Biomedical subjects

Marcelo Kugelmas

Publications and source records attributed to Marcelo Kugelmas.

12 recordsLinked to original sources

PubMed2005

Using pegylated interferon and ribavirin to treat patients with chronic hepatitis C.

Hepatitis C virus is the most common chronic blood-borne infection in the United States. The advent of new treatment regimens using pegylated interferons in combination with ribavirin has led to improved sustained viral response rates for some genotypes in large multicenter trials. Advances in the management of side effects and toxicities have expanded the pool of treatable patients. A recent National Institutes of Health consensus conference recommended that all patients who have bridging hepatic fibrosis and moderate inflammation together with detectable viremia should receive treatment with pegylated interferon and ribavirin. Unfortunately, these medications are very expensive and have significant side effects. Hematologic toxicities include anemia and leukopenia. These can be managed with close monitoring, use of growth factors, or dose reductions. Depression also can be caused or exacerbated by these medicines and may require treatment with a selective serotonin reuptake inhibitor, comanagement with psychiatry, or cessation of pegylated interferon and ribavirin treatment. Contraception is imperative because ribavirin is highly teratogenic. Influenza-like symptoms of fatigue, nausea, and mild fevers can be helped by quality patient education and support including frequent office visits. Data from randomized controlled trials demonstrating improvements in long-term survival as a result of treatment are not yet available, but it appears that patients who have no detectable virus six months after treatment have a good chance of remaining virus free for at least five years.

Antiviral Agents↗

PubMed2005

Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy.

Patients with advanced hepatitis C virus (HCV) are at risk of death and are candidates for liver transplantation. After transplantation, HCV recurs and may rapidly progress to cirrhosis and graft loss. Treatment is needed to prevent progression of disease and minimize recurrence after liver transplantation. We evaluated the effectiveness, tolerability, and outcome of a low accelerating dose regimen (LADR) of antiviral therapy in the treatment of patients with advanced HCV. One hundred twenty-four patients (male/female ratio 81:43; age range 37-71 years; 70% genotype 1) were treated with LADR. Sixty-three percent had clinical complications of cirrhosis (ascites, spontaneous bacterial peritonitis, varices, variceal hemorrhage, encephalopathy). The mean Child-Turcotte-Pugh (CTP) score was 7.4 +/- 2.3, and the mean MELD score was 11.0 +/- 3.7. Fifty-six patients were CTP class A, 45 were class B, and 23 were class C. Forty-six percent were HCV RNA-negative at end of treatment, and 24% were HCV RNA-negative at last follow-up. Sustained virological response (SVR) was 13% in patients infected with genotype 1 HCV and 50% in patients infected with non-1 genotypes (P < .0001). Non-1 genotype, CTP class A (genotype 1 only), and ability to tolerate full dose and duration of treatment (P < .0001) were predictors of SVR. Twelve of 15 patients who were HCV RNA-negative before transplantation remained HCV RNA-negative 6 months or more after transplantation. In conclusion, in a sizeable proportion of patients with advanced HCV, LADR may render blood free of HCV RNA, stabilize clinical course, and prevent posttransplantation recurrence.

Adult↗

PubMed2004

Management of hepatitis C: evaluating suitability for drug therapy.

Chronic hepatitis C virus infection is a common and serious disease. Although an estimated 2.7 million persons in the United States have this disease, most have not yet been diagnosed. Recent advances in treatment provide successful cure in 50 to 80 percent of cases. Current drug therapy consists of a combination of pegylated interferon and ribavirin. Although all patients with chronic hepatitis C virus infection are potential candidates for treatment, pharmacologic therapy has a number of contraindications. Evaluation of suitability for treatment includes a thorough search for comorbid medical and psychiatric conditions that can be contraindications. Initial testing involves anti-hepatitis C virus antibodies, but definitive diagnosis of active disease requires detection of viral RNA. Most patients require a liver biopsy to determine the amount of hepatic fibrosis and ongoing hepatocellular inflammation. Viral genotype also should be determined: type 1 requires 12 months of treatment and does not respond as well as types 2 and 3, which require only six months of treatment. Common side effects of drug therapy include anemia, anorexia, depression, fatigue, fever, headache, myalgia, nausea, and erythema at the injection site.

Algorithms↗

PubMed2004

Impact of pretransplant diagnosis of hepatocellular carcinoma on cadveric liver allocation in the era of MELD.

The allocation system based on the Model for End-stage Liver Disease (MELD) has led to more patients diagnosed with hepatocellular carcinoma (HCC) being transplanted. We hypothesized that more patients misdiagnosed with HCC are also being transplanted, leading to inappropriate organ allocation. Therefore, we retrospectively analyzed all liver transplants at our center from July 14, 2000, to October 22, 2002 (N = 172; 129 pre-MELD, 43 post-MELD), comparing pretransplant HCC diagnosis to explant histology. Thirty patients met the United Network for Organ Sharing (UNOS) diagnostic criteria for pretransplant HCC diagnosis. There were 25 men (median age, 52.5 yr), and 80% had hepatitis C. The proportion of patients transplanted who had an HCC diagnosis increased from 12% (15/129) pre-MELD to 35% (15/43) post-MELD implementation (P < 0.01). Three of 15 (20%) transplanted pre-MELD and 5 of 15 (33%) transplanted post-MELD lacked HCC in the explant (P = 0.10). Of the three false-positives pre-MELD, one was Status 2B already, and two received living-donor livers. Of the 5 false-positives post-MELD, three had score upgrades that led to early transplantation (13 to 29, 20 to 29, and 9 to 24) while two had MELD scores of 35 and 36 already. The percentage of organs that could have gone to patients with more advanced liver disease without HCC increased from 0% (0/129) pre-MELD to 7% (3/43) post-MELD (P < 0.01). Since the implementation of MELD, the proportion of patients transplanted who had an HCC diagnosis nearly tripled, and a small but significant proportion of organs are now going to patients misdiagnosed with HCC. More stringent HCC diagnostic criteria will be required to decrease the effect that misdiagnosis has on organ allocation.

Carcinoma, Hepatocellular↗

PubMed2004

Liver biopsy.

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Biopsy, Needle↗

PubMed2004

Hepatic artery chemoembolization for hepatocellular carcinoma in patients listed for liver transplantation.

We retrospectively analyzed all listed patients having hepatic artery chemoembolization (HACE) for hepatocellular carcinoma (HCC) stage T2 or less. Outcomes were transplantation, waiting list removal, death, and HCC recurrence. Twenty patients (mean age 55.7 years; 15 males) were identified. Twelve (60%) were transplanted, seven (35%) were removed from the list and one (5%) remains listed. Fourteen (70%) are alive. All 12 transplanted patients are alive (mean 2.94 years); one of seven removed from the list is alive (mean 1.45 years). Survival was significantly higher for those transplanted or listed vs. removed from the list (100% vs. 14.3%, p = 0.0002). No HCC's recurred. Three patients (15%) were removed from the list after prolonged waiting times before MELD. Hepatic artery chemoembolization induced deterioration and removal from the list of one (5%) patient. Survival for those transplanted was excellent(100%), but overall survival was significantly lower (61.3%) at a mean 5.48 years. Hepatic artery chemoembolization for listed patients with <or=euro T2 stage HCC is beneficial, but must be weighed against decreased waiting times and risk of HACE-induced deterioration. This balance is influenced greatly by the MELD system's determination of waiting times for HCC patients.

Carcinoma, Hepatocellular↗

PubMed2003

Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E.

There are few data evaluating plasma and/or peripheral blood monocyte cytokine concentrations/production or attempts to manipulate proinflammatory cytokines in nonalcoholic steatohepatitis (NASH). A pilot project in a general clinical research center evaluated the effects of a step 1 American Heart Association diet plus aerobic exercise with or without 800 IU of vitamin E daily on cytokine profiles and liver enzyme levels in 16 patients with biopsy-proven NASH. Biochemical assessment of liver function, lipid profiles, and body mass index significantly improved during the first 6 weeks of therapy and remained stable during the following 6 weeks. Plasma hyaluronic acid (HA) concentrations decreased in parallel with weight loss. Plasma tumor necrosis factor (TNF) concentrations were significantly elevated in patients with NASH and similar to patients with stable alcoholic cirrhosis but not as elevated as in patients with acute alcoholic steatohepatitis (AH). Although plasma TNF, interleukin 8 (IL-8), and IL-6 concentrations were all significantly elevated compared with control values, only plasma IL-6 levels significantly decreased with therapy. Peripheral blood monocyte TNF, IL-8, and IL-6 production was significantly elevated in patients with NASH but did not significantly decrease. Independent effects of vitamin E were not observed in this small sample. In conclusion, patients with NASH have dysregulated cytokine metabolism similar to, but less pronounced than abnormalities documented in AH. Cytokine values generally did not decrease significantly with weight loss with or without vitamin E over the duration of the study. Lifestyle modifications (low-fat diet and exercise) were associated with improvement in liver enzymes, cholesterol, and plasma HA levels in patients with NASH, whereas the level of vitamin E supplementation used in this short-term pilot study provided no apparent added benefit.

Adult↗

PubMed2003

Model for End-Stage Liver Disease score does not predict patient or graft survival in living donor liver transplant recipients.

Although living donor liver transplantation (LDLT) is a successful procedure for most recipients, outcomes in patients who undergo transplantation as United Network for Organ Sharing status 2A are marginal. There are no published data on living donor liver transplant recipient outcomes relative to Model for End-Stage Liver Disease (MELD) scores. Such information could be useful in living donor liver transplant recipient selection. We retrospectively analyzed all non-fulminant hepatic failure, right hepatic lobe, adult-to-adult living donor liver transplant recipients at our center between August 1997 and March 2002. We calculated MELD scores at the time of LDLT and correlated scores with 1-year patient and graft survival and hospital days during the 90-day post-LDLT period. There were 62 recipients with greater than 6 months of follow-up: 38 men, 24 women; mean age, 47.9 years; 42 white, 1 black, 17 Hispanic, and 2 Asian patients. Twenty-nine patients had hepatitis C virus infection; 4 patients, hepatitis C virus infection and alcoholic liver disease; 4 patients, alcoholic liver disease; 4 patients, cryptogenic cirrhosis; 13 patients, primary sclerosing cholangitis; 5 patients, autoimmune hepatitis; and 3 patients, primary biliary cirrhosis. Mean and median MELD scores were 15.2 and 13, respectively (range, 6 to 40). One-year patient and graft survival were 59 of 62 patients (95%) and 52 of 62 patients (84%), respectively. There was no statistically significant difference between median MELD scores of dead versus living patients (15 v 13; P =.15) or patients who underwent retransplantation versus those who did not (16.5 v 13; P =.30). Mean and median hospital days in the 90-day post-LDLT period were 23.7 and 16.0 days, respectively. Living donor liver transplant recipients with a MELD score of 18 or greater had significantly more hospital days compared with recipients with a MELD score less than 18 (35.2 v 19.8 days; P =.01). In conclusion, MELD scores did not predict post-LDLT patient or graft survival at 1 year. However, higher MELD scores (> or =18) were associated with more hospital days during the 3-month post-LDLT period.

Female↗

PubMed2003

Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation.

Primary sclerosing cholangitis (PSC) is the fourth leading diagnosis in liver transplant recipients in the United States. The disease is known to recur in 15% to 30% of liver transplant recipients. We set out to investigate how different immunosuppression regimens affected natural history of PSC after liver transplantation at our center. We reviewed records of all patients who underwent a liver transplantation at our institution in between 1988 and 2000 and had a diagnosis of PSC at the time of liver transplantation. Primary sclerosing cholangitis recurred in 15 of 71 patients (21.1%) who had complete records and survived more than 30 days after liver transplantation. Although recurrence of primary sclerosing cholangitis was most often seen (but not statistically significantly so) in patients who received maintenance corticosteroids, the time to recurrence was not significantly different between those who were treated with maintenance, those who were not successfully weaned, and those who successfully weaned off corticosteroids within 3 months after liver transplantation. Orthoclone (OKT3) therapy (Ortho-Biotech, Inc., Raritan, NJ) was associated with a higher risk of primary sclerosing cholangitis recurrence (29% versus 10%, P <.05). Recurrence was not influenced by immunosuppression with either cyclosporine or tacrolimus. Coexistent inflammatory bowel disease was a cause of failure to wean off corticosteroids, was associated with a shorter time to recurrence of sclerosing cholangitis, and was responsible for significant comorbidity (colon cancer in 7.3%). Primary sclerosing cholangitis recurrence is commonly seen after liver transplantation. More immunosuppression seems to be detrimental to the outcome of our patients with sclerosing cholangitis: use of OKT3 was associated with a greater incidence of recurrence. Length of corticosteroid use did not affect timing or risk of recurrence, and because it has been proven that early corticosteroid withdrawal after liver transplantation is beneficial, we continue to recommend this practice.

Adult↗

PubMed2003

Hepatitis C virus therapy, hepatocyte drug metabolism, and risk for acute cellular rejection.

We recently reported on a series of patients who experienced acute cellular rejection (ACR) during the treatment of hepatitis C virus (HCV) infection in our posttransplantation cohort. Our hypothesis is that HCV clearance improves hepatic microsomal function, which in turn results in lower trough cyclosporine (CyA) and tacrolimus (TAC) levels, predisposing the patient to ACR. Records of all patients receiving transplants for HCV infection at our center from 1993 to June 2002 were reviewed. Two hundred three patients were identified. Thirty-seven patients (18%) were treated with interferon-based therapies in combination with ribavirin. Twelve patients were selected for analysis because they became HCV RNA negative during therapy, and 18 patients with no antiviral response were selected as controls (7 other patients had incomplete data or had switched from one immunosuppression [IS] therapy to the other). Baseline IS levels were compared with the first available level after documented negative HCV RNA results in the study group and the last on-treatment IS level in the control group. We also compared frequency and percentage of change in IS levels during therapy. Mean decline in CyA trough levels in the study group was from 187.28 ng/mL at baseline to 118.14 ng/mL immediately after becoming HCV RNA negative (-36.92%; P =.018). Mean decline in TAC levels was from 7.34 ng/mL at baseline to 5.02 ng/mL immediately after becoming HCV RNA negative (-29.17%; P =.044). Overall, 6 of 12 patients who cleared HCV RNA during therapy experienced ACR; 1 patient died as a result of ACR. Using percentage of decrease from baseline IS level, we combined results for patients administered CyA and TAC and found a significant decrease from baseline IS levels in responders (-31.8% after HCV RNA clearance on treatment; P =.0001). Nonresponders experienced a 0.98% decline in IS levels while on treatment, and the difference was significant compared with the change in the responder group (P =.006). A greater proportion of antiviral therapy responders also experienced trough IS levels 20% less than baseline than nonresponder controls during therapy (P =.0006). In conclusion, IS levels decreased significantly in patients responding favorably to anti-HCV therapy. This decrease in IS levels may have a key role in predisposing these patients to ACR.

Alkaline Phosphatase↗

PubMed2002

Chronic mucoid Pseudomonas aeruginosa cholangitis complicating ERCP in a CF patient.

We report a case of P. aeruginosa cholangitis in an adult with cystic fibrosis (CF). The patient had a past history of cholecystectomy and a new finding of intrahepatic biliary duct stricture. Evaluation and treatment with endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous biliary tract drainage was complicated by post-procedure pain and fever. The only organism recovered from biliary drainage was P. aeruginosa. Southern blot analysis of respiratory and biliary cultures confirmed that the isolates were identical. Despite aggressive antibiotic therapy and drainage, persistent cholangitis and infection have not been eradicated after 6 months. The most likely mechanism of infection of the biliary tract was direct introduction of the upper respiratory tract pathogen during the diagnostic procedure.

Adult↗

PubMed2002

Living donor liver transplant recipients achieve relatively higher immunosuppressant blood levels than cadaveric recipients.

Two recent brief reports suggest that recipients of living donor liver transplants achieve higher levels of immunosuppressive agents than cadaveric (CAD) liver transplant recipients administered the same dose. These results could have important implications regarding the dosing of immunosuppressives in living donor liver transplant recipients. We report our findings relative to immunosuppressive doses and levels in a cohort of 46 living donor liver transplant recipients. Immunosuppressive blood levels and doses were recorded weeks 1, 2, 3, and 4 and months 2, 3, 4, 5, and 6 for 46 living donor liver transplant recipients and 66 matched CAD liver transplant recipients who underwent transplantation between August 1997 and May 2001. The ratio of level to dose also was recorded at each interval. The mean overall cyclosporine A dose was similar in living donor liver transplant recipients (323 mg/d) compared with CAD recipients (344 mg/d; P = not significant [NS]). The mean overall tacrolimus dose was 15% lower in patients who underwent living donor liver transplantation (LDLT; 5.7 mg/d) than CAD transplantation (6.7 mg/d), although statistical significance was not achieved (P =.08). The mean overall cyclosporine A level was 18% higher in those undergoing LDLT (275 ng/mL) than CAD transplantation (234 ng/mL; P =.015). The mean overall tacrolimus level was the same in living donor liver transplant recipients (10.8 ng/mL) and CAD recipients (10.2 ng/mL; P = NS). The overall cyclosporine A level-dose ratio was 26% higher for those undergoing LDLT (0.83) than CAD transplantation (0.66; P =.01). The overall tacrolimus level-dose ratio was 26% higher for those undergoing LDLT (1.82) than CAD transplantation (1.44; P =.01). In conclusion, (1) living donor liver transplant recipients achieve higher blood levels of tacrolimus and cyclosporine A for a given dose compared with CAD recipients, and (2) this difference is observed up to 6 months after transplantation, when hepatic regeneration is completed.

Adult↗