treatment options for hepatitis c virus ( hcv ) infection in renal transplant ( rtx ) patients are limited .
the conventional treatment of interferon ( ifn ) injection with ribavirin carries the risk of allograft rejection .
conversely , not treating for hcv is associated with increased morbidity and mortality due to progressive liver dysfunction , infections , malignancy , vasculitis , glomerulonephritis , and new onset diabetes .
the availability of second generation oral anti - viral drugs has opened new avenues for hcv treatment .
although used successfully in liver transplant situation , there is no available literature for their use in rtx patient .
we share our early experience of a rtx patient with hcv infection treated successfully with combination pill of sofosbuvir ( sof ) and ledipasvir ( ldv ) ( harvoni ) , heralding a new era of safe , ifn - free , oral , anti - hcv therapy
a 43-year - old male renal allograft recipient , presented at the sixth year follow up with significant weight loss of 6 kg over 3 months . prior to renal transplantation he was hypertensive , nondiabetic and hcv negative ( confirmed by standard elisa and polymerase chain reaction [ pcr ] test ) .
induction therapy included basiliximab 2 doses ( 20 mg each ) followed by triple drug immuno - suppression ( prednisolone , tacrolimus , mycophenolate mofetil [ mmf ] ) he received two units blood transfusion in the peritransplant period .
he was receiving prednisolone 5 mg daily , mmf500 mg thrice daily , and tacrolimus 1 mg twice daily .
his other medications included nifedipine 20 mg thrice daily , metoprolol 50 mg once daily and calcium carbonate 500 mg twice daily .
laboratory evaluation showed de novo new onset diabetes mellitus after transplant ( fasting blood glucose 225 mg / dl , hemoglobin a1c 11.9 ) , elevated liver enzymes ( aspartate transaminase 89
iu / l [ normal < 40 ] , gamma glutamyl transferase 150 iu / l , biliburin 1 mg% , serum albumin 4 g / dl ) , normal renal functions ( serum creatinine 0.9 mg% ) , normal hemogram , and chest x - ray .
furthermore , the evaluation showed hbsag negative , anti - hcv serology positive status due to hcv genotype 1 with high viral load ( 10,800,000 iu / ml ) .
diabetes was initially controlled with insulin and later he was switched to oral sitagliptin - metformin combination .
his serum transaminases level remained elevated over next 9 months with persistent high hcv load ( 106,074,000 iu / ml ) .
the patient was counseled about the risk of allograft rejection with existing anti - hcv therapy , and lack of treatment guidelines for using oral new anti - viral agents in rtx situation . however , with recent treatment success with newer oral anti - viral agents in non - rtx situation , the patient consented to take oral anti - viral therapy under closed supervision .
he received the fixed - dose combination of ldv and sof ( harvoni ) , manufactured by gilead sciences . for next 12 weeks . at 3 weeks ( after starting treatment )
doppler ultrasound and radionuclide study with technetium-99m - diethylene - triamine - pentaacetate were normal .
his serum cyclosporine trough level was in the acceptable range ( 110.2 ng / ml whole blood at 3 weeks while baseline was 95 ng / ml by liquid chromatography - tandem mass spectrometry normal range 80150 on long - term ) .
he continues to do clinically well at four months posttreatment in addition , after completion of oral anti - viral therapy he is off anti - diabetic treatment with maintained euglycemia and normal liver functions .
liver disease is an important cause of morbidity and mortality in rtx recipients , especially with hcv infection .
abnormal liver functions test are reported in 724% of rtx recipients , with liver failure as the cause of death in 828% of long - term survivors .
liver disease in rtx patient may be due to viral infections ( hepatitis b virus or hcv , epstein - barr virus , or cytomegalovirus ) , drugs ( azathioprine or cyclosporine ) , iron overload ( hemosiderosis ) or alcohol abuse .
hcv infection in immuno - suppressed rtx recipient is associated with significant morbidity and mortality .
patients with hcv - positive status prior to transplantation have increased risk of posttransplant liver disease with a relative risk ( rr ) of 5.0 .
one large meta - analysis , that included 6365 hcv positive patients reported increased risk for death ( rr 1.79 ) and allograft failure ( rr 1.56 ) .
hcv infection additionally causes heightened immuno - suppression thereby increasing the risk of sepsis in the initial years post - rtx and liver disease in later years that progresses more rapidly compared to the nontransplant situation to chronic hepatitis , cirrhosis , and liver cancer .
hcv infection is also associated with increased risk for new onset diabetes after transplantation ( nodat ) , de novo glomerulonephritis and mixed cryoglobulinemia - related vasculitis that may lead to graft loss or recipient death .
interestingly , the present case highlights that the patient who developed nodat associated with hcv infection may have a collateral benefit of getting cured of diabetes with control of hcv infection .
efforts to minimize the incidence of post - rtx hcv infection must focus on viral screening of both donors and recipients using sensitive methods in the pretransplant stage .
third generation elisa serology for the detection of hcv has high sensitivity ( > 98% ) .
the latter is confirmed by a gold standard pcr test that detects hcv rna antigen , which should be done in all patients prior to transplant .
the index patient was negative for hcv by elisa and pcr in pre - rtx evaluation .
he probably acquired hcv infection from blood transfusions ( tested negative by elisa ) received in peritransplant period though a remote possibility of missed hcv infection in pretransplant evaluation exists .
the latter may occur in patients who have intermittent viremia from the sequestered virus in the liver or peripheral mononuclear cells leading to negative serum hcv status .
the standard care for the patients with hcv genotype 1 infection in non - rtx scenario is pegylated ifn plus ribavirin with newer direct acting anti - viral protease inhibitor ( boceprevir or telaprevir ) for 48 weeks .
the overall sustained virological response ( svr ) rate in patients infected with hcv genotype 1 is poor ( < 50% ) compared to genotype 2 or 3 ( approximately 7580% ) more so in patients on dialysis ( nearly one - third ) .
current treatment option approved for patients ineligible to receive inf in hcv genotype 1 infection is 24 weeks of sof and ribavirin .
rtx is a contraindication to ifn therapy due to its limited efficacy , increased risk of acute rejection , high cost , and significant side effects .
however , ifn mono - therapy is to be considered in kidney transplant recipients with hcv infection having fibrosing cholestatic hepatitis or life - threatening vasculitis .
ribavirin in the post - rtx state does not produce sustained virologic response despite lowering of transaminase level .
current clinical strategy in the post - rtx hcv infection is manipulation of immunosuppressive therapy ( minimizing corticosteroid , avoidance of anti - lymphocyte antibody , and to replace tacrolimus with cyclosporine ) .
however , there is an urgent need for newer anti - hcv therapies with greater safety and efficacy than ifn and ribavirin in rtx patient .
the drugs used as  add - on oral therapy  in hcv treatment include ribavarine , telaprevir , boceprevir , or simeprevir in different combinations .
the advent of newer second generation anti - virals like sof -ldv , ombitasvir - paritaprevir plus dasabuvir , daclatasvir - asunaprevir , and simeprevir - sof has widened the therapeutic options with reported svr above 90% .
the novel oral anti - viral agents are likely to cause a paradigm shift in the treatment of hcv infection in post - rtx state by simplifying current therapy of shorter duration and also eliminating the need for response guided therapeutic approach .
the choice between these agents depends primarily on the potential for drug interactions and drug toxicity .
the combination therapies are preferred as they provide better viral suppression than mono - therapy with less chance of viral escape based on complementary resistance profiles .
there is no additional benefit by extension of the duration of treatment to even 24 weeks .
addition of ribavirin to a ldv - sof combination increases toxicity without any additional efficacy .
ldv - sof combination has favorable adverse effect profile ( common side effects rated as mild and not leading to drug discontinuation like fatigue , headache , nausea , diarrhea , and insomnia reported in 1020% ) , minimal drug interactions , and easy to administer ( single pill daily ) .
ldv is an inhibitor of the hcv ns5a protein that is required for viral replication , postreplication assembly , and secretion .
sof , a nucleotide pro - drug and an inhibitor of the hcv ns5b rna - dependent rna polymerase , acts as a chain terminator .
sofosobuvir , the backbone of the new standard of care for hcv infection , offers a number of potential benefits such as high rates of sustained virologic response , high barrier to resistance , tolerability , pan - genotype efficacy ( hcv genotype 16 ) , need for shortened duration of treatment , usefulness in cirrhosis , human immunodeficiency virus co - infection and liver transplantation .
sof ( 400 mg ) in combination with ldv ( 90 mg ) ( harvoni ) has been proven to be efficacious , tolerable and safe in series of clinical trials , both in treatment - nave and treatment - experienced patients with 1224 weeks of therapy ( depending presence or absence of cirrhosis , treatment experience , and genotype ) with high sustained viral response .
the index rtx patient with a very high viral load without cirrhosis showed a remarkable response as early as 3 weeks after therapy .
shorter duration for 8 weeks can be considered in treatment - nave patients without cirrhosis who have pretreatment hcv rna of < 6 million iu / ml .
both sof and ldv are substrates of p - glycoprotein inducers ( like rifampicin ) with implication for potential drug interactions but it does not demonstrate significant drug interactions with immunosuppressant drugs .
the development of ifn free oral anti - hcv therapy may be a major breakthrough in anti - hcv management in rtx patient .
the dual drug combination therapy appears to be an important arrow in our quiver now for targeting hcv infection in high - risk rtx .
such combination therapy may shorten and simplify treatment regimens even in the post - rtx scenario ushering a new era of safer , simpler and more effective therapy .
however , the utility versus the risk of such new therapy has to be scrutinized carefully by studies involving a sizeable cohort of rtx patients having long - term follow - up for reliable assessment of such therapeutic intervention . medwin hospital , nampally , hyderabad , andhra pradesh , india .
 liver disease due to hepatitis c infection in renal transplant recipients is difficult to treat and often associated with reduced patient survival . 
 a 43-year - old male , a renal allograft recipient , presented at 6 years follow - up with significant weight loss over 3 months . 
 he was detected to have new onset diabetes mellitus together with hepatitis c virus ( hcv ) infection ( genotype 1 ) . 
 his hcv load remained high despite the change of immuno - suppression from tacrolimus to cyclosporine . 
 a decision to treat with a new anti - viral combination of ledipasvir and sofosbuvir for 12 weeks was taken . within 3 weeks 
 , his raised serum transaminases levels normalized and viral load became undetectable . at the end of 16 weeks 
 , he continues to do well with normal renal function , has sustained remission from hepatitis c infection and resolution of diabetes . 
Introduction
Case Report
Discussion
Conclusion
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