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D Mutimer

Publications and source records attributed to D Mutimer.

At least 19 recordsLinked to original sources
PubMed2006

Review article: hepatitis B and liver transplantation.

Liver transplantation is an excellent treatment for hepatitis B virus infected patients who have acute or chronic liver failure and/or primary liver cancer. Advances in antiviral prophylaxis prevent clinically significant graft re-infection for the majority of patients. Graft and patient survival has improved significantly during the past decade, and results of transplantation for hepatitis B virus are now superior to those achieved for most other indications. In particular, the availability of lamivudine and adefovir have transformed outcome. The addition of lamivudine to passive immunoprophylaxis with hepatitis B virus immunoglobulin prevents re-infection in most cases. Adefovir should be added to this combination when the patient develops lamivudine resistance before transplantation. The significance of serum hepatitis B virus DNA positivity in the absence of circulating hepatitis B surface antigen is uncertain. Hepatitis B virus infection of the graft can be observed when prophylaxis is inadequate, when the donor liver contains latent hepatitis B virus infection (so-called de novo infection from the hepatitis B virus core antibody positive donor), and when the donor is exposed to third party infection (sexual or nosocomial transmission). Established hepatitis B virus graft infection is a good indication for combination nucleoside analogue therapy. Combination therapy can achieve sustained suppression of viral replication, and hepatitis B e antigen and hepatitis B surface antigen clearance can also be observed.

Antiviral Agents↗
PubMed2006

Pegylated interferon alpha-2b for patients with HCV recurrence and graft fibrosis following liver transplantation.

Chronic hepatitis C is a principal indication for liver transplantation. Recurrent viral infection is inevitable and graft disease is common. We report tolerability, safety and efficacy of pegylated interferon alpha 2b (PEG-IFN) monotherapy for patients with hepatitis C virus (HCV) recurrence and fibrosis after liver transplantation. Repeated measurements of serum HCV titer permitted assessment of the kinetics of the antiviral response for all patients. We screened 63 patients transplanted for HCV at our center for antiviral treatment, 14 were eligible and treated, but only 6 completed the proposed 52 weeks of therapy. Eight were withdrawn because of severe/life-threatening side effects/events, including liver dysfunction (4 patients). None of those 8 achieved a sustained virological response (SVR). Five of 6 who completed treatment were HCV RNA negative at the end of treatment, and 2 achieved an SVR. Viral kinetics were similar to published observations for treatment of non-transplanted HCV patients. Patients with genotype non-1 infection displayed a more rapid decline of viral titer than was observed for genotype 1 infection. Post-transplant HCV patients are frequently unsuitable for, or intolerant of PEG-IFN. Liver dysfunction was a major concern.

Adult↗
PubMed2005

Impact of targeted oral ganciclovir prophylaxis for transplant recipients of livers from cytomegalovirus-seropositive donors.

OBJECTIVES: Symptomatic cytomegalovirus (CMV) infection can cause significant morbidity and occasional mortality after liver transplantation. In a previous audit, we showed that donor CMV seropositivity (D+) was a risk factor for symptomatic infection, and we estimated the likely clinical and financial impact of 14 weeks of oral ganciclovir prophylaxis given to recipients of CMV-seropositive organs. In August 2001, we adopted this policy of targeted oral ganciclovir prophylaxis for recipients of CMV-seropositive livers. METHOD: The additional costs of adopting targeted prophylaxis policy for 1 year, patient and doctor compliance with the new strategy, and its clinical impact were analysed. RESULTS: Targeted prophylaxis reduced the incidence of symptomatic CMV infection from 9.5% (in the earlier cohort that did not receive prophylaxis) to 5.8% (P = NS). Symptomatic infection was not observed in CMV-seropositive recipients of CMV-seropositive donor livers (P = 0.06 for comparison of the 2 cohorts), but the incidence of symptomatic infection in the CMV-seronegative recipients of CMV-seropositive organs did not change. However, symptomatic infection appeared to be less severe and was delayed by ganciclovir prophylaxis (median time from transplantation to symptom onset 96 vs. 39 days without prophylaxis). Death attributable to CMV infection was not observed in the cohort that received prophylaxis. The additional cost associated with implementation of the prophylaxis strategy was 108,068 pounds sterlings. CONCLUSION: Targeted CMV prophylaxis with oral ganciclovir reduces the incidence and severity of symptomatic infection and appears to be a cost-effective means of improving outcome following liver transplantation.

Adult↗
PubMed2004

Fulminant liver failure due to severe veno-occlusive disease after haematopoietic cell transplantation: a depressing experience.

BACKGROUND: Between 1988 and 2002, eight patients were referred to our unit from other institutions, for management of fulminant hepatic failure (FHF) complicating severe veno-occlusive disease (VOD). AIM: To review our experience with these patients. METHODS: Retrospective analysis of medical case notes. RESULTS: In 7/8 cases, a histological diagnosis of VOD was confirmed by transjugular liver biopsy or post-mortem examination. All had undergone high-dose chemotherapy. Cyclophosphamide was included in the conditioning regimen of six patients. All developed encephalopathy and four progressed to grade 3 or 4 encephalopathy. All patients died, none surviving >75 days after haematopoietic cell transplantation. Three were listed for liver transplantation: one underwent transplantation, and two died before transplantation could be performed. Two suffered significant complications of transjugular liver biopsy. One underwent transjugular intrahepatic porto-systemic venous stent (TIPS) insertion. DISCUSSION: FHF complicating severe VOD is associated with multi-organ failure, and has a very poor prognosis. Our experience and that described in published literature, questions the benefits of measures such as liver transplantation or prolonged intensive care.

Adult↗
PubMed2004

The use of lamivudine for patients with acute hepatitis B (a series of cases).

There are limited data on the use of lamivudine for patients with severe forms of acute hepatitis B. We report our experience with the use of lamivudine in six patients with acute HBV infection. Lamivudine was justified by disease severity for four patients and by concerns about risk of chronicity for two patients. The diagnoses of the treated patients were: fulminant liver failure (two patients), severe acute hepatitis B, protracted acute hepatitis B, and new HBV infection in the renal dialysis setting (two patients, one with severe liver injury). Serum HBV DNA titres ranged from 10(5) to 10(7) copies/mL prior to commencement of lamivudine. Lamivudine treatment was associated with a decline in serum HBV DNA and serum transaminases in all patients. All but one patient survived. A 58-year-old man with fulminant hepatitis and multiple organ failure died despite antiviral treatment. When possible, HBeAg and HBsAg seroconversion was documented during follow-up. In the absence of a randomized, prospective study of lamivudine in patients with severe acute hepatitis B, our data encourage the use of this safe and well tolerated drug.

Acute Disease↗
PubMed2004

Acute myeloid leukaemia presenting as cholestatic hepatitis.

A 40 year old man presented with abdominal pain, jaundice, weight loss, and hepatosplenomegaly. Liver function tests revealed cholestatic jaundice and a computed tomography scan showed an enlarged liver, with a normal biliary tree. Liver biopsy showed diffuse infiltration by neutrophils, monocytoid cells, and blasts. Peripheral blood film and bone marrow were consistent with acute myeloid leukaemia. After treatment with chemotherapy using an acute myeloid leukaemia protocol (UK Medical Research Council AML-12), there was complete resolution of jaundice and the patient went into complete molecular remission.

Acute Disease↗
PubMed2003

Paracetamol poisoning--impact of pack size restrictions.

BACKGROUND: Pack sizes of paracetamol available to the public were reduced by legislation in 1998. OBJECTIVE: To study the effect of the legislation on paracetamol poisoning related admissions to an accident and emergency department and to a tertiary referral liver unit. METHOD: Data were obtained from the University Hospitals, Birmingham, UK (UHB) Trust Information Service and the Queen Elizabeth Hospital liver unit records on (a) the number of patients admitted to hospital because of paracetamol overdose and (b) the number of patients admitted to the liver unit with parcetamol-induced hepatotoxicity. RESULTS: Prior to legislation, an average of 360 people a year were admitted to UHB. However, following the change in legislation the number of admissions has fallen to an average of 250 people per year. This represents a reduction of 31%. Prior to legislation, an average of 76 people per year were admitted to the liver unit. Post-legislation this number has dropped to an average of 38 per year representing a reduction of 50%. CONCLUSION: Legislation restricting paracetamol pack-size reduced the incidence and severity of poisoning.

Acetaminophen↗
PubMed2002

Guidelines for laboratory monitoring of treatment of persistent virus infections.

A growing number of antiviral agents are available for treatment of persistent viral infections. This has increased the requirement for virology laboratories to undertake sophisticated assays for monitoring the efficacy of treatment and identifying drug failure at an early stage. The consensus guidelines within this article address the laboratory requirements for monitoring treatment of the herpes viruses, HIV-1, Hepatitis B and Hepatitis C.

Chickenpox↗
PubMed2002

Liver transplantation in haemophilia.

We report our UK single-centre experience of liver transplantation in haemophilia patients with chronic hepatitis C (HCV) infection. Between March 1990 and March 2001, 16 patients were referred for transplant assessment and 11 (mean age 46 years: nine haemophilia A, two haemophilia B) have been transplanted. Factor concentrate replacement was administered using a continuous infusion regimen following initial bolus dosing. Concentrate infusion was discontinued at a median of 36 h (range 24-72 h) post transplant. Nine patients remain alive at a median of 5 years post transplant (6 months to 11 years). One patient died 6 years post transplant from myocardial infarction. The other patient died of liver failure as a consequence of HCV infection 3 months following a second transplant, having developed HCV cirrhosis within 1 year of receiving his initial graft. Five of the seven patients who have had annual liver biopsy surveillance have developed histological changes of HCV hepatitis at a median of 3 years post transplant (1 year to 9 years). One of these patients progressed to cirrhosis at 3 years 5 months post transplant. Two patients have shown no evidence of HCV hepatitis at 2 years 8 months and 9 years post transplant respectively. The outcome of liver transplantation in haemophilic patients is good and is associated with relatively little morbidity.

Adult↗
PubMed2002

Hepatitis associated with Chinese herbs.

Traditional Chinese herbal medicines are widely available in Western society and are popular as a form of 'natural' alternative medicine. Their use is increasing, as they are perceived to be free of side effects, but they remain largely unregulated. We describe two patients who suffered severe hepatitis, one of whom died, after taking Chinese herbal remedies for minor complaints. We also review the English-language literature on hepatitis associated with Chinese herbs. Two products appear to be implicated frequently: Jin bu huan was taken by 11 patients, and Dictamnus dasycarpus was taken by six patients, including both fatal cases. It is difficult to provide conclusive evidence of what caused hepatitis, as these products are mixtures that may contain adulterants. These cases highlight not only the potential dangers of these products to consumers but also the need for greater control of their manufacture and use.

Adult↗
PubMed2002

Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C.

BACKGROUND AND AIM: Cirrhosis with liver failure due to hepatitis C virus (HCV) infection is the most common indication for liver transplantation (LT). Reinfection of the transplanted liver by HCV is inevitable, and aggressive hepatitis with accelerated progression to graft cirrhosis may be observed. Of concern, recent reports suggest that the outcome of LT for HCV may have deteriorated in recent years. Determinants of rate of progression to cirrhosis in the immunocompetent non-transplant patient are well defined, and the most powerful determinant is patient age at the time of infection. Following LT for HCV, recipient age does not affect outcome of HCV reinfection. However, the impact of donor age on graft fibrosis progression rate following LT has not been examined. METHODS: We have examined post-transplant biopsies to assess histological activity, including fibrosis stage (scored 0-6 units, 6 representing established cirrhosis), and to calculate fibrosis progression rates in 101 post-transplant specimens from 56 HCV infected LT patients. Univariate and multivariate analyses examined the impact of parameters including recipient and donor age and sex on fibrosis progression rate, and on predicted time to cirrhosis. RESULTS: For the cohort, median fibrosis progression rate was 0.78 units/year, and median interval from transplantation to development of cirrhosis was 7.7 years. In multivariate analysis, donor age (not recipient age) was a powerful determinant (p=0.02) of fibrosis progression rate. When the liver donor was younger than 40 years, median progression rate was 0.6 units/year and interval to cirrhosis was 10 years. When the donor was aged 50 years or more, median progression rate was 2.7 units/year and interval to cirrhosis only 2.2 years. During the observation period there has been a significant increase in donor age (p=0.01) but date of transplantation per se is not a determinant of progression rate when included in multivariate analyses. CONCLUSIONS: Donor age has a major influence on graft outcome following transplantation for HCV. The changing organ donor profile will affect the long term results of LT for HCV. These observations have important implications for donor liver allocation.

Adult↗
PubMed2001

Hepatitis B virus infection: resistance to antiviral agents.

Chronic hepatitis B virus (HBV) infection imposes an enormous public health burden. In patients with chronic hepatitis and high levels of viral replication, inhibitors of the virus polymerase can reduce serum titre and favourably affect the inflammatory process in the liver. Lamivudine, a reverse transcriptase inhibitor, is the first nucleoside analogue to be licensed for treatment of chronic HBV infection. Treatment effects a rapid and profound decrease of serum virus titre, with attendant clinical benefit. Unfortunately drug-resistant species may emerge after 6 months of suppressive therapy. Lamivudine-resistant species have specific amino acid substitutions in the HBV-encoded polymerase. Emergence of these species is frequently associated with loss of clinical benefit. Published data suggest that lamivudine-resistant species exhibit cross-resistance to famciclovir, thereby limiting the potential use of famciclovir with lamivudine as combination therapy. Adefovir is under clinical evaluation for treatment of wild-type and lamivudine-resistant HBV. Preliminary data suggest that adefovir achieves potent inhibition of both species. Studies of drug resistance have followed hot-on-the-heels of the development of potent antiviral therapy for chronic HBV.

Antiviral Agents↗