Intestine as source of cytokines and growth factors.

BACKGROUND: The activation status of intestinal immune system cells is much higher than that of analogous peripheral cells. Increased serum concentrations of proinflammatory cytokines have been reported in various pathologic conditions; however, the source of these mediators has not been elucidated. OBJECTIVE: To assess the role of the human intestine and its lymphatic system in production of growth factors and proinflammatory cytokines. MATERIAL AND METHODS: Twenty liver transplant recipients and 20 donors were included in the study. Blood samples were obtained from the artery supplying the intestine, the portal vein, and a peripheral vein during liver harvesting in donors and after transplantation in recipients. An enzyme-linked immunosorbent assay was used to assess serum concentrations of IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and hepatocyte growth factor (HGF). RESULTS: In transplant recipients, IL-6 concentration in arterial blood was lower than that in portal blood (P < .049), whereas in donors, there was no significant difference in these concentrations. Neither recipients nor donors demonstrated significant differences in arterial or portal blood concentrations of TNF-alpha, TGF-beta, or HGF. CONCLUSIONS: In healthy human beings, the intestine is not a substantial source of IL-6, TNF-alpha, TGF-beta, or HGF. However, in patients with liver cirrhosis, the intestine is an important source of IL-6 but not of the other studied growth factors and cytokines.

Safety and efficacy of steroid-free immunosuppression with tacrolimus and daclizumab in liver transplant recipients: 6-year follow-up in a single center.

BACKGROUND: Avoidance of steroid therapy after solid-organ transplantation has become a major challenge. Corticosteroid (CS)-free maintenance immunosuppression not only eliminates the well-known adverse effects but also may improve long-term outcome. OBJECTIVE: To investigate whether a CS-free regimen of tacrolimus (Tac) in combination with daclizumab (Dac) induction therapy provides adequate coverage after orthotopic liver transplantation. PATIENTS AND METHODS: This 6-year, single-center, retrospective study included 25 liver transplant recipients randomized to a Tac/CS regimen (n = 18) vs a Tac/Dac regimen (n = 7) according to the protocol of the MASTER (Monoclonal Antibodies vs STERoids) Study. RESULTS: No significant difference was observed in patient and graft survival between treatment arms: 94.4% in the Tac/CS group vs 71.4% in the Tac/Dac group. The incidence of biopsy-proved acute rejection episodes was 23.5% in the Tac/CS group vs 14.3% in the Tac/Dac group (P = NS). Total duration of hospitalization did not differ significantly between groups: 46.5 days in the Tac/CS group vs 73.9 days in the Tac/Dac group. Liver function as estimated using serum alanine aminotransferase and aspartate aminotransferase activity and bilirubin concentration, was not significantly different between the groups during 5 years posttransplantation. However, after 6 years, alanine aminotransferase activity was significantly greater in the Tac/Dac group compared with the Tac/CS group. CONCLUSIONS: A CS-free regimen of Tac/Dac is as effective as Tac/Cs in achieving good patient and graft survival. However, no substantial benefits insofar as the safety of Tac/Dac therapy were evident during long-term follow-up.

Results of a 6-month, multicenter, open-label, prospective study concerning efficacy and safety of mycophenolate sodium in de novo kidney transplant recipients.

BACKGROUND: Mycophenolate sodium (MPS) was designed to reduce the gastrointestinal side effects of mycophenolic acid. The aim of our study was to determine the safety and efficacy of MPS in de novo renal transplant recipients. PATIENTS AND METHODS: This 6-month, multicenter, open-label, single-arm, prospective study was carried out in three centers in Poland. Thirty patients were recruited. Immunosuppressive regimen contained of MPS and cyclosporine (CsA) with or without steroids. RESULTS: The 6-month graft and patient survival was 100%. The incidence of suspected acute rejection episodes (ARE) was 5/30 (16.7%), including biopsy-proven ARE in 2 (6.7%) cases. ARE reversed after therapy. At month 6, the mean serum creatinine level was 1.4 mg/dL, and the mean creatinine clearance (according to the Cockroft-Gault formula) was >70 mL/min. The most frequent adverse effects included diarrhea, delayed graft function, anemia, and lymphocele. Among infections, most common were infections of urinary tract, cytomegalovirus infections, and infections of respiratory tract. Only three patients (10.0%) terminated the study prematurely, including two who discontinuated because of an adverse event, and one because of noncompliance. CONCLUSIONS: An immunosuppressive regimen, including MPS and CsA, with or without steroids, provided effective antirejecton prophylaxis and was well tolerated.

Early hyperglycemia after allogenic kidney transplantation.

BACKGROUND: The aim of the study was to establish the impact of early hyperglycemia on development of diabetes mellitus (DM) in patients after kidney transplantation and to evaluate possible risk factors for post-transplantation DM. We also sought to assess the impact of early hyperglycemia and DM on the renal graft function in the long term (3 year follow-up). MATERIAL/METHODS: 1200 transplant patients from one center, were followed up for 3 years. The rate of chronic rejection, CMV infection, hypertension and dyslipidemia were analyzed. The renal allograft function was examined and pancreatic function peptide C concentration was determined. RESULTS: Early hyperglycemia (within first week after transplantation) was detected in 76 out of 1131 patients (6.7%). In this group within three years observation posttransplantation diabetes mellitus (PTDM) was observed in 57 patients (relative risk 75%). In comparison, transplanted patients with good early glucose control had 8% risk of developing DM within the same period after transplantation. In addition early hyperglycemia predisposed to worse renal graft function and higher proteinuria. The incidence of hypertension as well as the rate of CMV infection was comparable in the DM group and in non-DM patients. PTDM patients had higher values of serum peptide C concentration (p < 0.05), additionally hyperinsulinemia was observed. The kidney allograft function assessed as serum creatinine level was significantly impaired after 3 years in PTDM group compared to non-DM patients. CONCLUSIONS: Our date show the importance of normal glucose concentration in early period after transplantation as predictive factor for diabetes mellitus development and worsening of transplanted organs.

Humoral immune response against mycobacterial antigens in children with tuberculosis.

Different clinical outcomes of tuberculosis (TB) are related to the balance between cell-mediated and humoral immunity and may depend on environmental and individual factors including age and sex. The purpose of this study was to analyze the humoral immune response to recombinant and native mycobacterial antigens in relation to clinical presentations of pulmonary TB in children. We examined 224 serum samples including 81 primary and 31 postprimary TB cases, 30 cases of latent TB infection, and 82 nontuberculosis controls. Commercially available ELISA assays detecting IgG, IgA, and IgM against antigens: 38 kDa, 16 kDa, 38 kDa, lipoarabinomannan (LAM), and A-60 were used. The results indicate that IgG production was very low in primary compared with postprimary TB (P<0.0001). IgM levels did not differ between the examined groups. Antibody levels strongly depended on the child's age. In infants aged below 1 there was no difference in the antibody level between the TB and control cases. Most positive cases were observed in children aged above 10. The influence of BCG vaccination on the antibody level was not seen. In all subgroups, person-to-person heterogeneity of antigen recognition was observed. We conclude that humoral immune response is associated with the phase of TB and is stronger in more advanced TB forms. IgG and IgA production against mycobacterial antigens is very low in young children.

Economic evaluation of sirolimus-based immunosuppressive regimens in kidney graft recipients.

INTRODUCTION: The aim of this study was an economic evaluation of three sirolimus (SRL)-based regimens in the first 2 years after renal transplantation. MATERIALS AND METHODS: The three SRL-based immunosuppressive regimens in renal transplant patients between June 2000 and September 2002 were: (1) SRL + steroids + cyclosporine (CsA) permanently; (2) SRL + steroids + tacrolimus (Tac); and (3) SRL + steroids + CsA, with CsA discontinuation at 3 months posttransplant. Ten patients were included in each group in an intent-to-treat analysis. Cost was calculated according to the hospital price list and recast into euros (EUR) with a 5% discount rate. RESULTS: The number of patients free of an acute rejection episode during 2 years posttransplant were 6, 8, and 5, with 2-year graft and patient survivals of 9, 10, and 9 for regimens 1, 2, and 3, respectively. As differences in clinical effects were not statistically significant, cost analysis was appropriate instead of cost-effectiveness analysis. The mean cost of the 2-year treatment was 15,759 EUR; 25,593 EUR; and 21,197 EUR per patient for regimens 1, 2, and 3, respectively. Sensitivity analysis for the main variables confirmed that the results were not dependent on changes in costs. CONCLUSIONS: Regimen 1 was the most economical immunosuppressive therapy during the 2 years after kidney transplantation. Studies on a larger group of longer observation would be more useful for clinical analysis.

Increased mRNA expression of transforming growth factor beta in the arterial wall of chronically rejected renal allografts in humans.

INTRODUCTION: Transforming growth factor beta (TGF-beta) has an established role in interstitial damage of renal transplants during chronic rejection (CR). However, its involvement in transplant vasculopathy is not clear. The aim of the study was to assess TGF-beta gene expression in the walls of large-caliber arteries within chronically rejecting renal allografts. We evaluated associations between gene expression of this factor and intimal thickness or clinical data. MATERIAL AND METHODS: Renal artery samples of kidney allografts were obtained from 20 hemodialysis patients with end-stage renal graft disease due to CR, who were undergoing graftectomy. The control group included 32 hemodialysis patients with end-stage renal disease, undergoing nephrectomy due to autosomal dominant polycystic kidney disease (n = 12), chronic pyelonephritis (n = 13), or kidney limited tumor (n = 7). Gene expression of TGF-beta was measured using real-time PCR. RESULTS: TGF-beta mRNA expression was 3.25-fold higher in CR than in control patients (P < .001). Expression of mRNA for this cytokine was not influenced by the following factors: intimal thickness; age; serum cholesterol, triglycerides and glucose; BMI; graft survival; time of dialysis before transplantation; total ischemic time; immunosuppressive regimen; incidence of acute rejection episode; panel reactive antibodies; and period of dialysis before graftectomy. TGF-beta is involved in neointimal formation in CR.

Posttransplant lymphoproliferative disorder: morphological picture and diagnostic difficulties.

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of both solid organ and bone marrow transplantation. It includes a wide spectrum of proliferative changes ranging from reactive hyperplasia, borderline lesions to malignant lymphomas. PTLD develops in 1% to 10% of transplant recipients. We present 10 cases of PTLD. Five developed after renal, four after liver, and one after heart transplantation. Among the early lesions, we diagnosed two reactive plasmacytic hyperplasias; one infectious mononucleosis-like PTLD; one polymorphic lesion; and one "mixed" case of plasmacytic hyperplasia in one tonsil with a polymorphic PTLD in the second one. Among the lymphomas, we observed three diffuse large B-cell lymphoma (DLBCL); one mantle lymphoma; and one Hodgkin lymphoma-like PTLD. The morphological pictures of six PTLD cases were typical and posed no diagnostic problems. In the one case of plasmacytic hyperplasia, the lymph node morphology was atypical with atrophy of lymphoid components accompanying plasma cell proliferation. Contrary to a good prognosis of early, reactive PTLD, this patient experienced a rapid course and succumbed to sepsis. The most difficult case was a rare Hodgkin lymphoma-like PTLD, which was diagnosed only by a bone marrow biopsy. Because of its noncharacteristic immunophenotype, it was primarily diagnosed as an anaplastic lymphoma of the T-cell type. After additional immunohistochemical studies (BOB and OCT2), we established the final diagnosis of Hodgkin lymphoma-like PTLD. Due to the increasing number of organ transplantations, doctors of various specialties may encounter PTLD.

Biliary liver cirrhosis secondary to cystic fibrosis: a rare indication for liver transplantation.

As more effective therapies prolong the lives of patients with cystic fibrosis, there are now more patients in this population diagnosed with liver diseases. Secondary biliary cirrhosis is not a rare complication of mucoviscidosis. It is diagnosed in 20% of patients with mucoviscidosis; in 2% it is accompanied by portal hypertension. On average patients with portal hypertension and its complications are 12 years old. Liver transplantation is an accepted method of treatment for children with cystic fibrosis and portal hypertension. It eliminates the cause of the portal hypertension, decreases life-threatening medical conditions, and improves their nutritional status and quality of life. Despite immunosuppressive treatment they do not seem to beat increased risk of upper respiratory tract infections. On the contrary improved respiratory function and status are generally observed. We present our first case of orthotopic liver transplantation performed in a 29-year-old man with cystic fibrosis. The donor was a 42-year-old woman who died of a ruptured cerebral aneurysm. The surgery was performed in September 2004. The patient received immunosuppression based on steroids, basiliximab, tacrolimus, and mycophenolic acid due to renal insufficiency. Antibiotic (meropenem) and antiviral prophylaxis (gancyclovir) were used. A 6-month period of observation confirmed the clinical data from the pediatric population-a good prognosis with improved nutritional status, respiratory function, and quality of life.

Pathomorphological features of acute rejection in patients after orthotopic liver transplantation: own experience.

INTRODUCTION: Acute hepatic allograft rejection remains an important problem following liver transplantation. Liver biopsy specimens show a combination of characteristic changes, first observed by Snover as a diagnostic triad: portal inflammation, bile duct damage, and central or portal vein endothelial inflammation (endothelitis or endothelialitis). The aim of this study was to describe our histopathological assessment of liver transplants. MATERIALS AND METHODS: In the period between September 2000 and June 2004, we evaluated 150 liver biopsy specimens from 105 liver recipients. RESULTS: Acute rejection was diagnosed in 26.6% of liver biopsies taken from 31.4% patients who demonstrated clinical symptoms of liver damage. In 90% of cases the rejection was described as minimal or mild, and in 10% as moderate. There was no episode of severe acute rejection. Only four biopsies (10%) showed nothing but Snover triad changes. In 9 (22.5%) cases only acute rejection was diagnosed; the remaining showed in addition to acute rejection the possibility of other concomitant pathologies: viral infection in 15 cases (37.5%), biliary flow obstruction in 11 cases (28.5%), functional cholestasis in two cases (5%), and ischemic complications in three cases (7.5%). CONCLUSIONS: Histologically confirmed acute rejection episodes were diagnosed in 14.9% liver recipients. Liver biopsy specimens, aside from Snover triad features, often showed other unspecific morphological changes. Differentiation of acute rejection from other accompanying diseases is sometimes difficult, requiring precise clinical data and pathologist experience.

Morphologic features of hepatitis C recurrence in patients after orthotopic liver transplantation-preliminary analysis of our case observations.

INTRODUCTION: Hepatitis C virus (HCV) recurrence is almost universal in patients after liver transplantation. The diagnosis of reinfection is more difficult than that of a primary process, as shown by our pathomorphologic analysis of cases of HCV recurrence. MATERIAL: During 5.5 years, 240 liver biopsies included 54 obtained from liver transplant recipients with primary HCV infections, among whom 26 (56.5%) had clinical signs and symptoms of hepatitis. Nineteen patients from this population underwent 30 liver biopsies. In addition, seven biopsies were performed in five patients without clinical signs of reinfection. RESULTS: In 44.2% of patients with HCV recurrence and 15% without reinfection, the intensity of the primary process in the native livers was assessed as high. Reinfection was found in all patients with liver carcinoma and 67% with hepatocyte dysplasia. Histologic signs of infection were estimated as minimal (n = 4), mild (n = 19), or moderate (n = 4). In five patients with reinfections and one without recurrence, histologic manifestations of acute rejection were also observed. In conclusion, HCV was the indication for liver transplantation in 22.4% cases. Clinical manifestation of recurrence was found in 56.5% of the patients, who tended to be older than those without disease recurrence. Upon microscopy, lobular lesions predominated over the portal changes. Factors predisposing to HCV recurrence were coexistence of other liver disorders, a high intensity of the inflammatory process, hepatocyte dysplasia, and/or hepatocellular carcinoma in the native liver and acute rejection episodes.

Outcome of four high-risk pregnancies in female liver transplant recipients on tacrolimus immunosuppression.

Pregnancies in women after liver transplantation are considered high risk due to the greater rate of complications observed in immunosuppressed graft recipients. We report successful outcomes of four high-risk pregnancies in female liver transplant recipients on tacrolimus-based immunosuppression. The patients, aged 23 to 32 years, at the time of conception were 12 to 59 months from transplantation (mean 30 months). Preterm labor was the most important pregnancy complication observed in these patients. One episode of acute graft rejection was observed. A variable demand for tacrolimus was noted during pregnancy. Despite complications all four pregnancies were successful. The mean gestational age at delivery was 34.4 weeks. The birth weight of the newborns varied from 1410 to 3490 g (mean 2303 g) and the mean Apgar score was 8. No structural malformations or early complications were observed in the newborns. Excluding the patient with acute rejection, the remaining three cases showed all liver parameters to remain stable.

Pregnancy and delivery after liver transplantation.

AIM: According to statistics, women constitute one-third of all liver recipients and approximately 75% of female recipients are of reproductive age. Successful liver transplantation in these patients results in the restoration of menstrual function and fertility. The aim of this study was to assess the course of pregnancy and delivery in liver-transplanted women. MATERIALS AND METHODS: We retrospectively analyzed data of 138 liver-transplanted women, aged from 18 to 63 years, who underwent regular gynecological evaluations. Among 77 patients of reproductive age, 11 women conceived and delivered babies. RESULTS: All patients have successfully delivered. The mean gestation age at delivery was 36.5 weeks. All neonates were delivered in a good state with no congenital abnormalities. Common pregnancy complications were preterm birth, anemia, intrahepatic cholestasis, and infection. In 1 case, graft rejection was observed due to willful discontinuation of immunosuppressive therapy. Two spontaneous vaginal deliveries and 9 caesarean sections were performed. All caesarean sections were performed for obstetrical indications: fetal intrauterine asphyxia (n = 4), breech presentation (n = 2), threatening intrauterine infection (n = 2), and preterm twin delivery (n = 1). CONCLUSION: High-risk pregnancies in liver-transplanted women are generally associated with good outcomes, although an increased rate of preterm labor, intrauterine infections, anemia, and cholestasis were observed. Pregnancy did not seem to impair graft function or accelerate rejection in patients receiving immunosuppressive therapy.

Diagnostic value of different serological tests for tuberculosis in Poland.

The aim of the study was to test the diagnostic accuracy of several serological assays for the diagnosis of tuberculosis (TB) in the Polish population. ELISA based assays detecting: 38 kDa+LAM - MycoM, MycoA and MycoG, 38 kDa - Pathozyme TB complex, 38 kDa+16 kDa - Pathozyme TB complex plus were used. The humoral immune response was analyzed in a group of 319 TB patients (289 adults and 30 children) and in a control group consisting of 66 sarcoidosis cases, 16 cases of mycobacterial infections other than tuberculosis, 35 lung cancer patients, and 70 healthy volunteers. Among the TB patients, there were 267 cases of pulmonary TB and 52 cases of extrapulmonary TB. Sensitivity varied between 32% (IgM) and 63% (IgA) and increased in culture positive tuberculosis and in chronic cases. Specificity was the highest for the tests based on recombinant antibodies (98%). Sensitivity of the IgG test in extrapulmonary TB was comparable with that in pulmonary TB. Overall, sensitivity of the examined tests was lower in children than in adults, but it varied depending on the age and phase of the disease. We conclude that the ELISA-based tests may be a useful tool for improving the diagnosis of TB, especially in adults and in those countries where the prevalence of culture positive and chronic cases is high.

Posttransplantation diabetus mellitus under calcineurin inhibitor.

BACKGROUND: The development of postransplantation diabetes mellitus (PTDM) is a serious complication of kidney transplantation. PTDM has a major impact on quality of life decreasing rates of patient and graft survival. It is well known that some currently used immunosuppressants are diabetogenic. Greater diabetogenicity of FK-506 has been reported in multicenter trials. We initiated a study of conversion from tacrolimus (FK-506) to cyclosporine (CsA) among kidney allograft recipients presenting with PTDM to evaluate whether this maneuver would ameliorate a diabetic state. METHODS: This analysis of 20 adult, renal allograft recipients presenting with PTDM assumed the need for insulin therapy or oral hypoglycemics before and after conversion of the immunosuppressive regimen. The criteria for evaluating the outcome were as follows: dose reduction of insulin or oral hypoglycemic agents, adequacy of glucose control, C-peptide levels, and insulin concentration. RESULTS: During the follow-up, we observed an improvement in the control of blood glucose in the converted group. In 13 patients, satisfactory glucose control was obtained without insulin or any other agent. In 3 patients a significant dose reduction of required insulin was possible. In another 2 patients who were insulin-dependent, the switch to oral hypoglycemic treatment was clinically possible after conversion. After conversion we observed significantly lowered fasting blood glucose levels and increased C-peptide levels. CONCLUSIONS: The conversion from a tacrolimus to a CsA-based immunosuppressive regimen resulted in better glucose metabolism. We demonstrated a positive effect of conversion on the diabetic state of patients with PTDM.

The impact of experience of a transplantation center on the outcomes of orthotopic liver transplantation.

The so-called learning factor has been disregarded for many years in analyzing the causes of surgical complications and post-operative mortality; it is also the case for OLT. In our center until April 2003, 209 OLT were performed in 196 patients. We evaluated the impact of experience of the transplantation team on the outcomes of liver transplantation. Thirty-four patients died (mortality rate, 16%) and 1-year survival rate, 64%. Mortality rates varied during different periods of observation due to increasing experience of the transplantation team. The causes of mortality were assessed for a series of 34 patients: it was 75% at the beginning of transplantation procedures while recent deaths have not recently exceeded 10% of cases.

Liver transplantation in hepatitis C virus-related cirrhosis.

End-stage liver disease associated with HCV infection has become one of the leading indications for liver transplantation and it is the most common disease recurring after liver transplantation. The aim of this retrospective study was to asses factors potentially affecting outcome in patients transplanted for HCV-related liver disease. Among 164 adult patients who underwent orthotopic liver transplantation from December 1994 to December 2002, 134 survived >2 months, including 25 with HCV-related liver disease. Mean follow-up after LTx was 24.8 months (range, 2.1-99.4). Anti-HCV was negative in all donors. The parameters considered in our analysis were: the course, outcome, and liver function tests at 1-year follow-up after HCV reinfection: the potential impact of maintenance and induction immunosuppressive regimens; and episodes of acute rejection. Deterioration of graft function because of HCV reinfection occurred in 16 patients (64%). Mean time for deterioration of liver function related to reinfection was 4.5 months (range, 0.83-23). Induction and maintenance immunosuppression did not affect outcome of HCV-infected liver transplant recipients. Aminotransferases were significantly higher among HCV-infected recipients than among the other patients in our series. There was a slight tendency for earlier recurrence of HCV hepatitis among patients treated with high-dose steroids because of acute rejection.

Effect of immunosuppressive regimen on acute rejection and liver graft function.

Despite the use of modern immunosuppressive drugs, acute liver rejection (AR) continues to affect up to 70% of transplant recipients. The aim of this retrospective study was to assess the incidence of acute rejection episodes in patients treated with different immunosuppressive protocols. In our series, 37.3% of patients developed a clinical episode of AR. Analysis of immunosuppression has shown that the most effective immunosuppressive protocols, with regard to prevention of AR, include: antibody anti-IL-2R (anti-IL-2R) + tacrolimus (Tac) + mycophenolate mofetil (MMF) + prednisolone (Pred); anti-IL-2R + tacrolimus (Tac) + Pred; or Tac + Pred (25% vs 28.6% vs 30.4%, respectively). The highest rate of AR (66.6%) was observed among patients with anti-IL-2R and Tac but no steroid treatment, mostly (77.7%) in the initial period after liver transplantation. There were no statistical differences in liver function tests between the group treated with a CsA-based versus a Tac-based therapy. Strong immunosuppression contributed to a relatively low incidence of clinical AR in our series. The lowest rate of AR was observed among patients treated with anti-IL-2R antibody. Tac, and Pred. Deprivation of steroids in the early phase after liver transplantation substantially increased the risk of acute rejection episodes despite the use of anti-CD25. There were no statistically significant differences in liver function tests among those treated with Tac versus CsA in the short-term follow-up.

Acute liver transplant rejection: incidence and the role of high-doses steroids.

The aim of this study was to assess the incidence of acute rejection (AR), and the efficacy of high doses of steroids during induction of immunosuppression for AR treatment. Fifty-five patients (33.5%) experienced AR episodes in our series; but, there were no deaths or retransplantations related to AR. The median time from liver transplantation to AR was 18.5 days (range, 2-351 days). In the group with the initial dose of methylprednisolone (MP) 0.05). After 1-year observation, liver function tests were similar in both AR and non-AR groups. The only biochemical parameter that was significantly lower in the non-AR group was the aspartate aminotransferase (AST). Liver function tests determined after 1-year follow-up were not significantly different between the groups with AR treated with doses of MP lower versus higher than 1.25 g. However, liver function tests in the group treated for AR with higher doses of MP were slightly better than in the remaining subjects. Recurrence of AR occurred in 5 cases in the group with lower doses of MP (1.25 g). A relatively low dose of MP was effective to treat AR. The tendency of AR patients treated with higher dose of MP to display better liver function needs further investigation. However, AR does not seem to affect later liver function.