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.


CONCLUSIONS
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.
Sharma
R K
RK
Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. rksharma@sgpgi.ac.in
Bansal
S B
SB
Gupta
A
A
Gulati
S
S
Kumar
A
A
Prasad
N
N
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006085:Graft Survival; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D011183:Postoperative Complications; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons; D003404:Creatinine