versus 18%; P = 0.001). Posttransplant 5-year overall survival was 41% versus 61% (P = 0.03), and disease-free survival was 29% versus 58% (P = 0.003) for secondary and primary LT, respectively. Of 98 patients treated by resection while initially eligible for transplantation, only 20 (20%) were secondarily transplanted, 17 of whom (17%) for tumor recurrence and 3 (3%) for hepatic decompensation. Transplantability of tumoral recurrence was 25% (17 of 69 recurrences). Compared with primarily transplanted patients, transplantable resected patients had a decreased 5-year overall survival (50% versus 61%; P = 0.05) and disease-free survival (18% versus 58%; P < 0.0001), despite the use of secondary LT. On a multivariate analysis including 271 patients eligible for transplantation and treated by either liver resection or primary LT, liver resection alone (P < 0.0001; risk ratio [RR] = 3.27) or liver resection with secondary LT (P < 0.05; RR= 1.87) emerged as negative independent factors of disease-free survival as compared with primary LT. A number of nodules > 3 (P = 0.002; RR= 2.02) and a maximum tumor size exceeding 30 mm (P < 0.0001; RR=1.93) were also predictive of lower disease-free survival. LT after liver resection is associated with a higher operative mortality, an increased risk of recurrence, and a poorer outcome than primary LT. In addition, liver resection as a bridge to LT impairs the patient transplantability and the chance of long-term survival of cirrhotic patients with HCC. Primary LT should therefore remain the ideal choice of treatment of a cirrhotic patient with HCC, even when the tumor is resectable.