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Biomedical subjects

Eric M Yoshida

Publications and source records attributed to Eric M Yoshida.

At least 19 recordsLinked to original sources
PubMed2006

Poor prediction of the glomerular filtration rate using current formulas in de novo liver transplant patients.

The utility of formulas estimating glomerular filtration rate (GFR) in liver transplant patients has not been well described. The purpose is to determine the correlation between the radionuclide GFR (rGFR) with formulas commonly used to estimate GFR. This study represented a secondary outcome measure of a multicenter randomized trial comparing the effectiveness of two immunosuppressive regimens in adult liver transplant patients (n=148). A total of 68 rGFR were measured, 33 at baseline and at 35 at three months after transplantation. GFR was estimated using 1/Scr and Cockcroft-Gault, MDRD, and Nankivell equations. At both time points assessed, all correlations with rGFR were poor: 1/Scr (r: 0.17 and 0.25), Cockcroft-Gault (r: 0.31 and 0.35), MDRD (r: 0.27 and 0.35), and Nankivell (r: 0.11 and 0.20). Accepted formulas to estimate GFR correlate poorly with rGFR during the first three months after liver transplantation. Recalibration of these formulas is required to improve the estimation of GFR in liver transplant patients.

Canada↗
PubMed2006

Retinal vein thrombosis associated with pegylated-interferon and ribavirin combination therapy for chronic hepatitis C.

An estimated 300 million people worldwide suffer from chronic hepatitis C with a prevalence of 0.8%-1.0% of the general population in Canada. An increasing pool of evidence exists supporting the use of pegylated- interferon (pegIFN) and ribavirin combination therapy for hepatitis C. We report a 49-year old male of North American aboriginal descent with chronic hepatitis C (genotype 2b). Biopsy confirmed that he had cirrhosis with a 2-wk history of left eye pain and decreased visual acuity. He developed retinal vein thrombosis after 16 of 24 wk of pegIFN-alpha 2a and ribavirin combination therapy. He was urgently referred to a retinal specialist and diagnosed with non-ischemic central retinal vein occlusion of the left eye. PegIFN and ribavirin combination therapy was discontinued and HCV RNA was undetectable after 16 wk of treatment. Hematologic investigations revealed that the patient was a factor V Leiden heterozygote with mildly decreased protein C activity. Our patient had a number of hypercoagulable risk factors, including factor V Leiden heterozygosity, cirrhosis, and hepatitis C that alone would have most likely remained clinically silent. We speculate that in the setting of pegIFN treatment, these risk factors may coalesce and cause the retinal vein thrombosis.

Antiviral Agents↗
PubMed2006

Dynamics of interferon-specific gene expression in peripheral blood of interferon alfa-naïve patients with genotype 1 chronic hepatitis C infection treated with albumin-interferon alfa.

Albumin-interferon alfa (alb-IFN) is a novel recombinant protein derived from IFNalpha-2b genetically fused to human albumin, which combines in a single polypeptide the antiviral properties of IFNalpha with the long serum half-life of albumin. Interferon alfa (IFNalpha) mediated biological responses stem from the engagement of IFNalpha with its target receptor and subsequent modulation of interferon-specific gene (ISG) expression. The dynamics of ISG expression were evaluated in a Phase 2a study conducted in IFNalpha naïve patients with genotype 1 chronic hepatitis C (CHC) treated with alb-IFN. Whole blood was obtained pre-dose and on days 7 and 28 from 47 patients enrolled to receive two subcutaneous injections of alb-IFN 14 days apart in five dose cohorts ranging from 200 to1200mug. Gene expression of nine candidate genes including four ISGs was determined by a TaqMan Real-time PCR assay. There was sustained >5-fold median induction on days 7 and 28 of the ISG's- OAS1, IRF7, IFI44 and IFI27. While all subjects showed a molecular response to alb-IFN, individual variability in pre-treatment gene expression levels and fold of modulation during treatment was observed. At days 7 and 28, induction of OAS1, IFI44 and IRF7 showed significant pair-wise correlation in individual patients (r>0.7 and P<0.001). There was no correlation of baseline expression or induction of gene expression with antiviral response. In conclusion, alb-IFN demonstrated robust induction of ISG that was consistent with the molecular response associated with an IFNalpha.

Journal Article↗
PubMed2006

A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients.

BACKGROUND/AIMS: Recombinant human albumin-interferon alfa (alb-IFN) is a novel 85.7-kD recombinant protein consisting of interferon alfa-2b genetically fused to human serum albumin. METHODS: A phase 2, open-label, dose-ranging study was conducted in IFN-alfa-naïve patients with genotype 1 chronic hepatitis C to evaluate the antiviral activity, safety, and pharmacokinetics of alb-IFN. Fifty-six patients were enrolled to receive two subcutaneous injections of alb-IFN 14 days apart in five dose cohorts of 200, 450, 670, 900, and 1,200 microg. RESULTS: A 2 log(10) IU/mL or greater reduction in hepatitis C virus (HCV) RNA at Week 4 was observed in 69% (18/26) of patients who received the higher alb-IFN doses of 900 and 1,200 microg. The mean HCV RNA reduction at Week 4 in these two higher-dose cohorts was 3.2 log(10) IU/mL. Modeling of viral kinetics demonstrated a biphasic response that was dose dependent. Adverse events were mostly mild to moderate in severity. The most common adverse events were headache (73%), chills (63%), fatigue (61%), and arthralgia (55%). The median terminal half-life was 141 h consistent with previous alb-IFN data from IFN-alfa-experienced patients. CONCLUSIONS: Alb-IFN demonstrated significant antiviral activity and was well tolerated in patients with HCV genotype 1 infection.

Adult↗
PubMed2006

Utilization of a liver allograft from a hepatitis B surface antigen positive donor.

With today's donor organ shortage, enhanced efforts must be made to utilize organs that previously would have been declined. We report a 26-year-old man with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection who received a liver transplant from an HBsAg-positive donor. HBV viremia (6,281,185 copies/ml) was seen early posttransplant despite lamivudine prophylaxis, but became negative with addition of adefovir. Virologic analysis revealed predominantly donor HBV strain immediately posttransplant. At 5 months there was an elevation of liver enzymes accompanied by histologic evidence of hepatitis. At this time, HCV-RNA was positive but HBV DNA was undetectable. Treatment with pegylated interferon and ribavirin resulted in sustained clearance of HCV RNA. Two years posttransplant, the patient has normal liver biochemistry and HCV and HBV viral load are undetectable with persistence of HBsAg. Our experience suggests that with effective antiviral therapy, the use of HBsAg seropositive donors is feasible in selected circumstances.

Adult↗
PubMed2006

Fatal postlymphoma chemotherapy hepatitis B reactivation secondary to the emergence of a YMDD mutant strain with lamivudine resistance in a noncirrhotic patient.

Hepatitis B reactivation is a well-known complication during or after chemotherapy in chronic hepatitis B (HBV) carriers. The current practice guidelines in Canada and the United States recommends patients receive antiviral prophylaxis prior to the onset of chemotherapy in chronic HBV carriers with lamivudine. We report a case of a 57-year-old man with follicular lymphoma on lamivudine prophylaxis and no clinical evidence of cirrhosis, and developed fatal HBV reactivation after the emergence of a YMDD mutant strain of HBV that confers lamivudine resistance. Fatal reactivation secondary to the development of lamivudine resistance has not, to date, been well- reported. Our experience indicates the need to carefully monitor patients for suspected drug- resistant HBV mutants with the addition of anti-viral agents effective against the YMDD mutational strain, when lamivudine resistance emerges.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Sexual health after orthotopic liver transplantation.

Many studies have reported improved health-related quality of life outcomes after orthotopic liver transplantation; however, specific research regarding sexual health in liver transplant recipients is limited. We surveyed liver transplant recipients to determine the prevalence of sexual dysfunction. Of the 320 adult liver transplant recipients surveyed by mailed questionnaire, 150 responded (42%). The median age was 54 years. A total of 62% of respondents were male, and 93% were at least 1 year after transplantation. Thirty-six respondents (24%) reported sexual dysfunction before transplantation; this persisted in 22 patients (15%) after transplantation. A total of 48 respondents (32%) reported de novo sexual dysfunction after transplantation. After transplantation, 23% of male and 26% of female respondents reported decreased libido, and 33% of men and 26% of women reported having difficulty reaching orgasm with intercourse. A total of 42% of respondents felt that immunosuppressive medication was the main contributing factor to their sexual problems: 33% and 35% of respondents receiving tacrolimus or cyclosporine monotherapy, respectively, experienced some degree of sexual problems after transplantation. Despite the reported sexual problems, 59% of respondents were "moderately" to "very satisfied" with their sexual relationships after transplantation. Nineteen percent of the respondents used sildenafil to improve their sexual function, and 65% of these reported benefit. In conclusion, sexual problem after orthotopic liver transplantation is a common but poorly studied problem. Although this single-center study has shed some light on the relationship between liver transplantation and sexual health, further prospective studies, involving larger study population and validated instruments, will be needed to better evaluate the influence of liver transplantation on recipients' sexual health.

Adult↗
PubMed2006

Hepatic dysfunction during and after lymphoma chemotherapy in patients with hepatitis C.

BACKGROUND: Hepatitis C is one of the most common causes of chronic liver disease. The literature regarding hepatic dysfunction in Hepatitis C patients during and after chemotherapy is limited. PURPOSE: The goal of this study was to determine the incidence of hepatic dysfunction in Hepatitis C positive patients during and/or after chemotherapy for lymphoma. METHODS: A retrospective chart review was performed. Patients included in the study were anti-hepatitis C virus positive patients treated with chemotherapy for lymphoma at the BC Cancer Agency since 1999. Serum transaminases and bilirubin were the primary criteria used to define and evaluate severity of hepatic dysfunction. Information regarding clinical outcomes was also collected. RESULTS: Forty-one eligible patients were identified. Twenty-four patient charts had sufficient information for review. Four patients met criteria for acute chemotherapy-associated hepatic dysfunction. No deaths secondary to acute hepatic dysfunction were identified. CONCLUSIONS: Hepatic dysfunction in patients with Hepatitis C being treated for lymphoma with chemotherapy occurs but is uncommon.

Comorbidity↗
PubMed2006

Acute management and secondary prophylaxis of esophageal variceal bleeding: a western Canadian survey.

BACKGROUND: Acute esophageal variceal bleeding (EVB) is a major cause of morbidity and mortality in patients with liver cirrhosis. Guidelines have been published in 1997; however, variability in the acute management and prevention of EVB rebleeding may occur. METHODS: Gastroenterologists in the provinces of British Columbia, Alberta, Manitoba and Saskatchewan were sent a self-reporting questionnaire. RESULTS: The response rate was 70.4% (86 of 122). Intravenous octreotide was recommended by 93% for EVB patients but the duration was variable. The preferred timing for endoscopy in suspected acute EVB was within 12 h in 75.6% of respondents and within 24 h in 24.6% of respondents. Most (52.3%) gastroenterologists do not routinely use antibiotic prophylaxis in acute EVB patients. The preferred duration of antibiotic therapy was less than three days (35.7%), three to seven days (44.6%), seven to 10 days (10.7%) and throughout hospitalization (8.9%). Methods of secondary prophylaxis included repeat endoscopic therapy (93%) and beta-blocker therapy (84.9%). Most gastroenterologists (80.2%) routinely attempted to titrate beta-blockers to a heart rate of 55 beats/min or a 25% reduction from baseline. The most common form of secondary prophylaxis was a combination of endoscopic and pharmacological therapy (70.9%). CONCLUSIONS: Variability exists in some areas of EVB treatment, especially in areas for which evidence was lacking at the time of the last guideline publication. Gastroenterologists varied in the use of prophylactic antibiotics for acute EVB. More gastroenterologists used combination secondary prophylaxis in the form of band ligation eradication and beta-blocker therapy rather than either treatment alone. Future guidelines may be needed to address these practice differences.

Acute Disease↗
PubMed2006

Recurrent hepatitis C post-transplantation: where are we now and where do we go from here? A report from the Canadian transplant hepatology workshop.

Approximately 400 liver transplants are performed in Canada every year and close to 6000 per year in the United States. Forty per cent to 45% of all liver transplants are performed for patients with underlying hepatitis C virus (HCV)-related liver disease. These patients have a different natural history, new complication risks and different treatment efficacy than nontransplant HCV patients. Every effort must be made to identify those patients at highest risk for progressive liver disease post-transplant. Recurrent HCV is an Achilles' heel to transplant hepatology. The true natural history of this disease is only starting to unravel and many questions remain unanswered on the optimal management of these patients after liver transplantation. The present report summarizes the literature and ongoing research needs that are specific to HCV-related liver transplantation.

Canada↗
PubMed2006

Acute fatty liver of pregnancy.

Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. Although the exact pathogenesis is unknown, this disease has been linked to an abnormality in fetal fatty acid metabolism. Early diagnosis of AFLP sometimes can be difficult because it shares features with other common conditions such as pre-eclampsia, viral hepatitis and cholestasis of pregnancy. However, a careful history and physical examination, in conjunction with compatible laboratory and imaging results, are often sufficient to make the diagnosis, and liver biopsy is rarely indicated. Supportive care and expeditious delivery are essential to optimal maternal-fetal outcomes and remain as the mainstay treatment for AFLP.

Acute Disease↗
PubMed2006

Liver transplant candidacy unsuitability: a review of the British Columbia experience.

BACKGROUND: Every centre has contraindications to liver transplantation and declares patients unsuitable for medical or nonmedical reasons. To date, there has been no published review of any centre's experience. METHODS: A retrospective chart review was completed from 1997 to 2001, inclusive of all patients referred for liver transplant to the British Columbia Transplant Society who were declared unsuitable for transplantation, as well as the reasons for unsuitability. RESULTS: One hundred fifty patients were considered to be unsuitable for transplantation. During this period, 167 transplants were performed and 737 patients were referred for candidacy. Data were missing on three patients; analysis was performed on the remaining 147. Patients' ages ranged from 15 to 72 years, and 33.3% were female. The most common primary liver disease was hepatitis C (n=53, 35%), followed by alcoholic liver disease (n=35, 24%) and autoimmune liver diseases (n=23, 16%). Medical contraindications constituted 74 patients (49.0%) and the most common reasons for unsuitability were no need of a liver transplant (29 patients [39%]), exclusion due to hepatoma or extrahepatic malignancy (20 patients [27%]) and multisystem failure (12 patients [16%]). Nonmedical contraindications constituted 73 patients. Failure to meet minimal alcohol criteria comprised the largest group (n=39, 53.4%) followed by inadequate social support (n=12, 16.4%), failure to follow up medical assessment (n=10, 13.7%) and drug abuse (n=6, 8.2%). CONCLUSIONS: Although many patients were declined for transplantation, the proportion is relatively small compared with the number of referred patients. Nonmedical reasons, including failure to meet alcohol criteria and lack of social support, remain a significant reason for unsuitability in British Columbia. Community intervention before transplant referral is recommended.

Adolescent↗
PubMed2005

Evaluation of renal function in liver transplant recipients receiving daclizumab (Zenapax), mycophenolate mofetil, and a delayed, low-dose tacrolimus regimen vs. a standard-dose tacrolimus and mycophenolate mofetil regimen: a multicenter randomized clinical trial.

Posttransplant chronic renal failure, secondary to calcineurin inhibitor agents, is emerging as a major problem in liver transplantation. We report a randomized clinical trial comparing daclizumab, delayed low-dose tacrolimus (target trough level 4-8 ng/mL, starting day 4-6), Investigational Arm (n = 72), to standard tacrolimus induction/maintenance dosing, Standard Arm (n = 76), with mycophenolate mofetil and tapering corticosteroids in both study arms. The end-points were renal function indicated by the Modification of Diet in Renal Disease (MDRD). There was no significant difference in patient survival (86.6% Investigational Arm vs. 92.9% Standard Arm; P = 0.21) or acute rejection (23.2% vs. 27.7%, respectively; P = 0.68). Statistically significant differences in median glomerular filtration rate (GFR) were found in favor of the Investigational Arm. With the CG equation, the GFR at the end of the first week was 110.7 vs. 89.6 mL/min (P = 0.019) without significant differences thereafter. With the MDRD, statistically significant differences extended to the first posttransplant month (86.8 vs. 70.1 mL/min/1.73 m(2); P < 0.001) with and was seen at month 6 (75.4 vs. 69.5 mL/min/1.73 m(2); P = 0.038). In conclusion, delayed low-dose tacrolimus, in combination with daclizumab and mycophenolate mofetil, preserves early renal function post-liver transplantation without the cost of increased acute rejection.

Antibodies, Monoclonal↗
PubMed2005

Liver transplantation for incidental cholangiocarcinoma: analysis of the Canadian experience.

Cholangiocarcinoma is a biliary tumor, which not infrequently complicates primary sclerosing cholangitis. It carries a poor prognosis and, with the exception of carefully selected individuals in research protocols, contraindicates orthotopic liver transplantation. There has been some suggestion that cholangiocarcinomas incidentally discovered at the time of transplantation carry a better prognosis. The goal of this retrospective study was to perform a national review of outcomes after liver transplantation in Canadian recipients found to have incidental cholangiocarcinoma in their explanted native liver. Six of the seven liver transplant centers in Canada provided clinical and follow-up information on all liver transplant recipients found to have incidental cholangiocarcinoma in their explants. The diagnosis or suspicion of cholangiocarcinoma prior to transplantation were exclusion criteria for this study. Ten individuals with cholangiocarcinoma were transplanted between 1996 and 2003. The median duration of follow-up was 28 months. Eight of the 10 had PSC. All of the tumors were stage I or II. The 3-year survival for these patients was 30%. The median time to recurrence was 26 months (95% confidence interval 13-37), and the median time to death was 30 months (95% confidence interval 28-53). In conclusion, although early survival of patients transplanted for incidental cholangiocarcinoma appears good, intermediate- and long-term survival rates are not better than for individuals historically transplanted with known cholangiocarcinoma. Aggressive investigation for cholangiocarcinoma is mandated. Incidentally found tumours remain a difficult treatment problem, and prospective adjuvant chemo-, radio-, and immunotherapies should be investigated.

Adult↗
PubMed2005

Severe desflurane hepatotoxicity after colon surgery in an elderly patient.

PURPOSE: To report a case of desflurane hepatotoxicity. CLINICAL FEATURES: An 81-yr-old woman with a remote history of abdominal surgery developed severe acute liver injury after general anesthesia with desflurane for resection of colonic cancer. Serum alanine aminotransferase and aspartate aminotransferase peaked at postoperative day six (2188 and 425 U*L(-1) respectively), with the development of coagulopathy with an international normalized ratio of 2.29 on postoperative day eight, progressive jaundice with a peak serum total bilirubin of 214 mumol*L(-1) on postoperative day 12 and hepatic encephalopathy on postoperative day ten. Other causes for liver disease were excluded. Treatment with corticosteroids was started. The liver biochemistry normalized completely by postoperative day 30 and the patient was discharged from hospital on postoperative day 21. CONCLUSIONS: To our knowledge, this represents only the third report of desflurane hepatotoxicity and the first with reversible fulminant liver failure. Our experience suggests that all fluorinated anesthetics may cause acute hepatic damage.

Aged↗
PubMed2005

Fatal reactivation of hepatitis B post-chemotherapy for lymphoma in a hepatitis B surface antigen-negative, hepatitis B core antibody-positive patient: potential implications for future prophylaxis recommendations.

In the absence of prophylaxis, the reactivation of hepatitis B in oncology patients who are hepatitis B carriers is a well-known and often fatal complication of chemotherapy. The current recommendations in Canada and the USA are that patients who are positive for hepatitis B surface antigen (HBsAg) receive antiviral prophylaxis prior to chemotherapy. We report a 67-year-old man with B-cell lymphoma who developed hepatitis B reactivation following chemotherapy with cyclophosphamide, adriamycin, vincristine, prednisone and rituximab. Pre-chemotherapy, the patient was negative for HBsAg, positive for hepatitis B core antibody (anti-HBc) and weakly positive for hepatitis B surface antibody. Despite treatment with lamivudine, the patient died of fulminant hepatic failure. Our experience indicates that patients who are negative for HBsAg but positive for anti-HBc are still at risk for reactivation of latent hepatitis B during and after chemotherapy and may be considered for prophylaxis.

Aged↗
PubMed2005

Transplant immunosuppressive agents in non-transplant chronic autoimmune hepatitis: the Canadian association for the study of liver (CASL) experience with mycophenolate mofetil and tacrolimus.

BACKGROUND: Conventional treatment of autoimmune hepatitis consists of either prednisone alone or in combination with azathioprine. Ten to 20% of patients do not respond to or are intolerant of this treatment. Novel drug treatments include immunosuppressive drugs such as tacrolimus (TAC), mycophenolate mofetil (MMF), methotrexate and cyclosporine. We describe a multi-centre Canadian experience with MMF and TAC. OBJECTIVE: To study a multi-centre patient population who had failed conventional therapy and were treated with non-conventional medical therapy for autoimmune hepatitis and document response. METHODS: Members of the Canadian Association for the Study of Liver (CASL) obtained MMF from Hoffmann-La Roche Ltd, as part of a compassionate release program, were contacted for standardized data on patients with AIH who received MMF or TAC. Response definitions based on aminotransferase changes were: Complete response (CR)-sustained normalization, partial response (PR)-improvement by greater than 50%, non-response (NR)-less than 50% improvement and relapse (RP)-initial CR or PR followed by an increase in aminotransferases. RESULTS: A total of 16 patients were identified: six in Ontario, one in Quebec, five in Alberta and four in British Columbia. Three were treated with TAC, eleven with MMF and two with combination MMF and TAC. CR was observed in 50%, PR in 12.5%, RP in 25% and NR occurred in 12.5%. The CR for MMF without TAC was approximately 64%. CONCLUSIONS: MMF is effective and well tolerated by patients with autoimmune hepatitis who do not respond to, or are intolerant of, conventional immunosuppressive agents.

Adult↗