Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This case-control study assessed risk factors and prognostic indicators of 350 episodes of bacterial pneumonia in 285 HIV-infected patients. On univariate analysis, intravenous drug abuse (p<0.001), regular cigarette smoking (p<0.001), cirrhosis (p=0.04), and history of a previous episode of pneumonia (p=0.04), were risk factors for community-acquired episodes of bacterial pneumonia, whereas length of hospitalization (p=0.01) was a risk factor only for nosocomial bacterial pneumonia. The small amount of circulating T CD4+ cells, (<100/mmc) was a risk factor in both groups of pneumonia (p<0.05). Stepwise logistic regression analysis revealed that IVDA in community-acquired episodes and low levels of circulating T CD4+ cells, both in community-acquired and hospital-acquired episodes, were independent risk factors for the development of bacterial pneumonia. The case-fatality rate observed in our study was 27%. On stepwise logistic regression analysis, T CD4+ cell counts >100/mmc (p<0.02), neutropenia (p=0.04), PO2 arterial level <70 mmHg (p=0.01), and Karnofsky score <50 (p=0.04) were independent indicators of mortality. According to a personally developed prognostic score, 211 episodes of pneumonia (60%) were classified as mild, 63 (18%) as moderate, and 76 (22%) as severe. Clinicians must carefully evaluate those variables that can influence the prognosis of bacterial pneumonia to make early identification of affected patients and to promptly establish the most appropriate therapeutic strategy in each case.
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PMID:[Bacterial pneumonia in HIV-infected patients] 1275 90

HIV-infected patients are living longer owing to effective treatment with highly active antiretroviral therapy (HAART). As a result, the extent and impact of hepatitis C virus (HCV) infection in this patient population are now becoming apparent. HIV infection accelerates the progression of HCV to cirrhosis, endstage liver disease, and death. The presence of each disease also influences treatment of the other, and appropriate management of side effects (e.g., anemia, neutropenia, depression) is crucial for treatment success. The HIV nurse is well positioned to treat, counsel, and support the HIV/HCV-coinfected patient by encouraging screening and providing education on the side effects of treatment, the means of managing side effects, and the resources available to assist in problems of substance abuse and depression.
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PMID:Hepatitis C virus/HIV coinfection: a new challenge for nurses in AIDS care. 1457 58

The efficacy and secondary effects of an induction dose of interferon-alpha2b (IFN-alpha2b) with ribavirin compared with standard combined treatment in naive patients with chronic hepatitis C infection were compared. A prospective study was undertaken between March 1998 and November 2001 in which 84 Spanish hospitals took part. Six hundred and fourteen naive patients (age range 18-65 years) diagnosed with chronic hepatitis C virus (HCV) infection and without cirrhosis or co-infection by other viruses, were included. Patients were divided into two groups. Group A (n = 304) received induction treatment with a daily dose of 5 MU of IFN-alpha2b for 4 weeks, followed by 5 MU three times a week with ribavirin (1000-1200 mg/day, according to weight) until completing 1 year of treatment. Group B (n = 310) received the standard dose of IFN-alpha2b of 3 MU three times per week for 48 weeks together with ribavirin (1000-1200 mg/day, according to weight). Both groups were completely comparable according to age, gender, body weight, transaminase levels, genotype, viral load and hepatic inflammatory activity (Knodell Index). No control group was included for ethical reasons. Pegylated interferon was not available at the time of the study. Serum baseline samples were collected for the determination of genotype. Samples were also collected at baseline, weeks 4, 12, 24, 48 and 72, in order to detect and quantify HCV-RNA. The efficacy of treatment was evaluated by means of sustained viral response (SVR) characterized by persistent negativity of HCV-RNA at the end of the follow-up period. At week 4, the response to treatment was greater in group A (49.6%) compared with group B (34.5%) (P = 0.0002), and was maintained until week 12 (64.1% compared with 55.8% respectively) (P = 0.03). These differences disappeared at week 24, when group A (69%) was compared with group B (65%) (NS). At week 48, the response rate for group A was 50.6% compared with group B 47.4% (NS), and at week 72, the SVR in group A was 46% compared with 40.3% for group B (NS). The global SVR was 43.1%. On analysing the response to treatment according to genotype and viral load, we found that the induction treatment was slightly superior in patients with genotype 1 and an elevated viral load (>2 x 10(6) copies/ml). They achieved a SVR in group A of 39.1% compared with 25.5% in group B (P < 0.05). However, this slight improvement obtained in group A, was achieved at the expense of a greater percentage of dropouts compared with group B (6.4% vs 2.2%, P < 0.01); a greater rate of side effects (58.5 vs 36.7%, P < 0.05) and also a greater percentage of neutropenia (3.1% vs 0.9%, P < 0.05). The induction treatment presented a better initial response, but this was not maintained at the end of treatment, and did not improve the results obtained with the standard treatment. Although the patients with genotype 1 and elevated viral load had a better response with the induction treatment, this was accompanied by a greater percentage of dropouts and secondary effects. It would be interesting to repeat this type of study in the future, using pegylated interferon.
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PMID:Comparative study of the efficacy of an induction dose of interferon-alpha2b with ribavirin compared with standard combined treatment in naive patients with chronic hepatitis C. 1463 77

Albendazole is a benzimidazole with wide spectrum coverage as an antiparasitic drug. Reported side effects have been minimal. We report the case of a patient who died with severe prolonged pancytopenia beginning during the third week of therapy for a pulmonary echinococcal cyst. This case was a 68-year-old man who presented with a large cystic lung mass. His medical history was significant for Child-Pugh class B cirrhosis. A prolonged course of albendazole was initiated. Two weeks later, the patient presented in septic shock with severe pancytopenia. The patient was initially resuscitated, but died after 10 days with no marrow recovery. Autopsy was consistent with albendazole-induced pancytopenia. This is the third human case of pancytopenia and the first death reported in relation to albendazole-induced pancytopenia. Neutropenia seems to be related more to higher dosage and longer duration of use. Albendazole sulfoxide peak dose and half life are significantly prolonged by liver disease and concomitant administration of certain drugs. The severity and duration of albendazole-induced pancytopenia in this case was likely related to the underlying liver disease. Frequent serial monitoring of blood counts and cessation of medication with any evidence of marrow toxicity in such patients is warranted.
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PMID:Death related to albendazole-induced pancytopenia: case report and review. 1577 24

On May 19, 2004, azacitidine (5-azacytidine; Vidaza(trade mark); Pharmion Corporation, Boulder, CO, http://www.pharmion.com) for injectable suspension received regular approval by the U.S. Food and Drug Administration (FDA) for the treatment of all subtypes of myelodysplastic syndrome (MDS). This report summarizes the basis for this approval. Effectiveness was demonstrated in one randomized, controlled trial comparing azacitidine administered s.c. with best supportive care (observation group) and in two single-arm studies, one in which azacitidine was administered s.c. and in the other in which it was administered i.v. The dose of azacitidine, 75 mg/m2/day for 7 days every 28 days, was the same in all three studies. In the randomized trial, study participants were well matched with respect to age, sex, race, performance status, MDS subtype, and use of transfusion during the 3 months before study entry. Patients in the observation arm were permitted by protocol to cross over to azacitidine treatment if their disease progressed according to prespecified criteria. During the course of the study, more than half of the patients in the observation arm did cross over to the azacitidine treatment arm. The primary efficacy end point was the overall response rate. Response consisted of complete or partial normalization of blood cell counts and of bone marrow morphology. The response rate in the azacitidine arm was about 16%; there were no responses in the observation arm. The response rates in the two single-arm studies were similar (13% and 19%). The responses were sustained, with median durations of 11 months and 17 months respectively. Responding patients who were transfusion dependent at study entry lost the need for transfusions. In addition, about 19% of patients had less than partial responses (termed improvement), and two-thirds of them became transfusion independent. Common adverse events associated with azacitidine treatment were gastrointestinal (nausea, vomiting, diarrhea, constipation, and anorexia), hematologic (neutropenia, thrombocytopenia), fevers, rigors, ecchymoses, petechiae, injection site events, arthralgia, headache, and dizziness. Liver function abnormalities occurred in 16% of patients with intercurrent hepatobiliary disorders and in two patients with previously diagnosed liver cirrhosis. Renal failure occurred in patients during sepsis and hypotension. There were no deaths attributed to azacitidine. Azacitidine, the first drug approved by the U.S. FDA for MDS, has a favorable safety profile and provides a clinical benefit of eliminating transfusion dependence and complete or partial normalization of blood counts and bone marrow blast percentages in responding patients.
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PMID:FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. 1579 20

Acute graft-versus-host disease is mainly a complication of allogeneic bone-marrow transplantation, and rarely seen after transplantation of solid organs. We describe a 68-year-old man who developed a maculopapular eruption and fever approximately 15 days after orthotopic liver transplantation for cryptogenic cirrhosis. At day 19, the patient developed abrupt neutropenia and diarrhea. Skin biopsy was performed and the specimen revealed basal cell layer vacuolization, necrotic keratinocytes, and satellite cell necrosis. Bone-marrow aspiration performed after the patient became pancytopenic revealed aplastic marrow with scattered lymphocytes and rare megakaryocytes. A diagnosis of acute graft-versus-host disease was made and an immunosuppressive drug regimen was initiated. Unfortunately, the patient died after support was withdrawn because of total ablation of his bone marrow and multiorgan failure. This report describes the rare presentation of acute graft-versus-host disease after solid organ transplantation, and that skin manifestations may be an early presenting sign.
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PMID:Rash and pancytopenia as initial manifestations of acute graft-versus-host disease after liver transplantation. 1585 89

The evolution of treatment of chronic hepatitis C virus infection has led to improved therapeutic efficacy. However, a major problem is the presence of side effects that require modification or withdrawal of drug therapy in 15-20% of cases. This could potentially influence the lack of sustained viral response in 50% of the cases. Side effects are common, even with pegylated interferon. This study aimed to assess the incidence and severity of infections based on the development of neutropenia associated with combined therapy with pegylated interferon-alpha2a plus ribavirin in 209 patients with chronic hepatitis C infection. All patients were administered pegylated interferon-alpha2a (180 microg/week) plus ribavirin (800 mg/day for 24 weeks in cases of nongenotype 1, or 1000-1200 mg/day for 48 weeks for genotype 1, according to whether patients weighed more or less than 75 kg). Patients with preexisting neutropenia of any cause or cirrhosis were excluded. Neutropenia was defined as a neutrophil count (NC) of <1500 cells/microl. Neutropenia was classified into three levels during treatment: 750<or=NC<1500 (level 1), 500<or=750 (level 2), and NC<500 cells/microl (level 3). Of the 209 patients, 114 did not develop neutropenia (mean 2100+/-804 cells/microl), while 95 had an NC<1500 cells/microl (mean 1100+/-250 cells/microl). It was found that patients who developed neutropenia during treatment of chronic hepatitis C virus infection with a combined therapy based on pegylated interferon-alpha2a plus ribavirin did not show a higher infection rate or increased severity of the disease.
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PMID:Incidence and severity of infections according to the development of neutropenia during combined therapy with pegylated interferon-alpha2a plus ribavirin in chronic hepatitis C infection. 1608 19

Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
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PMID:Treatment of chronic hepatitis B infection using interferon. 1610 70

Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48-weeks of full-dose peg-interferon-alpha-2a (n = 4) or alpha-2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients > or =12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 +/- 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end-of-treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV-RNA (p = 0.005) and a length from LT to therapy between 2-4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease > or =1-log10 at week 4 and/or 2-log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg-interferon withdrawal in 16 (29%) subjects. In 15 patients with post-treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.
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PMID:Hepatitis C recurrence after liver transplantation: Viral and histologic response to full-dose PEG-interferon and ribavirin. 1686 10

Recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) has been associated with progression to cirrhosis in approximately 20% of patients, 5 years postoperatively. Accelerated decompensation has also been noted when compared with cirrhosis in non-transplant patients. Different treatment strategies are available for recurrent HCV infection post-OLT, but efforts are hindered by the modest response rates, poor tolerability and the risk of rejection as well as graft loss. Anti-HCV immunoglobulin therapy to prevent graft infection with HCV has no established role at present but studies are ongoing. Treatment prior to transplantation in patients with decompensated cirrhosis has been evaluated but the results are too preliminary to make firm recommendations. Prophylactic interferon-based antiviral therapy in the early postoperative period to prevent graft infection was shown to have low response rates and high rates of adverse effects. Treatment of established recurrent HCV infection with combination peginterferon (pegylated interferon) and ribavirin is associated with 10-59% sustained virological response and the predictive value of a positive early virological response has been validated in the post-transplant setting. Improvement in inflammatory activity after viral eradication is well established, but fibrosis regression or stabilisation is less predictable and factors such as rejection and biliary complications may still contribute to graft loss. Most studies have initiated therapy at least 6 months postoperatively in order to optimise patient tolerance and enable the addition of ribavirin. The use of adjuvant agents to treat drug-induced neutropenia and anaemia in this population is evolving and becoming a crucial part of therapy. Determination of optimal doses of both pegylated interferon and ribavirin, and guidance on when to stop treatment, as well as improving tolerability are important steps in achieving higher response rates and minimising drug toxicity.
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PMID:Management of hepatitis C infection after liver transplantation. 1742 5


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