Cyclosporine A Protects Against Primary Biliary Cirrhosis Recurrence After Liver Transplantation

Primary biliary cirrhosis (PBC) reoccurs in a proportion of patients following liver transplantation (LT). The aims of our study were to evaluate the risk factors associated with PBC recurrence and determine whether recurrent disease constitutes a negative predictor for survival. One hundred and eight patients receiving LT for end‐stage PBC were studied. Recurrent disease was diagnosed in 28 patients (26%). Probability of recurrent PBC at 5 years was 13% and 29% at 10 years with an overall incidence of 3.97 cases per 100 patient years. By univariate Cox analysis use of tacrolimus (HR 6.28, 95% CI, 2.44–16.11, p < 0.001) and mycophenolate mofetil (HR 5.21, 95% CI, 1.89–14.33, p = 0.001) were associated with higher risk of recurrence; whereas use of cyclosporine A (CsA) and azathioprine were associated with reduced risk of recurrence (HR 0.13, 95% CI 0.05–0.35, p < 0.001 and HR 0.27, 95% CI 0.11–0.64, p = 0.003, respectively). In the multivariate Cox analysis, only CsA was independently associated with protection against recurrence (HR 0.17, 95% CI 0.06–0.71, p = 0.02). Five‐year probability of survival was 83% and 96%, in patients without and with recurrence (log‐rank test, p = 0.3). Although PBC transplant recipients receiving CsA have a lower risk of disease recurrence, the development of recurrent PBC did not impact on long‐term patient survival.     

Long-term survival and impact of ursodeoxycholic acid treatment for recurrent primary biliary cirrhosis after liver transplantation.

The recurrence of primary biliary cirrhosis (PBC) in the hepatic allograft may impact patient and graft survival with long-term follow-up. The efficacy of ursodeoxycholic acid (UDCA) for treatment of recurrent PBC after liver transplantation (LT) remains less well known. The aims of this study were as follows: 1) to determine the significance of recurrent PBC on overall survival among PBC patients who underwent LT, and 2) to determine the efficacy of UDCA treatment after LT in patients with recurrent PBC. A retrospective cohort study was conducted of 154 PBC patients who underwent LT with at least 1 yr of follow-up after transplantation from 1985 through 2005. A total of 52 patients with recurrent PBC were identified. After adjusting for age and gender, recurrent PBC was not associated with death or liver retransplantation (hazard ratio, 0.97, 95% confidence interval, 0.41-2.31; P = 0.9). A total of 38 patients with recurrent PBC received UDCA at an average dose of 12 mg/kg/day for a mean duration of 55 months. Over a 36-month period, an estimated 52% of UDCA-treated patients experienced normalization of serum alkaline phosphatase and alanine aminotransferase compared to 22% of untreated patients. There was no significant difference in the rate of histological progression between subgroups. UDCA did not influence patient and graft survival. In conclusion, the development of recurrent PBC has little impact on long-term survival or need for retransplantation. While UDCA therapy is associated with biochemical improvement, its role in delaying histologic progression remains unknown. In this short period of treatment, UDCA was not associated with improved patient and graft survival compared to untreated patients.     

The effect of immunosuppressive regimens on the recurrence of primary biliary cirrhosis after liver transplantation

Recurrence of primary biliary cirrhosis (PBC) has been described in liver transplant recipients. Type of immunosuppression has been reported to influence the frequency of recurrence. The aim of this study is to evaluate the occurrence and pattern of recurrent PBC in our liver transplant recipients and determine any association of immunosuppressive agents with its recurrence. Patients who underwent orthotopic liver transplantation (OLT) for PBC were identified from the University of Chicago Liver Transplant Database. Recurrent PBC was diagnosed based on specific pathological criteria. Of 46 patients who underwent OLT for PBC between 1984 and 2000, a total of 7 patients (15%) were diagnosed with recurrent PBC at a median of 78 months (range, 27 to 120 months) after OLT. Forty-three percent of patients were administered cyclosporine, whereas 57% were administered tacrolimus before disease recurrence. Rates of recurrence were not different between patients maintained on cyclosporine therapy (16%) compared with those maintained on tacrolimus therapy (18%; P = 1.0). There also was no difference in frequency of rejection episodes or duration of corticosteroid therapy between those who did and did not have recurrent PBC. In conclusion, recurrent PBC developed in a small number of patients 2 years or longer after OLT. In our population, there was no difference in recurrence rates between those administered cyclosporine or tacrolimus for immunosuppression. (Liver Transpl 2003;9:733-736.)     

Recurrent primary biliary cirrhosis: peritransplant factors and ursodeoxycholic acid treatment post-liver transplant.

Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT) in up to one-third of patients. These patients are typically asymptomatic, can be identified by abnormal liver biochemistries, and have evidence of histologic recurrence on liver biopsy. The effect of treatment on recurrence has not been determined. This pilot study evaluates the factors associated with recurrent PBC and describes our experience using ursodeoxycholic acid treatment in this patient population. Forty-eight patients with PBC were followed for at least 1 yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase. Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients with recurrent PBC had a trend toward longer warm ischemia times and more episodes of acute cellular rejection in the first year posttransplant, but this was not significant in multivariate analysis. Donor or recipient age, donor and recipient cytomegalovirus status, and dose of immunosuppression did not correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum alkaline phosphatase in the majority. In conclusion, recurrent PBC is not infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit post-OLT. Treatment effects on long-term survival are not known.     

Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation.

Only a subset of hepatitis C virus (HCV)-infected patients develop progressive hepatic fibrosis after liver transplantation (LT). Hepatic stellate cell (HSC) activation is a pivotal step in hepatic fibrosis and precedes clinically apparent fibrosis. We determined whether early HSC activation, measured in 4-month protocol post-LT biopsies, is predictive of subsequent development of more histologically severe recurrence of HCV. Early (4 month) post-LT HSC activation, as measured by alpha-smooth muscle actin (alpha-SMA) staining, was determined in liver biopsies from recipients with severe (fibrosis score > or = 2, n = 13) and with mild (fibrosis score of 0, n = 13) recurrence of HCV at one-year post-LT. Immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) was used to generate HSC activation scores (regional and total). Total HSC activation scores at 4 months were similar in patients with severe and mild HCV recurrence (3.9 +/- 2.0 vs. 2.7 +/- 2.2, P = 0.2). Regional HSC activation, assessed as parenchymal (zones 1, 2, and 3) or mesenchymal (portal tracts and fibrous septa), was different between the study groups, with higher mesenchymal scores predictive of progression. No patients in the mild recurrence group had detectable mesenchymal alpha-SMA staining vs. 46% (6/13) of patients with severe recurrence (P < 0.01). Mesenchymal activation of HSC had a specificity and positive predictive value of 100% for development of progressive fibrosis in liver allografts of patients with hepatitis C.In conclusion, early activation of mesenchymal HSCs is a marker for progressive fibrosis in patients with hepatitis C post-LT and may help select patients who would benefit from HCV or HSC-targeted therapy.     

Early Detection of Hepatocellular Carcinoma Recurrence in the Posttransplant Population: A Comparison of RETREAT and Cleveland Clinic Florida Scoring System

BackgroundLiver transplantation (LT) for hepatocellular carcinoma (HCC) is curative in most cases; however, recurrence is observed in some patients. The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score is an externally validated scoring system for prediction of post-LT HCC recurrence. The Cleveland Clinic Florida Scoring System (CCFSS) is a potential new scoring system for prediction of HCC recurrence. Our study aimed to compare the RETREAT and CCFSS.MethodsWe conducted a retrospective cohort study of 52 adult patients with HCC who underwent LT at a tertiary care center. Mantel-Haenszel chi-square analyses were conducted to compare the RETREAT and CCFSS classifications for detecting HCC recurrence.ResultsA total of 52 patients underwent LT. The median follow-up period was 37 months. Four patients had post-LT HCC recurrence, with all recurrences occurring within 2 years of LT. The RETREAT score was better able to detect low, moderate, and high levels of risk (P < .001), compared to the CCFSS score (P = 0.480). Both risk scores had a sensitivity of 75%; the specificity of the RETREAT score was 95.8%, whereas the specificity of the CCFSS was 60.4%. Alpha-fetoprotein level at the time of LT was associated with HCC recurrence (P = .014).ConclusionsThis is the first study to evaluate the CCFSS as a potential new scoring system to predict HCC recurrence after LT. The RETREAT score is more specific than the CCFSS. The incorporation of alpha-fetoprotein level at the time of LT improves the estimation of HCC recurrence in the post-LT period.     

Combination of interferon alfa-2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C

Recurrent hepatitis C virus (HCV) infection is an important cause of fibrosis and cirrhosis after liver transplantation (LT), with histological recurrence developing in at least 50% of patients within the first year. The aim of this study is to assess the safety and efficacy of interferon alfa-2b plus ribavirin in treating histological recurrent HCV after LT. Since 1998, patients with HCV with significant histological recurrence (fibrosis ≥ 3 and/or histological activity index ≥ 5) or progressive cholestatic disease after LT were treated with interferon alfa-2b (3 million units subcutaneously three times weekly) plus ribavirin (800 to 1,000 mg/d) for 12 months. Immunosuppression was tapered to cyclosporine/FK506 monotherapy. HCV RNA was assessed at entry, week 24, end of treatment, and 6 months after therapy. The primary end point was loss of HCV RNA 6 months after therapy, whereas the secondary end point was histological response. Fifty-four patients met criteria for treatment and have completed follow-up. Patients were mainly men (71% men; mean age, 51 ± 5 years) with genotype 1 infection (88%) and high viral load (mean HCV RNA, 38 ± 9 mEq/mL). Dose modification was required in 72% of patients because of cytopenia or side effects. Intent-to-treat analysis showed that serum HCV RNA was undetectable in 19 patients (35%) week 24, 21 patients (38%) week 48, and 16 patients (30%) at the 6-month follow-up. Paired liver biopsy results (before and within 6 months after treatment) were available for 35 patients. Patients who achieved viral eradication had no significant progression of fibrosis after 1 year of therapy. In summary, combination therapy is a reasonable antiviral option for recurrent HCV infection for established post-LT hepatitis and appears to prevent histological progression of disease if viral eradication is successful. (Liver Transpl 2002;8:1000-1006.)     

Potential Benefit of Mixed Lymphocyte Reaction Assay-based Immune Monitoring After Living Donor Liver Transplantation for Recipients With Autoimmune Hepatitis

Background

Recipients with autoimmune hepatitis (AIH) have a higher incidence of both rejection and recurrence after liver transplantation (LT) when compared with cholestatic liver diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). This is due to the lack of an immune monitoring system, making it difficult to control immunosuppressant agents. In this study, we examine the benefit of the carboxyfluorescein diacetate succinimidyl ester–mixed lymphocyte reaction (CFSE-MLR) monitoring system for evaluating the immune status in recipients with AIH and PBC/PCS after LT.

Method

Recipients who underwent LT (9 AIH and 11 PBC/PSC) from 2002 to 2013 at Hiroshima University were enrolled in this study. The correlation between the result of CFSE-MLR and the outcome, bacteremia, rejection, and/or recurrence was examined.

Result

The cumulative survival rates for 5 years after LT revealed preferable outcomes for both groups (AIH 85.7%, PBC/PCS 80%). None of the recipients in the AIH group developed bacteremia during 90 days after LT, whereas three recipients from the PBC/PCS group (27%) developed bacteremia. The recurrence rate (AIH 33%, PBC/PSC 27%) was the same as the reported data; however, there was a lower incidence of acute rejection rate in our institution (AIH 11%, PBC/PSC 27%). In the CFSE-MLR assay, the stimulation index of CD4⁺ T cells in the anti-self reaction was increased in recurrent cases, whereas no elevation of anti-donor reaction was observed in either CD4⁺ or CD8⁺ T cells.

Conclusion

Optimization of the immunosuppressant agents based on the CSFE-MLR assay after LT achieved a preferable outcome in recipients with both AIH and PBC/PCS. Therefore, CFSE-MLR assay might be a useful tool for predicting the recurrence of autoimmune liver diseases by monitoring anti-self reactivity of CD4⁺ T cells.     

Entecavir Combined With Short-term Hepatitis B Immunoglobulin in Preventing Hepatitis B Virus Recurrence in Liver Transplant Recipients

BackgroundThe combination of nucleoside analogs and long-term hepatitis B immunoglobulin (HBIG) is considered to be the standard regimen for preventing hepatitis B virus (HBV) recurrence after liver transplant (LT). However, long-term use of HBIG causes many adverse effects. The aim of this study was to evaluate the effect of nucleoside analogs entecavir combined with short-term HBIG in preventing HBV recurrence after LT.MethodsThis retrospective study assessed the effect a combination of entecavir and short-term HBIG in prophylaxis of HBV recurrence among 56 LT recipients who had undergone the procedure because of HBV-associated liver disease at our center between December 2017 and December 2021. All patients received entecavir treatment combined with HBIG for the prevention of hepatitis B recurrence, and HBIG treatment was withdrawn within 1 month. The patients were followed up to determine levels of hepatitis B surface antigen, antibody to hepatitis B surface antigen (HBsAb), and HBV-DNA and the recurrence rate of HBV.ResultsOnly 1 patient appeared positive for hepatitis B surface antigen at 2 months post-LT. The overall HBV recurrence rate was 1.8%. The HBsAb titers of all patients gradually decreased over time, with a median of 376.6 IU/L at 1 month post-LT and a median of 13.47 IU/L at 12 months post-LT. During the follow-up period, the HBsAb titer of the preoperative HBV-DNA–positive patients remained at a lower level than that of HBV-DNA–negative patients.ConclusionsEntecavir combined with short-term HBIG can exert a good effect for the prevention of HBV reinfection post-LT.     

Impact of cytomegalovirus infection,year of transplantation,and donor age on outcomes after liver transplantation for hepatitis C

Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is almost universal. However, variables that hasten the progression of allograft injury have not been fully defined. Cytomegalovirus (CMV) is a common infection post-LT, and its impact on the course of post-LT HCV infection remains unclear. We investigated the impact of CMV infection on patient and graft outcomes in 93 consecutive HCV-infected liver transplant recipients. Data were collected prospectively, with surveillance cultures for CMV and protocol liver biopsies. CMV infection (defined as isolation of CMV from blood and treatment with ganciclovir) occurred in 25 patients (26.9%). Graft failure (defined as cirrhosis, relisting for LT, re-LT, or death) was significantly more common in CMV-positive compared with CMV-negative patients (52% v 19.1%; P = .002). Fibrosis stage 2 or greater on the 4-month liver biopsy specimen was more common in CMV-infected patients (45% v 16.4%; P = .01). Patients who underwent LT in more recent years had an increased risk for graft failure. Donor and recipient age, CMV infection, and mycophenolate mofetil use were significantly associated with graft failure in a stepwise multivariate analysis. CMV infection occurs in approximately one quarter of HCV-infected liver transplant recipients and is an independent risk factor for graft failure in these patients. Whether CMV mediates this by inducing increased immunosuppression or directly enhancing HCV replication requires further study. (Liver Transpl 2002;8:362-369.)     

Pre-transplant treatment of hepatocellular carcinoma: assessment of tumor necrosis in explanted livers

Although liver transplantation (LT) is likely the most effective therapy for localized hepatocellular cancer (HCC), limited donor livers have resulted in prolonged waiting times for transplant. Pre-transplant therapy such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA) may be needed to sustain patients who are waiting. Records, imaging studies, and pathology to identify tumor necrosis on 15 explanted livers with HCC were reviewed. Forty-nine nodules were removed from 15 explanted livers. Five nodules in three livers that received no pre-transplant therapy were excluded from the study. Of the remaining 44 nodules in 12 patients, 29 (66%) had 75% or more tumor necrosis. Fifteen nodules in five patients had <75% necrosis and these were due to local/non-local recurrences or perhaps suboptimal treatment with RFA, TACE or cisplatin gel injection. Mean waiting time for LT was 162.5 d. Nine of 13 patients had a different number of nodules when listed as were seen at explant, although stage changed in only three patients. One patient died 48 months post-LT (recurrent HCC), while the remaining patients are alive 2-55 months post-LT. We conclude that pre-transplant treatments for HCC are generally effective in achieving tumor necrosis. Factors involved in eventual extent of HCC seen at LT may include adequacy of treatment, accuracy of imaging techniques, local/non-local recurrences, and time waiting for transplant. We now need to determine if tumor necrosis can allow patients to wait longer for transplant and eventually affect long-term outcome.     

Influence of liver-disease etiology on long-term quality of life and employment after liver transplantation

The etiology of liver disease would expectedly affect health‐related quality of life (HRQoL) and employment after liver transplantation (LT), but studies are scarce. We sent the 15D HRQoL instrument and an employment questionnaire to all 401 adult LT patients alive in Finland in 2007. The response rate was 89% (n = 353; mean of eight yr since LT). In age‐adjusted analysis, patients transplanted for primary sclerosing cholangitis (PSC; n = 56), primary biliary cirrhosis (PBC; n = 72), acute liver failure (ALF; n = 76), alcoholic cirrhosis (n = 38), or liver tumor (n = 22) exhibited comparable HRQoL, whereas the combined group of miscellaneous chronic liver diseases (n = 89) exhibited significantly higher HRQoL scores (p = 0.003). Among working‐aged patients (20–65 yr at LT), employment rates were highest in the PSC (56%) group and lowest in the ALF (39%) and PBC (29%) groups. In age‐adjusted logistic regression, patients with PSC or alcoholic cirrhotics were 2.4‐ and 2.5‐fold more likely to resume work after LT than patients with PBC. In conclusion, HRQoL scores late after LT were in general relatively high and comparable among disease groups. Patients with PSC or alcoholic cirrhosis were most likely to resume work after LT. The relatively low employment among patients with ALF may merit enhanced rehabilitation efforts.     

Recurrence of primary biliary cirrhosis after liver transplantation: Histologic estimate of incidence and natural history

The goals of this study were to determine the rate of recurrent primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT) based on strict morphologic criteria and to evaluate histologic progression of recurrent PBC over time. Strict criteria for PBC recurrence were established as the presence of a florid duct lesion or destructive lymphocytic cholangitis within a dense portal infiltrate. Of the 784 OLTs performed at the Mayo Clinic during the first 12 years of the program, 100 met criteria for the PBC study group, and 35 met criteria for the control group. Strict histologic criteria for recurrent PBC were observed in 17 of 100 (17%) study patients (14 with florid duct lesion, 3 with destructive lymphocytic cholangitis within dense portal infiltrate). Mean follow-up for the PBC group was 4.7 years (range, 1.0 to 13.8). Mean time to recurrence was 3.7 years (median, 3.1; range, 0.3 to 7.9). In those who met strict criteria for recurrent PBC, 2 of 17 progressed to septal fibrosis (stage 3). No florid duct lesions, destructive lymphocytic cholangitis, or septal fibrosis were observed in the control group. Other less specific morphologic features of PBC (portal infiltrates, plasma cells, dense lymphoplasmacytic infiltrates, and lymphocytic cholangitis) were also evaluated in the course of this study. Based on strict criteria, a conservative histologic estimate of the rate of recurrent PBC is 17% with a mean of 4.7 years of follow-up. When criteria for histologic recurrence are expanded to include moderate lymphocytic cholangitis with lymphoplasmacytic portal infiltrate, the recurrence rate of PBC is estimated as 26%. (Liver Transpl 2003;9:1086-1093.)     

A systematic review of the performance of the model for end-stage liver disease (MELD) in the setting of liver transplantation.

The Model for End-Stage Liver Disease (MELD) score is now used for allocation in liver transplantation (LT) waiting lists, replacing the Child-Turcotte-Pugh (CTP) score. However, there is debate as whether it is superior to CTP score to predict mortality in patients with cirrhosis on the LT waiting list and after LT. We reviewed studies comparing the accuracy of MELD vs. CTP score in transplantation settings. We found that in studies of the LT waiting list (12,532 patients with cirrhosis), only 4 of 11 showed MELD to be superior to CTP in predicting short-term (3-month) mortality. In addition, 2 of 3 studies (n = 1,679) evaluating the changes in MELD score (DeltaMELD) showed that DeltaMELD had better prediction for mortality than the baseline MELD score. The impact of MELD on post-LT mortality was assessed in 15 studies (20,456 patients); only 6 (9,522 patients) evaluated the discriminative ability of MELD score using the concordance (c) statistic (the MELD score had always a c-statistic < 0.70). In 11 studies (19,311 patients), high MELD score indicated poor post-LT mortality for cutoff values of 24-40 points. In re-LT patients, 2 of 4 studies evaluated the discriminative ability of MELD score on post-LT mortality. Finally, several studies have shown that the predictive ability of MELD score increases by adding clinical variables (hepatic encephalopathy, ascites) or laboratory (sodium) parameters. On the basis of the current literature, MELD score does not perform better than the CTP score for patients with cirrhosis on the waiting list and cannot predict post-LT mortality.     

Recurrence-Free Long-Term Survival After Liver Transplantation in Patients with 18F-FDG Non-Avid Hilar Cholangiocarcinoma on PET

The aim of this retrospective study was to assess the value of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) for predicting biological tumor behavior and outcome after liver transplantation (LT) in patients with otherwise unresectable hilar cholangiocarcinoma (HC). Preoperative ¹⁸F-FDG-PET scanning was performed in 13 patients with type IV Klatskin tumor before LT. PET+ status indicated patients with an increased pretransplant ¹⁸F-FDG uptake, whereas PET− recipients had no increased preoperative ¹⁸F-FDG uptake on PET. Pretransplant PET findings were correlated with histopathological tumor characteristics and patient outcome after LT. Eight patients demonstrated positive preoperative PET findings (61.5%), whereas five patients had no increased preoperative ¹⁸F-FDG tumor uptake (38.5%) on PET. One PET+ patient died after 1 month due to liver allograft dysfunction. Seven PET+ liver recipients developed tumor recurrence, whereas five PET− patients were tumor-free alive after a median of 76 months post-LT (p = 0.001). The 2-year recurrence-free survival rate after LT was 100% in PET− patients and 28.6% in the PET+ population (log-rank = 0.008). Our results suggest that patients with ¹⁸F-FDG non-avid HC on PET may achieve recurrence-free long-term survival after LT.     

Factors influencing the progression of fibrosis in patients with recurrent hepatitis C after liver transplantation under antiviral therapy: a retrospective analysis of 939 liver biopsies in a single center.

Recurrent hepatitis C after liver transplantation (LT) is a major problem, since up to 30% of patients develop cirrhosis only 5 years after LT in the absence of antiviral therapy. The aim of this study was to examine the rate of progression of fibrosis and its associated risk factors in patients submitted to an early antiviral treatment post-LT. Included in the study were 105 patients submitted to LT between September 1990 and December 2004, 70 of whom were treated with interferon and/or ribavirin. A total of 939 liver biopsies were studied. The median fibrosis stage was 0.8 after 1 year post-LT, 1.1 after 3 years, 1.3 after 5 years, and 1.5 after 10 years. LT recipients with fibrosis >2 (13% at 10 years) had a significantly reduced survival rate (63% vs. 87% at 10 years, P = 0.03). Univariate analysis disclosed that recipient male gender, antiviral therapy before LT, LT after 1998, induction immunosuppressive regimen including tacrolimus, induction immunosuppressive regimen including mycophenolate (or without azathioprine), and short duration of prednisolone (<12 months) were significantly associated with progression of fibrosis. In a multivariate analysis, recipient male gender (P = 0.04), antiviral treatment before LT (P = 0.001), and initial immunosuppressive regimen without azathioprine (P = 0.03) were associated with progression of fibrosis. In conclusion, our study has documented that fibrosis progression is not linear over time and that occurrence of severe fibrosis is related to previously described factors related to immunosuppressive regimen or donor age and also to a past history of pre-LT antiviral therapy.     

Recurrent deep-vein thrombosis based on homozygous factor V Leiden mutation acquired after liver transplantation

Several genetic liver diseases can be treated by liver transplantation (LT). However, some genetic defects also may be acquired by this procedure. We describe a patient who developed recurrent deep-vein thromboses after LT for hepatitis C virus-associated hepatocellular carcinoma on the basis of a homozygous Leiden mutation of the factor V gene in the donor liver. Liver donors with a history of venous thrombosis should be screened for the presence of activated protein C (APC) resistance. In addition, we recommend looking for APC resistance in liver recipients who develop venous thromboembolic disease in the post-LT course. Molecular analysis of donor tissue may be necessary to make a definite diagnosis of factor V Leiden mutation in these patients. As a consequence, intensified postoperative thromboprophylaxis or lifelong anticoagulant therapy may be necessary if this thrombophilic gene defect is detected. (Liver Transpl 2003;9:870-873.)     

The Impact of Diabetes Mellitus on Fibrosis Progression in Patients Transplanted for Hepatitis C

Despite the recognition of numerous factors for aggressive hepatitis C virus (HCV) recurrence after liver transplantation (LT) our understanding of this phenomenon is incomplete. We tested the hypothesis that diabetes mellitus (DM) was implicated. One hundred sixty-three patients undergoing primary LT for HCV from 1990 to 2004 were evaluated and biopsies were scored according to the modified Ishak score. Severe recurrence of HCV was defined as a fibrosis score > or = 4 within 6 years of LT. Risk factors assessed included recipient, donor and transplant variables. Fifty-four patients (33.1%) had a fibrosis score > or = 4 at the end of the study period. Factors associated with progression to severe fibrosis was donor age (p = 0.008) especially donor age >55 (p = 0.038, HR 2.43), pre-LT DM (p = 0.039, HR 2.68) and DM post-LT (p = 0.004, HR 3.28). The combination of receiving a liver from a donor older than 55 years and having DM post-LT was associated with an 8.38-fold risk of progression to severe fibrosis (p = 0.000124) when compared to patients not diabetic post-LT who received livers from donors aged <55 years. These data indicate that diabetic status is one of the more important variables determining the severity of HCV recurrence and is synergistic with donor age. This observation may provide an additional management opportunity to modify the impact of HCV recurrence.     

Sleeve gastrectomy prior to liver transplantation is superior to medical weight loss in reducing posttransplant metabolic complications

Strategies to optimize the management of obesity-related metabolic complications after liver transplantation (LT) are needed. We examined the effect of pre-LT sleeve gastrectomy (SG), as compared to medical weight loss (MWL), on post-LT outcomes. This is a cohort study of adults (≥18 years) with medically complicated obesity who were eligible for pre-LT SG and underwent LT from January 1, 2006 to June 1, 2016. Logistic regression models evaluated the association of SG on post-LT diabetes and hypertension, defined as new-onset or progressive disease post-LT. Cox regression models evaluated the association of SG on recurrent and de novo nonalcoholic fatty liver disease (NAFLD). Among 70 LT recipients who were eligible for pre-LT SG, 14 (20%) underwent SG and 56 (80%) underwent MWL only. Mean follow-up was 5.2 years post-LT. The SG cohort sustained higher % total body weight loss at 3 years post-LT (28.9% vs. 5.4%, p < .001). In multivariable analyses, SG was associated with significantly lower risk of post-LT diabetes (OR 0.04, 95% CI 0.00–0.41, p = .01), hypertension (OR 0.15, 95% CI 0.04–0.67, p = .01), and recurrent and de novo NAFLD (HR 0.19, 95% CI 0.04–0.91, p = .04). When compared to MWL, SG resulted in sustained weight loss and significantly lower risk of diabetes, hypertension, and recurrent and de novo NAFLD post-LT.     

Liver Transplantation in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: The Influence of Viral Characteristics on Clinical Outcome

Background

Hepatitis B virus (HBV) relapse and/or hepatocellular carcinoma (HCC) recurrence remains a major concern for patients who undergo liver transplantation (LT) because of HBV-related HCC. This study investigates the correlation between HBV relapse and HCC recurrence and it explores factors that affect patient outcomes after LT.

Methods

Between September 2002 and August 2009, 78 consecutive patients who underwent LT because of HBV-related HCC were enrolled in this study. Serum samples obtained before LT were assayed both for virological factors associated with HBV DNA and for genotypic characteristics of the virus. All patient clinicopathological features and virological factors were assessed further by univariate and multivariate analyses to determine prognostic factors.

Results

During a median follow-up period of 29.4 months, 13 (16.6 %) patients experienced HCC recurrence and 18 (23.1 %) patients experienced HBV relapse. HBV relapse exhibited a close association with HCC recurrence (p = 0.004) and led to unfavorable overall survival after LT. Multivariate analysis of prognostic factors showed that the basal core promoter (BCP) mutation independently predicted a shorter survival period free from HBV relapse (p = 0.036). Moreover, with the exception of unfavorable tumor characteristics, the BCP mutation was found to be an important prognostic factor that affected HCC recurrence after LT (p = 0.042).

Conclusions

In this study, the HBV–BCP mutation was identified as an important predictor of post-LT clinical outcomes in patients with HBV-related HCC. Therefore, we recommend that aggressive antiviral treatment may be considered for patients associated with this risk factor.