hepatitis c virus ( hcv ) infection is a leading cause of end - stage liver disease and hepatocellular carcinoma [ 1 , 2 ] .
hcv - related liver disease is the most common indication for orthotopic liver transplantation in the usa and northern europe and for living donor liver transplantation ( ldlt ) in japan [ 3 , 4 , 5 ] .
unfortunately , liver transplantation is not a cure for hcv infection , and the occurrence of graft reinfection with hcv is universal , leading to progression of liver fibrosis and occasionally to graft loss at rates higher than in transplant patients not infected with hcv [ 5 , 6 ] . in japan , because of long - standing legal difficulties associated with cadaveric donation , ldlt is the main type of liver transplantation for end - stage liver disease .
the sustained virologic response ( svr ) rate was 40% in donors of ldlt treated with pegylated interferon ( peginterferon ) plus ribavirin , although adverse events were commonly observed even in nontransplanted patients receiving this treatment .
reported that the dose reduction rate and the discontinuation rate of peginterferon plus ribavirin treatment was 40 and 42% , respectively .
recent progress in the development of direct - acting antivirals ( daas ) against hcv has made it possible to eradicate hcv effectively and to shorten the treatment duration compared to the previous standard of care , i.e. peginterferon plus ribavirin .
treatment with the hcv ns5b polymerase inhibitor sofosbuvir plus ribavirin for 12 weeks was shown to lead to high rates of svr ( 97% ) in japanese patients infected with chronic hcv genotype 2 .
asian - pacific countries , including japan , account for 50% of all chronic hepatitis b virus ( hbv ) infection globally . given the prevalence of hbv , ldlt from hepatitis b core antibody - positive donors to recipients
was occasionally performed with passive immunization with hyperimmune hepatitis b immunoglobulin ( hbig ) plus nucleos(t)ide analogs . here , we report on an ldlt recipient who was reinfected with hcv genotype 2a after receiving a graft from a hepatitis b core antibody - positive donor .
hcv genotype 2a was eradicated by a 12-week treatment with sofosbuvir plus ribavirin with hbig plus entecavir , one of the nucleos(t)ide analogs , for the successful prevention of hbv reappearance .
a 66-year - old japanese woman developed liver failure due to cirrhosis and hcv genotype 2a infection .
she was a treatment - nave patient , but her il28b rs8099917 was a favorable genotype ( tt ) .
two years prior to ldlt , she has been diagnosed with liver cirrhosis due to hcv infection without liver biopsy .
she had been infected with hcv after having received a blood transfusion during childbirth at the age of 30 years . at ldlt , she had peripheral edema with a meld ( model for end - stage liver disease ) score of 12 .
ldlt with a right liver graft from a hepatitis b core antibody - positive donor was performed in february 2015 .
five months after ldlt , the hcv rna level was 5.8 log iu / ml , and she was diagnosed with graft reinfection with hcv genotype 2a .
combination treatment with 400 mg daily of sofosbuvir and 400 mg daily of ribavirin was commenced .
her height , body weight , and body mass index were 1.56 m , 50 kg , and 20.5 , respectively .
her laboratory data before treatment are shown in table 1 . the hcv rna level before treatment was 5.8 log iu / ml .
after ldlt , she received triple immunosuppressive therapy consisting of tacrolimus ( 3 mg daily ) , mycophenolate mofetil , and basiliximab with passive immunization with hbig and 0.5 mg daily of entecavir .
four weeks after initiating the combination treatment with sofosbuvir and ribavirin , hcv rna levels were undetectable .
she completed this treatment for 12 weeks and achieved svr at 24 weeks following the termination of this treatment ( svr24 ) ( fig .
1 ) . there was no evidence of hbv reactivation . because her hemoglobin level was 12.2 g / dl before the commencement of this treatment , an oral iron preparation was also started .
after 2 months of treatment , her hemoglobin level fell to 10.8 mg / dl .
then , the dose of ribavirin was decreased to 200 mg daily , and her hemoglobin level improved to 12.8 g / dl ( fig .
, she did not develop evidence of bone marrow suppression , such as observed in peginterferon - plus - ribavirin treatment .
no serious adverse events were observed . during treatment , the trough level of tacrolimus remained stable .
we presented a female patient with living donor - related graft reinfection with hcv genotype 2a who was treated with a combination of sofosbuvir and ribavirin for 12 weeks .
although several daas have drug - drug interactions , no changes in this patient 's drug protocol , which included immunosuppressants and combination treatment of sofosbuvir plus ribavirin , were necessary in this case .
peginterferon plus ribavirin with or without daas may be attempted , but the use of peginterferon is restricted by severe side effects and inadequate efficacy . in addition , interferon has an immune - mediated cytotoxicity , occasionally causing allograft dysfunction .
interferon - free therapy is a viable treatment option and improves treatment efficacy [ 15 , 16 , 17 , 18 , 19 , 20 ] .
this case suggests that daas are well tolerated and effective for the eradication of hcv from post - liver transplantation patients . in the present case of ldlt , graft reinfection with hcv genotype 2
the patient achieved svr24 , although she had anemia as an adverse event , and anti - hcv treatment was continued without blood transfusion .
curry et al .   reported that common adverse events of combination treatment with sofosbuvir and ribavirin were fatigue ( in 38% of patients ) , headache ( 23% ) , and anemia ( 21% ) after liver transplantation .
charlton et al .   reported that the most common adverse events were fatigue ( 30% ) , diarrhea ( 28% ) , headache ( 25% ) , and anemia ( 20% ) during a 24-week combination treatment course of sofosbuvir plus ribavirin after liver transplantation . in the present study ,
the patient received a liver graft from a hepatitis b core antibody - positive donor , and , in general , hbv from these donors is transmitted to recipients at a high rate .
therefore , passive immunization with hbig plus treatment with entecavir were provided to prevent hbv reactivation .
curing hcv infection with daas in hbv / hcv coinfection and monitoring for hbv reactivation should be performed , because daas against hcv do not have any effect on hbv replication , unlike interferon . in the present case ,
the patient was treated with hbig and entecavir , and there was no evidence of hbv reactivation .
recently , more effective regimens with daas against hcv have been reported [ 22 , 23 ] .
these regimens may make it possible to shorten the duration of treatment and to make it easier to achieve svr .
the use of interferon - free regimens is possible for the eradication of hcv in post - ldlt patients with grafts from hepatitis b core antibody - positive donors , as was demonstrated by our patient , who was successfully treated with hbig and entecavir to prevent hbv reactivation . in conclusion ,
12-week treatment with sofosbuvir plus ribavirin is relatively safe and highly effective for the eradication of hcv genotype 2 in ldlt patients .
the other authors declare that there is no conflict of interest regarding the publication of this manuscript .
 direct - acting antivirals ( daas ) are relatively safe and highly effective for the eradication of hepatitis c virus ( hcv ) in liver transplant recipients . in this case study 
 , we present a female with a graft reinfected with hcv genotype 2 who was treated with a combination of sofosbuvir and ribavirin after living donor liver transplantation ( ldlt ) . because the graft was from a hepatitis b core antibody - positive donor , passive immunization with hyperimmune hepatitis b immunoglobulin ( hbig ) and entecavir 
 were also provided to prevent hepatitis b virus ( hbv ) reactivation . 
 it became clear that the combination of sofosbuvir and ribavirin promptly led to a sustained virologic response and that this combination was safe to treat graft reinfection with hcv genotype 2 after ldlt . 
 adverse events caused by daas were not observed , except for slight anemia . 
 hbig and entecavir were useful in the prevention of hbv reactivation . in conclusion 
 , the present case indicated that daa treatment for graft reinfection with hcv is safe and effective in ldlt from hepatitis b core antibody - positive donors . 