Begin typing your search above and press return to search.
EPUB Before Print

FULL TEXT

ARTICLE
Efficacy of Posttransplant Ledipasvir-Sofosbuvir in the Treatment of Patients Who Have Undergone Chronic Hepatitis C-Related Liver Transplant

Objectives: This study investigated the efficacy of ledipasvir-sofosbuvir, a newly developed direct-acting antiviral drug combination for hepatitis C virus infection recurrence in patients who have developed cirrhosis secondary to hepatitis C virus and who have undergone liver transplant.

Materials and Methods: We retrospectively analyzed 27 patients who underwent liver transplant due to hepatitis C virus-related cirrhosis and who received ledipasvir-sofosbuvir for 12 weeks between January 1, 2016 and December 31, 2017 following transplant procedures conducted at the Inonu University Turgut Ozal Medical Center Gastroenterology Department between January 1, 2008 and December 31, 2017. None of the donors had hepatitis C virus infection. Most donor grafts used in transplants were from children of recipients, with the remaining donated grafts from husbands (7%), nephews (4%), wives (7%), and deceased donors (7%).

Results: Twenty patients were ultimately included in the study. Hepatitis C virus genotypes, hepatitis C virus RNA, blood counts, and liver enzyme levels of patients before and at 1, 2, and 6 months after treatment were evaluated. At the end of month 6, in addition to hepatitis C virus RNA levels of all patients decreased to unmeasurable levels, levels of alanine and aspartate aminotransferase and gamma-glutamyltransferase had also significantly decreased (all P < .001). None of the patients experienced a complication that led to cessation of treatment.

Conclusions: With its reliability and high success rate, the ledipasvir-sofosbuvir combination is a strongly preferable treatment for patients who have undergone liver transplant due to chronic hepatitis C virus-related cirrhosis and who have virus recurrence posttransplant.


Key words : Cirrhosis, Direct-acting antiviral, Hepatitis C virus

Introduction

Hepatitis C virus (HCV) infection is one of the most prominent reasons for cirrhosis; today, about 71 million people around the world are chronically infected with HCV. Hepatitis C virus infection could show a variety of clinical and histologic findings in the long term. From mild liver damage to cirrhosis and hepatocellular carcinoma (HCC) following pervasive liver fibrosis, many histologic changes of differing spectrums can be observed.1 Hepatitis C virus infection causes approximately 350 000 deaths per year.2 In endemic areas, patients with chronic HCV constitute more than half of patients with HCC and cirrhosis. The causes of about 27% of cirrhosis and about 25% of HCC cases throughout the world are because of HCV.3

In general, HCV infection is a considerable global burden; however, patients in western countries primarily have burden due to presence of this virus before or after liver transplant. Chronic HCV infection causes several liver disorders along with their complications. Recurrent HCV infection is still among the primary reasons for posttransplant morbidity and mortality. Development of new antiviral medicines and providing more detailed information on HCV recurrence to patients have led to positive results after liver transplant.4 With improved surgical techniques and positive develop­ments in the treatment of immunosuppression, organ rejection, and infection, liver transplant in needy patients is clearly the best therapeutic option.5

Detailed information on the HCV life cycle and its genomic structure has led to the discovery of direct-acting antivirals (DAAs), which target the virus genome.6 Direct-acting antivirals have provided a revolution in the treatment of chronic HCV infection. These agents can be used both before and after transplant. Compared with older-generation pharmaceutical agents, these medicines can be administered regardless of comorbid disorders and show a high level of success. As a result, DAAs have changed the course of HCV infections and have shown that this disorder can be cured.7,8

In this study, we aimed to show the treatment efficacy of combined ledipasvir-sofosbuvir, which is an outstanding DAA treatment. This combination has been increasingly administered to transplant patients who develop cirrhosis secondary to chronic HCV infection and who have recurrent HCV.

Materials and Methods

Case selection and data compilation
In this retrospective study, we analyzed medical records of 27 patients who underwent a liver transplant to treat chronic liver disease due to HCV infection between January 1, 2008 and December 31, 2017 and who received ledipasvir-sofosbuvir treatment for 12 weeks from January 1, 2016 to December 31, 2017. All patients were treated at the Inonu University Turgut Ozal Medical Center Gastroenterology Department (Malatya, Turkey).

The study was in accordance with Helsinki Declaration guidelines, human study regulations, and ethical rules and was approved by the Malatya Clinical Researches Ethical Board (approval number: 2018/18-10).

Patient age, sex, and HCV genotypes and 1-month, 2-month, and 6-month HCV RNA, aspartate amino­transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyltransferase (GGT), total bilirubin, albumin, international nor­malized ratio, hemoglobin, and platelet levels were obtained from medical records in the hospital automation system. None of the donors had HCV infection. Parameter results before treatment were also collected. Patients younger than 18 years old were not included in the study; included patients were 18 years old or older, received liver transplant, and had HCV infection. Of 27 patients, 17 (62.9%) were men and 10 (27.1%) were women. Seven patients were not included in the final analyses because of irregular 6-month follow-up. Most living-donor grafts were from children of recipients, with remaining grafts from husbands (7%), nephews (4%), wives (7%), and deceased donors (7%). Because our study was retrospective, patients received no study-related invasive procedures.

Statistical analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 22.0, IBM Corporation, Armonk, NY, USA). Data are presented as means ± standard deviation. In an effort to compare multiple data, Friedman test was used; if differences were found in dual comparisons, data were analyzed with Wilcoxon test. P < .05 was considered significant.

Results

Of 20 study patients included in the final analyses, 13 (65%) were men and 7 (35%) were women (age range, 53-85 y). With regard to patient genotype, 18 (90%) were subtype GT1b and 2 (10%) were subtype GT4. Eleven patients (55%) had previous HCV treatment (ribavirin ± pegylated-interferon), and 9 patients (45%) were treatment naive. The mean HCV RNA level of patients before treatment was 63.62 ± 126.47 million/copies. At 1 month, mean level was 0.78 ± 3.16 million/copy; however, HCV RNA levels were 0 at 2 and 6 months after treatment, which was a significant decrease (P < .001) (Figure 1 and Table 1). When we compared HCV RNA levels before start of treatment versus at 1, 2, and 6 months after treatment, levels were significantly different (P < .05, P < .05, and P < .05, respectively). When HCV RNA levels at month 1 versus at month 2 and at month 1 versus at month 6 were compared, no significant difference was shown (P > .05 and P > .05; Table 2). Difference in decrease between before treatment to that shown at month 1 was the most statistically significant.

Mean levels of AST, ALT, and GGT were 62.10 ± 43.79, 53.90 ± 25.22, and 201.55 ± 160.99 U/L, respectively, before treatment; 38.20 ± 39.05, 33.25 ± 20.10, and 137.65 ± 150.15 U/L, respectively, at month 1; 22.35 ± 8.81, 34.90 ± 47.92, and 90.45 ± 77.47 U/L, respectively, at month 2 ; and 21.40 ± 9.52, 27.15 ± 39.99, and 66.95 ± 55.19 U/L, respectively, at month 6 (reference ranges are 5-34 U/L for AST, 0-55 U/L for ALT, and 9-64 U/L for GGT). Levels of AST, ALT, and GGT were significantly decreased before versus after treatment (all P < .001) (Figure 2 and Table 1).

When AST levels before treatment versus after treatment were compared, we observed a significant decrease (P < .05 for all time points). When we compared month 1 versus month 2 of treatment, the difference in AST was significant (P < .05), as was the difference between month 1 and month 6 (P < .05); however, no significant difference was found between month 2 and month 6 (P > .05) (Table 2). The most significant decrease occurred between start of treatment and month 6.

When ALT levels before treatment versus after treatment were compared, we observed a significant decrease (P < .05 for all time points). However, differences in ALT levels at month 1 versus at month 2 and at month 2 versus at month 6 were not significant (both P > .05) (Table 2). The most significant decrease occurred between start of treatment versus at 1 month of treatment.

With regard to changes in GGT levels, differences were significantly decreased from start of treatment versus that shown at month 1, 2, and 6 (all P < .05). However, differences in GGT levels at month 1 versus at month 2 were not significant (P > .05), but differences in month 1 versus month 6 (P < .05) and month 2 versus month 6 (P < .05) were significant (Table 2). The most significant decrease occurred between start of treatment and month 2 of treatment.

With regard to the other analyzed parameters, no significant differences were shown among month 1, 2, and 6 levels for alkaline phosphatase, total bilirubin, albumin, international normalized ratio, hemoglobin, and platelet count (P > .05)

Discussion

With regard to chronic HCV, treatment options are swiftly increasing thanks to the development of DAAs, a group of pharmaceutical agents that have provided over 95% sustained viral response (SVR) but that remain quite expensive.9

The ION trials10-12 have had considerable importance because they were the first to extensively evaluate treatment of patients with chronic HCV with agents not containing interferon or ribavirin. The most frequent adverse effects observed were weakness, headache, insomnia, and nausea. The studies also showed that adding ribavirin to the ledipasvir-sofosbuvir combination not only failed to increase efficacy but also caused an increase in toxicity. Removing ribavirin from chronic HCV treatment resulted in less side effects, less frequent laboratory tracking, elimination of teratogenicity risk, increased treatment compliance in patients, and increased quality of life because the combination only required 1 daily dose.13 Our study did not entirely overlap with the ION trials as we did not record side effects in detail and the patients who were treated were ones who had recurrence after transplant. When we consider the lack of serious side effects during treatment and 100% SVR reached at week 12 of treatment and that our study provided results similar to the ION trials, we suggest the inclusion of the ledipasvir-sofosbuvir combination in treatment guidelines for HCV.

In the SOLAR trials,14,15 the acquisition of a SVR in patients with decompensated cirrhosis was associated with early recovery in Child-Turcotte-Pugh and Model for End-Stage Liver Disease scores, thus suggesting that virus eradication improved hepatic function and swiftly reduced damage and inflammation due to HCV replication. The high SVR rates obtained among patients, who represented a large spectrum of patients having symptoms ranging from mild histologic disorder to compensated cirrhosis, were found to be similar to outcomes shown in the ION-1 and ION-2 trials, where patients without liver transplant received ledipasvir-sofosbuvir with or without ribavirin treatment for 12 or 24 weeks. However, extending treatment to 24 weeks did not provide any additional benefit. As a result of these studies, treatment of patients who had decompensated cirrhosis before and after liver transplant with a ledipasvir-sofosbuvir plus ribavirin combination resulted in a higher rate of SVR in patients with advanced liver disorders. In this group of patients, it was recommended that 12 weeks of treatment could be sufficient. In our study, similar to the SOLAR trials, patients with GT1 and GT4 HCV RNA subtypes who received liver transplant secondary to HCV and later developed recurrence and were given 12 weeks of ledipasvir-sofosbuvir treatment also had 100% SVR at week 12.

The phase II SIRIUS trial, a double-blind, placebo-controlled, and randomized study that included 20 different centers in France, was carried out by Bourliere and associates16 between October 2013 and October 2014. In their HCV GT1 subtype group, patients with compensated cirrhosis and who previously received pegylated-interferon and protease inhibitor treatment but did not reach SVR were enrolled in the study. The study included 114 men (74%), with 98 (63%) in the HCV GT1a group, 55 (35%) in the GT1b group, and 2 patients in the GT1 group. One group of 77 patients received ledipasvir-sofosbuvir plus ribavirin for 12 weeks, and the second group of 78 patients received ledipasvir-sofosbuvir for 24 weeks. In the ribavirin group, 1 patient was removed from the study due to adverse effects. Thus, of 77 patients in the ledipasvir-sofosbuvir plus ribavirin group, 74 (96%) reached SVR; of 77 patients in the ledipasvir-sofosbuvir group, 75 (97%) reached SVR. Relapse of HCV after treatment was observed in 3 patients in the ledipasvir-sofosbuvir plus ribavirin group and 2 patients in the ledipasvir-sofosbuvir group. Asthenia was the most frequent adverse effect, with headache and itching also observed. As a result, with regard to treatment success, no significant differences were found between the 2 groups, as both groups reached high SVR rates. Both treatment options were observed to be reliable and tolerable. Because similar success rates were obtained, a short-term regimen of 12 weeks of ribavirin was the preferred protocol for patients who cannot have longer treatment. In the study by Bourliere and associates,16 SVR rates at 12 weeks of ledipasvir-sofosbuvir plus ribavirin treatment were higher than rates obtained in patients with compensated cirrhosis in the ION-2 trial. In our study, patients who received 12 weeks of ledipasvir-sofosbuvir treatment achieved 100% SVR at week 12. Patients in our study did not receive ribavirin; thus, our study showed that high success rates could be obtained with only the ledipasvir-sofosbuvir combination.

The phase II LONESTAR controlled, open-label, randomized study carried out by Lawitz and colleagues17 at a US transplantation institute in Texas between November 2012 and December 2012 analyzed 100 patients with chronic HCV GT1 (87% with GT1a, 13% with GT1b) without hepatitis B virus or human immunodeficiency virus coinfection. Some patients received ribavirin twice per day (1000 or 1200 mg/day depending on weight), with ledipasvir administered once per day at 90 mg plus 400 mg sofosbuvir. Sixty patients in cohort A (treatment naive without cirrhosis) were divided into 3 random groups (1:1:1) (group 1: 8 wk of ledipasvir-sofosbuvir; group 2: 8 wk of ledipasvir-sofosbuvir plus ribavirin; group 3: 12 wk of ledipasvir-sofosbuvir). Forty patients in cohort B (compensated cirrhosis who received previous protease inhibitor containing pegylated-interferon + ribavirin) without a SVR yield were divided into 2 random groups (group 4: 12 wk ledipasvir-sofosbuvir; group 5: 12 wk ledipasvir-sofosbuvir plus ribavirin treatment). In total, 12 patients showed posttreatment HCV relapse and 1 patient was removed from the study because of adverse effects. At the end of treatment, SVR rates were 95% in group 1, 100% in group 2, 95% in group 3, 95% in group 4, and 100% in group 5. The most frequently reported adverse effects were nausea, anemia, and headache.

The above findings showed that the ledipasvir-sofosbuvir combination alone or together with ribavirin does have the potential for successful treatment in patients with chronic HCV (GT1 subtype) irrespective of treatment history or existence of compensated cirrhosis. Because of the relatively lower number of patients in the groups, we believe that further clinical studies are needed to determine the best treatment period and ribavirin’s contribution to treatment.17 Although patients in our study were liver transplant recipients, similar to the outcomes of these other studies, ledipasvir-sofosbuvir treatment provided a high treatment efficacy in both treatment-naïve and treatment-experienced patients.

In a study from Ueda and associates18 that included 6 liver transplant centers in Japan, data from October 2015 to March 2016 were analyzed. The study included 54 patients with HCV GT1b subtype who developed recurrence after living-donor liver transplant with some patients having previous treatment. The patients received ledipasvir-sofosbuvir for 12 weeks. Of 54 patients, 53 completed treatment (1 patient died from pneumonia during treatment). When all 54 patients were considered, 53 (98%) reached SVR. However, for the 53 who completed treatment, all (100%) reached SVR. These results showed that 12 weeks of ledipasvir-sofosbuvir treatment effectively allowed the study patients with recurrent HCV GT1b infection after living-donor liver transplant to reach SVR.18 In our study, 90% (18/20) of treated patients with posttransplant HCV recurrence were in the GT1b subtype group, with 100% SVR obtained at the end of the treatment (week 12).

In a German study from Ciesek and colleagues19 that included patients seen at 2 centers between October 2014 and August 2015, 30 patients in the HCV GT1 subtype group were analyzed (10 with GT1, 16 with GT1b, 4 with subgroup atypical GT1). Patients had received previous orthotopic liver transplant and had HCV recurrence. Included patients were divided into 2 groups, with 1 group administered 12 weeks of ledipasvir-sofosbuvir plus ribavirin and the other group administered ledipasvir-sofosbuvir for 24 weeks. One patient died from myocardial infection, and increased frequency of anemia was shown in the ribavirin group, which imposed a risk of myocardial ischemia. Overall, SVR was obtained posttreatment in 29/30 patients (96.6%). Decreased AST and ALT levels were also observed, with AST decreasing from 54.7 to 24.1 U/L after treatment (P = .0014) and ALT decreasing from 65 to 27.59 U/L after treatment (P = .0062). As a result, the ledipasvir-sofosbuvir combination was observed to be reliable and effective in transplant recipients with HCV recurrence. No treatment failure was observed in patients,19 and the significant decrease in aminotransferase levels and SVR at week 12 were the primary clinical indicators of recovery after treatment. The results shown in our study with regard to biochemical parameters were similar.

In a US study from Shoreibah and colleagues20 that included data from 2014 to 2016, 60 patients with HCV GT1 subtype (47 with GT1a; and 13 with GT1b) who developed posttransplant HCV recurrence were included. Thirty-three patients were treatment naïve, 27 were treatment experienced, and 9 developed posttransplant cirrhosis. Four patients were not included in the statistical analyses due to non­compliance with follow-up visits. Included patients were divided into 2 groups administered 12 or 24 weeks of ledipasvir-sofosbuvir. All patients in both groups (100%) reached SVR. Before treatment, ave­rage ALT was 63.0 ± 41.5 U/L, with 29.7 ± 49.9 U/L after treatment (P < .0001). The ledipasvir-sofosbuvir treatment combination without ribavirin was an effective treatment in liver transplant recipients with recurrent HCV infection. No serious adverse effects were observed in the study, with a high toleration and success rate.20 Similarly, in our study, at the end of 12 weeks of ledipasvir-sofosbuvir treatment, both 100% SVR was obtained and significantly decreased AST and ALT levels were recorded.

In Elfeki and associates,21 which included 2 US centers and data collected from November 2014 to November 2015, 46 liver transplant recipients with HCV GT1 subtype (26 with GT1a, 13 with GT1b, and 7 with atypical subtype GT1) were treated. All patients had HCV recurrence, and 25 patients had previous treatment. The patients were divided into 2 groups depending on liver fibrosis staging, with ledipasvir-sofosbuvir without ribavirin administered to 32 patients with early-stage fibrosis (F0-F2) for 12 weeks and to 14 patients with advanced-stage fibrosis (F3-F4) or cholestatic hepatitis for 24 weeks. At end of treatment, all patients (100%) in both groups achieved SVR. Headache and insomnia were the most frequent adverse effects, but none were serious. In addition, significant decreases in aminotransferase levels were reported from before to after treatment, with AST decreasing from 89.0 to 34.0 U/L (P < .01) and ALT decreasing from 89.0 to 32.0 U/L (P < .001). Thus, 12 and 24 weeks of ledipasvir-sofosbuvir without ribavirin RBV in patients who had HCV recurrence after liver transplant was successful.21 Our findings agreed with these results.

Saab and associates22 conducted a clinical study with 85 patients seen between September 2014 and June 2016 at the University of California Los Angeles Medical Center. Patients with HCV GT1 infection and posttransplant recurrence were included in the study, with 46 patients being treatment naïve and 39 having treatment experience. Patients were divided into 2 main groups who were administered ledipasvir-sofosbuvir or ledipasvir-sofosbuvir plus ribavirin. The 42 patients who received ledipasvir-sofosbuvir were divided into 2 subgroups, with 18 treated for 12 weeks and 24 treated for 24 weeks. The 43 patients who received ledipasvir-sofosbuvir plus ribavirin were also divided into 2 subgroups, with 33 treated for 12 weeks and 10 treated for 24 weeks. Ribavirin was administered twice per day at 600 mg/day, ledipasvir was administered once a day at 90 mg, and sofosbuvir was administered at 400 mg. Of 18 patients in the 12-week group and 24 patients in the 24-week group without ribavirin, 17 (94%) and 23 (96%) achieved SVR. In patients who received ribavirin, 31/33 (94%) achieved SVR in the 12-week group and 9/10 (90%) achieved SVR in the 24-week group. Results for AST and ALT significantly decreased from before to after treatment, from 62.4 to 25.6 U/L for AST (P < .001) and from 76.8 to 24.6 U/L for ALT (P = .001). The study concluded that ledipasvir-sofosbuvir with or without ribavirin as a non-interferon-based treatment option was effective and well tolerated in patients with HCV infection recurrence after liver transplant.22 Similarly, in our study, liver enzyme levels (AST, ALT, and GGT) significantly decreased and SVR at week 12 was achieved in our patients with HCV recurrence after liver transplant.

Conclusions

Patients with chronic HCV recurrence after liver transplant were successfully treated with DAAs in our study. The ledipasvir-sofosbuvir combination was effective and reliable in HCV treatment and appears to be the best option among this group of pharmaceutical agents. However, further studies are needed to compare the benefits of the ledipasvir-sofosbuvir combination with other non-interferon-based treatments to understand the optimal patient population for treatment.


References:

  1. Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, et al. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018;69(2):461-511.
    CrossRef - PubMed
  2. Zaltron S, Spinetti A, Biasi L, Baiguera C, Castelli F. Chronic HCV infection: epidemiological and clinical relevance. BMC Infect Dis. 2012;12 Suppl 2:S2.
    CrossRef - PubMed
  3. Webster DP, Klenerman P, Dusheiko GM. Hepatitis C. Lancet. 2015;385(9973):1124-1135.
    CrossRef - PubMed
  4. Kanižaj TF. Liver transplantation in patients with hepatitis C. In: Smolic M, Vcev A, Wu GY, eds. Update on Hepatitis C. IntechOpen; 2017. https://www.intechopen.com/books/update-on-hepatitis-c/liver-transplantation-in-patients-with-hepatitis-c.
    CrossRef - PubMed
  5. Meirelles Junior RF, Salvalaggio P, Rezende MB, et al. Liver transplantation: history, outcomes and perspectives. Einstein (Sao Paulo). 2015;13(1):149-152.
    CrossRef - PubMed
  6. Perez AB, Garcia F. Resistance to direct antiviral agents for hepatitis C virus infection. Impact on clinical practice? Germs. 2016;6(4):123-124.
    CrossRef - PubMed
  7. Spengler U. Direct antiviral agents (DAAs) - A new age in the treatment of hepatitis C virus infection. Pharmacol Ther. 2018;183:118-126.
    CrossRef - PubMed
  8. Sugawara Y, Hibi T. Direct-acting agents for hepatitis C virus before and after liver transplantation. Biosci Trends. 2018;11(6):606-611.
    CrossRef - PubMed
  9. Walsh N, Durier N, Khwairakpam G, Sohn AH, Lo YR. The hepatitis C treatment revolution: how to avoid Asia missing out. J Virus Erad. 2015;1(4):272-275.
    CrossRef - PubMed
  10. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898.
    CrossRef - PubMed
  11. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493.
    CrossRef - PubMed
  12. Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888.
    CrossRef - PubMed
  13. Alqahtani SA, Afdhal N, Zeuzem S, et al. Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials. Hepatology. 2015;62(1):25-30.
    CrossRef - PubMed
  14. Charlton M, Everson GT, Flamm SL, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149(3):649-659.
    CrossRef - PubMed
  15. Manns M, Samuel D, Gane EJ, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016;16(6):685-697.
    CrossRef - PubMed
  16. Bourliere M, Bronowicki JP, de Ledinghen V, et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis. 2015;15(4):397-404.
    CrossRef - PubMed
  17. Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383(9916):515-523.
    CrossRef - PubMed
  18. Ueda Y, Ikegami T, Akamatsu N, et al. Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C virus genotype 1b infection after living donor liver transplantation: a Japanese multicenter experience. J Gastroenterol. 2017;52(8):986-991.
    CrossRef - PubMed
  19. Ciesek S, Proske V, Otto B, et al. Efficacy and safety of sofosbuvir/ledipasvir for the treatment of patients with hepatitis C virus re-infection after liver transplantation. Transpl Infect Dis. 2016;18(3):326-332.
    CrossRef - PubMed
  20. Shoreibah M, Orr J, Jones D, Zhang J, Venkata K, Massoud O. Ledipasvir/sofosbuvir without ribavirin is effective in the treatment of recurrent hepatitis C virus infection post-liver transplant. Hepatol Int. 2017;11(5):434-439.
    CrossRef - PubMed
  21. Elfeki MA, Abou Mrad R, Modaresi Esfeh J, et al. Sofosbuvir/ledipasvir without ribavirin achieved high sustained virologic response for hepatitis C recurrence after liver transplantation: two-center experience. Transplantation. 2017;101(5):996-1000.
    CrossRef - PubMed
  22. Saab S, Rheem J, Jimenez MA, et al. Effectiveness of ledipasvir/sofosbuvir with/without ribavarin in liver transplant recipients with hepatitis C. J Clin Transl Hepatol. 2017;5(2):101-108.
    CrossRef - PubMed


DOI : 10.6002/ect.2019.0183


PDF VIEW [237] KB.

From the 1Department of Internal Medicine, 2Department of Gastroenterology, and the 3Department of Hematology, Inonu University, Faculty of Medicine, Malatya, Turkey
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Yasir Furkan Cagin, Department of Gastroenterology, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
Phone: +90 422 341 0660 4112
E-mail: yafur@hotmail.com