Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients.

The aim of this study was to evaluate the efficacy and safety of interferon-alpha (IFN-alpha) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-alpha three times weekly for 6 months. After IFN-alpha therapy, 18 patients (43%) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-alpha therapy. Repeated liver biopsy was performed in 16 patients after 6-24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-alpha therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-alpha therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0-84 months). IFN-alpha seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.

Clinical course of concomitant Hbv and Hcv infection in renal allograft recipients.

We evaluated the impact of concomitant infection with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) on the clinical course after renal transplantation (Tx). In 335 patients (pts) transplanted between 1991 and 1993 we found 30 (9%) recipients who were positive for Hepatitis B surface antigen (HBsAg) (ELISA, Organon) and anti-HCV antibodies (immunoblot assay Lia Tek) preTx. Chronic liver disease (CLD) (two-fold or greater increase in serum ALT and AST levels for at least six months) developed in 40.7% coinfected pts as compared to 24.4% and 25.7% pts infected only with HCV or HBV, respectively. Maintenance immunosuppression consisted of P + Aza + CsA, mean follow-up time was 28 +/- 15 months. The mean time of the onset of CLD was 3.0 months (range: 1-18 months) after Tx. Percutaneous liver biopsy performed in 5 CLD pts revealed chronic active hepatitis (CAH) in 4 and chronic persistent hepatitis (CPH) in 1 pt. Four pts who had CAH and were positive for HCV RNA (RT PCR) in serum and for HBcAg in liver tissue, received interferon-alpha therapy for 6 months. Clinical improvement of liver function was observed in all of them, but none cleared HBsAg or HCV RNA. One pt lost his graft due to acute rejection. Concomitant infection with HBV and HCV is associated with the high risk of development of CLD early after Tx. We recommend that pretransplant evaluation of both anti-HCV and HBsAg positive pts should include liver biopsy to exclude potential recipients with CAH.

[Tuberculosis in patients after kidney transplantation]. / Gruzlica u chorych po przeszczepieniu nerki.

Infection caused by Mycobacterium tuberculosis is common among population in Poland. We analyzed the effect of tuberculosis (TB) on patients and graft survival in the group of renal allograft recipients (RAR), treated in our center. Among 1669 renal allograft recipients transplanted from 1981 to 1992, tuberculosis developed in 33 (2%) patients (16 M/17F, age: 22-57 years). The patients were on following immunosuppressive regiments" Pred+Aza+CsA (12 pts), Pred+Aza (12), Pred+CsA (6) and Pred+Aza+CsA+ATG (3). Acute rejection was diagnosed in 27 of them and was treated with methyloprednisone pulses, and in a few cases additionally with ATG (2 pts) or OKT3 (1 pt). In two pts TB had been diagnosed and successfully treated in the past. In 6 pts, on chest X-ray done immediately before transplantation, healed primary lesion (Ghon complex) had been seen. In 16 pts TB developed in the early posttransplant period (median: 3.8 +/- 1.8, range: 1-6 months) and in 17--late after transplantation (median: 31.2 +/- 1.8, range: 13-156 months). In 19 pts symptoms developed soon after treatment of acute rejection. Clinical manifestations include pulmonary TB (30 pts) and extrapulmonary lesions (15 pts): pleural TB (3 pts), miliary TB (5 pts), tuberculous lymphadenitis (1 pt), uveitis (1 pt), renal allograft (2 pts), skeletal (2 pts) and GI tract (1 pt). Diagnosis of TB was made based on clinical presentation and radiologic findings and it was confirmed by positive cultures in 18 pts, by tissue biopsy in 4 pts and by autopsy examination in 9 pts. Treatment regimen included one of the following drug combinations: INH+EMB+RMP (20 pts), INH+RMB+RMP+PZA (10 pts) or INH+EMB+SM (3 pts). Three pts died before TB was recognized and 4 deaths occurred after treatment was started. All these pts developed renal failure. 26 pts were treated for 3-12 months (median, range: 7.8 +/- 2.9) and in 24 of them complete remission was achieved. In this group renal function remained stable in 16 pts and 6 pts developed terminal failure due to chronic rejection. Authors conclude: 1. TB remains a frequent complication in RAR but can be successfully treated when diagnosed early. 2. Extrapulmonary TB is common in RAR. 3. TB deteriorates one year patients (75%) and graft (49%) survivals.

Treatment of chronic hepatitis B and C with interferon-alpha in renal allograft recipients: preliminary results.

We evaluated the effects of treatment with interferon (IFN) on liver disease and renal allograft function in ten immunosuppressed cadaver kidney recipients. Two females and eight males (mean age 39 years) with biopsy-proven chronic active hepatitis (n = 8) or persistent hepatitis (n = 2) and serum positive for hepatitis B surface antigen (HBsAg) and HBe antigen (n = 5) or serum positive for anti-HCV antibodies (n = 3) or serum positive for HBsAg, anti-HCV and anti-HDV antibodies (n = 2) received 3 million units IFN thrice weekly of 6 months. All patients responded with a reduction in serum aminotransferase activity and in five of them liver function completely normalized. Three patients among five infected with HBV cleared HBeAg. During the follow-up period liver function remained stable in 9 patients after discontinuation of IFN therapy. Three patients lost their grafts due to rejection 1, 2, and 4 months after IFN therapy, respectively. In six patients renal function remained stable during and after IFN therapy. We conclude that in selected groups of renal allograft recipients IFN can be used safely and effectively for the treatment of chronic viral hepatitis.