Partial splenic embolization and peg‐IFN plus RBV in liver transplanted patients with hepatitis C recurrence: safety,efficacy and long‐term outcome

Bárcena R, Moreno A, Foruny JR, Blázquez J, Graus J, Riesco JM, Blesa C, García‐Hoz F, Sánchez J, Gil‐Grande L, Nuño J, Fortún J, Rodriguez‐Sagrado MA, Moreno A. Partial splenic embolization and peg‐IFN plus RBV in liver transplanted patients with hepatitis C recurrence: safety, efficacy and long‐term outcome.
Clin Transplant 2010: 24: 366–374. © 2009 John Wiley & Sons A/S. Abstract: Background: There is limited information on the long‐term outcome in liver transplant (LT) subjects undergoing partial splenic embolization (PSE) prior to full dose pegylated interferon/ribavirin (peg‐IFN/RBV). Methods: Retrospective review of eight LT subjects after PSE and antiviral therapy. Results: Baseline platelets and neutrophils were <50 000 cells/mL and <1000 cells/mL in 75% and 50%. Mean splenic infarction volume was 85 ± 13%. PSE produced major complications in three (37.5%): recurrent sterile netrophilic ascites and renal insufficiency (n = 2), and splenic abscess (n = 1). Full‐dose peg‐IFN/RBV was started in seven (87.5%), with two early withdrawals (28.6%) despite early virological response (toxicity and infection); both subjects died. Anemia led to RBV dose‐adjustment in six (86%), with human recombinant erythropoietin (EPO) use in four (57%). No peg‐IFN adjustments or granulocyte‐colonies stimulating factor were needed. Two patients reached sustained virological response (SVR) (28.6%). Two non‐responders maintained prolonged therapy with biochemical/histological improvement. After a median follow‐up of 151 wk, we observed significant improvements in hematological parameters, aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and prothrombin activity. Conclusions: Extensive PSE after LT produced significant morbidity (37.5%). Peg‐IFN/RBV was completed in five out of seven (71%), with SVR in two (28.6%). RBV adjustement due to anemia was high despite EPO use. Only patients able to complete or maintain antiviral therapy survived, with long‐term significant benefits in hematological parameters and liver function tests.     

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.     

Recurrent hepatitis C after liver transplantation: A nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin

Liver transplant recipients with recurrent hepatitis C virus (HCV) infection often have histological hepatitis, and in some patients, graft failure develops. The aim of this nonrandomized study is to determine the efficacy and tolerability of interferon alfa (IFN alfa) alone and IFN alfa and ribavirin combination therapy in such patients. Forty transplant recipients with recurrent hepatitis were initiated on therapy with IFN alfa-2b at 3 million units (MU) three times weekly for 1 month followed by 5 MU three times weekly for 5 months. Twenty patients were administered IFN alfa-2b, 3 MU three times weekly for 1 month followed by 5 MU three times weekly for 11 months, and ribavirin, 600 mg, twice daily orally for 12 months concurrently. The primary end point was sustained clearance of serum HCV RNA, and secondary end points were serum alanine aminotransferase (ALT) level normalization and histological improvement. Thirty patients completed 6 months of IFN-alfa monotherapy and 15 patients completed 12 months of IFN alfa and ribavirin combination therapy. End-of-treatment biochemical responses were similar in the two groups (IFN alfa, 20% v combination therapy, 25%); however, viral clearance was greater in the combination-therapy group (40% v 15%; P = .04). Six months after the completion of therapy, only 1 patient (2.5%) in the IFN-alfa group and 4 patients (20%) in the combination-therapy group were HCV RNA negative (P = .03). Serum ALT and HCV RNA levels declined significantly in both groups during therapy. There was no improvement in inflammatory grade, and fibrosis score was worse in both groups. Ten patients (25%) in the IFN-alfa group and 5 patients (20%) in the combination-therapy group withdrew because of adverse effects. We conclude that in liver allograft recipients with recurrent hepatitis C, combination therapy with IFN alfa and ribavirin is more efficacious than treatment with IFN alfa alone. However, the efficacy is limited by tolerability. (Liver Transpl 2001;7:863-869.)     

Efficacy and Safety of Sofosbuvir‐Based Antiviral Therapy to Treat Hepatitis C Virus Infection After Kidney Transplantation

There is no approved therapy for hepatitis C virus (HCV) infection after kidney transplantation, and no data regarding the use of new‐generation direct antiviral agents (DAAs) have been published so far. The aims of this pilot study were to assess the efficacy and safety of an interferon‐free sofosbuvir‐based regimen to treat chronic HCV infection in kidney transplant recipients. Twenty‐five kidney transplant recipients with chronic HCV infection were given, for 12 (n = 19) or 24 weeks (n = 6), sofosbuvir plus ribavirin (n = 3); sofosbuvir plus daclatasvir (n = 4); sofosbuvir plus simeprevir, with (n = 1) or without ribavirin (n = 6); sofosbuvir plus ledipasvir, with (n = 1) or without ribavirin (n = 9); and sofosbuvir plus pegylated‐interferon plus ribavirin (n = 1). A rapid virological response, defined by undetectable viremia at week 4 after starting DAA therapy, was observed in 22 of the 25 patients (88%). At the end of therapy, HCV RNA was undetectable in all patients. At 4 and 12 weeks after completing DAA therapy, all had a sustained virological response. The tolerance to anti‐HCV therapy was excellent and no adverse event was observed. A significant decrease in calcineurin inhibitor levels was observed after HCV clearance. New‐generation oral DAAs are efficient and safe to treat HCV infection after kidney transplantation.     

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.     

干扰素α治疗HBeAg阳性慢性乙型肝炎应答不佳的优化疗效研究

目的 观察干扰素α（IFNα）联合阿德福韦酯（ADV）和替比夫定（LdT）序贯治疗对IFNα治疗应答不佳的HBeAg阳性慢性乙型肝炎（CHB）的临床疗效.方法 选择2010年2月至2013年4月浙江省绍兴市第六人民医院收治的接受IFNα治疗24周后应答不佳的HBeAg阳性CHB患者86例.根据患者意愿分为继续单用IFNα治疗组21例,IFNα联合ADV治疗组30例,改用LdT序贯治疗组35例.采用x2检验比较三组患者治疗48周时的ALT复常率、HBV DNA低于检测值下限（500拷贝/mL）的比例、HBeAg及HBsAg血清学转换率.结果 治疗48周时,继续单用IFNα治疗组的ALT复常率为52.6％ （10/19）,低于IFNα联合ADV治疗组（86.7％,26/30）和LdT序贯治疗组（84.8％,28/33）,差异有统计学意义（x2=6.913和6.361,P＜0.05）;继续单用IFNα治疗组的HBV DNA低于检测值下限（500拷贝/mL）的比例为26.3％（5/19）,低于IFNα联合ADV治疗组（60.0％,18/30）和LdT序贯治疗组（54.5％,18/33）,差异有统计学意义（x2=11.33和3.895,P＜0.05）;继续单用IFNα治疗组没有HBeAg转阴或血清学转换,而IFNα联合ADV组和LdT序贯治疗组分别有6例（20.0％,6/30）和7例（21.2％,7/33）发生HBeAg转阴或血清学转换（x2=4.330和4.657,P ＜0.05）.三组患者均未发生HBsAg转阴或血清学转换.IFNα联合ADV治疗组与LdT序贯治疗组之间的ALT复常率、HBV DNA低于检测值下限率和HBeAg转阴或血清学转换率比较差异无统计学意义（x2=0.042,0.019和0.064,P ＞0.05）.结论 对于IFNα治疗应答不佳的HBeAg阳性CHB患者,IFNα联合ADV治疗或LdT序贯治疗可明显改善患者的肝功能和病毒学应答,两种治疗方案疗效相近.     

Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation.

Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon-based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon-based therapy in a selected group of liver transplant recipients. Twenty-three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated-interferon alpha-2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA-undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 +/- 2.37 vs. 5.64 +/- 2.94 units before and after treatment, respectively; P =.016). However, 5 of these 11 patients had no histologic improvement in follow-up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P <.01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection.     

The road map toward an hepatitis C virus‐free transplant population

Antiviral therapy to eradicate hepatitis C virus (HCV) infection improves outcomes in patients undergoing liver transplantation (LT) for advanced chronic HCV with or without hepatocellular carcinoma. Traditionally, antiviral therapy focused on the use of interferon (IFN)‐based regimens, with antiviral treatment initiated in the posttransplant period once recurrent HCV disease with fibrosis in the allograft was identified. The use of IFN‐based therapy was limited in pretransplant patients with advanced liver disease. Earlier intervention, either before transplantation or early after LT, is now feasible with the advent of second‐generation direct‐acting antiviral agents (DAAs) with superior tolerability and efficacy to IFN‐based therapy. These agents have the potential to reduce the number of patients developing HCV‐related complications requiring LT and retransplantation, as well as reducing the demand for donor organs. We discuss the pros and cons of pretransplant, peritransplant, and posttransplant therapy with current DAAs, citing available data from clinical trials and real‐world experience.     

Sustained virologic response to therapy of recurrent hepatitis C after liver transplantation is related to early virologic response and dose adherence.

Sustained virologic response (SVR) after antiviral therapy for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients is consistently lower than that achieved in non-LT patients. We evaluated efficacy and safety of pegylated interferon (IFN) and ribavirin (RBV) therapy in LT recipients with recurrent HCV and factors associated with SVR. All subjects with histologic evidence of recurrent HCV were intended to be treated for 48 weeks with full-dose pegylated IFN; target dose of RBV was 800 mg/day. Thirty-five LT recipients with recurrent HCV, median age 48.5 years, 77% genotype 1, and median pretreatment HCV RNA 6.4 log10 IU/mL were treated between January 2000 and February 2006. Antiviral therapy was discontinued prematurely in 15 subjects as a result of adverse events. Median overall treatment duration was 46 weeks. Early virologic response at week 12 was seen in 17 (49%) and an end-of-treatment virological response in 19 (54%) patients. SVR was achieved in 13 patients (37%), and all 9 patients followed for >1 year after treatment had durable response. Patients with SVR had significantly lower pretreatment HCV RNA (5.7 vs. 6.5 log10 IU/mL, P=0.003), more likely to have a week 12 virological response (85% vs. 27%, P=0.0009) and received higher cumulative doses of pegylated IFN (75% vs. 33%, P=0.029) and RBV (90% vs. 26%, P=0.016) compared with patients whose disease did not respond to therapy. In conclusion, SVR was achieved in 37% of patients with recurrent hepatitis C after LT. Similar to non-LT patients, those with lower pretreatment HCV RNA, a week 12 virological response, and pegylated IFN and RBV dose adherence were more likely to achieve SVR.     

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.     

Association of high IFN‐γ plasma levels with low B‐cell counts in renal transplant recipients with stable long‐term graft function

Daniel V, Naujokat C, Sadeghi M, Renner FC, Weimer R, Opelz G. Association of high IFN‐γ plasma levels with low B‐cell counts in renal transplant recipients with stable long‐term graft function.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01067.x
© 2009 John Wiley & Sons A/S. Abstract: Recently, we reported that patients with long‐term stable good graft function had higher interferon‐gamma (IFN‐γ) and lower IL‐4 plasma levels late as compared with early post‐transplant. These patients had more often detectable CD3⁺CD4⁺CD25⁺IFN‐γ⁺Foxp3⁺ peripheral blood lymphocytes (PBL) late post‐transplant than patients with impaired graft function. We therefore speculated that high plasma IFN‐γ late post‐transplant might contribute to the maintenance of graft acceptance. Using ELISA and four‐color flow cytometry, plasma cytokines and PBL subpopulations were measured in 65 renal transplant recipients with stable graft function late post‐transplant. High IFN‐γ plasma levels were associated with low CD19⁺ B PBL (r = ?0.329; p = 0.009) and low activated CD3⁺CD8⁺DR⁺ T PBL (r = ?0.266; p = 0.035). Plasma IFN‐γ increased with time post‐transplant (r = 0.288; p = 0.022) and was not associated with the dose of immunosuppressive drugs (p = n.s.). High plasma IFN‐γ was not associated with serum creatinine (r = 0.038; p = 0.765). Five patients showed evidence of chronic allograft nephropathy in previous biopsies and none of them exhibited increased plasma IFN‐γ. In patients with good long‐term graft function, high IFN‐γ plasma levels were associated with low numbers of B PBL and activated CD8⁺ T PBL. High IFN‐γ plasma levels might prevent the development of an immunological alloresponse and thereby contribute to the maintenance of graft acceptance.     

Clinical Benefits of Antiviral Therapy in Patients with Recurrent Hepatitis C Following Liver Transplantation

Pegylated interferon (pegIFN) and ribavirin eradicates hepatitis C virus (HCV) in one third of liver recipients with recurrent disease. Side effects are frequent and potentially life threatening. Our aim was to define the long-term benefits of antiviral therapy in recurrent HCV. Eighty-nine (89) recipients (genotype 1: 86.5%) were treated with IFN (n = 31) or pegIFN (n = 58) plus ribavirin and 75 untreated contemporaneous disease-matched controls. The major end point was survival from transplantation. Survival, progression to cirrhosis and clinical decompensation since start of therapy were compared between sustained virologic responders (SVRs) and nonresponders (NRs). Results revealed 44 patients died during the follow-up (20% treated vs. 35% controls; p = 0.05). Patient survival was higher in treated compared to controls (7 years: 74% vs. 62%; p = 0.04). Among treated patients, an SVR was achieved in 37% (IFN 16% vs. peg-IFN 48%; p = 0.03). About 2/33 SVRs and 16/56 NRs died (p = 0.01) due to HCV-disease (56%), IFN-induced rejection (11%), both causes (11%) or others (22%). Five-year survival was greater in SVRs than in NRs (93% vs. 69%, p = 0.032). In patients without baseline cirrhosis, progression to cirrhosis occurred more frequently in NRs (27/42 vs. 6/16; p = 0.06). The 5-year risk of graft decompensation was higher in NRs (33% vs. 16%; p = 0.04). Antiviral therapy is associated with improved long-term outcome in recurrent HCV.     

Successful rescue of severe recurrent hepatitis C with interferon and ribavirin in a liver transplant patient

BACKGROUND: Rapid graft dysfunction caused by hepatitis C virus (HCV) reinfection, although uncommon, is a disastrous complication in liver transplant patients. Finding an effective therapy for this subgroup of patients with severe recurrent HCV is a priority. METHOD: We describe a successful rescue of a 46-year-old man with recurrent hepatitis C (HCV genotype 1b) using long-term interferon (IFN) and ribavirin. The patient had a very aggressive type of posttransplantation HCV infection, as judged by biochemical and histologic findings. RESULTS: Despite high pretreatment values of serum alanine aminotransferase (ALT; peak value of 901 IU/L) and HCV-RNA (2.3 x 10(6) copies/ml), the combination therapy with IFN and ribavirin produced a rapid normalization of the serum ALT values, accompanied by the clearance of serum HCV-RNA. Although HCV-RNA reappeared in the serum at 3 months, the patient had continued ALT normalization and histological improvement with follow-up of over 26 months to date after the initiation of the combination therapy. CONCLUSION: This observation suggests that IFN in combination with ribavirin may offer an effective therapeutic option for liver transplant patients with severe recurrent hepatitis C.     

Predictive Factors of Lack of Response to Antiviral Therapy Among in Patients With Recurrent Hepatitis C After Liver Transplantation

The current therapy for hepatitis C recurrence after liver transplantation OLT is based on interferon (IFN) and ribavirin (RBV) in monotherapy or combination. The rate of sustained virological response (SVR) varies between 10% and 45%. We have retrospectively analyzed factors that could predict SVR after antiviral therapy. We analyzed 42 patients who completed a cycle of therapy with natural or pegylated IFN plus RBV. There were 15 (35.7%) patients who obtained an SVR. The following factors were significantly associated with a lack of SVR: donor age ≥50 years (P = .046); donor body mass index (BMI) > 27 (P = .016); genotype 1 versus 2 to 3 (P = 0.010), aspartate transferase (AST) before therapy ≥ 140 U/L (P = .046), alanine transferase before therapy ≥ 280 U/L (P = .055), use of natural IFN versus pegylated IFN (P = .016). The only factors remaining after multivariate analysis were: donor BMI, AST before therapy and genotype. Our data confirmed that genotype 1 was associated with poorer outcomes; other additional parameters can influence the response to antiviral therapy.     

Real‐world experience with daclatasvir plus sofosbuvir ± ribavirin for post‐liver transplant HCV recurrence and severe liver disease

Optimizing therapy of post‐transplant HCV recurrence remains important, especially in advanced liver disease. We evaluated daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in patients with post‐liver transplant recurrence in a real‐world European cohort at high risk of decompensation or death within 12 months. Recommended treatment was DCV 60 mg plus SOF 400 mg once daily for 24 weeks; RBV use/shorter treatment duration was at physicians’ discretion. Patients (N = 87) were 70% male, 93% white, and mostly infected with HCV genotypes 1b (48%), 1a (32%), or 3 (9%); 37 (43%) had cirrhosis (16 decompensated), five had fibrosing cholestatic hepatitis. Sustained virologic response at post‐treatment week 12 (SVR12) was 94% (80/85) in a modified intention‐to‐treat analysis: 95% (58/61) without RBV and 92% (22/24) with RBV, with no virologic failures. SVR12 was 100% (80/80) in an as‐observed analysis excluding five nonvirologic failures. Four patients (5%) discontinued therapy for adverse events (AEs); 16 (18%) experienced serious AEs. One patient died on treatment and five during follow‐up. Most AEs were associated with advanced liver disease and unrelated to therapy. No clinically significant drug–drug interactions were observed. DCV + SOF ± RBV was well tolerated and achieved high SVR12 (94%) in patients with post‐transplant HCV recurrence, including patients with severe liver disease.     

Efficacy of interferon based antiviral therapy for recurrent hepatitis C in patients who received steroid free immunosuppression for liver transplantation

BACKGROUND: In this article, we explore the virological response to two types of interferon based treatment in recurrent hepatitis C virus in liver recipients who received thymoglobulin induction. METHODS: Fifty consecutive patients were randomized to receive PEG interferon alpha 2b (1.0 microg/kg per week), ribavirin (800 mg/d) plus amantadine (200 mg/d), or PEG interferon alpha 2b (1.0 microg/kg per week) plus ribavirin (800 mg/d). The primary endpoint was absence of hepatitis C virus RNA 6 months posttreatment. The secondary endpoint was change in fibrosis at 1 year. RESULTS: Only 30 patients completed 1 year of treatment. In an intention to treat analysis, the sustained virological response (SVR) rate was 26% in I/R/A group and 50% in I/R group. By per protocol, the overall SVR rate was 57%. Fibrosis progression by at least one stage was noted in 37% patients. Twenty-nine percent of patients who achieved SVR had shown fibrosis progression by at least one stage whereas 46% nonresponders showed fibrosis progression (P=NS). CONCLUSION: This is the first study exploring the efficacy of pegylated interferon-based antiviral treatment in patients who received a steroid-free protocol. Our data is encouraging and shows that if liver transplant recipients can tolerate treatment for 1 year there is a reasonable chance of SVR.     

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.     

Treatment of chronic hepatitis B and C with interferon-alpha in renal allograft recipients: preliminary results

Abstract We evaluated the effects of treatment with interferon (IFN) on liver disease and renal allograft function in ten immunosuppressed cadaver kidney recipients. Two females and eight males (mean age 39 years) with biopsy-proven chronic active hepatitis ( n = 8) or persistent hepatitis ( n = 2) and serum positive for hepatitis B surface antigen (HBsAg) and HBe antigen ( n = 5) or serum positive for anti-HCV antibodies ( n = 3) or serum positive for HBsAg, anti-HCV and anti-HDV antibodies ( n = 2) received 3 million units IFN thrice weekly of 6 months. All patients responded with a reduction in serum aminotransferase activity and in five of them liver function completely normalized. Three patients among five infected with HBV cleared HBeAg. During the follow-up period liver function remained stable in 9 patients after discontinuation of IFN therapy. Three patients lost their grafts due to rejection 1, 2, and 4 months after IFN therapy, respectively. In six patients renal function remained stable during and after IFN therapy. We conclude that in selected groups of renal allograft recipients IFN can be used safely and effectively for the treatment of chronic viral hepatitis.     

Antiviral combination therapy for lamivudine‐resistant hepatitis B reinfection after liver transplantation

Abstract Development of resistance is a major issue in antiviral treatment of hepatitis B reinfection after liver transplantation. Antiviral combination therapy is discussed for therapy or prevention of this breakthrough of viral replication. Eight patients were enrolled into this retrospective analysis after liver transplantation for chronic hepatitis B infection. All had reinfection of the graft and breakthrough of HBV during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy with lamivudine and interferon‐α 2 a (group I, n = 4) or lamivudine and famciclovir (group II, n = 4) was initiated. Combination therapy was started 61 months (group I) and 25 months (group II) after liver transplantation. It markedly reduced the viral replication rate in all patients despite lamivudine resistance. In group I three of four patients and in group II two of four patients became HBV‐DNA negative. Two long‐term responders were observed in group I, and none in group II. No patient became HBsAg negative or lost HbeAg. Pretreatment elevated ALT and AST levels were significantly reduced. No severe complications, and especially no rejection episodes, occurred. Lamivudine in combination with other antiviral agents, especially interferon‐α, might be a therapeutic option for hepatitis B reinfection after liver transplantation. Suppression of virus replication to the point of undetectable values is possible even in patients with lamivudine‐resistant virus mutations.