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Russell H Wiesner

Publications and source records attributed to Russell H Wiesner.

At least 37 records · Page 2Linked to original sources
PubMed2004

MELD and other factors associated with survival after liver transplantation.

Allocation of cadaveric livers for transplantation in the United States is now based on the severity of illness as determined by the model for end-stage liver disease (MELD) score, a function of bilirubin, creatinine and international normalized ratio (INR). The aim of our study was to determine the association of various pre-transplant risk factors, including the MELD score, on patient survival after orthotopic liver transplantation (OLT). The medical records of 499 consecutive patients (233 female, 266 males, mean age 50.9 +/- 10.6 years) undergoing cadaveric OLT at our institution between June 1990 and February 1998 were reviewed. In the 407 patients alive at the latest contact, follow-up was 4.7 years, with a minimum of 20 months (maximum of 9.4 years). Variables considered for analysis included MELD score, age, pre-transplant renal dysfunction requiring dialysis, Child-Pugh classification, underlying liver disease, diabetes mellitus, and heart disease (ischemic/valvular/other). There were 92 deaths during follow-up. In univariate analysis, the MELD score, renal failure requiring hemodialysis pre-OLT, age > 42 years, and underlying etiology of liver disease were significantly associated with death during long-term follow-up. In multivariate models, age, underlying etiology of liver disease and renal failure requiring hemodialysis were independent predictors of death after OLT.

Female↗
PubMed2003

Dynamics of cytomegalovirus replication during preemptive therapy with oral ganciclovir.

The degree and dynamics of cytomegalovirus (CMV) replication were investigated in blood samples that were prospectively collected in the context of a placebo-controlled study evaluating the efficacy of preemptive oral ganciclovir for the prevention of CMV disease after liver transplantation. The degree of viral replication was strongly associated with progression to CMV disease or viremia (risk ratio, 8.8 and 51.5 among patients with virus loads < or =2860 and >2860 copies/10(6) peripheral blood leukocytes, respectively). Preemptive oral ganciclovir therapy diminished the incidence of CMV disease or viremia but did not completely suppress higher levels of CMV replication. Six (21%) of 29 patients had persistent CMV replication during preemptive oral ganciclovir therapy; 2 patients subsequently developed "breakthrough" CMV syndrome. This study identifies a relative cutoff virus load that predicts subsequent development of CMV disease and highlights the inability of oral ganciclovir to suppress CMV replication in a subset of patients.

Administration, Oral↗
PubMed2003

Subclinical reactivation of hepatitis B virus in liver transplant recipients with past exposure.

Transmission of hepatitis B infection has been reported in liver transplant recipients whose donor livers were negative for hepatitis B surface antigen (HBsAg) and positive for antibody to hepatitis B core antigen (anti-HBc). These infections usually have a mild clinical course and no adverse effects on survival. However, the outcome of liver transplant recipients with serologic evidence of past infection to hepatitis B virus (HBV) is unknown. The prevalence of HBV DNA positivity by polymerase chain reaction (PCR) pretransplantation in HBsAg-negative, anti-HBc-positive people is reported to be 0% to 32%. To assess the prevalence of HBV DNA in pretransplantation serum and liver tissue and to determine the clinical outcome of HBsAg-negative, anti-HBc-positive recipients, we retrospectively reviewed the first 693 orthotopic liver transplantations performed at Mayo Clinic between March 19, 1985, and May 25, 1996. Pretransplantation specimens of frozen serum and liver tissue were available for HBV DNA by PCR for 35 of 56 HBsAg-negative, anti-HBc-positive recipients. Twenty-two recipients had positive serologic findings for anti-HBc alone, and 13 were positive for anti-HBc and antibody to HBsAg (anti-HBs). Pretransplantation prevalence of HBV DNA in HBsAg-negative, anti-HBc-positive recipients was 6% (serum) to 29% (liver). Of those recipients whose liver was HBV DNA-positive pretransplantation, 40% also had evidence of HBV DNA in posttransplantation liver biopsy specimens, and this finding was more common in patients co-infected with hepatitis C. None of the recipients became antigenemic (HBsAg-positive) or developed clinical hepatitis B posttransplantation. Thus, prophylactic intervention (eg, antiviral or antinucleoside analog therapy) is not warranted after liver transplantation in HBsAg-negative, anti-HBc-positive recipients. In our experience, infected donor livers are the most common source of de novo posttransplantation hepatitis B infection in transplant recipients.

DNA, Viral↗
PubMed2003

Outcome of liver transplantation for familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant disorder caused by mutation in the transthyretin gene. The most common mutation is substitution of valine for methionine at position 30 (MET30). Liver transplantation (LT) is the preferred treatment. After LT, although many patients show stabilization or improvement in the disease, adverse outcomes have been reported in those who have malnutrition, long-standing disease, and non-MET (NMET) mutations at position 30. Our aim is to compare survival and outcome of symptoms associated with FAP after LT in patients with MET30 and NMET30 mutations. Medical records of all patients who underwent LT for amyloidosis at our institution were reviewed to obtain demographic information and clinical features, such as severity of neuropathy, diarrhea, orthostatic hypotension, and posterior wall or ventricle septal thickness before and after LT. Fifteen patients underwent LT for amyloidosis at our institution between 1990 and 2000 (MET30, n = 5; NMET30, n = 7; hereditary amyloidosis, n = 2; primary amyloidosis, AL type, n = 1). Patients with hereditary and primary amyloidosis were excluded from analysis. One- and 3-year survival rates after LT in MET30 patients were 100%. Before LT, five of five patients had sensorimotor neuropathy; five of five patients had diarrhea, and four of five patients had orthostatic hypotension. After LT, improvement or stabilization of neuropathy was seen in two of five patients; of diarrheal symptoms, in three of five patients; and of orthostatic hypotension, in three of four patients. One- and 3-year survival rates after LT in NMET30 patients were 100% and 85.7%, respectively. Before LT, six of seven patients had sensorimotor neuropathy, six of seven patients had diarrhea, and five of seven patients had orthostatic hypotension. After LT in this group, improvement or stabilization of neuropathy was seen in two of six patients; of diarrhea, in six of six patients; and of orthostatic hypotension, in five of five patients. Before LT, posterior wall and/or ventricle septal thickness was increased in two of five MET patients and seven of seven NMET patients. Five of seven NMET30 patients (71.4%) who received a combined liver and heart transplant had stabilization, and two patients in the NMET group and one patient in the MET group had progression of heart disease. Outcomes for LT for patients with FAP with MET or NMET mutations were similar. Earlier LT for patients with FAP with MET30 or NMET30 mutation would improve outcomes after LT.

Adult↗
PubMed2003

Risk factors for and clinical course of non-anastomotic biliary strictures after liver transplantation.

Non-anastomotic biliary stricture (NAS) formation is a major complication of liver transplantation. We prospectively determined the time to development of responsiveness to treatment, and clinical outcomes following NAS formation. In addition, an extensive analysis of the association of recipient, donor, and clinical variables with NAS formation was performed. A total of 749 consecutive patients was studied in a prospective, protocol-based fashion. Seventy-two patients (9.6%) developed NAS at a mean of 23.6 +/- 34.2 weeks post-transplantation. Non-anastomotic biliary stricture formation resolved in only 6% of affected patients. Although patient survival was not affected, retransplantation and graft loss rates were significantly greater in recipients who developed NAS. In contrast to previous reports, a pretransplant diagnosis of HCV was associated with a low frequency of NAS formation. The incidence of NAS was independently associated with pretransplant diagnoses of PSC and autoimmune hepatitis. Hepatic artery thrombosis, and prolonged warm and cold ischemia times were also independent risk factors for NAS formation. We conclude that NAS developed in approximately 10% of primary liver transplant recipients. A pretransplant diagnosis of autoimmune hepatitis has been identified as a novel independent risk factor for NAS formation. Development of NAS significantly attenuates graft but not patient survival.

Adult↗
PubMed2003

Acquired (non-Wilsonian) hepatocerebral degeneration: complex management decisions.

Portal systemic encephalopathy, in its many guises, can be reversible after medical management or liver transplantation. It is much less certain whether patients with a longstanding neurodegenerative syndrome (known in the medical vernacular as acquired hepatocerebral degeneration) can improve. Impressive neuroimaging abnormalities have been reported in this entity.(1) However, the combination of a severe disabling neurologic deficit and widespread magnetic resonance abnormalities tempers the enthusiasm of transplant surgeons to proceed with liver transplantation. In our liver transplantation program, we were recently confronted with such a case, and present herein not only the characteristic magnetic resonance imaging findings but also some of the dilemmas of management.

Brain↗
PubMed2003

Recurrence of primary biliary cirrhosis after liver transplantation: Histologic estimate of incidence and natural history.

The goals of this study were to determine the rate of recurrent primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT) based on strict morphologic criteria and to evaluate histologic progression of recurrent PBC over time. Strict criteria for PBC recurrence were established as the presence of a florid duct lesion or destructive lymphocytic cholangitis within a dense portal infiltrate. Of the 784 OLTs performed at the Mayo Clinic during the first 12 years of the program, 100 met criteria for the PBC study group, and 35 met criteria for the control group. Strict histologic criteria for recurrent PBC were observed in 17 of 100 (17%) study patients (14 with florid duct lesion, 3 with destructive lymphocytic cholangitis within dense portal infiltrate). Mean follow-up for the PBC group was 4.7 years (range, 1.0 to 13.8). Mean time to recurrence was 3.7 years (median, 3.1; range, 0.3 to 7.9). In those who met strict criteria for recurrent PBC, 2 of 17 progressed to septal fibrosis (stage 3). No florid duct lesions, destructive lymphocytic cholangitis, or septal fibrosis were observed in the control group. Other less specific morphologic features of PBC (portal infiltrates, plasma cells, dense lymphoplasmacytic infiltrates, and lymphocytic cholangitis) were also evaluated in the course of this study. Based on strict criteria, a conservative histologic estimate of the rate of recurrent PBC is 17% with a mean of 4.7 years of follow-up. When criteria for histologic recurrence are expanded to include moderate lymphocytic cholangitis with lymphoplasmacytic portal infiltrate, the recurrence rate of PBC is estimated as 26%.

Bile Ducts↗
PubMed2003

Recent advances in liver transplantation.

Advances in liver transplantation continue to evolve but are hampered by continued increasing shortages in donor organs. This has resulted in a high incidence of patients dying while on the United Network for Organ Sharing waiting list. Indeed, we continue to assess ways of expanding the donor pool by using marginal donors, living donor liver transplantation, split liver transplantation, domino transplantation, and hepatic support systems to prolong survival long enough for the patient to undergo liver transplantation. Changes in the liver allocation policy to reduce the number of people dying while waiting for an organ are discussed. Implementation of the model for end-stage liver disease allocation system should help alleviate the problem of increasing deaths of patients while on the waiting list. Recurrent disease, particularly recurrent hepatitis C, continues to be a major problem, and effective therapy is needed to prevent both progression of hepatitis C and recurrence in the graft and avoid retransplantation. The use of pegylated interferon in combination with ribavirin holds promise for improving the success in overcoming recurrent hepatitis C. Finally, advances in immunosuppression have reduced the incidence of acute cellular rejection and chronic rejection. However, these therapies have been fraught with metabolic complications that are now affecting quality of life and long-term survival. Tailoring immunosuppressive regimens to the individual patient is discussed.

Hepatitis, Viral, Human↗
PubMed2003

Effect of minimal listing criteria on waiting list registration for liver transplantation: a process-outcome analysis.

OBJECTIVE: To determine the level of association between minimal listing criteria (MLC) recognition and outcomes associated with waiting list registration for liver transplantation (LT). PATIENTS AND METHODS: A total of 147 patients and 201 patients were identified as first-time referrals for LT evaluation between January 1, 1997, and November 30, 1997 (cohort A), and December 1,1997, and December 31, 1998 (cohort B), respectively. Relevant demographic and clinical information was abstracted from medical records. Minimal listing criteria were defined as a Child-Turcotte-Pugh (CTP) score of 7 or higher. RESULTS: Patient age, sex, hepatic disease etiology, and mean CTP scores were similar between cohorts A and B. However, the proportion of registered patients in cohort B with CTP scores of 7 or higher increased significantly after formal MLC recognition (96% vs 82% for cohort A; P=.001). In cohort A, waiting list registration was based on patient age, male sex, nonalcohol-related hepatic disease, and a CTP score of 7 or higher in the absence of formal MLC. The rate of first-time patient referral was also increased in cohort B vs cohort A after formal MLC recognition (80% vs 69%, respectively; P=.002) despite similar clinical characteristics. Although the number of patients with a CTP score of 10 or higher was greater in cohort B vs cohort A, the proportion of patients with advanced end-stage liver disease was similar (29% vs 26%, respectively; P=.72). CONCLUSION: The explicit recognition of MLC was strongly associated with improvements in appropriate waiting list registration for LT.

Cohort Studies↗
PubMed2002

Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial.

The use of postdetection antiviral treatment of cytomegalovirus (CMV) as a strategy to prevent infection and disease in solid-organ transplant patients has not been evaluated by placebo-controlled trials. We carried out such a study in 69 patients who had received liver transplants and had positive results of CMV polymerase chain reaction within 8 weeks after transplantation but did not have concomitant CMV infection or disease. These patients were randomly assigned to receive placebo or oral ganciclovir for 8 weeks. CMV infection developed in 21% and disease developed in 12% of placebo recipients (P =.022), compared with 3% and 0%, respectively, among ganciclovir recipients (P =.003). Similarly, in the placebo arm, 55% and 36% of CMV-negative patients who received organs from CMV-positive donors developed CMV infection or disease, respectively (P =.02), compared with 11% and 0% of such patients in the ganciclovir arm (P <.01). Oral ganciclovir administered on CMV detection by PCR prevents CMV infection or disease after liver transplantation.

Administration, Oral↗
PubMed2002

Pirfenidone in the treatment of primary sclerosing cholangitis.

Our aim was to evaluate the safety and assess the efficacy of pirfenidone, an antifibrotic drug, in patients with primary sclerosing cholangitis (PSC). Twenty-four patients with PSC were enrolled in this pilot study. Oral pirfenidone, 2400 mg daily, was given for one year. Liver biochemistries were determined at three-month intervals. The Mayo risk score was calculated, and liver biopsy and endoscopic cholangiography were performed at entry and at one year of treatment. No significant changes in liver biochemistries were noted at the end of the treatment period or at any of the three-month intervals. The Mayo risk score did not change significantly, and no significant changes were noted in the degree of inflammation, fibrosis, histologic stage of disease, or cholangiographic findings at the end of the treatment period. Adverse events occurred in 20/24 (83%) patients, but disappeared shortly after pirfenidone was discontinued. Pirfenidone did not benefit patients with PSC, and it was frequently associated with adverse events. The results of this pilot study discourage further trials of pirfenidone in patients with PSC.

Administration, Oral↗
PubMed2002

Liver allograft iron accumulation in patients with and without pretransplantation hepatic hemosiderosis.

There is a paucity of data regarding hepatic allograft iron accumulation in patients undergoing orthotopic liver transplantation (OLT) in whom severe iron overload was present in the native explanted liver. Our aim is to evaluate the frequency and cellular distribution of stainable iron in early and late post-OLT hepatic allograft biopsy specimens from patients undergoing their first OLT who had excess iron in their native explanted liver. We compared iron-staining patterns in hepatic allograft biopsy specimens at approximately 1 month (early) and 1 to 2 years (late) post OLT in 41 patients with hepatic iron indices greater than 1.9 in the explanted liver (cases) with a selected group of matched controls without explant hemosiderosis. Our cases included 6 patients with a pre-OLT diagnosis of hereditary hemochromatosis and 35 patients with cirrhosis and secondary iron overload. Early iron deposition was mild in most cases, commonly affected Kupffer's cells, and was seen with similar frequency in cases and controls (41% v 27%; P =.29). Stainable iron was observed in 20 donor livers (12 cases, 8 controls), and all 20 subjects showed stainable iron in 1-month hepatic allograft biopsy specimens. Liver samples from 35 matched pairs were studied for late iron deposition. Iron deposition was observed in 43% of cases versus 17% of controls (P =.06). In conclusion, the frequency of stainable iron in early hepatic allograft biopsy specimens was not different between patients with versus without pre-OLT hepatic hemosiderosis. There was a suggestion that patients with severe pre-OLT hemosiderosis had a greater frequency of iron accumulation in late hepatic biopsy specimens.

Adult↗
PubMed2002

Impact of cytomegalovirus infection, year of transplantation, and donor age on outcomes after liver transplantation for hepatitis C.

Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is almost universal. However, variables that hasten the progression of allograft injury have not been fully defined. Cytomegalovirus (CMV) is a common infection post-LT, and its impact on the course of post-LT HCV infection remains unclear. We investigated the impact of CMV infection on patient and graft outcomes in 93 consecutive HCV-infected liver transplant recipients. Data were collected prospectively, with surveillance cultures for CMV and protocol liver biopsies. CMV infection (defined as isolation of CMV from blood and treatment with ganciclovir) occurred in 25 patients (26.9%). Graft failure (defined as cirrhosis, relisting for LT, re-LT, or death) was significantly more common in CMV-positive compared with CMV-negative patients (52% v 19.1%; P =.002). Fibrosis stage 2 or greater on the 4-month liver biopsy specimen was more common in CMV-infected patients (45% v 16.4%; P =.01). Patients who underwent LT in more recent years had an increased risk for graft failure. Donor and recipient age, CMV infection, and mycophenolate mofetil use were significantly associated with graft failure in a stepwise multivariate analysis. CMV infection occurs in approximately one quarter of HCV-infected liver transplant recipients and is an independent risk factor for graft failure in these patients. Whether CMV mediates this by inducing increased immunosuppression or directly enhancing HCV replication requires further study.

Age Factors↗
PubMed2002

Preliminary results: outcome of liver transplantation for hepatitis B virus varies by hepatitis B virus genotype.

Hepatitis B virus (HBV) is a leading cause of liver failure throughout the world. HBV has seven different genotypes based on variations within the viral nucleotide sequence. Initially, patients who underwent liver transplantation for HBV had high recurrence rates and poor survival. Recently, improved outcomes have been reported when patients are administered hepatitis B immunoglobulin (HBIg) infusions to maintain high serum hepatitis B surface antibody titers after transplantation. Unfortunately, recurrence rates are still high in patients with active pretransplant HBV replication. The aims of this study are to evaluate the impact of HBV genotype on pretransplantation HBV replication and posttransplantation HBV recurrence rate, morbidity, and mortality. Sera from 22 patients who underwent transplantation for HBV at our center were tested for HBV genotype by an enzyme-linked immunosorbent assay technique using monoclonal antibodies to the pre-S2 region. All patients were administered HBIg after transplantation; 5 patients were administered both lamivudine and HBIg. HBV genotypes were distributed as follows: genotype A (10 patients), genotype C (6 patients), genotype D (5 patients), and genotype E (1 patient). Pretransplantation HBV replication was most common with genotype A (80%), whereas less so with genotypes C (33%) and D (40%). Nine patients (41%) developed recurrent HBV infection: genotype A (2 patients; 20%), genotype C (3 patients; 50%), and genotype D (4 patients; 80%). Mortality was greatest with genotype D (40%). Our data suggest that patients with genotype A have the lowest risk for HBV recurrence despite having the highest rate of pretransplantation HBV viral replication. Patients with genotype D appear to have the highest risk for HBV recurrence and mortality. Additional larger multicenter studies are needed to confirm these findings.

Adult↗