Long‐term,maintenance MMF monotherapy improves the fibrosis progression in liver transplant recipients with recurrent hepatitis C

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case–control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well‐matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.     

Pre‐emptive antiviral therapy in living donor liver transplantation for hepatitis C: observation based on a single‐center experience

Reports of large series in living donor liver transplantation (LDLT) for hepatitis C virus infection (HCV) are scarce. Between 1996 and 2008, 105 LDLTs were performed at the University of Tokyo for HCV. Rapid induction of antiviral treatment with interferon (IFN) and ribavirin (RBV) was attempted per protocol regardless of the clinical presentation of recurrent HCV (pre‐emptive treatment approach). Treatment was continued for 12 months after serum HCV‐RNA became negative (ETR: end‐of‐treatment response) and judged as a sustained viral response (SVR) after another 6 months of negative results without treatment. A fixed treatment period was not defined unless an ETR was achieved (no‐stopping approach). Flexible dose adjustments were allowed. Ninety‐five patients were eligible for pre‐emptive therapy. Forty‐three (45%) patients experienced an ETR, and 32 (34%) achieved SVR. Nonadherence to full‐dose INF and RBV had little impact on the viral response. Evaluation using the Kaplan–Meier method to incorporate the cumulative time‐dependent nature of the no‐stopping approach estimated SVR rate at 53% by the fifth year. Survival rate at 5 years was 79% for the HCV recipients and did not differ significantly from our non‐HCV series. In LDLT for HCV, pre‐emptive IFN–RBV‐based treatment with the application of no‐stopping approach is feasible and effective.     

Impact of human herpesvirus-6 on the frequency and severity of recurrent hepatitis C virus hepatitis in liver transplant recipients

A role of tumor necrosis factor-alpha (TNF-alpha) In the immunopathogenesis of hepatitis C virus (HCV) infection has been proposed. The novel herpes virus, human herpes virus-6 (HHV-6), is amongst the most potent inducers of cytokines, including TNF-alpha. The impact of HHV-6 viremia on the progression of recurrent HCV hepatitis was assessed in 51 HCV-positive liver transplant recipients. The frequency of recurrent HCV hepatitis did not differ between patients with HCV viremia (47.6%, 10/21) as compared with those without HCV viremia (46.7%, 14/30, p = 0.9). However, the patients with HHV-6 viremia had a significantly higher fibrosis score upon HCV recurrence than those without HHV-6 viremia (mean 1.5 vs. 0.3, p = 0.01). An association between cytomegalovirus (CMV) viremia and HCV recurrence was not documented; 50% (15/30) of the patients with CMV viremia and 42.8% (9/21) of those without CMV viremia had recurrent HCV hepatitis (p > 0.5). Receipt of ganciclovir (administered upon the detection of CMV viremia) was associated with lower total Knodell score (mean 5.2 vs. 6.9, p = 0.05) and a trend towards lower fibrosis score (mean 0.44 vs. 1.00, p = 0.12) in patients with recurrent HCV hepatitis. Thus, HHV-6 viremia in HCV-positive liver transplant recipients identified a subgroup of patients at increased risk for early fibrosis upon HCV recurrence.     

Occult hepatitis B virus infection in liver transplant recipients with recurrent hepatitis C: relationship with donor age and fibrosis progression

Abstract:  Liver transplantation (OLT) recipients who receive a graft from donors positive for hepatitis B virus (HBV) anti-core antibodies may develop overt " de novo " HBV infection. The study was undertaken to explore how often HBV infection may remain occult after OLT for hepatitis C, and whether it may represent a factor of graft fibrosis progression. We studied 30 consecutive patients transplanted for hepatitis C liver disease. Specimens from the native liver and from the graft were searched for occult HBV infection (O-HBV). In the native liver, 8/30 patients had detectable O-HBV; during the follow-up, O-HBV infection was demonstrated in 14 graft specimens. Graft O-HBV was associated with older donor age (≥50 yr; 8/9 vs. 6/21, p < 0.005). Recipients with graft O-HBV and no O-HBV in the native liver who received their grafts from donors aged >40 yr had faster fibrosis progression than recipients with no post-transplant O-HBV, whose grafts came from donors aged >40 yr and recipients whose grafts came from donors aged ≤40 yr (4/7 vs. 1/7 vs. 2/16, p < 0.05). In OLT recipients, O-HBV is more likely to occur when grafts are obtained from aged donors and may affect the rate of fibrosis progression because of recurrent hepatitis C.     

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.     

Longer survival of liver transplant recipients with hepatitis virus coinfections

Hepatitis virus coinfections [HBV plus HCV coinfection (HBV/HCV) or HBV plus HDV coinfection (HBV/HDV)] may progress more rapidly to cirrhosis than hepatitis B or C monoinfections in immunocompetent patients. Only limited information is available on the outcome of coinfected patients after liver transplantation. We studied survival rates of 204 patients with viral hepatitis transplanted at our center between 1972 and 1997. HBV/HDV and HBV/HCV coinfections were present in 23 and nine individuals, respectively, while 97 patients had monoinfection by HCV and 75 had HBV monoinfection. Survival of coinfected patients was significantly longer than that of monoinfected patients (14.4 +/- 0.9 vs. 8.5 +/- 0.6 yr; p = 0.0003). The same was true for graft survival (p = 0.0002). In Cox's regression, viral coinfection (p = 0.0001), absence of hepatocellular carcinoma (HCC) (p = 0.00001) and no retransplantation (p = 0.02) were independently associated with patient survival. After exclusion of patients with HCC (n = 62), survival of coinfected patients was still significantly longer than that of monoinfected individuals (p = 0.002). The improved outcome was similar for both HBV/HDV and HBV/HCV coinfections. In contrast to immunocompetent patients, individuals with multiple hepatitis virus infections had an improved outcome after liver transplantation. Thus, viral coinfections may be associated with ameliorated courses of diseases under certain conditions.     

Liver-kidney recipients with chronic viral hepatitis C treated with interferon-alpha

Antiviral therapy with interferon-alpha (IFN-alpha) and pegylated IFN-alpha (PEG-IFN-alpha) for chronic hepatitis C (HCV)-infected kidney recipients remains controversial. IFN-alpha is not recommended in most cases because it induces severe acute graft rejection. However, IFN-alpha, as PEG-IFN-alpha, is associated with a more pronounced immune response, and is well tolerated in HCV-infected liver recipients without causing graft rejection. In combined liver-kidney transplant (LKT) recipients, IFN-alpha has been occasionally used and appears to be well tolerated. All LKT recipients with a functioning kidney and liver having a HCV replication and who needed IFN-alpha therapy have been included in the study. The occurrence of liver and/or renal acute rejection as well as the HCV replication has been collected. A total of 12 LKT patients treated with PEG-IFN-alpha plus ribavirin have been studied. No acute rejection was observed. Renal function remained stable during and after discontinuing treatment, without any graft dysfunction. Two patients had a partial viral response and four had a sustained viral response. All patients, whatever their viral response, had decreased liver-enzyme levels. Response to PEG-IFN-alpha therapy was correlated with steroid dose and transaminase level when PEG-IFN-alpha was started. These data suggest that the combination therapy of PEG-IFN-alpha plus ribavirin did not have a higher risk of acute kidney-graft rejection after liver-kidney transplantation.     

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.     

Chronic liver disease in kidney recipients with hepatitis C virus infection

BACKGROUND: The prevalence of anti-hepatitis C virus (HCV) positive test is higher among patients in dialysis and in kidney recipients than in general population. Hepatitis C virus infection is the main cause of chronic liver disease in renal transplant patients. Liver biopsy and virological analysis were performed to clarify the grade of liver damage in kidney recipients. METHODS: Renal recipients patients with at least 5 yr under immunosuppression were submitted to clinical and laboratory analysis. Patients who tested anti-HCV positive were candidates to liver biopsy with no regard to transaminase levels. RESULTS: Forty-five patients tested anti-HCV positive and 42 anti-HCV negative. Twenty-six anti-HCV and RNA-HCV positive patients were submitted to liver biopsy. Seventy-three percentage of these patients presented chronic active hepatitis, from these only one patient presented cirrhosis. Only 29% of the anti-HCV positive group presented elevated alanine aminotransferase levels. Anti-HCV positive patients presented longer previous time on dialysis and less rejection episodes than the group anti-HCV negative (p < 0.05). All anti-HCV positive patients but one tested RNA-HCV positive by polymerase chain reaction (PCR). CONCLUSIONS: In this series the prevalence of anti-HCV positive is 51.7%. Most of the patients presented liver damage in histology caused by HCV. However, we found only mild or minimal fibrosis and inflammatory activity grade, despite 10 yr of HCV infection and 5 yr of immunosuppressive treatment. Only one patient presented cirrhosis (4%). Performing serial liver biopsies in a long-term follow-up is needed to clarify the impact of HCV infection in renal transplant patients.     

Antithymocyte globulin induction therapy in hepatitis c-positive liver transplant recipients

It is unclear whether antithymocyte globulin (ATG) induction therapy in hepatitis C-positive (HCVpositive) liver transplant recipients influences the risk of developing recurrent HCV disease. Multiple acute rejection episodes and high-dose steroids and/or OKT3 used to treat acute rejection increase the risk of graft loss from HCV. We studied the impact of ATG induction on graft and patient survival in HCVpositive liver transplants performed since 1990. Recipients who died or lost their grafts within 1 month of transplantation were excluded. Second, third, and fourth grafts were excluded, as were patients with stage III or IV hepatocellular carcinoma. There were 443 cadaveric liver transplants in adult recipients, of whom 142 (32%) were HCV positive. The incidence of biopsy-proven acute rejection was less in patients who received ATG induction, 34.2% (ATG induction) versus 66.6% (no ATG induction) (P = .01). ATG induction did not influence the risk of graft loss from HCV-related disease (P ≤ .75). When only HCV-related graft loss was considered, 10-year graft survival for HCV-positive recipients was 74% (ATG induction) versus 68.2% (no ATG induction). Whether ATG induction was given or not had no significant impact on either overall graft survival (P = .39) or patient survival (P = .11) in HCVpositive recipients. Presented at the Fifth Biennial Meeting of the American Hepato-Pancreato-Biliary Association, Fort Lauderdale, Florida, April 14–17, 2005     

Chronic hepatitis C virus infection in renal transplant: treatment and outcome

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common cause of liver disease in post-renal transplant period and causes poor patient and graft survival. We analyzed the effects of antiviral therapy using ribavirin monotherapy or ribavirin in combination with interferon (IFN)-alpha in our kidney transplant recipients with chronic hepatitis C. METHODS: Total of 14 patients received antiviral therapy, all of whom had stable graft function, raised aminotransferases and positive HCV viremia at the start of treatment. Eight patients received ribavirin alone for a period of six months to two yr, in doses of 400-800 mg daily. Five patients received IFN-alpha therapy for a period of two months to 1.5 yr, in doses of 1.5 million units daily or three million units thrice weekly with ribavirin. One patient received pegylated IFN 50 microg once weekly in combination with ribavirin. The response was seen in terms of biochemical and virological improvement at the end of study period. RESULTS: In patients treated with ribavirin alone (n = 8), mean alanine aminotransferase (ALT) levels before and after treatment were significantly different (198.4 +/- 147.6 and 104.8 +/- 66.5 IU/L respectively; p < 0.05). ALT levels normalized completely in three patients at the end of treatment, improved in three patients and deteriorated in two. Only in one of eight patients on ribavirin alone, HCV-RNA became negative after six months of treatment while in the rest (n = 7) HCV-RNA continued to be positive. In subjects on IFN plus ribavirin (n = 6), the mean ALT levels decreased significantly (from 280.2 +/- 114.9 IU/L at baseline to 71 +/- 49 IU/L at end of therapy; p < 0.05). Two patients had sustained remission (33.3%) on IFN plus ribavirin (persistently negative HCV-RNA), two patients relapsed after initial remission and in two patients treatment was stopped after two months because of graft dysfunction. Totally four patients developed graft dysfunction at some time during the course of IFN therapy (66.6%), but it was discontinued in only two (33.3%). All patients regained normal creatinine levels after discontinuation of IFN, although one patient developed chronic allograft nephropathy as shown by kidney biopsy. Four patients in IFN group developed leucopenia. Two patients developed severe anemia one of whom required blood transfusion and one developed severe flu-like syndrome requiring stoppage of therapy. CONCLUSION: Ribavirin monotherapy in renal transplant recipients with chronic hepatitis C infection results in good biochemical response but is not associated with virological clearance. IFN in combination with ribavirin is effective in two-thirds of patients after a minimum therapy of six months, but it is poorly tolerated, results in graft dysfunction in significant number of patients, and relapse can occur after stopping treatment.     

Virological response for recurrent hepatitis C improves long‐term survival in liver transplant recipients

Recurrent hepatitis C virus (HCV) infection occurs universally and is regarded as a major cause of mortality after liver transplantation (LT) for HCV‐related end‐stage liver disease. We conducted this large, single‐center, retrospective study to ascertain the long‐term impact of virological response to treatment of recurrent hepatitis C on survival of LT recipients. From August 1987 to October 2011, 285 patients have received interferon‐based antiviral therapy for recurrent hepatitis C. Of these 285, 245 patients were enrolled in this study. One hundred and twenty‐six patients (51.4%) achieved sustained virological response (SVR). Relapsers (undetectable HCV‐RNA at end of treatment, becoming positive afterward) comprised 9.0% (22/245), and nonresponse (NR; never achieving undetectable HCV‐RNA) 39.6% (97/245). The median follow‐up after completion of antiviral treatment was 2081 days. Using Kaplan–Meier method, patients who achieved SVR were shown to have significantly better 5‐year patient survival (95.2%) than the NR group (49.9%) (P < 0.001), and a trend toward better 5‐year survival than relapsers (87.5%) (P = 0.14); relapsers had a significantly longer survival than NR group (P = 0.005). When compared with NR, SVR and relapse appeared to be significant predictors of better survival, independent of underlying characteristics. In conclusion, virological response, especially SVR, translates into markedly improved long‐term patient outcomes in patients transplanted for hepatitis C.     

Vitamin D supplementation improves response to antiviral treatment for recurrent hepatitis C

In immune‐competent patients, higher vitamin D levels predicted sustained viral response (SVR) following interferon (INF) and ribavirin therapy for chronic hepatitis C. This study aimed to verify the influence of vitamin D serum levels and/or vitamin D supplementation in predicting SVR rates for recurrent hepatitis C (RHC). Forty‐two consecutive patients were treated for RHC with combination therapy with INF‐α and ribavirin for 48 weeks. Vitamin D serum levels were measured in all patients before antiviral therapy. In 15 patients oral vitamin D3 supplementation was administered to avoid further bone loss. SVR was observed in 13 patients; it was achieved in 1/10 severely vitamin D deficient (≤10 ng/ml) patients, in 6/20 deficient (>10 and ≤20 ng/ml) and in 6/12 with near normal (>20 ng/ml) 25‐OH vitamin D serum levels (P < 0.05). Cholecalciferol supplementation, in the presence of a normal or near normal baseline vitamin D concentration, (improvement of chi‐square P < 0.05, odds ratio 2.22) and possessing a genotype other than 1 (improvement of chi‐square P < 0.05, odds ratio 3.383) were the only variables independently associated to SVR. In conclusion, vitamin D deficiency predicts an unfavourable response to antiviral treatment of RHC. Vitamin D supplementation improves the probability of achieving a SVR following antiviral treatment.     

Results of live donor liver transplantation in patients with hepatitic C virus infection: the HCV 3 trial experience

Chronic hepatitis C virus (HCV) is the most common disease indication for liver transplantation (LT). Outcomes are compromised by near universal recurrence of HCV. A prospective multi-center randomized study to evaluate immunosuppressive strategies in HCV+ transplant recipients provided the opportunity to assess impact of live donor (LD) LT. Two hundred and ninety-five patients undergoing LT for HCV (260 deceased donor [DD] recipients/35 LD recipients), randomized to three regimens, were followed for two yr for patient and graft survival and rate and severity of recurrent HCV. Biopsies were performed at baseline, 3, 12, and 24 months. One- and two-yr patient survival for LD recipients was 88.1% and 81.1% vs. 90.5% and 84.6% for DD recipients (p = 0.5665). One- and two-yr graft survival for LD recipients was 82.9% and 76.2% vs. 87.9% and 81.7% for DD recipients (p = 0.3921). Recurrent HCV did not account for more deaths or graft losses in the LD recipients. In this prospective study, controlled for immunosuppression, use of LD organs did not increase the rate or severity of HCV recurrence. The more elective nature of LDLT affords an opportunity to manipulate donor and recipient factors that can impact upon outcomes.     

Lamivudine monoprophylaxis for liver transplant recipients with non-replicating hepatitis B virus infection

Background: The aim of this study was to evaluate the efficacy of lamivudine (LAM) monoprophylaxis for patients with non-replicating hepatitis B virus (HBV) infection at orthotopic liver transplantation (OLT). METHODS: Among 128 liver recipients with HBV infection between 1994 and 2004 transplanted at our institution, 60 had non-replicating HBV infection at the time of OLT. Of those, 26 patients received LAM prophylaxis (monoprophylaxis group) and 34 patients received LAM and hepatitis B immunoglobulin (HBIG) prophylaxis (combination group) after OLT. RESULTS: Median follow-up after OLT was 67 and 54 months, for monoprophylaxis and combination groups respectively. One and five yr patient/graft survival were 96/85% and 96/80% in monoprophylaxis group, and 85/79% and 67/55% in combination group. HBV DNA was re-detected or increased >10(5) IU/mL in four patients (15%) at 20-29 month in monoprophylaxis group and six (18%) at 4-35 months in combination group. Recurrent hepatitis was seen in two patients (8%) at 27 and 45 months and monoprophylaxis group and three (9%) at 21-35 months in combination group. The rate of recurrence was not statistically different between two groups. CONCLUSION: LAM monoprophylaxis seemed to be effective for OLT recipients with HBV infection who had non-replicating HBV at transplantation. HBIG administration may play a less valuable role in preventing HBV recurrence in this group of patients.     

Kidney transplant performed after liver transplant: a single center experience

Changes in liver allocation due to institution of the model for end-stage liver disease/PELD criteria have led to an increase in the number of patients receiving liver transplants who have elevated creatinine. Whether these patients' renal dysfunction is reversible or not and whether they should receive combined liver and kidney transplants (KTXs) are individualized decisions, although some criteria are becoming clearer. A part of this decision must consider the outcomes of patients who have liver transplants alone but later require KTXs. We herein describe our single-center experience with this patient population. Our data show that KTX subsequent to liver transplantation (TX) is generally safe and effective, with a possibly higher surgical complication rate than standard KTX. Outcomes analysis showed not statistically different patient survival of KTXs performed after liver transplant (KALT) compared with KTX alone. Death censored graft survival was statistically lower in the KALT group but this largely accrued in the first three yr after transplant and was nearly equivalent by 10 yr.     

Treatment of genotype‐1 hepatitis C recurrence after liver transplant improves survival in both sustained responders and relapsers

The aim of this study was to evaluate the factors affecting the response to treatment and how it could affect survival in a large series of genotype‐1 HCV‐transplanted patients. Three‐hundred and twenty six genotype‐1 HCV patients were enrolled. One hundred and ninety‐six patients (60.1%) were nonresponders and 130 (39.9%) showed negative HCV‐RNA at the end of treatment. Eighty‐four of them (25.8%) achieved sustained virological response, while 46 (14.1%) showed viral relapse. Five‐year cumulative survival was significantly worse in nonresponders (76.4%) compared with sustained viral response (93.2) or relapsers (94.9%). Sustained responders and relapsers were therefore considered as a single ‘response group’ in further analysis. Pretreatment variables significantly associated with virological response at multivariate regression analysis were the absence of ineffective pretransplant antiviral therapy, the recurrence of HCV‐hepatitis more than 1 year after transplant, an histological grading ≥4 at pretreatment liver biopsy, a pretreatment HCV‐RNA level <1.2 × 10⁶ IU/ml, and the absence of diabetes. As expected, also on‐treatment variables (rapid and early virological response) were significantly associated to the response to antiviral treatment. In conclusion, this study shows that postliver transplant antiviral treatment results in beneficial effect on survival not only in sustained responders but also in relapsers.     

Pegylated interferon alpha-2b plus ribavirin in the treatment of post-liver transplant recurrent hepatitis C

BACKGROUND: Histological recurrence of the hepatitis C virus (HCV) occurs in the majority of persons transplanted for cirrhosis as a result of HCV. Herein we analyze our experience with the use of both conventional and pegylated (PEG) interferon (IFN) in combination with ribavirin (RBV) in liver transplant recipients with recurrent HCV. Methods: Patients transplanted between 1992 and 2001 with post-orthotopic liver transplantation (OLT) histological recurrence of HCV, and who were treated with at least 6 months of IFN or PEG-IFN in combination with RBV were included in this analysis. A retrospective chart review was performed. Results: A total of 31 patients were included. Fifteen were treated with IFN/RBV and 16 with PEG-IFN/RBV. Of these 16, 11 had been begun on IFN/RBV and were changed to PEG-IFN/RBV because of persistent viremia. Three patients (20%) in the IFN/RBV group and six patients (37.5%) in the PEG-IFN/RBV group experienced a virologic response (VR) on therapy. Of the six patients experiencing VR in the PEG-IFN/RBV group, three (50%) were IFN/RBV non-responders. There were two sustained VRs (SVR). The 65.6% of all patients experienced a biochemical response (BR) on therapy. Seven deaths were observed. Dose modifications of IFN or PEG-IFN (87.1%) and RBV (80.6%) and the requirement for hematopoietic growth factors were frequent. Conclusions: Treatment of recurrent HCV infection with combination of IFN or PEG-IFN and RBV produced an on-therapy VR in 29% and BR in 65% of patients. Hematologic toxicity and dose modifications were frequent. Our experience with antiviral therapy for HCV post-OLT remains disappointing but PEG-IFN + RBV appears to produce VR in a sizable portion of IFN + RBV non-responders.     

Advanced donor age increases the risk of severe recurrent hepatitis C after liver transplantation

The association between donor age and the severity of recurrent hepatitis C and, whether there is any donor age above which severity of recurrence increases significantly, were analyzed. A total of 131 liver grafts of hepatitis C virus (HCV)‐infected recipients were selected for the study. Distribution of donor age was compared between grafts with and without severe recurrence. The risk of developing severe recurrence as well as the hepatitis‐free, severe hepatitis‐free and HCV‐related graft survival was compared between different donor age groups. Mean donor age was higher for grafts with severe recurrence (P = 0.007). The risk of developing severe recurrence within 2 years post‐transplant increased with donors aged ≥50 years (RR = 1.34) and donors aged ≥70 years (RR = 1.61). Five‐year severe hepatitis‐free survival rates decreased progressively when donor age was over 50 years (P < 0.001). The study shows 50 and 70 years as the donor age cut‐off points above which the evolution of HCV‐infected recipients worsens.