Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Symptomatic viral hepatitis A usually only requires supportive therapy and the majority of cases are managed in the community. The prodromal symptoms of nausea, anorexia and lethargy tend to improve with the onset of clinical jaundice. Fulminant hepatic failure is said to be an uncommon complication, occurring in only 0.14-0.35% of hospitalized cases. However, an increasing incidence has been documented in some northern European countries where up to 20% of cases of fulminant viral hepatitis is due to hepatitis A. This trend parallels the increasingly delayed exposure to hepatitis A and the increased severity of the illness when contracted in later life. The risk of developing fulminant hepatic failure is best monitored using coagulation factor assays, with the prothrombin time and factor V levels being the most favoured. The diagnosis is established with the onset of encephalopathy. Patients progressing to grade 4 encephalopathy have a reasonably good prognosis compared to other aetiologies and survival rates of up to 67% have been obtained with medical management, despite the co-existence of such complications as cerebral oedema, renal and respiratory failure and the metabolic sequelae of acute liver failure. Nevertheless, some patients require emergency liver transplantation and 10 such patients have been reported to date. Transplantation is especially required in older patients (> 40 years) and those who are jaundiced for > 7 days before the onset of encephalopathy. The serum bilirubin and the prothrombin time complement these parameters in the decision making process.
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PMID:Management of acute and fulminant hepatitis A. 147

Interferon-alpha-2a is a recombinant interferon with antiviral, antitumour and immunomodulatory properties. Clinical studies have demonstrated that the drug offers therapeutic benefit in patients with some forms of chronic viral hepatitis. Remission, as measured by clearance of viral DNA and hepatitis B 'e' antigen (HBeAg), and normalisation of serum alanine aminotransferase levels, is observed in approximately 30 to 45% of patients with chronic hepatitis B receiving interferon-alpha-2a (2.5 to 18MU administered 3 times/week); about 5 to 15% of untreated controls remit spontaneously every year. Complete recovery [with loss of hepatitis B surface antigen (HBsAg)] is usually noted in < 20% of treated individuals. Similar response rates have been reported in the relatively small number of children evaluated to date. Although numerous studies have shown that interferon-alpha-2a (at various dosages) induces biochemical amelioration of chronic hepatitis C in approximately 50 to 75% of patients, relapse is common. Thus, long term remission may only be observed in about 15 to 30% of treated patients. On the other hand, this disorder remits spontaneously in only a few patients. The role of interferon-alpha-2a in the treatment of chronic hepatitis D remains unclear. Although preliminary data suggest it may be beneficial, cessation of therapy is generally followed by relapse. As with other types of interferons, most patients receiving interferon-alpha-2a experience an 'influenza-like' syndrome, which tends to diminish with continuing therapy. Other effects such as fatigue, lethargy, anorexia and weight loss are usually dose-limiting. Serum neutralising antibodies develop in approximately 10 to 20% of treated patients. Thus, although response rates are less than optimal, interferon-alpha-2a is a drug of first choice amongst the limited therapeutic options available for the management of well-compensated chronic viral hepatitis B or C.
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PMID:Interferon-alpha-2a. A review of its pharmacological properties and therapeutic use in the management of viral hepatitis. 858 31

Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN alpha induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN alpha, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN alpha-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN alpha dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN alpha-induced depression: antidepressant pretreatment or symptomatic treatment once IFN alpha has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN alpha-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN alpha-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN alpha and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabilizer should be initiated.
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PMID:Neuropsychiatric adverse effects of interferon-alpha: recognition and management. 1569 25

A previously healthy 4-year-old boy was admitted because of acute liver failure. He was icteric, lethargic, had elevated ammonia and abnormal liver function tests. Serology was negative for viral hepatitis. There was no history of hepatotoxic drugs. Family history was unremarkable. The child was taken to the operating room for a living-related hepatic transplant. Frozen section showed massive hepatic leukemic infiltration and hepatocellular necrosis. Bone marrow aspiration confirmed the diagnosis of acute lymphoblastic leukemia (ALL). Transplant was withheld and chemotherapy was attempted. He died the following day due to systemic leukemic infiltration, cerebral edema, and severe anoxic ischemic encephalopathy.
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PMID:Acute lymphoblastic leukemia presenting in fulminant hepatic failure. 1610 32

Side effects of interferon-ribavirin combination therapy limit the sustained viral response achievable in hepatitis C virus (HCV) patients. Coupling ribavirin to macromolecular carriers that target the drug to the liver would reduce systemic complications. The aim of this study was to evaluate the efficacy of a hemoglobin-ribavirin conjugate (HRC 203) in murine hepatitis virus strain 3 (MHV-3) induced viral hepatitis. HRC 203 had greater anti-viral activity on both isolated hepatocytes and macrophages, whereas both ribavirin and HRC 203 inhibited production of the pro-inflammatory cytokines interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) by macrophages. In vivo, untreated MHV-3-infected mice all developed clinical and biochemical signs of acute viral hepatitis and died by day 4 post infection. Livers recovered from untreated infected mice showed greater than 90% necrosis. In contrast, survival was enhanced in both ribavirin- and HRC 203-treated mice with a marked reduction in biochemical [ALT(max) 964 +/- 128 IU/L (ribavirin); 848 +/- 212 IU/L (HRC 203)] and histological evidence of hepatic necrosis (<10% in ribavirin/HRC 203 vs. 90% in untreated controls). Clinically, HRC 203-treated mice behaved normally, in contrast to ribavirin-treated mice, which developed lethargy and abnormal fur texture. In conclusion, targeted delivery of ribavirin to the liver alters the course of MHV-3 infection as demonstrated by prolonged survival, improved behavior, and reduced signs of histologically evident disease, as well as inhibition of viral replication and production of inflammatory cytokines in vitro.
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PMID:Targeted delivery of ribavirin improves outcome of murine viral fulminant hepatitis via enhanced anti-viral activity. 1649 40

Smoking causes a variety of adverse effects on organs that have no direct contact with the smoke itself such as the liver. It induces three major adverse effects on the liver: direct or indirect toxic effects, immunological effects and oncogenic effects. Smoking yields chemical substances with cytotoxic potential which increase necro-inflammation and fibrosis. In addition, smoking increases the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF- alpha) that would be involved in liver cell injury. It contributes to the development of secondary polycythemia and in turn to increased red cell mass and turnover which might be a contributing factor to secondary iron overload disease promoting oxidative stress of hepatocytes. Increased red cell mass and turnover are associated with increased purine catabolism which promotes excessive production of uric acid. Smoking affects both cell-mediated and humoral immune responses by blocking lymphocyte proliferation and inducing apoptosis of lymphocytes. Smoking also increases serum and hepatic iron which induce oxidative stress and lipid peroxidation that lead to activation of stellate cells and development of fibrosis. Smoking yields chemicals with oncogenic potential that increase the risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis and are independent of viral infection as well. Tobacco smoking has been associated with suppression of p53 (tumour suppressor gene). In addition, smoking causes suppression of T-cell responses and is associated with decreased surveillance for tumour cells. Moreover, it has been reported that heavy smoking affects the sustained virological response to interferon (IFN) therapy in hepatitis C patients which can be improved by repeated phlebotomy. Smoker's syndrome is a clinico-pathological condition where patients complain of episodes of facial flushing, warmth of the palms and soles of feet, throbbing headache, fullness in the head, dizziness, lethargy, prickling sensation, pruritus and arthralgia.
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PMID:Heavy smoking and liver. 1703 78

Viral hepatitis and toxins comprise most common causes of fulminate hepatic failure that are often diagnosed with standard laboratory tests. Herein we discuss a rare, difficult to diagnosis etiology of acute liver failure (ALF). A 62-year-old man presented with a two-week history of fever and fatigue. At four days before admission he became lethargic. His past medical and drug histories were unremarkable. Physical examination revealed generalized jaundice, fever and loss of consciousness. Laboratory tests showed elevated liver transaminases with direct hyper-bilirubinemia. Abdominal ultrasonography and CT scan showed hepatosplenomegaly and para-aortic abdominal lymphadenopathy. A further work-up included liver biopsy. The histopathology and imunohistochemistry was compatible with diffuse large B-cell lymphoma. He underwent high dose glucocorticoid therapy but his condition deteriorated rapidly and he died eight days after admission. ALF as an initial manifestation of malignant hepatic infiltration is extremely rare yet should be considered in all patients with unknown hepatic failure that are highly suspicious for malignant neoplasm.
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PMID:Fulminate hepatic failure as an initial presentation of non-hodgkin lymphoma: a case report. 2487 70