Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within 5 to 14 days of onset of grade 3 or 4 coma, liver biopsies were obtained in 14 of 15 consecutive patients who recovered from fulminant hepatitis. In 9 patients, follow-up biopsy was obtained 6 to 60 months after acute hepatitis and autopsy was performed in 2 patients who died in 4 months from complications of hepatitis (aplastic anemia) or of corticosteroid therapy (sepsis). During fulminant illness the biopsy findings were: multilobular necrosis in 4 patients, confluent (bridging) necrosis in 9, and only portal inflammation in 1. The duration or the grade of coma did not correlate with the severity of necrosis on the biopsy. Follow-up biopsy showed development of chronic (active) hepatitis in 3 of 9 patients (with cirrhosis in one of these). Chronic liver disease was not found in the two autopsies. If fulminant hepatitis is the result of vigorous cell-mediated immune attack on hepatocytes, then this process cannot always eradicate chronic hepatitis B surface antigenemia, nor can it always prevent the development of chronic (active) hepatitis or cirrhosis.
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PMID:The liver during and after fulminant hepatitis. 89 67

Two research groups recently and independently, isolated a hepatotropic flavivirus from human sera. The two viruses, named GB virus C and hepatitis G virus (HGV), were subsequently discovered to represent the same virus, which was associated with acute and chronic hepatitis of the non-A-E type. The prevalences of infection with HGV have now been investigated in various groups of the Thai population, some of which [e.g. thalassaemic children, patients with chronic liver disease, carriers of antibodies to hepatitis B virus and/or hepatitis C virus (HCV), prostitutes and intravenous-drug users (IVDU)] were assumed to be at high risk. Samples of sera were investigated by reverse-transcriptase PCR, using four primers created from the 5' untranslated region of HGV. The prevalence of HGV infection among the healthy controls (1%-5%) was found to be much less than that among thalassaemic children (32.6%), asymptomatic carriers of anti-HCV (20.4%), IVDU (18.2%), aplastic anaemia patients (14.3%) and prostitutes (10%), although similar to that in patients with chronic liver disorders. These results confirm a parenteral route of transmission for HGV and emphasise the need for further research to determine the clinical significance of this virus.
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PMID:Prevalence of infection with hepatitis G virus among various groups in Thailand. 961 58

TTV, the transfusion transmissible hepatitis virus infects mainly patients at risk for parenteral exposure and hence, prone to develop chronic liver disease, as well as healthy populations worldwide. Most TTV infections appear to occur parenterally, with viremia detected frequently in blood donors and blood products. The substantial proportion of asymptomatic individuals never exposed to blood-borne agents, and its high prevalence among healthy subjects implicates the fecal-oral route as another potential for transmission. According to the TTV DNA levels detected in liver tissue, it apparently replicates in hepatocytes, and TTV DNA is present in sera of patients with posttransfusion hepatitis of unknown etiology closely correlated with ALT levels. However, TTV initiating the development of chronic liver disease or causing posttransfusion hepatitis could not be confirmed, as most patients positive for TTV DNA remain asymptomatic and those progressing towards chronic liver disease are invariably coinfected with either the hepatitis B or C virus. Also, TTV coinfection does not aggravate the symptoms associated with hepatitis B or C. Similarly, it does not cause posthepatitis aplastic anemia, and high-risk patients can immunologically clear the viral DNA. In conclusion, being widely distributed and apparently nonpathogenic, TTV might represent an opportunistic but innocent virus reminiscent of hepatitis G virus, with a negligible role in the etiology of chronic liver disease.
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PMID:Transfusion transmissible virus TTV and its putative role in the etiology of liver disease. 1126 79

Anemia is a frequently observed manifestation during the clinical course of chronic liver disease. In this study, we retrospectively reviewed the hospital files of 500 chronic liver disease patients and assessed the frequency, etiology and morphology of anemia in 50 patients who fulfilled the criteria to be included in the study. The mean age of the patients was 48+/-16 years and male/female ratio was 1.4/1. The mean hemoglobin value was 9.54+/-2.03 g/dl. The mean MCV was 82.9+/-10.52 fl. Iron deficiency anemia, defined as absent bone marrow iron stores, was the most common anemia present in 50% of patients. Classical laboratory criteria used in the diagnosis of iron deficiency anemia (MCV < 80 fl, ferritin < 10 ng/ml) could not be applicable to all of the patients with iron deficiency anemia and hepatic disorders. Hemolytic anemia due to hypersplenism was the second most common anemia (24%) followed by anemias, namely anemia due to gastrointestinal hemorrhage (22%), anemia of chronic disease (8%), beta-thalassemia major (8%), folate deficiency (6%), vitamin B12 deficiency (4%), macrocytic anemia (2%), aplastic anemia (2%) and immune hemolytic anemia (2%). Twenty-eight percent of the patients had more than a single cause of anemia. Morphologically, microcytic anemia was the most common seen in 46% of the patients followed by normocytic (42%) and macrocytic anemia (12%). As patients do not always present with classical laboratory findings and may have more than a cause of anemia, a complex diagnostic approach should be considered in anemic patients with hepatic disorders.
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PMID:Erythrocytes: Anemias in Chronic Liver Diseases. 1139 3

Thrombocytopenia is a condition of unusually low level of platelets in blood, resulting from an imbalance between the production and destruction of platelets, and is associated with aplastic anemia, myelodysplasia, and idiopathic thrombocytopenic purpura (ITP). Thrombocytopenia can also be associated with severe chronic liver disease as a result of several factors that may act in concert, including reduced production of the endogenous thrombopoietic growth factor, thrombopoietin (TPO). This article examines the nature of thrombocytopenia, ITP, and TPO.
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PMID:Thrombopoietin agonists for the treatment of thrombocytopenia in liver disease and hepatitis C. 1962 64

Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically significant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirin-induced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by deficiency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.
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PMID:Spectrum of anemia associated with chronic liver disease. 1978 28

Since its discovery, the thrombopoietin (TPO) pathway has been an important pharmaceutical target for the treatment of thrombocytopenia. The first generation of TPO mimetics included peptide agents sharing homology with endogenous TPO, but these introduced a risk of antibody formation to endogenous TPO and were not successful. However, second-generation TPO mimetics or TPO receptor agonists (RAs) are currently being used to treat thrombocytopenia associated with a number of conditions, such as immune thrombocytopenia (ITP), severe aplastic anaemia (SAA), and hepatitis C virus-associated chronic liver disease. Accumulating efficacy and safety data suggest that the role of TPO-RAs in the treatment of thrombocytopenia may evolve in the near future with broader use of these agents in ITP and SAA, as well as approval in other indications, potentially including myelodysplastic syndromes, chemotherapy-associated thrombocytopenia, and post-transplant thrombocytopenia. This review provides an overview of clinical data on the efficacy and safety of TPO-RAs, emphasising recent findings that may expand their clinical utility.
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PMID:Beyond immune thrombocytopenia: the evolving role of thrombopoietin receptor agonists. 2827 23

Introduction: The thrombopoietin receptor agonists (TPO-RAs) are a class of drugs that have been FDA-approved for immune thrombocytopenia (ITP), periprocedural thrombocytopenia in patients with chronic liver disease (CLD), aplastic anemia, and thrombocytopenia associated with antiviral treatment of hepatitis C. Avatrombopag is a TPO-RA that is currently FDA-approved for ITP and periprocedural thrombocytopenia in patients with CLD and is currently undergoing evaluation for chemotherapy-induced thrombocytopenia (CIT) in an international phase III clinical trial. Areas covered: This paper summarizes the chemistry, pharmacodynamics, and pharmacokinetics of avatrombopag. In addition, the authors review the efficacy and safety of avatrombopag, covering clinical trials in patients with ITP and in patients with CLD scheduled to undergo a procedure. Expert opinion: Avatrombopag has demonstrated efficacy in patients with ITP. With its low side-effect burden, absence of hepatotoxicity, ease of use as an oral medication, and lack of food-drug interactions, avatrombopag is a favorable option for ITP, though there is a lack of long-term safety data. In periprocedural thrombocytopenia in patients with CLD, avatrombopag is comparable to lusutrombopag, another TPO-RA. Finally, the results of the study of avatrombopag in CIT are eagerly awaited, as there are no currently approved medications for this indication in the USA.
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PMID:An evaluation of avatrombopag for the treatment of thrombocytopenia. 3309 74