Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Clinical toxicity of the interferons. 751 63

Thirty-one patients with hepatic metastases from colorectal carcinoma were treated with carboplatin (CBDCA), 55 mg/m2, given in a 4-hour intra-arterial infusion daily for 5 days, and 5-fluorouracil, 900 mg/m2, given in a 20-hour intra-arterial infusion daily for 5 days. Cycles were administered every 5 weeks. Objective responses were observed in 16 (51.6%) patients (5 complete and 11 partial responses). Another 13 patients maintained stable disease, and 2 patients rapidly progressed. The overall median survival was 23.5 months. The 16 patients with objective response had a median survival of 26.5 months. In this series, no evidence of biliary sclerosis, cholecystitis, chemical hepatitis, or myelosuppression was observed. Complications of drug delivery system were observed in 14 (45.16%) patients. In conclusion, intra-arterial hepatic chemotherapy with CBDCA-5FU was associated with a modest benefit, expressed in good quality responses and extended survival of approximately 2 years in about half of the treated patients.
 ...
PMID:Intra-arterial hepatic treatment with carboplatin (CBDCA) and 5-fluorouracil (5-FU) in metastases from colorectal carcinoma. 842 1

Azathioprine can cause severe myelosuppression. The inherited activity of the enzyme thiopurine methyltransferase has been recently recognised as a major factor in the susceptibility to myelosuppression. Thiopurine methyltransferase deficiency occurs at a frequency of one in 300 and is associated with profound myelosuppression after a short course of azathioprine. Very low thiopurine methyltransferase activity represents the TPMTL/TPMTL genotype, and can be detected before therapy with azathioprine is started. We describe the first documented case of azathioprine-induced severe myelosuppression due to thiopurine methyltransferase deficiency in autoimmune liver disease. The azathioprine dose was low (1 mg/kg) and pancytopenia occurred after 56 days therapy. It would be advisable to measure thiopurine methyltransferase activity before patients with autoimmune hepatitis are exposed to azathioprine.
 ...
PMID:Azathioprine-induced myelosuppression due to thiopurine methyltransferase deficiency in a patient with autoimmune hepatitis. 855 Oct 1

We have developed a single-catheter technique for percutaneous isolated liver chemoperfusion (PILP) with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) for the treatment of malignant liver tumors. We report here the surgical technique, pharmacokinetics, and effectiveness of PILP in multiple advanced liver tumors. Twenty-eight patients with hepatocellular carcinoma (HCC) and 18 with metastatic liver tumors underwent a total of 61 PILPs with HVI-CHP. HVI-CHP was accomplished mainly by the single-catheter technique using a novel four-lumen, two-balloon catheter; it was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. Under HVI-CHP, either doxorubicin 960-150 mg/m2) or cisplatin (150-200 mg/m2) was infused via the hepatic artery. The PILP was completed successfully in all 61 trials. Two of forty-six patients died early; one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Excluding these two deaths, the treatments were well tolerated. The major side effects were mild to moderate chemical hepatitis and reversible myelosuppression. Of the 27 evaluable HCC patients, 17 (63%) had an objective tumor response (5 complete and 12 partial responses). In 15 patients with colorectal hepatic metastases (CHM), 7 had a sharp decrease in serum carcinoembryonic antigen (CEA) levels (to < 50% of their pretreatment levels) after treatment. However, a single PILP had limited efficacy in terms of the durability of remission (< or = 6 months in most CHM patients, as assessed by CEA levels). These results indicate that PILP with HVI-CHP has high efficacy in most patients with multiple advanced liver tumors. In addition, the results suggest a role of multiple treatment courses of PILP in the induction of long-term remission, especially for patients responsive to the first treatment.
 ...
PMID:Percutaneous isolated liver chemoperfusion for treatment of unresectable malignant liver tumors: technique, pharmacokinetics, clinical results. 967 Feb 70

Human herpesvirus (HHV)-6 and -7 are novel members of the beta-herpesvirus family that maintain latency in the human host after primary infection. Reactivation from latency and/or increased degree of viral replication occurs during periods of immune dysfunction. The clinical effect of HHV-6 and HHV-7 reactivation in recipients of liver transplants is now being recognized. Clinical illnesses such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in a number of anecdotal reports. Moreover, a growing body of evidence suggests that the more important effect of HHV-6 and HHV-7 reactivation on the outcomes of liver transplantation may be mediated indirectly by their interactions with the other beta-herpesvirus-cytomegalovirus (CMV). Coinfection among these three beta-herpesviruses in clinical syndromes that were classically ascribed to be solely caused by CMV has been shown and has raised substantial interest in the potential role of HHV-6 and HHV-7 as copathogens in the direct and indirect illnesses caused by CMV. This article reviews the current scientific data on the role and the magnitude of impact of HHV-6 and HHV-7 infection on the outcomes of liver transplantation.
 ...
PMID:The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation. 1214 55

Limitin has sequence homology with alpha interferon (IFN-alpha) and IFN-beta and utilizes the IFN-alpha/beta receptor. However, it has no influence on the proliferation of normal myeloid and erythroid progenitors. In this study, we show that limitin has antiviral activity in vitro as well as in vivo. Limitin inhibited not only cytopathic effects in encephalomyocarditis virus- or herpes simplex virus (HSV) type 1-infected L929 cells, but also plaque formation in mouse hepatitis virus (MHV) type 2-infected DBT cells. In addition, administration of limitin to mice suppressed MHV-induced hepatitis and HSV-induced death. The antiviral activity may be mediated in part by 2',5'-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity. While limitin has antiviral activity as strong as that of IFN-alpha in vitro (the concentration that provided 50% inhibition of cytopathic effect is approximately 30 pg/ml), IFN regulatory factor 1 (IRF-1) dependencies for induction of an antiviral state were different for limitin and IFN-alpha. In IRF-1-deficient fibroblasts, a higher concentration of limitin than of IFN-alpha was required for the induction of antiviral activity and the transcription of proteins from IFN-stimulated response element. The unique signals and the fewer properties of myelosuppression suggest that a human homolog of limitin may be used as a new antiviral drug.
 ...
PMID:Antiviral activity of limitin against encephalomyocarditis virus, herpes simplex virus, and mouse hepatitis virus: diverse requirements by limitin and alpha interferon for interferon regulatory factor 1. 1291 74

Recent years have witnessed a growing interest in the role of human herpesvirus (HHV) type 6 and type 7 as emerging pathogens or copathogens in transplant recipients. Both HHV-6 and HHV-7 belong to the beta-herpesvirus family and are closely related to another member of the family, cytomegalovirus. After the primary infection, these viruses remain latent in the human host and can reactivate after transplantation. Various clinical processes such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in association with herpesvirus. Moreover, a growing body of evidence suggests that the major impact of HHV-6 and HHV-7 reactivation in transplantation is related to indirect effects, such as their association with cytomegalovirus disease, increased opportunistic infections, and graft dysfunction and rejection. The pathogenesis of HHV-6 and HHV-7 during the post-transplantation period, the methods used for their diagnosis, and the evaluation of antiviral drugs and strategies for their prevention and treatment are now the subject of extensive research.
 ...
PMID:[Human herpesvirus type 6 and type 7 in transplant recipients]. 1452 8

Patients with chronic hepatitis B are at risk of reactivation of viral hepatitis during chemotherapy. We report a case of hepatitis B reactivation occurring in association with single-agent gemcitabine chemotherapy in the absence of significant myelosuppression. Gemcitabine is a nucleoside analog that can affect cell-mediated immunity, and this may contribute to an increased risk of reactivation of hepatitis B. We advise caution when administering chemotherapy to patients who are hepatitis B surface antigen positive, even when using relatively nontoxic palliative single-agent cytotoxic drugs. Monitoring of liver function tests will identify hepatitis, and measurement of hepatitis B DNA levels may help distinguish chemotherapy-induced hepatitis from hepatitis B virus reactivation.
 ...
PMID:Gemcitabine and reactivation of hepatitis B. 1471 36

We report a case of acute promyelocytic leukemia (APL) with drug-induced hypersensitivity syndrome associated with Epstein-Barr virus (EBV) infection. A 33-year-old woman was admitted because of APL. After complete remission was obtained with the use of all-trans retinoic acid (ATRA), intensive chemotherapy was administered. She developed high grade fever and severe systemic erythematous eruptions followed by cervical lymphoadenopathy, hepatosplenomegaly, hepatitis and hypotension in a state of myelosuppression during consolidation chemotherapy. Systemic corticosteroids alleviated the symptoms. Since an anti-EB VCA IgM antibody titer was continuously positive, persistent infection of EBV was suspected. In this case, EBV infection may have contributed to the development of drug-induced hypersensitivity syndrome.
 ...
PMID:Acute promyelocytic leukemia with drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection. 1496 84

Human herpesvirus 6 (HHV-6) infections occur in > 95% of humans. Primary infection, which occurs in early childhood as an asymptomatic illness or manifested clinically as roseola infantum, leads to a state of subclinical viral persistence and latency. Reactivation of latent HHV-6 is common after liver transplantation, possibly induced and facilitated by allograft rejection and immunosuppressive therapy. Since the vast majority of humans harbor the virus in a latent state, HHV-6 infections after liver transplantation are believed to be mostly due to endogenous reactivation or superinfection (reactivation in the transplanted organ). In a minority of cases, however, primary HHV-6 infection may occur when an HHV-6 negative individual receives a liver allograft from an HHV-6 positive donor. The vast majority of documented HHV-6 infections after liver transplantation are asymptomatic. In a minority of cases, HHV-6 has been implicated as a cause of febrile illness with rash and myelosuppression, hepatitis, pneumonitis, and encephalitis after liver transplantation. In addition, HHV-6 has been associated with a variety of indirect effects such as allograft rejection, and increased predisposition and severity of other infections including cytomegalovirus (CMV), hepatitis C virus, and opportunistic fungi. Because of the uncommon nature of the clinical illnesses directly attributed to HHV-6, there is currently no recommended HHV-6-specific approach to prevention. However, ganciclovir and valganciclovir, which are primarily intended for the prevention of CMV disease, are also active against HHV-6 and may prevent its reactivation after transplantation. The treatment of established HHV-6 disease is usually with intravenous ganciclovir, cidofovir, or foscarnet, complemented by reduction in the degree of immunosuppression. This article reviews the current advances in the pathogenesis, clinical diagnosis, and therapeutic modalities against HHV6 in the setting of liver transplantation.
 ...
PMID:Human herpesvirus 6 infections after liver transplantation. 1949 84


<< Previous 1 2 3 Next >>