Introduction Transjugular intrahepatic portosystemic shunt (TIPS) is indicated in the management of portal vein thrombosis or stenosis, portal hypertension and for veno-occlusive disease in post-liver transplant (LT) patients. Previous series have reported 1-year mortality rates of 14%–67%. A MELD score >15 at the time of insertion may indicate a poor long term prognosis. We aimed to evaluate the safety of TIPS after LT at a UK tertiary referral centre. Methods We retrospectively analysed data from the Royal Free Hospital TIPS database between 1st January 1991 and the 31st January 2011. All patients who had undergone TIPS following LT were included. Results During the period studied 629 patients received a TIPS. In the same period 1192 liver transplant operations were performed. 10 TIPS were inserted into patients following LT for recurrent cirrhosis with refractory ascites (4), veno-occlusive disease (3) and portal vein thrombosis (3). The original indications for transplantation were PSC (3), PBC (3), Hepatitis C (1), Autoimmune (1), Primary Oxalosis (1) and Acute Liver Failure (1). We noted a median survival of 38 months. Survival at 1 and 5 years was 100% and 60% respectively. The median MELD at the time of TIPS insertion was 12 (range 7–19). No correlation between the MELD score at the time of TIPS insertion and survival was demonstrated (p=0.62). Conclusion These results suggest that TIPS can be performed safely after LT and that survival rates better than those previously reported can be achieved. We suggest TIPS should be used in carefully selected candidates following LT as a definitive treatment for patients not suitable for re-transplant or as a bridge to re-transplantation. The alternative of re-transplantation should always be considered prior to TIPS insertion where indicated. Competing interests None declared. References 1. Saad WEA, et al. Transjugular intrahepatic portosystemic shunts in liver transplant recipients for management of refractory ascites: clinical outcome. J Vasc Interv Radiol 2010;21:218–23. 2. Kim JJ, et al. Transjugular intrahepatic portosystemic shunts in liver transplant recipients. Liver Int 2008;28:240–8. 3. Feyssa E, et al. MELD score less than 15 predicts prolonged survival after transjugular intrahepatic portosystemic shunt for refractory ascites after liver transplantation. Transplantation 2011;91:786–92.

BACKGROUND:Reducing immunosuppression not only reduces complications but also may lessen recurrent hepatitis C virus (HCV) infection after liver transplantation. PATIENTS/METHODS:HCV-infected cirrhotic patients randomised to tacrolimus monotherapy (MT) or triple therapy (TT) using tacrolimus 0.1 mg/kg/day, azathioprine 1 mg/kg/day, and prednisolone 20 mg/day, tapering over 3 months. RESULTS:Twenty-seven patients (MT) and 29 (TT)--median follow up 661 days (range, 1-1603). Rejection episodes (protocol/further biopsies) within first 3 months and use of empirical treatment were evaluated. New rejection was diagnosed if repeat biopsy (5-day interval) did not show improvement. Treated rejection episodes: 20 MT (15 biopsy-proven) vs. 24 TT (21 biopsy-proven), with 19 (MT) vs. 24 (TT) methylprednisolone boluses. Overall: 35 episodes (MT) and 46 (TT). Fewer MT patients had histological rejection (70%) than TT patients (86%), with fewer episodes of rejection (18.5% vs. 10%), and more moderate rejection (22% vs. 41%). The MT group had higher early tacrolimus levels. Rates of renal dysfunction, retransplantation, and death were not significantly different. CONCLUSION:Tacrolimus monotherapy is a viable immunosuppressive strategy in HCV-infected liver transplant recipients.

In HCV cirrhotic patients after liver transplantation, survival and recurrence of HCV appears to be worsening in recent years. Donor age has been suggested as a cause. However, it is not clear if early and/or late mortality is affected and whether donor age is a key factor, as opposed to changes in immunosuppression. The aim of this study was to assess impact of donor age and other factors with respect to the severity of HCV recurrence posttransplant. A consecutive series of 193 HCV cirrhotic patients were transplanted with cadaveric donors, median age 41.5 years (13–73) and median follow-up of 38 months (1–155). Donor age and other factors were examined in a univariate/multivariate model for early/late survival, as well as fibrosis (grade 4 or more, Ishak score) with regular biopsies, 370 in total, from 1 year onwards. Results of the study indicated that donor age influenced only short-term (3 months) survival, with no significant effect on survival after 3 months. Known HCC independently adversely affected survival, as did the absence of maintenance azathioprine. Severe fibrosis (stage ≥ 4) in 51 patients was related to neither donor age nor year of transplantation, but it was independently associated with combined biochemical/histological hepatitis flare (OR 2.9, 95% CI 1.76-4.9) whereas maintenance steroids were protective (OR 0.4, 95% CI 0.23-0.83). In conclusion, in this cohort donor age did not influence late mortality in HCV transplanted cirrhotic patients or development of severe fibrosis, which was related to absence of maintenance steroids and a hepatitis flare. Maintenance azathioprine gave survival advantage. (Liver Transpl 2005;11:386–395.)

Immunosuppression is a main determinant for the increased Hepatitis C Virus (HCV) replication after liver transplantation and the accelerated course of recurrent HCV liver disease. We present two patients both with diabetes, renal dysfunction with proteinuria converted to sirolimus therapy, who cleared serum HCV RNA without antiviral treatment. This is a potentially important observation that should stimulate study into factors that may help viral clearance from blood.

Background: In recent years, liver transplantation in patients with hepatocellular cancers and cirrhosis has been restricted to those with small cancers (<5 cm for solitary and <3 cm for multifocal HCC with <3 nodules). The selection of patients for liver transplantation is based on pre-operative imaging. The accuracy of imaging correlated with explant histology and the effect of tumour stage has not been evaluated in this selected population. Methods: In this study, prospectively collected data for 30 patients who underwent orthotopic liver transplantation for cirrhosis complicated by small hepatocellular carcinoma (HCC) at a single centre have been reviewed with the aim of correlating radiological findings, explant histology and patient outcome. Patients who underwent orthotopic liver transplantation between 1995 and 1999 had plain and contrast-enhanced dual-phase spiral CT (DCT) scans of the liver. Patients suspected of having HCC on CT scan or due to elevated serum alpha-fetoprotein underwent iodized oil CT (IOCT). Following transplantation, the explanted liver was serially sectioned at 10-mm intervals and examined by a pathologist blinded to the results of imaging. Data collected prospectively on imaging and histology were compared with outcome data. The median period of follow-up was 1,139 days (range 690–1,955 days) after transplantation. All patients were followed up by clinical assessment, assessment of serum alpha-protein levels and imaging when indicated. Results: All the patients transplanted fulfilled the selective criteria on the basis of imaging (solitary HCC <5 cm in diameter or multifocal HCC <3 cm in diameter with <3 nodules). Of the 30 patients transplanted, 46 HCCs were detected on explant histology with a median size of 24 mm (range 6–75 mm). Ten patients had multifocal disease (median number of lesions 2, range 2–4). No significant difference was observed between IOCT and DCT with regards to the sensitivity (67.4 vs. 68%) and specificity (78.97 vs. 88.6%) of detecting HCCs. IOCT had a positive predictive value of 78.9% as compared to 82.8% for DCT. IOCT had an overall sensitivity of 40% as compared to 30% for DCT in detecting multifocal disease (not significant). Histological assessment of the explanted livers showed that 8 patients had well-, 17 moderate and 5 poorly differentiated HCCs. Tumour size and the presence of multifocal disease did not influence survival in this study. Microvascular invasion was more common with larger tumours (from 38% with lesions less than 40 mm in diameter to 60% with lesions >40 mm in diameter; p < 0.01) and with moderately (29.4%) or poorly differentiated (60%) HCCs than well-differentiated HCC (12.5%) (p < 0.04 and 0.01 for well- vs. moderately and poorly differentiated HCC, respectively). Microvascular invasion on explant histology was associated with poor survival. Of the 17 transplant recipients without vascular invasion, 15 were alive at 1 and 2 years in comparison to 7 of 9 with microscopic vascular invasion (p < 0.01). Four patients died in the post-transplant period due to recurrent HCC. Overall survival [after excluding early post-transplant sepsis-induced deaths (n = 4)] at 1 year was 83.3%. Conclusions: Selective criteria for transplantation of HCC in cirrhosis are associated with a 1-year and 3-year survival rate of 73.3% (including early post-transplant sepsis-induced deaths). IOCT and DCT are similar in their ability to detect unifocal or multifocal HCC. Tumour size and number are not predictive of recurrence with these selective criteria, but microscopic vascular invasion is a bad prognostic factor.

Background. Calcineurin inhibitors (CNIs) are the first-line immunosuppressive agents administered after liver transplantation, but they cause renal impairment. Two recent randomized trials report cellular rejection and liver graft loss when mycophenolate mofetil (MMF) monotherapy was used as a renal-sparing agent. Our experience with MMF in the same setting but with longer follow-up is described. Methods. In 45 patients with serum creatinine more than 120 &mgr;mol/L or creatinine clearance less than 50 mL/min, 2 g MMF per day was administered (median 29 months, 1–49 months) either as monotherapy (with all other immunosuppression withdrawn in 1 month) in 16 patients (group I) or in combination with low-dose CNI (trough tacrolimus ≤5 ng/mL, cyclosporin A ≤50 ng/mL) in 29 patients (18 patients without [group II] and 11 patients with [group III] previous refractory rejection [rejection after two episodes of treated rejection]). Results. In group I (median interval receiving MMF, 33 months), only one patient (6%) experienced cellular rejection, and serum creatinine normalized in five of eight patients long term. In group II (median follow-up 26.5 months), none of 18 experienced rejection, and serum creatinine normalized in 6 of 10 long term. In group III (median follow-up 34 months), 5 of 11 patients (45%) experienced further rejection, one was not steroid responsive, and serum creatinine normalized in four of eight patients long term. There was no graft loss or death as a result of rejection. Conclusions. Our cohort with prolonged follow-up showed significant improvement in renal function with both MMF monotherapy and in combination with low-dose CNI with minimal rejection (five of six steroid responsive) and no graft loss. MMF substitution is a therapeutic strategy that deserves more extensive use in liver transplantation.

Liver TransplantationVolume 9, Issue 7 p. 780-781 Letter To The EditorFree Access Protocol biopsies in liver transplantation Andrew K. Burroughs, Andrew K. Burroughs FRCP andrew.burroughs@talk21.com Liver Transplantation & Hepatobiliary Unit, Royal Free Hospital, London, NW 3 2QG, Teephone: 004-4207-472-6229, FAX: 004-4207-472-6226Search for more papers by this authorDavid W. Patch, David W. Patch FRCP Liver Transplantation & Hepatobiliary Unit, Royal Free Hospital, London, NW 3 2QG, Teephone: 004-4207-472-6229, FAX: 004-4207-472-6226Search for more papers by this authorRosa Stigliano, Rosa Stigliano MD Liver Transplantation & Hepatobiliary Unit, Royal Free Hospital, London, NW 3 2QG, Teephone: 004-4207-472-6229, FAX: 004-4207-472-6226Search for more papers by this authorLaura Cecilioni, Laura Cecilioni MD Liver Transplantation & Hepatobiliary Unit, Royal Free Hospital, London, NW 3 2QG, Teephone: 004-4207-472-6229, FAX: 004-4207-472-6226Search for more papers by this author Andrew K. Burroughs, Andrew K. Burroughs FRCP andrew.burroughs@talk21.com Liver Transplantation & Hepatobiliary Unit, Royal Free Hospital, London, NW 3 2QG, Teephone: 004-4207-472-6229, FAX: 004-4207-472-6226Search for more papers by this authorDavid W. Patch, David W. Patch FRCP Liver Transplantation & Hepatobiliary Unit, Royal Free Hospital, London, NW 3 2QG, Teephone: 004-4207-472-6229, FAX: 004-4207-472-6226Search for more papers by this authorRosa Stigliano, Rosa Stigliano MD Liver Transplantation & Hepatobiliary Unit, Royal Free Hospital, London, NW 3 2QG, Teephone: 004-4207-472-6229, FAX: 004-4207-472-6226Search for more papers by this authorLaura Cecilioni, Laura Cecilioni MD Liver Transplantation & Hepatobiliary Unit, Royal Free Hospital, London, NW 3 2QG, Teephone: 004-4207-472-6229, FAX: 004-4207-472-6226Search for more papers by this author First published: 30 December 2003 https://doi.org/10.1002/lt.500090723Citations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume9, Issue7July 2003Pages 780-781 ReferencesRelatedInformation