David Patch - Academia.edu (original) (raw)

Papers by David Patch

Research paper thumbnail of Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies

Cancer Treatment Reviews, 2006

Background: Although transarterial chemoembolization (TACE) improves survival in patients with he... more Background: Although transarterial chemoembolization (TACE) improves survival in patients with hepatocellular carcinoma (HCC), it is not known if TACE combined with other treatments is beneficial. Aim: To evaluate the evidence for improved outcomes in HCC with a multimodal treatment approach involving TACE. Method: PubMed search for all cohort and randomized trials (n = 84) evaluating TACE combined with other therapies; meta-analysis performed where appropriate. Results: A meta-analysis involving 4 RCTs showed a significant decrease in mortality favouring combination treatment (TACE plus percutaneous ablation) compared to monotherapy in patients with either small (<3 cm) or large HCC nodules (>3 cm) (OR, 0.534; 95% CI, 0.288-0.990; p = 0.046). TACE combined with local radiotherapy improved survival in patients a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r h e a l t h . c o m / j o u r n a l s / c t r v with tumour thrombosis of the portal vein in 7 non-randomized studies. Two RCTs and 13 non-randomized studies showed that TACE prior to hepatic resection does not improve survival nor tumour recurrence. Conversely, 2 RCTs and 5 comparative studies showed that transarterial injection of chemotherapeutic drugs mixed with lipiodol (TOCE) following hepatectomy confers survival benefit and less tumour recurrence. TACE before liver transplantation is safe and reduces drop-out rate from the waiting list, but there is no current evidence of improvement in subsequent survival or recurrence rate. Conclusions: A combined approach involving TACE and percutaneous ablation improves survival. Adjuvant TOCE improves outcome after hepatectomy. TACE is useful to control tumours burden while on the waiting list for OLT. Multimodal treatment seems to be the best way to optimize TACE outcomes in HCC.

Research paper thumbnail of Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score

Journal of Cachexia, Sarcopenia and Muscle, 2016

Research paper thumbnail of Case report Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantion for HCV cirrhosis

Immunosuppression is a main determinant for the increased Hepatitis C Virus (HCV) replication aft... more 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

Research paper thumbnail of Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with and without underlying cirrhosis

Cardiovascular and interventional radiology

To retrospectively determine the acute safety and chronic outcomes of transjugular intrahepatic p... more To retrospectively determine the acute safety and chronic outcomes of transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with hemodialysis-dependent end-stage renal disease for control of bleeding and refractory ascites. Four dialysis-dependent patients and one renal transplant recipient (glomerular filtration rate, 27 mL/min) underwent TIPS creation for treatment of refractory ascites (n = 3) and recurrent portal hypertensive bleeding (n = 1). A sixth patient developed unrelated renal failure 3 years after initial TIPS formation and presented with encephalopathy at that time. All had nearly normal liver function test results and no previous baseline encephalopathy. Three dialysis recipients underwent dialysis immediately after the TIPS procedure in an intensive care unit; one did not. There were no complications of fluid overload or pulmonary edema after TIPS creation in the patients who immediately underwent dialysis. The one patient in whom dialysis was delayed developed respiratory failure and shock liver (ie, ischemic hepatitis). Ascites resolved in all three patients, and no recurrent variceal bleeding occurred during a mean follow-up of 17 months. Severe, grade 2-4 hepatic encephalopathy developed in all patients; in one patient, its onset was delayed until the onset of renal failure 3 years after the original TIPS procedure. Shunt reduction was required in four cases and competitive variceal embolization was required in one to reduce portosystemic diversion. No less than grade 1 episodic baseline encephalopathy was present in all patients despite continued use of the maximum prescribed medical therapy thereafter. TIPS creation is effective in controlling ascites and bleeding in functionally anephric patients, but at the cost of marked and disproportionate hepatic encephalopathy. Prompt, acute postprocedural dialysis and fluid management is critical for safe creation of a TIPS in dialysis-dependent patients.

Research paper thumbnail of Reply to Dr. Krag et al

Research paper thumbnail of An evaluation of emergency sclerotherapy of varices in randomized trials: looking the needle in the eye

Endoscopy, 2006

The role of sclerotherapy for acute variceal bleeding is challenged by vasoactive drugs and by li... more The role of sclerotherapy for acute variceal bleeding is challenged by vasoactive drugs and by ligation. A meta-analysis was performed to evaluate whether sclerotherapy remains a gold standard in acute variceal bleeding. Sclerotherapy was evaluated across four randomized trial groups: (a) combined with vasoconstrictors vs. vasoconstrictors alone (five trials, with 400 patients); (b) vs. vasoconstrictors alone (15 trials, with 1296 patients); (c) vs. combination of vasoconstrictors and sclerotherapy (eight trials, with 1026 patients); (d) vs. ligation (12 trials, with 1309 patients). We used the risk difference (absolute risk reduction) as our main effect measure. The efficacy of acute sclerotherapy was highest vs. ligation at 95 %, with a small advantage for ligation (an overtube was used in eight trials) of 2.5 % (95 % CI 0.4 % to 4.6 %) ( P = 0.018), but no survival difference. Efficacy of sclerotherapy combined with vasoconstrictors vs. vasoconstrictors alone was 86 %, whereas it was 83 % for sclerotherapy vs. vasoconstrictors alone. In both these groups sclerotherapy was superior for control of bleeding at, respectively, 16.3 % (95 % CI 8.7 % to 23.9 % ( P = 0.0001) and 5.9 % (95 % CI, 1.5 % to 10.3 %) ( P = 0.008), with increased survival in the latter. In the combination group of sclerotherapy with vasoconstrictors, the efficacy of sclerotherapy alone was 69 %, with the combination superior in controlling bleeding, at 13.2 % (95 % CI, 8.4 % to 18.1 %) ( P &amp;amp;amp;amp;amp;amp;lt; 0.0001) but with no survival difference. This comparison of sclerotherapy across trials demonstrates a problem in defining its real efficacy. The conclusive evidence for substituting banding ligation or the combination of vasoconstrictors with sclerotherapy as better therapeutic approaches has not been provided in randomized trials. Sclerotherapy can remain a gold standard in variceal bleeding but there is scope for further studies of ligation and vasoactive drugs.

Research paper thumbnail of Digital image analysis of liver collagen predicts clinical outcome of recurrent hepatitis C Virus 1 year after liver transplantation

Liver Transplantation, 2011

Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to pre... more Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to predict. We evaluated collagen proportionate area (CPA), a quantitative histological index, at 1 year with respect to the first episode of clinical decompensation. Patients with biopsies at 1 year after liver transplantation were evaluated by Ishak stage/grade, and biopsy samples stained with Sirius red for digital image analysis were evaluated for CPA. Cox regression was used to evaluate variables associated with first appearance of clinical decompensation. Receiver operating characteristic (ROC) curves were also used. A total of 135 patients with median follow-up of 76 months were evaluated. At 1 year, median CPA was 4.6% (0.2%-36%) and Ishak stage was 0-2 in 101 patients, 3-4 in 23 patients, and 5-6 in 11 patients. Decompensation occurred in 26 (19.3%) at a median of 61 months (15-138). Univariately, CPA, tacrolimus monotherapy, and Ishak stage/grade at 1 year were associated with decompensation; upon multivariate analysis, only CPA was associated with decompensation (P = 0.010; Exp(B) = 1.169; 95%CI, 1.037-1.317). Area under the ROC curve was 0.97 (95%CI, 0.94-0.99). A cutoff value of 6% of CPA had 82% sensitivity and 95% specificity for decompensation. In the 89 patients with hepatic venous pressure gradient (HVPG) measurement, similar results were obtained. When both cutoffs of CPA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 6% and HVPG ≥ 6 mm Hg were used, all patients decompensated. Thus, CPA at 1-year biopsy after liver transplantation was highly predictive of clinical outcome in patients infected with hepatitis C virus who underwent transplantation, better than Ishak stage or HVPG.

Research paper thumbnail of Rejection rates in a randomised trial of tacrolimus monotherapy versus triple therapy in liver transplant recipients with hepatitis C virus cirrhosis

Background. Reducing immunosuppression not only reduces complications but also may lessen recurre... more 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 ¢rst 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 MTgroup 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.

Research paper thumbnail of Induction of Autoimmune Hepatitis by Pegylated Interferon in a Liver Transplant Patient with Recurrent Hepatitis C Virus

Transplantation, 2006

... Amar Dhillon. ... j.1432-2277.2008.00729.x CrossRef. European Journal of Gastroenterology &am... more ... Amar Dhillon. ... j.1432-2277.2008.00729.x CrossRef. European Journal of Gastroenterology & Hepatology Postmarketing hepatic adverse event experience with PEGylated/non-PEGylated drugs: a disproportionality analysis Hauben, M; Vegni, F; Reich, L; Younus, M European ...

Research paper thumbnail of Severe Venoocclusive Disease after Liver Transplantation Treated with Transjugular Intrahepatic Portosystemic Shunt

Transplantation, 2006

Venoocclusive disease (VOD) is due to hepatic sinusoidal lining injury leading to portal hyperten... more Venoocclusive disease (VOD) is due to hepatic sinusoidal lining injury leading to portal hypertension; its incidence after liver transplantation is about 2%. When severe, it does not respond to medical therapy and has a high mortality; retransplantation is the only therapeutic option. However, there are no detailed data regarding the use of transjugular intrahepatic portosystemic shunt for VOD after liver transplantation. We describe two patients who developed severe VOD after liver transplantation, failed defibrotide therapy, and were treated by transjugular intrahepatic portosystemic shunt (TIPS). The portal hypertension resolved completely and one had full histological recovery. We believe that TIPS should be attempted as it may resolve progressive portal hypertension and the hepatic congestion, while allowing the clinician time for listing for further liver transplantation if the patient fails to respond.

Research paper thumbnail of Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial

The Lancet, 2011

Background-Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia... more Background-Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of endorgan disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise.

Research paper thumbnail of 131 Female HCV cirrhosis liver transplant recipients have worse fibrosis progression due to recurrent hcv than male HCV recipients

Journal of Hepatology, 2006

S 58 POSTERS 37 62), 16 M/7 E Group I patients received continuous, groups II and III intermitten... more S 58 POSTERS 37 62), 16 M/7 E Group I patients received continuous, groups II and III intermittent MARS replacement. Results: Group I: 6 ALF [cryptogenic (3), acute viral hepatitis B (1), Bud&Chiari syndrome (1) and heat-stroke (1)] and 1 ACLF (AAH). 4 ALF were successfully transplanted (3.2 mean MARS sessions; range: 1 5; 10.2 hours/session) with a mean delay of 42 hours after admission. 1 ALF completely recovered liver function after 3 MARS sessions and 1 died in multiorgan failure. The patient with ACLF received LT after 9 sessions. In-hospital survival rate was 86%. Group II: 2 patients had primary graft dysfunction (PGD) and 7 cholestasis (Brb > 20 mg/dl) associated with renal failure in 3 cases. Both PGD died; in one case after 5 sessions without reaching retransplantation and the other despite 1 session and retransplantation. The 6 other patients improved hepatic and renal function avoiding retransplantation after 3 MARS sessions and one died due to sepsis. In-hospital survival rate was 67%. Group III: All patients improved after a set of 3 sessions, although 3 required a new set of 3 sessions, 2, 3 and 9 months after the first ones. Mean time free of pruritus was 6.6 months. No severe side effects related to the extracorporeal therapy were seen. Conclusions: MARS seems to be safe in different situations surrounding LT, so clinical trials are warranted in this setting. As in non-LT patients, control of refractory pruritus clearly improved with MARS.

Research paper thumbnail of Liver Transplantation and Hepatitis C Virus: Systematic Review of Antiviral Therapy

Transplantation, 2005

Antiviral therapy for recurrent hepatitis C after liver transplantation is increasingly used. Thi... more Antiviral therapy for recurrent hepatitis C after liver transplantation is increasingly used. This systematic review presents both viral and histological response in three areas: pretransplant (5 studies/180 patients), preemptive therapy soon after transplant (10 studies/417 patients), and therapy for established disease (75 studies/2027 patients). There were only 16 randomized studies (543 patients). Significant dose reductions and drug stoppage rates occurred. The data on histological improvement and risk of rejection are conflicting. Even the best antiviral therapy (pegylated interferon/ribavirin) is neither easily used nor reasonably effective. The best strategy will be pretransplant treatment, most likely with newer agents.

Research paper thumbnail of Liver Transplantation and Recurrent Hepatocellular Carcinoma: Predictive Value of Nodule Size in a Retrospective and Explant Study

Transplantation, 2006

Background. Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains... more Background. Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains a major cause of post-LT death. Methods. To assess which preoperative and postoperative variables were related to recurrence of HCC after LT in patients with cirrhosis and HCC, we evaluated 96 patients with cirrhosis (74 with known HCC and 22 with incidental HCC) who survived more than 1 month after LT. Results. The median waiting list time was 36 days (range 1-370 days), and the median interval from detection to transplant was 180 days (range 14 -1460 days). The size of largest nodule on imaging was strongly associated with recurrence (odds ratio 1.03; 95% confidence interval 0.99 -1.06; Pϭ0.064) when transplantation was performed for known HCC. Among postoperative variables, only the largest nodule diameter (independently of the number of smaller nodules) was multivariately associated with recurrence (odds ratio 1.05; 95% confidence interval 1.01-1.08; Pϭ0.005). The best predictive cutoff was 35 mm in diameter, based on a receiver operating curve with 1-, 3-, and 5-year recurrence-free survival of 90%, 73%, and 49%, respectively, for patients with a nodule 35 mm in diameter or more compared with 96%, 93%, and 89% (Pϭ0.0005), respectively, for patients with smaller nodules. Conclusions. In our cohort with a short waiting list time, only the largest nodule diameter, especially in the explant, predicted recurrence after LT independently of the number of nodules. New proposals for increasing the diameter of the largest nodule as a selection criteria for LT do not agree with our data, which on the contrary indicate the optimal nodule diameter should be 35 mm or less.

Research paper thumbnail of Clinical outcome of HCV-related graft cirrhosis and prognostic value of hepatic venous pressure gradient

Transplant International, 2009

Research paper thumbnail of Heparin effect on thromboelastography after transjugular intrahepatic portosystemic shunt procedure

Scandinavian Journal of Gastroenterology, 2009

In patients with cirrhosis and bacterial infection there is impaired coagulation and a heparin ef... more In patients with cirrhosis and bacterial infection there is impaired coagulation and a heparin effect on thromboelastography (TEG). Our aim was to assess the presence of a heparin effect on heparinase I-modified TEG in patients before and after transjugular intrahepatic portosystemic shunt (TIPS). Our hypothesis was that, given the presence of a portosystemic gradient of endotoxaemia, and the role of endotoxaemia on the release of heparinoids, the inflow of portal blood after TIPS might reveal heparinoids through a heparin effect on TEG. Blood samples for heparinase I-modified TEG were taken before, 1 h after, 6 h after and the morning after TIPS, with further daily samples being taken until any TEG changes had reverted to baseline. A heparin effect was defined as an improvement of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =20% in a TEG variable after addition of heparinase I. We studied 10 patients (six males, mean age 48.8 years, mean Child score 8.8). The aetiology of liver disease was alcohol in six patients, Budd-Chiari syndrome in two, and hepatitis C virus and cryptogenic cirrhosis in one each. Indications for TIPS were recurrent variceal bleeding in four patients, refractory ascites or hydrothorax in four and Budd-Chiari syndrome in two. There was a statistically significant worsening in TEG parameters after TIPS placement. In eight patients a heparin effect appeared after TIPS and disappeared within 24-48 h. We report the appearance of a transient heparin effect in systemic venous blood after TIPS in patients with cirrhosis or Budd-Chiari syndrome, suggesting the presence of heparinoid substances in the portal venous system in these patients.

Research paper thumbnail of Severe, Acute Liver Injury and Khat Leaves

New England Journal of Medicine, 2010

To the Editor: The chewing of khat leaves (Catha edulis) is a widespread recreational custom in E... more To the Editor: The chewing of khat leaves (Catha edulis) is a widespread recreational custom in East Africa and the Arabian Peninsula. The plant con-tains the alkaloids cathine and cathinone, which have amphetamine-like properties and produce a variety of pleasurable ...

Research paper thumbnail of Hepatic venous pressure gradient to assess fibrosis and its progression after liver transplantation for HCV cirrhosis

Liver Transplantation, 2007

Progression of fibrosis following recurrent hepatitis C virus (HCV) infection is frequent after l... more Progression of fibrosis following recurrent hepatitis C virus (HCV) infection is frequent after liver transplantation (LT). Histology remains the gold standard to assess fibrosis, but the value of hepatic venous pressure gradient (HVPG) is being explored. We evaluated patients with recurrent HCV infection after LT to assess whether HVPG correlates with liver histology, particularly fibrosis. A total of 90 consecutive patients underwent 170 HVPG measurements concomitant with transjugular liver biopsy (TJB), with 31.5 (range, 6-156) months of follow up. Median biopsy length was 22 mm and total portal tract count was 12 (complete 6, partial 6). Median HVPG was 4 mmHg: 38% of patients &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =6 mmHg (portal hypertension, PHT), 13% &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =10 mmHg. HVPG correlated with Ishak stage (r = 0.73, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) for mild (0-3) and severe fibrosis (4-6), and grade score (r = 0.47, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), but neither correlated with interval from LT nor biopsy length. HVPG was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =10 mmHg in 15 patients: 12 had stage 5 or 6, and 3 severe portal expansion. HVPG was repeated in 49, between 7 and 60 months with weak correlation to fibrosis score (r = 0.30, P = 0.045). A total of 12 patients with HVPG &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =6 mmHg had fibrosis score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =3, while 8 patients had normal HVPG but fibrosis stage &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =4. These discrepancies were mostly associated with specific histological features such as perisinusoidal fibrosis rather than errors in measuring HVPG. In 29 with HVPG &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 mmHg at 1 yr, none decompensated compared to 4 of 13 (31%) with PHT. In conclusion, HVPG correlates with fibrosis and its progression, due to recurrent HCV infection, assessed in TJB.

Research paper thumbnail of Immunosuppression and donor age with respect to severity of HCV recurrence after liver transplantation

Liver Transplantation, 2005

In HCV cirrhotic patients after liver transplantation, survival and recurrence of HCV appears to ... more 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.

Research paper thumbnail of Liver transplantation for HCV cirrhosis: Improved survival in recent years and increased severity of recurrent disease in female recipients: Results of a long term retrospective study

Liver Transplantation, 2007

In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster ... more In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster progression of recurrent disease to overt cirrhosis have been reported. Our aims were to 1) assess patient survival and development of severe recurrent disease (Ishak fibrosis score Ͼ 3) in different transplant years; and 2) model the effects of pre-and post-liver transplantation (LT) variables on the severity of recurrent disease. A multicenter retrospective analysis was conducted on 502 consecutive HCV-positive transplant recipients between January 1990 and December 2002. Protocol liver biopsies were obtained at 1, 3, 5, 7, and 10 yr post-LT in almost 90% of the patients. All 502 patients were included in the overall survival analysis, while only the 354 patients with a follow-up longer than 1 yr were considered for the analysis of predictors of disease progression. The overall Kaplan-Meier survival rates were 78.7%, 66.3%, and 58.6%, at 12, 60, and 120 months, respectively, and a trend for a better patient survival over the years emerged from all 3 centers. The cumulative probability of developing HCV-related recurrent severe fibrosis (Ishak score 4-6) in the cohort of 354 patients who survived at least 1 yr remained unchanged over the years. Multivariate analysis indicated that older donors (P ϭ 0.0001) and female gender of recipient (P ϭ 0.02) were the 2 major risk factors for the development of severe recurrent disease, while the adoption of antilymphocytic preparations was associated with a less aggressive course (P ϭ 0.03). Two of these prognostic factors, donor age and recipient gender, are easily available before LT and their combination showed an important synergy, such that a female recipient not only had a much higher probability of severe recurrent disease than a male recipient but her risk increased with the increasing age of the donor, reaching almost 100% when the age of the donor was 60 or older. In conclusion, a trend for a better patient survival was observed in more recent years but the cumulative probability of developing severe recurrent disease remained unchanged. The combination of a female recipient receiving an older graft emerged as a strong risk factor for a severe recurrence. Liver Transpl 13: 733-740, 2007.

Research paper thumbnail of Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies

Cancer Treatment Reviews, 2006

Background: Although transarterial chemoembolization (TACE) improves survival in patients with he... more Background: Although transarterial chemoembolization (TACE) improves survival in patients with hepatocellular carcinoma (HCC), it is not known if TACE combined with other treatments is beneficial. Aim: To evaluate the evidence for improved outcomes in HCC with a multimodal treatment approach involving TACE. Method: PubMed search for all cohort and randomized trials (n = 84) evaluating TACE combined with other therapies; meta-analysis performed where appropriate. Results: A meta-analysis involving 4 RCTs showed a significant decrease in mortality favouring combination treatment (TACE plus percutaneous ablation) compared to monotherapy in patients with either small (<3 cm) or large HCC nodules (>3 cm) (OR, 0.534; 95% CI, 0.288-0.990; p = 0.046). TACE combined with local radiotherapy improved survival in patients a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r h e a l t h . c o m / j o u r n a l s / c t r v with tumour thrombosis of the portal vein in 7 non-randomized studies. Two RCTs and 13 non-randomized studies showed that TACE prior to hepatic resection does not improve survival nor tumour recurrence. Conversely, 2 RCTs and 5 comparative studies showed that transarterial injection of chemotherapeutic drugs mixed with lipiodol (TOCE) following hepatectomy confers survival benefit and less tumour recurrence. TACE before liver transplantation is safe and reduces drop-out rate from the waiting list, but there is no current evidence of improvement in subsequent survival or recurrence rate. Conclusions: A combined approach involving TACE and percutaneous ablation improves survival. Adjuvant TOCE improves outcome after hepatectomy. TACE is useful to control tumours burden while on the waiting list for OLT. Multimodal treatment seems to be the best way to optimize TACE outcomes in HCC.

Research paper thumbnail of Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score

Journal of Cachexia, Sarcopenia and Muscle, 2016

Research paper thumbnail of Case report Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantion for HCV cirrhosis

Immunosuppression is a main determinant for the increased Hepatitis C Virus (HCV) replication aft... more 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

Research paper thumbnail of Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with and without underlying cirrhosis

Cardiovascular and interventional radiology

To retrospectively determine the acute safety and chronic outcomes of transjugular intrahepatic p... more To retrospectively determine the acute safety and chronic outcomes of transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with hemodialysis-dependent end-stage renal disease for control of bleeding and refractory ascites. Four dialysis-dependent patients and one renal transplant recipient (glomerular filtration rate, 27 mL/min) underwent TIPS creation for treatment of refractory ascites (n = 3) and recurrent portal hypertensive bleeding (n = 1). A sixth patient developed unrelated renal failure 3 years after initial TIPS formation and presented with encephalopathy at that time. All had nearly normal liver function test results and no previous baseline encephalopathy. Three dialysis recipients underwent dialysis immediately after the TIPS procedure in an intensive care unit; one did not. There were no complications of fluid overload or pulmonary edema after TIPS creation in the patients who immediately underwent dialysis. The one patient in whom dialysis was delayed developed respiratory failure and shock liver (ie, ischemic hepatitis). Ascites resolved in all three patients, and no recurrent variceal bleeding occurred during a mean follow-up of 17 months. Severe, grade 2-4 hepatic encephalopathy developed in all patients; in one patient, its onset was delayed until the onset of renal failure 3 years after the original TIPS procedure. Shunt reduction was required in four cases and competitive variceal embolization was required in one to reduce portosystemic diversion. No less than grade 1 episodic baseline encephalopathy was present in all patients despite continued use of the maximum prescribed medical therapy thereafter. TIPS creation is effective in controlling ascites and bleeding in functionally anephric patients, but at the cost of marked and disproportionate hepatic encephalopathy. Prompt, acute postprocedural dialysis and fluid management is critical for safe creation of a TIPS in dialysis-dependent patients.

Research paper thumbnail of Reply to Dr. Krag et al

Research paper thumbnail of An evaluation of emergency sclerotherapy of varices in randomized trials: looking the needle in the eye

Endoscopy, 2006

The role of sclerotherapy for acute variceal bleeding is challenged by vasoactive drugs and by li... more The role of sclerotherapy for acute variceal bleeding is challenged by vasoactive drugs and by ligation. A meta-analysis was performed to evaluate whether sclerotherapy remains a gold standard in acute variceal bleeding. Sclerotherapy was evaluated across four randomized trial groups: (a) combined with vasoconstrictors vs. vasoconstrictors alone (five trials, with 400 patients); (b) vs. vasoconstrictors alone (15 trials, with 1296 patients); (c) vs. combination of vasoconstrictors and sclerotherapy (eight trials, with 1026 patients); (d) vs. ligation (12 trials, with 1309 patients). We used the risk difference (absolute risk reduction) as our main effect measure. The efficacy of acute sclerotherapy was highest vs. ligation at 95 %, with a small advantage for ligation (an overtube was used in eight trials) of 2.5 % (95 % CI 0.4 % to 4.6 %) ( P = 0.018), but no survival difference. Efficacy of sclerotherapy combined with vasoconstrictors vs. vasoconstrictors alone was 86 %, whereas it was 83 % for sclerotherapy vs. vasoconstrictors alone. In both these groups sclerotherapy was superior for control of bleeding at, respectively, 16.3 % (95 % CI 8.7 % to 23.9 % ( P = 0.0001) and 5.9 % (95 % CI, 1.5 % to 10.3 %) ( P = 0.008), with increased survival in the latter. In the combination group of sclerotherapy with vasoconstrictors, the efficacy of sclerotherapy alone was 69 %, with the combination superior in controlling bleeding, at 13.2 % (95 % CI, 8.4 % to 18.1 %) ( P &amp;amp;amp;amp;amp;amp;lt; 0.0001) but with no survival difference. This comparison of sclerotherapy across trials demonstrates a problem in defining its real efficacy. The conclusive evidence for substituting banding ligation or the combination of vasoconstrictors with sclerotherapy as better therapeutic approaches has not been provided in randomized trials. Sclerotherapy can remain a gold standard in variceal bleeding but there is scope for further studies of ligation and vasoactive drugs.

Research paper thumbnail of Digital image analysis of liver collagen predicts clinical outcome of recurrent hepatitis C Virus 1 year after liver transplantation

Liver Transplantation, 2011

Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to pre... more Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to predict. We evaluated collagen proportionate area (CPA), a quantitative histological index, at 1 year with respect to the first episode of clinical decompensation. Patients with biopsies at 1 year after liver transplantation were evaluated by Ishak stage/grade, and biopsy samples stained with Sirius red for digital image analysis were evaluated for CPA. Cox regression was used to evaluate variables associated with first appearance of clinical decompensation. Receiver operating characteristic (ROC) curves were also used. A total of 135 patients with median follow-up of 76 months were evaluated. At 1 year, median CPA was 4.6% (0.2%-36%) and Ishak stage was 0-2 in 101 patients, 3-4 in 23 patients, and 5-6 in 11 patients. Decompensation occurred in 26 (19.3%) at a median of 61 months (15-138). Univariately, CPA, tacrolimus monotherapy, and Ishak stage/grade at 1 year were associated with decompensation; upon multivariate analysis, only CPA was associated with decompensation (P = 0.010; Exp(B) = 1.169; 95%CI, 1.037-1.317). Area under the ROC curve was 0.97 (95%CI, 0.94-0.99). A cutoff value of 6% of CPA had 82% sensitivity and 95% specificity for decompensation. In the 89 patients with hepatic venous pressure gradient (HVPG) measurement, similar results were obtained. When both cutoffs of CPA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 6% and HVPG ≥ 6 mm Hg were used, all patients decompensated. Thus, CPA at 1-year biopsy after liver transplantation was highly predictive of clinical outcome in patients infected with hepatitis C virus who underwent transplantation, better than Ishak stage or HVPG.

Research paper thumbnail of Rejection rates in a randomised trial of tacrolimus monotherapy versus triple therapy in liver transplant recipients with hepatitis C virus cirrhosis

Background. Reducing immunosuppression not only reduces complications but also may lessen recurre... more 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 ¢rst 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 MTgroup 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.

Research paper thumbnail of Induction of Autoimmune Hepatitis by Pegylated Interferon in a Liver Transplant Patient with Recurrent Hepatitis C Virus

Transplantation, 2006

... Amar Dhillon. ... j.1432-2277.2008.00729.x CrossRef. European Journal of Gastroenterology &am... more ... Amar Dhillon. ... j.1432-2277.2008.00729.x CrossRef. European Journal of Gastroenterology & Hepatology Postmarketing hepatic adverse event experience with PEGylated/non-PEGylated drugs: a disproportionality analysis Hauben, M; Vegni, F; Reich, L; Younus, M European ...

Research paper thumbnail of Severe Venoocclusive Disease after Liver Transplantation Treated with Transjugular Intrahepatic Portosystemic Shunt

Transplantation, 2006

Venoocclusive disease (VOD) is due to hepatic sinusoidal lining injury leading to portal hyperten... more Venoocclusive disease (VOD) is due to hepatic sinusoidal lining injury leading to portal hypertension; its incidence after liver transplantation is about 2%. When severe, it does not respond to medical therapy and has a high mortality; retransplantation is the only therapeutic option. However, there are no detailed data regarding the use of transjugular intrahepatic portosystemic shunt for VOD after liver transplantation. We describe two patients who developed severe VOD after liver transplantation, failed defibrotide therapy, and were treated by transjugular intrahepatic portosystemic shunt (TIPS). The portal hypertension resolved completely and one had full histological recovery. We believe that TIPS should be attempted as it may resolve progressive portal hypertension and the hepatic congestion, while allowing the clinician time for listing for further liver transplantation if the patient fails to respond.

Research paper thumbnail of Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial

The Lancet, 2011

Background-Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia... more Background-Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of endorgan disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise.

Research paper thumbnail of 131 Female HCV cirrhosis liver transplant recipients have worse fibrosis progression due to recurrent hcv than male HCV recipients

Journal of Hepatology, 2006

S 58 POSTERS 37 62), 16 M/7 E Group I patients received continuous, groups II and III intermitten... more S 58 POSTERS 37 62), 16 M/7 E Group I patients received continuous, groups II and III intermittent MARS replacement. Results: Group I: 6 ALF [cryptogenic (3), acute viral hepatitis B (1), Bud&Chiari syndrome (1) and heat-stroke (1)] and 1 ACLF (AAH). 4 ALF were successfully transplanted (3.2 mean MARS sessions; range: 1 5; 10.2 hours/session) with a mean delay of 42 hours after admission. 1 ALF completely recovered liver function after 3 MARS sessions and 1 died in multiorgan failure. The patient with ACLF received LT after 9 sessions. In-hospital survival rate was 86%. Group II: 2 patients had primary graft dysfunction (PGD) and 7 cholestasis (Brb > 20 mg/dl) associated with renal failure in 3 cases. Both PGD died; in one case after 5 sessions without reaching retransplantation and the other despite 1 session and retransplantation. The 6 other patients improved hepatic and renal function avoiding retransplantation after 3 MARS sessions and one died due to sepsis. In-hospital survival rate was 67%. Group III: All patients improved after a set of 3 sessions, although 3 required a new set of 3 sessions, 2, 3 and 9 months after the first ones. Mean time free of pruritus was 6.6 months. No severe side effects related to the extracorporeal therapy were seen. Conclusions: MARS seems to be safe in different situations surrounding LT, so clinical trials are warranted in this setting. As in non-LT patients, control of refractory pruritus clearly improved with MARS.

Research paper thumbnail of Liver Transplantation and Hepatitis C Virus: Systematic Review of Antiviral Therapy

Transplantation, 2005

Antiviral therapy for recurrent hepatitis C after liver transplantation is increasingly used. Thi... more Antiviral therapy for recurrent hepatitis C after liver transplantation is increasingly used. This systematic review presents both viral and histological response in three areas: pretransplant (5 studies/180 patients), preemptive therapy soon after transplant (10 studies/417 patients), and therapy for established disease (75 studies/2027 patients). There were only 16 randomized studies (543 patients). Significant dose reductions and drug stoppage rates occurred. The data on histological improvement and risk of rejection are conflicting. Even the best antiviral therapy (pegylated interferon/ribavirin) is neither easily used nor reasonably effective. The best strategy will be pretransplant treatment, most likely with newer agents.

Research paper thumbnail of Liver Transplantation and Recurrent Hepatocellular Carcinoma: Predictive Value of Nodule Size in a Retrospective and Explant Study

Transplantation, 2006

Background. Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains... more Background. Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains a major cause of post-LT death. Methods. To assess which preoperative and postoperative variables were related to recurrence of HCC after LT in patients with cirrhosis and HCC, we evaluated 96 patients with cirrhosis (74 with known HCC and 22 with incidental HCC) who survived more than 1 month after LT. Results. The median waiting list time was 36 days (range 1-370 days), and the median interval from detection to transplant was 180 days (range 14 -1460 days). The size of largest nodule on imaging was strongly associated with recurrence (odds ratio 1.03; 95% confidence interval 0.99 -1.06; Pϭ0.064) when transplantation was performed for known HCC. Among postoperative variables, only the largest nodule diameter (independently of the number of smaller nodules) was multivariately associated with recurrence (odds ratio 1.05; 95% confidence interval 1.01-1.08; Pϭ0.005). The best predictive cutoff was 35 mm in diameter, based on a receiver operating curve with 1-, 3-, and 5-year recurrence-free survival of 90%, 73%, and 49%, respectively, for patients with a nodule 35 mm in diameter or more compared with 96%, 93%, and 89% (Pϭ0.0005), respectively, for patients with smaller nodules. Conclusions. In our cohort with a short waiting list time, only the largest nodule diameter, especially in the explant, predicted recurrence after LT independently of the number of nodules. New proposals for increasing the diameter of the largest nodule as a selection criteria for LT do not agree with our data, which on the contrary indicate the optimal nodule diameter should be 35 mm or less.

Research paper thumbnail of Clinical outcome of HCV-related graft cirrhosis and prognostic value of hepatic venous pressure gradient

Transplant International, 2009

Research paper thumbnail of Heparin effect on thromboelastography after transjugular intrahepatic portosystemic shunt procedure

Scandinavian Journal of Gastroenterology, 2009

In patients with cirrhosis and bacterial infection there is impaired coagulation and a heparin ef... more In patients with cirrhosis and bacterial infection there is impaired coagulation and a heparin effect on thromboelastography (TEG). Our aim was to assess the presence of a heparin effect on heparinase I-modified TEG in patients before and after transjugular intrahepatic portosystemic shunt (TIPS). Our hypothesis was that, given the presence of a portosystemic gradient of endotoxaemia, and the role of endotoxaemia on the release of heparinoids, the inflow of portal blood after TIPS might reveal heparinoids through a heparin effect on TEG. Blood samples for heparinase I-modified TEG were taken before, 1 h after, 6 h after and the morning after TIPS, with further daily samples being taken until any TEG changes had reverted to baseline. A heparin effect was defined as an improvement of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =20% in a TEG variable after addition of heparinase I. We studied 10 patients (six males, mean age 48.8 years, mean Child score 8.8). The aetiology of liver disease was alcohol in six patients, Budd-Chiari syndrome in two, and hepatitis C virus and cryptogenic cirrhosis in one each. Indications for TIPS were recurrent variceal bleeding in four patients, refractory ascites or hydrothorax in four and Budd-Chiari syndrome in two. There was a statistically significant worsening in TEG parameters after TIPS placement. In eight patients a heparin effect appeared after TIPS and disappeared within 24-48 h. We report the appearance of a transient heparin effect in systemic venous blood after TIPS in patients with cirrhosis or Budd-Chiari syndrome, suggesting the presence of heparinoid substances in the portal venous system in these patients.

Research paper thumbnail of Severe, Acute Liver Injury and Khat Leaves

New England Journal of Medicine, 2010

To the Editor: The chewing of khat leaves (Catha edulis) is a widespread recreational custom in E... more To the Editor: The chewing of khat leaves (Catha edulis) is a widespread recreational custom in East Africa and the Arabian Peninsula. The plant con-tains the alkaloids cathine and cathinone, which have amphetamine-like properties and produce a variety of pleasurable ...

Research paper thumbnail of Hepatic venous pressure gradient to assess fibrosis and its progression after liver transplantation for HCV cirrhosis

Liver Transplantation, 2007

Progression of fibrosis following recurrent hepatitis C virus (HCV) infection is frequent after l... more Progression of fibrosis following recurrent hepatitis C virus (HCV) infection is frequent after liver transplantation (LT). Histology remains the gold standard to assess fibrosis, but the value of hepatic venous pressure gradient (HVPG) is being explored. We evaluated patients with recurrent HCV infection after LT to assess whether HVPG correlates with liver histology, particularly fibrosis. A total of 90 consecutive patients underwent 170 HVPG measurements concomitant with transjugular liver biopsy (TJB), with 31.5 (range, 6-156) months of follow up. Median biopsy length was 22 mm and total portal tract count was 12 (complete 6, partial 6). Median HVPG was 4 mmHg: 38% of patients &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =6 mmHg (portal hypertension, PHT), 13% &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =10 mmHg. HVPG correlated with Ishak stage (r = 0.73, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) for mild (0-3) and severe fibrosis (4-6), and grade score (r = 0.47, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), but neither correlated with interval from LT nor biopsy length. HVPG was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =10 mmHg in 15 patients: 12 had stage 5 or 6, and 3 severe portal expansion. HVPG was repeated in 49, between 7 and 60 months with weak correlation to fibrosis score (r = 0.30, P = 0.045). A total of 12 patients with HVPG &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =6 mmHg had fibrosis score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =3, while 8 patients had normal HVPG but fibrosis stage &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =4. These discrepancies were mostly associated with specific histological features such as perisinusoidal fibrosis rather than errors in measuring HVPG. In 29 with HVPG &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 mmHg at 1 yr, none decompensated compared to 4 of 13 (31%) with PHT. In conclusion, HVPG correlates with fibrosis and its progression, due to recurrent HCV infection, assessed in TJB.

Research paper thumbnail of Immunosuppression and donor age with respect to severity of HCV recurrence after liver transplantation

Liver Transplantation, 2005

In HCV cirrhotic patients after liver transplantation, survival and recurrence of HCV appears to ... more 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.

Research paper thumbnail of Liver transplantation for HCV cirrhosis: Improved survival in recent years and increased severity of recurrent disease in female recipients: Results of a long term retrospective study

Liver Transplantation, 2007

In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster ... more In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster progression of recurrent disease to overt cirrhosis have been reported. Our aims were to 1) assess patient survival and development of severe recurrent disease (Ishak fibrosis score Ͼ 3) in different transplant years; and 2) model the effects of pre-and post-liver transplantation (LT) variables on the severity of recurrent disease. A multicenter retrospective analysis was conducted on 502 consecutive HCV-positive transplant recipients between January 1990 and December 2002. Protocol liver biopsies were obtained at 1, 3, 5, 7, and 10 yr post-LT in almost 90% of the patients. All 502 patients were included in the overall survival analysis, while only the 354 patients with a follow-up longer than 1 yr were considered for the analysis of predictors of disease progression. The overall Kaplan-Meier survival rates were 78.7%, 66.3%, and 58.6%, at 12, 60, and 120 months, respectively, and a trend for a better patient survival over the years emerged from all 3 centers. The cumulative probability of developing HCV-related recurrent severe fibrosis (Ishak score 4-6) in the cohort of 354 patients who survived at least 1 yr remained unchanged over the years. Multivariate analysis indicated that older donors (P ϭ 0.0001) and female gender of recipient (P ϭ 0.02) were the 2 major risk factors for the development of severe recurrent disease, while the adoption of antilymphocytic preparations was associated with a less aggressive course (P ϭ 0.03). Two of these prognostic factors, donor age and recipient gender, are easily available before LT and their combination showed an important synergy, such that a female recipient not only had a much higher probability of severe recurrent disease than a male recipient but her risk increased with the increasing age of the donor, reaching almost 100% when the age of the donor was 60 or older. In conclusion, a trend for a better patient survival was observed in more recent years but the cumulative probability of developing severe recurrent disease remained unchanged. The combination of a female recipient receiving an older graft emerged as a strong risk factor for a severe recurrence. Liver Transpl 13: 733-740, 2007.