Biomedical subjects

David J Mutimer

Publications and source records attributed to David J Mutimer.

5 recordsLinked to original sources

PubMed2006

Impact of donor age and year of transplantation on graft and patient survival following liver transplantation for hepatitis C virus.

BACKGROUND: Hepatitis C virus (HCV) infection has become the most common indication for liver transplantation (LT). Graft and patient survival are adversely affected by recurrent infection of the graft. Recent publications have described an inferior outcome for recently transplanted HCV patients and have highlighted the impact of advancing donor age on severity of recurrent HCV. The donor age at which a measurable impact on graft and patient outcome can be observed has not clearly been defined. In addition, the impact of donor age on graft and patient survival for non-HCV patients needs to be examined. METHODS: We have examined a large European liver transplant database to define the impact of transplantation date and donor age on graft and patient survival for HCV patients (n = 4,736) and the impact for a comparison group of transplanted alcoholic liver disease patients (ALD, n = 5,406). RESULTS: For the entire cohorts, graft and patient survival of HCV patients was inferior to ALD patients. Since 1987, there has been a steady and ongoing improvement in the outcome of transplanted ALD patients, an improvement not observed for HCV patients. Every year since 1989, there has been an increase in liver donor age. Graft and patient survival for both ALD and HCV cohorts was adversely affected by advancing donor age. Comparison of graft and patient survival for HCV and ALD cohorts was made according to donor age (donor age subgrouped <20, 20-30, 30-40, 40-50, 50-60 and >60 years of age). For donors younger than 40 years of age, HCV and ALD recipient graft and patient survival are not significantly different. For donors older than 40, HCV recipient graft survival is inferior to ALD graft survival, an inferiority that increases for each advancing decade of donor age. For donors older than 50 years, HCV recipient patient survival is inferior to ALD patient survival, an inferiority that increases when the donor age is greater than 60 years. CONCLUSION: The results of liver transplantation for European HCV patients is inferior to a comparison group of ALD patients, and have not improved during the past 15 years. Liver donor age has increased significantly during that period. Advancing donor age has an adverse influence on graft and patient survival for ALD and HCV patients, but a significantly greater impact is observed for HCV patients when the donor is older than 40 years.

Adolescent↗

PubMed2005

Outcomes following liver transplantation for seronegative acute liver failure: experience during a 12-year period with more than 100 patients.

Seronegative hepatitis is a common cause of acute liver failure (ALF) requiring liver transplantation. The primary aim of this study was to examine outcomes following transplantation in this group and to identify factors associated with early (<2 months) mortality. Patients studied were 110 consecutive cases of seronegative ALF transplanted at the Queen Elizabeth Hospital, Birmingham, between January 1992 and January 2004. Univariate analysis of 44 pretransplantation recipient, donor, and operative variables was performed initially to identify factors associated with early posttransplantation mortality. Variables identified as significant or approaching significance were analyzed using stepwise multiple logistic regression analysis. Survival following transplantation for seronegative hepatitis was 83%, 81%, and 73% at 2, 12, and 60 months, respectively. The majority (71%) of deaths occurred within the 1st 2 months and sepsis / multiorgan dysfunction was the most common cause of early death. Univariate analysis revealed 9 variables predicting early death. Subsequent multivariate analysis identified high donor body mass index (BMI; a possible surrogate marker for hepatic steatosis) as the most important predictor of early death (P = .009; odds ratio, 1.2; 95% confidence interval, 1.0-1.3). Recipient age >50 (P = .015; odds ratio, 4.2; 95% confidence interval, 1.3-14.1) and non-Caucasian recipient ethnicity (P = .015; odds ratio, 4.9; 95% confidence interval, 1.2-19.2) were other variables associated with early death on multivariate analysis. This study specifically examined factors that determine the early outcome of transplanted seronegative ALF patients. In conclusion, we found that donor and recipient factors identify patients who have a high chance of early death after transplantation.

Adolescent↗

PubMed2003

Outcome of liver transplantation for patients infected by hepatitis C, including those infected by genotype 4.

Predictors of hepatitis C virus (HCV)-related liver disease posttransplantation are still unclear. The impact of HCV genotype on outcome of transplantation has been studied, but conclusions are not in agreement. The role of HCV genotype 4 on the result of liver transplantation requires further study. The aim of this study is to examine the outcome of liver transplantation for patients with HCV genotype-4 infection. The study group included 128 patients who underwent transplantation for HCV infection: 28 patients, genotype 1; 11 patients, genotype 2; 19 patients, genotype 3; and 32 patients, genotype 4. For 64 of 128 patients, genotype was known and an assessable histological specimen was available. Median interval from transplantation to biopsy was 1.92 years (range, 0.24 to 11.48 years). Twenty-six percent of HCV genotype-4 patients developed either severe fibrosis or cirrhosis versus 6.7% in the genotype non-4 group (P =.04). A statistically significant greater fibrosis progression rate was observed in genotype-4 than genotype non-4 patients. In univariate and multivariate analysis, rapid liver fibrosis was associated with the presence of HCV genotype-4 infection. In addition, donor and recipient age and graft warm ischemic time also were associated with rate of fibrosis progression. Five-year cumulative rates for the development of cirrhosis or severe liver fibrosis were 84% in genotype-4 and 24% in genotype non-4 patients (P =.02). Five-year survival rates for patients with genotypes 1, 2/3, and 4 were 72%, 80%, and 79%, respectively (P =.8). In conclusion, 5-year survival for patients who underwent transplantation for HCV genotype-4 infection was similar to that of genotype non-4 patients; however, more severe fibrosis and rapid fibrosis progression was observed after transplantation in patients with genotype-4 infection.

Adult↗

PubMed2003

Hepatitis B and C virus infections in the immune compromised.

PURPOSE OF REVIEW: This review compares and contrasts the natural history and treatment of hepatitis B and C virus infections in three principal populations of immune compromised individuals: (1) patients co-infected with HIV; (2) patients with liver failure secondary to hepatitis B or C virus infection who undergo liver transplantation, and (3) patients with hepatitis B or C virus infection who undergo anticancer chemotherapy. RECENT FINDINGS: Chronic liver disease resulting from hepatitis B or C virus infection progresses more rapidly in patients co-infected with HIV than in HIV negative patients. Treatment protocols for antiviral therapy are, however, similar to those used in immunocompetent individuals and although few long-term results are available, the efficacy of interferon and ribavirin therapy in hepatitis C virus/HIV infection and lamivudine in HIV/hepatitis B virus infection has been proven in the short-term. Perhaps the most important consideration is the timing of administering treatments to co-infected patients. For patients with well preserved CD4 counts and hepatitis C virus/HIV co-infection, the hepatitis infection should be treated as early as possible to avoid drug interactions of hepatitis C virus antivirals with antiretroviral therapy. Also, response to hepatitis C virus treatment appears better when treatment is administered in the context of preserved immune function. Conversely, in hepatitis B virus/HIV co-infection, hepatitis B virus antivirals are best administered with anti-retroviral therapy, thus preventing the selection of HIV viral species which may be resistant to the drugs used for hepatitis B virus. Improved graft and patient survival after liver transplant and with anticancer chemotherapy in hepatitis B virus infected patients has been proven using lamivudine prophylaxis. However, although therapy for hepatitis C virus recurrence after liver transplantation would seem rational, limited success with current treatment protocols has been achieved. SUMMARY: Although the prognosis of hepatitis B and C virus infections in the immune compromised may be inferior to that of immunocompetent individuals, such patients should have full evaluation of their viral hepatitis, and antiviral therapy should be considered.

Antineoplastic Agents↗

PubMed2002

Genetically modified interferon: is there a consensus yet?

The treatment of patients with chronic hepatitis C virus infection has evolved during the last decade from interferon monotherapy to combination therapy with interferon and ribavirin. National and international guidelines recommend either 6 or 12 months of interferon/ribavirin combination therapy depending on the pre-treatment virological status of the patient. However, the choice for second-line treatment of patients who do not achieve sustained viral clearance with combination therapy has yet to be defined. This commentary examines previously published studies of the use of consensus interferon for hepatitis C virus infected patients. The characteristics of the treated populations and response to treatment are examined. The current and potential roles for this type of interferon in the treatment of hepatitis C virus infection are considered.

Antiviral Agents↗