Antiviral treatment for hepatitis B virus recurrence following liver transplantation

The purpose of this study was to identify the factors associated with the recurrence of hepatitis B virus (HBV) following liver transplantation (LT) for HBV‐related disease and to recognize the outcome of treatment for HBV recurrence with oral nucleos(t)ide analogues. Six hundred and sixty‐seven LTs were performed for HBsAg‐positive adult patients in our institute from 1996 to 2010. HBV prophylaxis was performed by hepatitis B immunoglobulin (HBIG) monotherapy or HBIG and entecavir combination therapy. There were 63 cases (11.4%) of HBV recurrences during a median follow‐up of 51 months. The median time to HBV recurrence was 22 months. A preoperative HBV DNA load of more than 10⁵ IU/mL, HBIG monotherapy, and hepatocellular carcinoma in the explant liver were independent risk factors for HBV recurrence following LT in multivariate analysis. Patient survival at 10 yr was 54.2% for HBV‐recurrent patients. Among patients with HBV recurrence, HBsAg seroclearance was achieved in 13 patients (20.6%), but HBsAg seroclearance did not affect survival in these patients after the recurrence of HBV (p = 0.28). The recurrence of HBV led to graft failure in six cases. HBV recurrence should be prevented by strict management of pre‐transplant HBV viremia and an effective post‐transplant HBV prophylaxis.     

Antiviral therapy for recurrent hepatitis C reduces recurrence of hepatocellular carcinoma following liver transplantation

Recurrence of hepatocellular carcinoma (HCC) is one of the major concerns following liver transplantation (LT). With the potential antitumor properties of interferon (IFN), their role in prevention of HCC recurrence is to be defined. We retrospectively reviewed 46 patients who underwent LT for hepatitis C virus (HCV)‐related HCC between January 2004 and December 2008. Twenty‐four (52.2%) patients with biopsy‐proven HCV recurrence received antiviral therapy (IFN group); their outcomes were compared with 22 patients (control group). There was no significant difference for tumor size, number, and type of neo‐adjuvant therapy between the two groups. The 1‐ and 3‐year overall patient survival (100% vs. 90.9% and 87.3% vs. 71.8%; P = 0.150) and tumor‐free survival (100% vs. 72.7% and 83.1% vs. 67.5%; P = 0.214) between IFN and control group were comparable. HCC recurrence was the most common cause of death (n = 6 of 12, 50%), all in the control group. During follow‐up, seven (15.2%) patients developed HCC recurrence: one (4.1%) in the IFN group and six (27.3%) in the control group (P < 0.05). In conclusions, HCC recurrence rate and related deaths were significantly lower in patients that received post‐transplant antiviral therapy for recurrent HCV.     

Effectiveness of early a-interferon therapy for hepatitis C virus infection recurrence after liver transplantation

Abstract  The results in this short series show that early and prolonged α-interferon therapy for hepatitis C virus recurrence after liver transplantation could bring some benefit to the infected liver grafts. The risk of graft rejection was clearly minimised by maintaining immunosup-pression at normal levels.     

Pediatric liver transplantation for hepatoblastoma: a single center experience

The objective of this study was to review our experience with liver transplantation (OLT) for hepatoblastoma (HB) patients. We evaluated retrospectively clinical features of seven pediatric patients with HB who underwent OLT at our institute from 2007 to February 2011. We investigated pretreatment extent of disease (PRETEXT) stage at diagnosis, type of procedure, complications, changes in serum alpha-fetoprotein (AFP) level, recurrences and metastases. The median age at surgery was 47 months (range, 11 months to 10.3 years). OLT was performed for PRETEXT stage III with a central location (n = 2) and for PRETEXT stage IV cases (n = 5). Five children underwent live donor OLT (LDLT) and two deceased donor OLT including one split deceased donor OLT. One patient received a hepatic vein stent insertion due to stenosis and another experienced biliary leakage which was treated with percutaneous drainage and conservative management. Postoperative serum AFP level remained below 20 ng/mL during follow-up period in six patients who were free of recurrences or metastases. Postoperative serum AFP levels in one patient with pulmonary metastasis were never below 20 ng/mL and increased gradually thereafter. A Pulmonary metastasis was discovered in the 2^nd month post-operative. The other 6 patients are free of tumor recurrences with 29.9 month median follow-up.Although the number of cases is small without long term follow-up data, OLT for unresectable HB confined to the liver following chemotherapy seemed to show good clinical results. The role of post transplantation serum AFP levels needs further investigation.     

Ribavirin therapy for hepatitis C infection following liver transplantation

Hepatitis C infection following orthotopic liver transplantation may lead to progressive chronic graft dysfunction. In this study, seven liver transplant recipients with chronic allograft dysfunction due to hepatitis C infection (one acquired and six recurrent infections) were treated with oral ribavirin for 6 months. Symptoms of lethargy, nausea and anorexia improved in all patients within 2 weeks of starting the drug, with a fall in serum AST of at least 40% by this time. Ribavirin-induced haemolysis was clinically significant in three patients, necessitating a reduction in the daily dose of ribavirin from 1.2 g to 0.2 g. Comparison of the pre- and post-treatment biopsy specimens in the four patients who tolerated the full dose of ribavirin and who had normal AST levels at the end of 6 months of treatment showed significant histological improvement with reduction in either lobular or periportal inflammation in all of the patients and a reduction in periportal fibrosis in one patient. HCV RNA remained detectable in serum in all of the patients at the end of the study.     

Living-donor liver transplantation: results of a single center

In the absence of cadaveric donor liver transplantation, living-donor liver transplantation (LDLT) is an alternative option for patients with end-stage liver disease. The objective of this study was to evaluate the outcome of LDLT at a single medical center in Turkey. We retrospectively analyzed the results of 101 LDLTs in 99 recipients with end-stage liver disease. We transplanted 49 right liver lobes, 16 left lobes, and 36 hepatic segments II and III. Most donors (46%) were parents of the recipients. Seventeen recipients had concomitant hepatocellular carcinoma and cirrhosis. Retransplantation was performed in two recipients. Ten hepatic arterial thromboses, 1 hepatic arterial bleeding, and 12 biliary leaks occurred in the early postoperative period. Most complications were treated with interventional techniques. Three hepatic vein stenoses, three portal vein stenoses, one hepatic arterial stenosis, and six biliary stenoses developed during the late postoperative period. Recipients with those complications were treated with interventional techniques. Mean follow-up was 14.2 +/- 10.9 months. During that time, no tumor recurrence was detected in any recipient with hepatocellular carcinoma. Twenty-two recipients died during the follow-up. At this time, the remaining 77 recipients (77%) are alive, exhibiting good graft function. In general, complication rates are slightly higher after LDLT than after cadaveric liver transplantation. However, most complications can be treated with interventional techniques. LDLT continues to be a life-saving option in countries without satisfactory cadaveric donation rates.     

Management of recurrence of hepatitis C infection following liver transplantation

Liver disease secondary to hepatitis C infection is the most common indication for liver transplantation. Infection of the allograft begins at the time of transplantation. The histological progression of hepatitis C infection is greatly accelerated in liver transplant recipients when compared to the natural history in immunocompetent patients. Chronic allograft injury is apparent in >50% of HCV-infected recipients in the first postoperative year. Approximately 10% of HCV-infected recipients die or lose their allograft secondary to hepatitis C-associated allograft failure and a further 30% will have cirrhosis by the end of the fifth postoperative year. Cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia and more severe histological recurrence. In contrast to non-HCV-infected recipients, treatment for acute cellular rejection is associated with attenuated patient survival among recipients with hepatitis C. Therapy with pegylated IFN (+/- ribavirin), although less efficacious than in immunocompetent patients, should be considered in recipients with histologically apparent recurrence of hepatitis C before jaundice develops. Ribavirin is poorly tolerated in liver transplant recipients, limiting efficacy of combination therapy. Ribavirin dosing should be adjusted for renal insufficiency. Passive immunity, through anti-HCV antibody preparations, has not been efficacious to date. The role of hepatitis C new immunosuppression agents in the management of posttransplant hepatitis C infection is still evolving.     

Preliminary results of immunosuppression with thymoglobuline pretreatment and hepatitis C virus recurrence in liver transplantation

Induction with thymoglobulin, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LT) has never been investigated. We report herein on the outcome of 22 HCV+ patients receiving thymoglobulin pretreatment and minimal immunosuppression after liver transplantation. Patient survival and acute rejection rates were good, with remarkably low dosages and levels of immunosuppression achieved with thymoglobulin, and without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressant was also possible in the majority of patients without complications. The HCV recurrence rate was similar to that reported in the literature, although lower HCV RNA viral loads were obtained with thymoglobulin and a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobulin is effective to protect against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.     

Relationship between hepatitis C virus recurrence and de novo diabetes after liver transplantation: the Hungarian experience

De novo diabetes mellitus is a common complication after liver transplantation. It is strongly associated with hepatitis C virus (HCV) infection. We analyzed the relationship between HCV recurrence and de novo diabetes among the Hungarian liver transplant population. This retrospective study included cases from 1995 to 2009 on 310 whole liver transplantations. De novo diabetes was defined if the patient had a fasting plasma glucose ≥126 mg/dL permanently after the third month post liver transplantation, and/or required sustained antidiabetic therapy. De novo diabetes occured in 63 patients (20%). The cumulative patient survival rates at 1, 3, 5, and 8 years were 95%, 91%, 88%, and 88% in the control group, and 87%, 79%, 79%, and 64% in the de novo group, respectively (P = .011). The majority of the patients in the de novo group were HCV positive (66% vs 23%). Early virus recurrence within 5 months was associated with the development of diabetes (80% vs 20% non-diabetic controls; P = .017). The fibrosis (2.05 ± 1.5 vs 1 ± 1; P = .039) and Knodell scores (3.25 ± 2 vs 1.69 ± 1.2; P = .019) were higher among the de novo group after antiviral therapy. Rapid recurrence, more severe viremia, and fibrosis showed significant roles in the developement of de novo diabetes after liver transplantation.     

Preemptive therapy for hepatitis C virus after living-donor liver transplantation

BACKGROUND: Living-donor liver transplantation (LDLT) is important for patients with end-stage viral hepatitis because of the cadaveric organ shortage. Preliminary results, however, indicate that LDLT might be disadvantageous for patients positive for hepatitis C virus (HCV). METHODS: The subjects were 23 patients who underwent LDLT for HCV cirrhosis. All the patients preemptively received antiviral therapy consisting of interferon-alfa2b and ribavirin, which was started approximately 1 month after the operation. The therapy continued for 12 months after the first negative HCV RNA test. The patients were then observed without the therapy for 6 months (group 1). The therapy was continued for at least 12 months even when the HCV RNA test remained positive (group 2). The subjects were removed from the protocol if they could not continue the therapy for 12 months because of adverse effects or could not start the therapy because of early death. RESULTS: Eight patients were removed from the protocol. Nine patients were assigned to group 1 and the other six to group 2. The sustained virologic response ratio was 39% (9 of 23). There was a significant difference between the groups in the histologic activity score 1 year after the therapy. The cumulated 3-year survival of the HCV-positive patients was 85%, which was comparable with that of patients negative for HCV (n=93 [90%]). CONCLUSIONS: The present preemptive antiviral protocol after LDLT is safe and might warrant a controlled study for confirming its benefit on graft survival.     

Response to antiviral therapy in liver transplant recipients with recurrent hepatitis C viral infection: a single center experience

Jain A, Sharma R, Ryan C, Safadjou S, Kashyap R, Mantry P, Maliakkal B, Orloff M. Response to antiviral therapy in liver transplant recipients with recurrent hepatitis C viral infection: a single center experience.
Clin Transplant 2010: 24: 104–111. © 2009 John Wiley & Sons A/S.   Abstract: 
Introduction:  Recurrence of hepatitis C virus (HCV) in hepatic allograft is a major concern after successful liver transplant (LTx).
Aim:  To examine the response rate to pegylated interferon (PEG–IFN) and ribavirin in post-LTx patients with HCV recurrence.
Patients and methods:  Between January 2003 and September 2006, 60 patients with biopsy proven HCV recurrence (46 males and 14 females) received PEG–IFN 2a (n = 40) or IFN 2b (n = 20) with ribavirin. All patients were followed until July 2007.
Results:  Fourteen patients (23.3%) tolerated antiviral therapy for less than six months and 10 (16.7%) discontinued therapy between six and 11 months. PEG–IFN dose was reduced in 21 (35%) patients and ribavirin dose was reduced in 16 (26.7%) patients. Overall, 55% patients achieved end of treatment response (EOT) and 35% sustained virological response (SVR). Mean Hepatitis Activity Index and Fibrosis Score pre-therapy was 5.8 ± 1.9 and 1.7 ± 1.3 and post-therapy, it was 4.4 ± 2.1 and 2.4 ± 1.6, respectively. Overall, three yr patient and graft survival was 73.9% and 69.2%, respectively. The patients with SVR had significantly lower viral load compared with other groups (p = 0.028).
Conclusion:  PEG–IFN and ribavirin therapy achieved 55% EOT and 35% SVR; 60% patients tolerated therapy. Biochemical response was observed in all groups of patients irrespective of virological response.     

The impact of disease recurrence on graft survival following liver transplantation: a single centre experience

Many diseases that cause liver failure may recur after transplantation. A retrospective analysis of the rate and cause of graft loss of 1840 consecutive adults receiving a primary liver transplant between 1982 and 2004 was performed to evaluate the rate of graft loss from disease recurrence. The risk of graft loss from recurrent disease was greatest, when compared to primary biliary cirrhosis (PBC), in those transplanted for hepatitis C virus (HCV) [hazard ratio (HR) 11.6; 95% confidence interval (CI) 5.1-26.6], primary sclerosing cholangitis (PSC) (HR 6.0; 95% CI 2.5-14.2) and autoimmune hepatitis (AIH) (HR 4.1; 95% CI 1.3-12.6). The overall risk of graft loss was also significantly greater in HCV (HR 2.1 vs. PBC; 95% CI 1.5-3.0), PSC (HR 1.6 vs. PBC; 95% CI 1.2-2.3) and AIH (HR 1.6; 95% CI 1.0-2.4) than in PBC. There was no statistically significant difference in the risk of graft loss because of recurrent disease, when compared with PBC, for patients transplanted for alcohol related liver disease, nonalcoholic steatohepatitis and fulminant hepatic failure. Disease recurrence is a significant cause of graft loss particularly in HCV, PSC and AIH. Recurrent disease, in part, explains the increased overall risk of graft loss in these groups.     

Management of hepatitis C virus infection recurrence after liver transplantation: an overview

Hepatitis C virus (HCV) infection is the major indication for liver transplantation worldwide. Its recurrence is virtually universal. Once reinfection is established, progression to cirrhosis occurs in 25%-30% of recipients within 5 years. Several studies have attempted to identify the ideal antiviral treatment for liver transplant recipients. At present, the management of recurrent HCV infection in liver transplant recipients is based on widely accepted indications, which represent a reliable guide to identify the “ideal” candidate for therapy, when therapy should be started, and what is to be expected in terms of side effects and response to treatment.     

Surgical complications following pancreaticoduodenectomy: results of a single center experience

Pancreaticoduodenectomy represents the only therapeutic option for cefalo-pancreatic and periampullary cancers. Surgical and anaesthesiological techniques development over the last twenty years has granted an operative mortality decrease. However, surgical morbidity is still high, with an incidence of 30-50%. A 20 year experience of a single Centre is examined retrospectively: 121 patients underwent pancreatic resection with radical intent. Type of operation or re-operation, operative mortality within 30 days, general and surgical morbidity, postoperative hospital stay were analysed. Average recovery time was 24 days (range 12-65); operative mortality was 5.8% (7/121); general morbidity, including medical and surgical complications, was observed in 47 patients (38.8%). Pancreatic fistula occurred in 16 patients (13.2%); ten of these underwent a second operation. Patients who underwent pancreaticoduodenctomy were divided as follows: 76 pts. received a pylours-preserving pancreaticoduodenectomy and 45 a Whipple's resection. Neither surgical complications incidence nor mortality rate were significantly different between the two groups. Postoperative complications following pancreaticoduodenectomy are still frequent and severe. In particular, pancreatic fistula represents the most relevant complication following pancreaticoduodenectomy. The Authors suggest that standard and meticulous surgical procedures together with continued efforts to improve postoperative follow-up, support early detection of complications and improvement of results in most patients.     

Simultaneous combined liver and kidney transplantation: a single center experience

Chava SP, Singh B, Stangou A, Battula N, Bowles M, O’Grady J, Rela M, Heaton ND. Simultaneous combined liver and kidney transplantation: a single center experience.
Clin Transplant 2010: 24: E62–E68. © 2010 John Wiley & Sons A/S. Abstract Renal dysfunction is common in patients awaiting liver transplantation (LT) and affects outcome following LT. Combined liver and kidney transplantation (CLKT) has been proposed as effective treatment for patients with chronic diseases of both organs, some with hepatorenal syndrome and for liver‐based metabolic diseases affecting kidney. This study is undertaken to analyze results of CLKT at a single center. Of 2690 LTs performed between 1992 and 2007, there were 39 CLKTs; most common indications were metabolic, cirrhosis and polycystic disease. With follow‐up of up to 170 months, 11 died (overall survival 71.8%); one‐, five‐, and 10‐yr patient and liver graft survival is 77%, 73.7%, and 73.7%, respectively, and kidney graft survival is 77%, 70%, and 70%, respectively. Survival among metabolic group (78.6%) appeared to be better than non‐metabolic group (68%); however, this difference was not significant (p = 0.39). Fifteen surviving patients (53.6%) have mild/moderate renal impairment (creatinine ≥125 μmol/L). None has severe renal failure (serum creatinine ≥250 μmol/L) or end‐stage renal disease requiring hemodialysis. CLKT has good results in selected groups of patients. It provides protection to kidney allograft in liver‐based metabolic diseases affecting kidney. The rate of acute rejection episodes of kidney is low. Significant proportion develops long‐term mild/moderate renal dysfunction. Careful attention to immunosuppression to minimize nephrotoxicity may help.