renal transplantation rates are low among patients highly sensitized to human leukocyte antigen ( hla ) because of the high rate of antibody - mediated rejection and subsequent graft loss .
it was recently reported , however , that preoperative desensitization using an anti - cd 20 antibody ( rituximab ) and intravenous immunoglobulin improved transplantation rates in patients highly sensitized to hla . in contrast , the significance of a positive lymphocytotoxic crossmatch in living donor liver transplantation ( ldlt ) is controversial .
successful ldlt using a liver graft in which the lymphocytotoxic crossmatch was highly positive is reported .
the recipient was a 41-year - old woman with end - stage liver disease due to alcoholic liver cirrhosis ( model for end - stage liver disease score 21 ) . at the age of 20 , she was gravida one , para one .
she was considered a candidate for liver transplantation because of repeated episodes of encephalopathy . because of the severe shortage of cadaveric donor grafts in japan , we planned an ldlt , and her husband was willing to donate his partial liver .
the abo blood type was identical , but the t lymphocytotoxic crossmatch titer was over 10,000 and the b lymphocytotoxic crossmatch titer was 128 ( complement method with the dilution technique according to the standard national institutes of health technique ) .
in addition , an examination of anti - hla antibodies using fluorescent microspheres revealed that the recipient had donor specific antibodies ( b51 and b52 ) .
after obtaining written informed consent from the patient and donor and the approval of the intra - institutional committee , we proceeded to the preoperative preparations .
for preoperative desensitization , the patient was first infused with rituximab 2  weeks before the scheduled surgery ( due to a catheter - associated infection , however , the operation was postponed and ldlt was performed 21  days after initiation of the rituximab therapy ) . as the antibody to hepatitis b core antigen was positive , entecavir ( 0.5  mg / day ) was administered for 3  weeks preoperatively to prevent a possible hepatitis b virus breakthrough .
on postoperative days 1 and 4 , 20  mg of anti - cd25 antibody ( basiliximab ) was administered in addition to the routine methylprednisolone and tacrolimus , as we were anxious about hyperacute rejection . besides , mycophenolate mofetil ( mmf ; 2,000  mg / day ) was started on postoperative day 7 .
the postoperative course was uneventful except for an episode of mild acute cellular rejection ( banff score 3 ) on postoperative day 27 , which responded promptly to steroid recycle therapy .
the liver biopsy specimen obtained at the time of the acute rejection showed mild infiltration of lymphocytes in the portal area and around the bile ducts .
one year after the ldlt , the lymphocytotoxic crossmatch remained negative and the patient has been well with good graft function.fig . 
acr acute cellular rejection , alt alanine aminotransferase , mmf mycophenolate mofetil , mp methylprednisolone , pe plasma exchange , tb total bilirubin , pod postoperative day the clinical profile of the present patient .
acr acute cellular rejection , alt alanine aminotransferase , mmf mycophenolate mofetil , mp methylprednisolone , pe plasma exchange , tb total bilirubin , pod postoperative day
the impact of a lymphocytotoxic crossmatch - positive liver graft on acute cellular rejection and graft survival remains controversial , both in deceased donor liver transplantation [ 3 , 4 ] and in ldlt [ 57 ] .
some institutions have reported significantly unfavorable outcomes in ldlt recipients with a positive lymphocytotoxic crossmatch [ 6 , 7 ] .
in contrast , our previous results   showed that if the titer is low ( no more than 32 ) , a positive lymphocytotoxic crossmatch does not adversely affect the graft or survival in patients without desensitization .
although the significance of a quantitative assessment of the lymphocytotoxic crossmatch has not been reported , the high titer in our present patient led to the need for perioperative desensitization to prevent early graft loss due to antibody - mediated rejection . after considering the results in the present patient ,
we have settled the indication criteria for preoperative desensitization therapy at the titer of 1,000 ( t lymphocyte crossmatch ) . in this patient ,
therefore , we applied preoperative desensitization using rituximab and plasmapheresis to reduce the high titer of preformed antibodies and b lymphocytes . as a result ,
the lymphocytotoxic crossmatch was negative after the 3rd plasmapheresis , and negativity was sustained thereafter .
preoperative desensitization using rituximab was introduced in abo - incompatible ldlt in 2003 and has dramatically improved the outcomes of abo - incompatible ldlt .
the appropriate dosage of rituximab is still controversial , but many previous studies have reported the administration of 375  mg / m of rituximab 13  weeks before the transplant . following these successful cases , we planned the administration of 375  mg / m ( 500  mg / body ) of rituximab 2  weeks before the operation [ 8 , 9 ] .
splenectomy is also considered to be effective to reduce antibody production , as the spleen is the site of antibody production .
after the operation , the suppression of t - cell function to prevent the initiation of t - cell - mediated antibody production was regarded as indispensable .
we have routinely used tacrolimus and steroid as an immunosuppressive regimen , and in this particular patient , we added basiliximab ( postoperative days [ pods ] 1 and 4 ) and mmf .
mild acute cellular rejection occurred about 3  weeks after the ldlt , but response to the steroid recycle therapy was prompt , and the lymphocytotoxic crossmatch was negative during this episode . in summary , we report a successful ldlt using a lymphocytotoxic crossmatch highly positive graft .
perioperative desensitization using plasmapheresis and rituximab may provide significant benefits for reducing anti - hla antibodies .
 we describe a successful living donor liver transplantation ( ldlt ) using a lymphocytotoxic crossmatch highly positive graft . a 41-year - old woman with alcoholic liver cirrhosis was referred as a potential candidate for ldlt , and her husband was willing to donate his partial liver . 
 as the t - lymphocytotoxic crossmatch titer was over 10,000 , the patient was first infused with rituximab for preoperative desensitization , and then five rounds of plasmapheresis were performed . after the third plasmapheresis , the lymphocytotoxic crossmatch test was negative . 
 a left liver graft including the caudate lobe was implanted , and anti - cd25 antibody ( basiliximab ) was administered on postoperative days 1 and 4 . 
 the postoperative course was uneventful except for an episode of mild acute cellular rejection on postoperative day 27 . 
 although the impact of a lymphocytotoxic crossmatch - positive liver graft on acute cellular rejection and graft survival in ldlt remains controversial , perioperative desensitization may provide benefits when using a highly sensitized liver graft . 