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Biomedical subjects

Robert A Fisher

Publications and source records attributed to Robert A Fisher.

At least 19 recordsLinked to original sources
PubMed2007

MELD-XI: a rational approach to "sickest first" liver transplantation in cirrhotic patients requiring anticoagulant therapy.

Priority for "sickest first" liver transplantation (LT) in the United States is determined by the model for end-stage liver disease (MELD). MELD is a good predictor of short-term mortality in cirrhosis, but it can overestimate risk when international normalized ratio (INR) is artificially elevated by anticoagulation. An alternate prognostic index omitting INR is needed in this situation. We retrospectively analyzed survival data for 554 cirrhotic veterans referred for consideration of LT prior to December 1, 2003 (training group). Using logistic regression we derived a predictive formula for 90-day pretransplant mortality incorporating bilirubin and creatinine but omitting INR. We normalized this formula to the same scale as MELD using linear regression. This yielded MELD-XI (for MELD excluding INR) = 5.11 Ln(bilirubin) + 11.76 Ln(creatinine) + 9.44. Accuracy of MELD-XI was validated in a holdout group of 278 cirrhotic veterans referred after December 1, 2003, and in an independent validation dataset of 7,203 cirrhotic adults listed for LT in the United States between May 1, 2001, and October 31, 2001. MELD-XI and MELD correlated well in training, holdout, and independent validation cohorts (r = 0.930, 0.954, and 0.902, respectively). In the holdout cohort, c-statistics of MELD vs. MELD-XI for mortality were, respectively, 0.939 vs. 0.906 at 30 days;0.860 vs. 0.841 at 60 days; 0.842 vs. 0.829 at 90 days; and 0.795 vs. 0.797 at 180 days. In the independent validation dataset, c-statistics for MELD vs. MELD-XI as predictors of 90-day survival were, respectively, 0.857 vs. 0.843 in noncholestatic liver diseases and 0.905 vs. 0.894 in cholestatic liver diseases. Comparable MELD and MELD-XI scores were associated with comparable prognosis. In conclusion, MELD-XI, despite omission of INR, is nearly as accurate as MELD in predicting short-term survival in cirrhosis. In patients treated with oral anticoagulants, substitution of MELD-XI for MELD may permit more accurate assessment of risk and more rational assignment of "sickest first" priority for LT.

Adult↗
PubMed2006

Human hepatocyte transplantation: worldwide results.

The conception and animal modeling of hepatocyte transplantation along with a partial listing of human hepatocyte infusions over the last 13 years have been detailed in authoritative reviews. However, to adequately best represent the worldwide effort of moving from highly successful clinical solid liver transplants "back to" isolated hepatocyte therapy requires repeating important concepts with explanations of how or why not animal experimental data translate to human experience. This overview summarizes 78 human clinical hepatocyte transplant experiences authenticated by the authors. The human cell infusion experiences are categorized by liver disease treated (metabolic, chronic, and acute liver failure), and these are accompanied by seminal in vitro and in vivo experimental data.

Cell Separation↗
PubMed2006

Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.

BACKGROUND: : The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined. METHODS: : Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome. RESULTS: : Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30-1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12-0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16-0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome. CONCLUSIONS: : Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

Adult↗
PubMed2006

Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C.

The objective of this study was to prospectively define outcomes of cirrhosis due to nonalcoholic steatohepatitis (NASH) and compare them with those associated with hepatitis C virus (HCV) infection. We compared 152 patients with cirrhosis due to NASH with 150 matched patients with cirrhosis due to HCV. Over 10 years, 29/152 patients with cirrhosis due to NASH died compared with 44/150 patients with HCV (P < .04). This was mainly due to the lower mortality rate in patients with Child class A cirrhosis due to NASH versus HCV (3/74 vs. 15/75; P < .004). There were no significant across-group differences in mortality in patients with Child class B or C cirrhosis. Sepsis was the most common cause of death in both groups; patients with NASH had a higher cardiac mortality (8/152 vs. 1/150; P < .03). Patients with Child class A cirrhosis due to NASH also had a significantly lower risk of decompensation, defined by a 2-point increase in Child-Turcotte-Pugh score (P < .007). Cirrhosis due to NASH was associated with a lower rate of development of ascites (14/101 vs. 40/97 patients at risk; P < .006). NASH also had a significantly lower risk of development of hepatocellular carcinoma (10/149 vs. 25/147 patients at risk; P < .01). In conclusion, compensated cirrhosis due to NASH is associated with a lower mortality rate compared with that due to HCV. It is also associated with a lower rate of development of ascites, hyperbilirubinemia, and hepatocellular carcinoma. However, cardiovascular mortality is greater in patients with NASH.

Ascites↗
PubMed2006

Allograft TNFbeta and IL16 polymorphisms influence HCV recurrence and severity after liver transplantation.

Hepatitis C (HCV) recurrence after liver transplantation is universal although severity varies. We explored whether certain donor cytokine gene polymorphisms may be useful markers of susceptibility to severe recurrence. Allograft tumor necrosis factor (TNF) beta and interleukin (IL) 16 gene polymorphisms were correlated with l-yr clinical outcome among HCV+ recipients. Recipients of donor TNFbeta(2,2) (n = 8) experienced less recurrence (50% vs. 71%, P < 0.05), less fibrosis (25% vs. 76%, P < 0.01), and less rejection (25% vs. 71%, P < 0.01) than donor TNFbeta(1,1) (n = 19). Recipients of donor TNFbeta(1,2) (n = 27) demonstrated an intermediate picture with less fibrosis (56%, P < 0.01) and less rejection (37%, P < 0.01) than TNFbeta(1,1). Recipients with donor IL16(TC) (n = 22) showed less recurrence (65% vs. 78%, P = 0.05), less fibrosis (53% vs. 67%, P = 0.06), and less rejection (41% vs. 55%, P = 0.06) than IL16(TT) (n = 32) genotype. Recipients of the combination TNFbeta(2,2)/IL16(TC) donor genotype had the most benign clinical outcome with less recurrence (33% vs. 75%, P < 0.01), no fibrosis (0% vs. 50%, P < 0.001), and fewer rejections (33% vs. 75%, P < 0.01) than donor TNFbeta(1,1)/IL16(TT) genotype. In vitro production of cytokines correlated with genotype. Release of soluble TNFbeta for TNFbeta(1,1) vs. TNFbeta(1,2) and TNFbeta(2,2) was 4803 +/- 2142 pg/mL vs. 5629 +/- 3106 (P = not significant [ns]) and 7180 +/- 3005 (P = ns). Release of soluble IL16 for IL16(TT) vs. IL16(TC) was 437 +/- 86 pg/mL vs. 554 +/- 39 (P = 0.06). In conclusion, allograft TNFbeta and IL16 gene polymorphisms may be useful markers to predict the severity of disease recurrence among HCV+ patients after liver transplantation.

Cells, Cultured↗
PubMed2006

Molecular techniques for identifying HCC origin and biology after orthotopic liver transplantation.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Liver transplantation represents the potentially curative treatment for small HCC. Recurrence after surgical resection and liver transplantation remains one of the major obstacles in further prolonging survival of patients with HCC. In the new liver, HCC might be of recipient or donor origin. One approach for investigating this question is by performing human identification and/or engraftment analysis. Distinction between recurrent and de novo HCC after orthotopic liver transplantation could allow for the development of important clinical and therapeutic strategies. Polymerase chain reaction amplification of highly polymorphic short tandem repeat DNA sequences, gene expression profiling, and fluorescence in situ hybridization were applied in a patient who developed a second HCC after orthotopic liver transplantation from an opposite gender donor. These techniques provided consistent evidence that the second HCC was a recurrence of the primary tumor.

Amelogenin↗
PubMed2005

Study of mRNA growth factors in urinary cells of kidney transplant recipients as predictors of chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is responsible for a significant proportion of graft loss. Current diagnostic methods for CAN are inadequate, and noninvasive assays for detecting allograft dysfunction/rejection and predicting long-term outcomes are a priority in transplantation. METHODS: Urine samples were collected from 48 kidney transplant recipients (KTR): 18 recipients with stable graft function (creatinine levels<2.0 mg/dL) and proteinuria of less than 500 mg/24 hr (Group 1); 18 recipients with stable graft function and proteinuria of greater than 500 mg/24 hr (Group 2); and 12 recipients with biopsy confirmed CAN. Urinary cell levels of transforming growth factor-beta1 (TGF-beta1) mRNA or epidermal growth factor (EGF) mRNA were measured using real-time quantitative PCR assay, and levels were correlated with renal allograft status. The integrity of RNA isolated from urine sediments was also assessed using the Agilent 2100 Bioanalyzer. RESULTS: Urinary cell TGF-beta1 mRNA levels were higher in the CAN group compared to Group 1 (P<0.0001) or Group 2 (P<0.0001). Urinary cell EGF mRNA levels were higher in Group 1 compared to Group 2 (P<0.0001) or the CAN group (P<0.0001). There were no significant differences in the urinary cell levels of EGF mRNA between patients with greater than 500 mg/24 hr proteinuria (Group 2) and the CAN group (P=0.75). CONCLUSION: These results demonstrate that urinary cell TGF-beta1 mRNA levels distinguish CAN patients from long-term transplant patients with stable renal function and varied levels of proteinuria. Urinary cells may be a good resource for the noninvasive diagnosis of CAN.

Adult↗
PubMed2005

Apolipoprotein E genotypes as predictors of high-risk groups for developing hyperlipidemia in kidney transplant recipients undergoing sirolimus treatment.

BACKGROUND: Hypercholesterolemia (HCHL) and hypertriglyceridemia (HTRG) have emerged as the most significant metabolic consequences of therapy with sirolimus. Lipid status can be exacerbated by a variety of factors in the posttransplant setting, including genetic factors. Apoliprotein E (Apo E) polymorphism is an established genetic risk factor for hyperlipidemia. We studied the association between Apo E gene polymorphisms and lipids after kidney transplantation in patients undergoing sirolimus treatment. METHODS: We studied 98 kidney transplant patients (KTP) with stable renal allograft undergoing sirolimus treatment: 39 with HCHL and HTRG within 90 days postsirolimus treatment (PST) and 59 without hyperlipidemia PST. Apo E genotyping was performed using INNO-LiPA-ApoE. RESULTS: The cholesterol and the triglyceride values between the groups were 323.3+/-71.6 vs. 180.9+/-31.2 mg/dL (P<0.001) and 318.9+/-97.2 vs. 159.7+/-38.7 mg/dL (P<0.001). There was a significant difference in the genotype distribution of the hyperlipidemia and normal groups (P=0.009) with the percentages in each group as follows: E2/2 and E3/2: 12.8 vs. 5.1%; E3/3: 69.2% vs. 86.4%; and E4/3 and E4/4: 18.0% vs. 8.5%. We observed a higher number of patients with the genotype E3/3 in the group without hyperlipidemia PST (P=0.039). E3/2 and E4/4 genotype frequencies were higher in patients with hyperlipidemia PST. LDL levels in the hyperlipidemia PST group was statistical significant higher (P<0.001) and we observed an association between Apo E allelic distribution and LDL (P=0.005). CONCLUSIONS: Genetic factors, as Apo E genotypes, could allow the early identification of patients who are at a high risk for developing hyperlipidemia PST.

Adult↗
PubMed2005

Antifungal management practices and evolution of infection in organ transplant recipients with cryptococcus neoformans infection.

BACKGROUND: Therapeutic practices for Cryptococcus neoformans infection in transplant recipients vary, particularly with regards to antifungal agent employed, and duration of therapy. The risk of relapse and time to recurrence is not known. We assessed antifungal treatment practices for cryptococcosis in a cohort of prospectively followed organ transplant recipients. METHODS: The patients comprised 83 transplant recipients with cryptococcosis followed for a median of 2.1 and up to 5.2 years. RESULTS: Patients with central nervous system infection (69% vs. 16%, P = 0.00001), disseminated infection (82.7% vs. 20%, P = 0.00001), and fungemia (29% vs. 8%, P = 0.046) were more likely to receive regimens containing amphotericin B than fluconazole as primary therapy. The use of fluconazole, on the other hand, was more likely for infection limited to the lungs (64% vs. 14%, P = 0.00002). Survival at 6 months tended to be lower in patients whose CSF cultures at 2 weeks were positive compared to those whose CSF cultures were negative (50% vs. 91%, P = 0.06). Maintenance therapy was employed in 68% (54/79) of the patients who survived >3 weeks. The median duration of maintenance therapy was 183 days; 55% received maintenance for > or = 6 months and 25% for >1 year. Relapse was documented in 1.3% (1/79) of the patients. CONCLUSIONS: A majority of the organ transplant recipients with cryptococcosis receive maintenance antifungal therapy for 6 months with low risk of relapse. These data can assist in trials to assess the optimal therapeutic approach and duration of therapy for cryptococcosis in transplant recipients.

Adult↗
PubMed2005

Allograft loss in renal transplant recipients with cryptococcus neoformans associated immune reconstitution syndrome.

This study describes the association of allograft loss and immune reconstitution syndrome (IRS) in the course of Cryptococcosis neoformans infection in renal transplant recipients. Patients comprised 54 renal allograft recipients with cryptococcosis in a prospective, multicenter study. IRS developed in 5.5% (3/54) of the renal transplant recipient with C. neoformans infection. The renal allograft was lost to chronic rejection in 66% (2/3) of the patients with cryptococcosis who developed IRS compared to 5.9% (3/51) of those who did not (P=0.012). Kaplan-Meier survival analysis showed that subsequent to cryptococcal infection the probability of allograft survival was significantly lower in patients who developed IRS compared to those who did not develop IRS (P=0.0004). Temporal association of graft loss with IRS suggests a common pathophysiologic basis for these entities with implications relevant for the optimal management of renal transplant recipients with cryptococcosis.

Cryptococcosis↗
PubMed2005

An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients.

BACKGROUND: We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. METHODS: The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. RESULTS: In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. CONCLUSIONS: This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.

Adult↗
PubMed2005

A new alloantigen-independent control for chronic allograft nephropathy rat models.

BACKGROUND: Isografts are used as controls in many transplant experiments. Our laboratory and others have noticed histological changes in control isograft groups of rats similar to allograft groups, suggesting alloantigen-independent factors contributing to chronic allograft nephropathy. However, the isograft model as a nonalloantigen control is flawed because of the potential of unrecognized minor antigen differences between rats. We designed a study using autografts to isolate alloantigen-independent factors in the rat renal transplant allograft model. MATERIALS AND METHODS: Male Lewis rats weighing 150-250 g underwent a procedure designed to mimic the injury of renal transplant, in which the left kidney was perfused with cold University of Wisconsin solution and subjected to similar cold and warm ischemic times as Lewis isograft rats undergoing renal transplanation. RESULTS: Six autograft rats were compared to five isograft and three single nephrectomy rats. Autograft rats showed normal kidney function according to serum BUN, Cr, and urinary protein. At 360 days, four of six autografts displayed normal renal parenchymal histology, whereas the remaining two autografts displayed histological changes scored as Banff acute rejection 1a and 1b. At sacrifice time, four of five isografts showed histological changes scored as Banff chronic rejection 1 and the single nephrectomy group showed normal histology in the remaining native kidney. CONCLUSIONS: Our data demonstrate that the chronic nephropathy observed in the isograft cannot be completely freed from suspicion of immunological origin. We propose that the autograft model for rat renal transplant research is a better nonimmunologic control than the isograft model for chronic allograft nephropathy.

Animals↗
PubMed2005

Outcomes of 385 adult-to-adult living donor liver transplant recipients: a report from the A2ALL Consortium.

OBJECTIVE: The objective of this study was to characterize the patient population with respect to patient selection, assess surgical morbidity and graft failures, and analyze the contribution of perioperative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT). SUMMARY BACKGROUND DATA: Previous reports have been center-specific or from large databases lacking detailed variables. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) represents the first detailed North American multicenter report of recipient risk and outcome aiming to characterize variables predictive of graft failure. METHODS: Three hundred eighty-five ALDLT recipients transplanted at 9 centers were studied with analysis of over 35 donor, recipient, intraoperative, and postoperative variables. Cox regression models were used to examine the relationship of variables to the risk of graft failure. RESULTS: Ninety-day and 1-year graft survival were 87% and 81%, respectively. Fifty-one (13.2%) grafts failed in the first 90 days. The most common causes of graft failure were vascular thrombosis, primary nonfunction, and sepsis. Biliary complications were common (30% early, 11% late). Older recipient age and length of cold ischemia were significant predictors of graft failure. Center experience greater than 20 ALDLT was associated with a significantly lower risk of graft failure. Recipient Model for End-stage Liver Disease score and graft size were not significant predictors. CONCLUSIONS: This multicenter A2ALL experience provides evidence that ALDLT is a viable option for liver replacement. Older recipient age and prolonged cold ischemia time increase the risk of graft failure. Outcomes improve with increasing center experience.

Adult↗
PubMed2005

Adult living donor versus deceased donor liver transplantation: a 6-year single center experience.

No long-term (>3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported. This is a prospective, IRB approved, 6-year comparison of A2ALLTx to ADDLTx. Data include: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 6 years, 202 ADDLTx (74.5%) and 69 A2ALLTx (25.5%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (48.1% vs. 42%). Data regarding overall patient and graft survival, monetary charges and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (11.5% vs. 23.9%) and more biliary complications (26.1% vs. 11.4%). Overall, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.

Adult↗
PubMed2004

Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death.

Despite the adoption of "sickest first" liver transplantation, pretransplant death remains common, and many early deaths occur despite initially low Model for End-stage Liver Disease (MELD) scores. From 1997-2003, we studied 507 cirrhotic United States veterans referred for consideration of liver transplantation to identify additional predictors of early mortality. Most of the patients were male (98%) with cirrhosis caused by hepatitis C and/or alcohol (88%). Data for 296 patients referred prior to February 27, 2002 (training group), were analyzed; findings were validated in 211 patients referred subsequently (validation group). In the training group, 61 patients (21%) died within 180 days without transplantation; their median initial MELD score was 21. MELD score, persistent ascites, and low serum sodium (<135 meq/L) were independent predictors of early mortality. In patients with a MELD score of less than 21, only low serum sodium and persistent ascites were independent predictors of mortality; for MELD scores above 21, only MELD was independently predictive. Prognostic significance of persistent ascites and low serum sodium for low MELD score patients was confirmed in the validation group. Risk varied continuously with worsening hyponatremia. Modifying MELD, by including points for persistent ascites and low serum sodium, improved prediction of early pretransplant mortality in low MELD score patients. In conclusion, persistent ascites and low serum sodium identify patients with cirrhosis with high mortality risk despite low MELD scores. Ascites, hyponatremia, and other findings indicative of hemodynamic decompensation merit further prospective study as prognostic indicators in patients awaiting liver transplantation, and should be considered in setting minimal listing criteria.

Adult↗
PubMed2004

Hepatocellular carcinoma in HCV-infected patients awaiting liver transplantation: genes involved in tumor progression.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death in the world. The present study aimed to investigate the genes involved in viral carcinogenesis and tumor progression in liver transplant recipients with hepatitis C virus (HCV) and HCC. To accomplish this, we performed the analysis of hepatic gene expression in HCV-infected liver recipient patients with stages of disease ranging from early cirrhosis with preserved volume and function to late cirrhosis with diminished volume and function with and without HCC. We found consistent differences between the gene expression patterns in HCV-HCC and those of early HCV-cirrhosis, late HCV cirrhosis, and normal control livers. The expression patterns in HCC were also readily distinguished between early and advanced HCC tumor stages. Moreover, we found different gene expression patterns between early cirrhosis and late cirrhosis. In conclusion, these findings confirm the presence of multiple molecular alterations during HCV-HCC hepatocarcinogenesis and, clinically, indicate the possibility for identifying prognostic factors associated with HCC progression in liver transplant patients waiting for a donor and/or posttransplantation recurrence.

Adult↗
PubMed2004

Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation.

Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon-based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon-based therapy in a selected group of liver transplant recipients. Twenty-three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated-interferon alpha-2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA-undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 +/- 2.37 vs. 5.64 +/- 2.94 units before and after treatment, respectively; P =.016). However, 5 of these 11 patients had no histologic improvement in follow-up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P <.01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection.

Adult↗