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

Cutaneous eruptions related to hepatitis C virus (HCV), a major cause of hepatitis in the setting of blood transfusion, intravenous drug abuse, organ transplantation, and hemodialysis, are typically reported as isolated cases. We encountered 35 cases of HCV infection associated with cutaneous eruptions. The present study evaluates paraffin-embedded, formalin-fixed tissue sections stained with hematoxylin and eosin from biopsy specimens of skin lesions from 35 patients seropositive for HCV. In 20 cases, reverse transcriptase polymerase chain reaction (RT-PCR) was performed using a probe for HCV RNA; the RNA was detected through the action of alkaline phosphatase on the chromogen nitroblue tetrazolium and bromochloroindolyl phosphate. The clinical spectrum comprised dermatomyositis-like photodistributed eruptions, palpable purpura, folliculitis, violaceous and perniotic acral lesions, ulcers, nodules, and urticaria. Lesions were also classified histopathologically by the dominant reaction pattern: vasculopathies of neutrophilic, lymphocytic, and granulomatous vasculitis and pauci-inflammatory subtypes (15 patients); palisading granulomatous inflammation (3 patients); sterile neutrophilic folliculitis (5 patients); dermatitis herpetiformis (1 patient); lobular panniculitis composed of neutrophilic lobular panniculitis in 2 patients and benign cutaneous polyarteritis nodosa in 1 patient; neutrophilic dermatoses, including neutrophilic urticaria, neutrophilic eccrine hidradenitis, and pyoderma gangrenosum (3 patients); interface dermatitis (3 patients); and low-grade lymphoproliferative disease of B-cell lineage representing marginal zone lymphoma in 1 patient and a clonal plasmacellular infiltrate in another patient. In most cases, whereas 1 of the aforementioned disorders defined the dominant reaction pattern, there was an accompanying secondary reaction pattern, defining a hybrid picture. Endothelial changes including endothelial cell enlargement and effaced heterochromatin with margination of the chromatin to the nuclear membrane were seen in several cases; in some cases similar cytopathic changes also involved the supporting pericytes, eccrine ductular cells, or keratinocytes. The RT-PCR analyses in 8 of 20 cases examined revealed HCV RNA expression in a focal, weak fashion in endothelia and perivascular inflammatory cells in those cases showing vasculopathic changes. Viral parasitism of endothelia may be important in cutaneous lesional propagation in the setting of HCV infection. Cross-reactivity between endogenous and viral antigens, leading to cellular and/or type II immune reactions; viral tropism to B lymphocytes, resulting in B cell expansion with resultant autoantibody production; and circulating immune complexes containing monoclonal cryoglobulins may also be of pathogenetic importance. Tropism of the virus to B lymphocytes provides a mechanism for the development of low-grade clonal B cell lymphoproliferative disease in this setting.
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PMID:The dermatopathologic manifestations of hepatitis C infection: a clinical, histological, and molecular assessment of 35 cases. 1282 11

The correlation between the length of viremia as detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and the clinical course of hepatitis A virus (HAV) infection was studied. Sixty-six consecutive patients with acute hepatitis A who were admitted to hospital in two infectious disease units in southern Italy were enrolled: 57 had a self-limited course of the disease (typical course), 4 a prolonged course, and 5 relapsing hepatitis. Plasma HAV RNA was sought by RT-PCR, using primers made at 5'-NTR of HAV, designed to amplify a 273-bp fragment and detected by 2% agarose gel and by hybridization with a specific biotinylated probe. In four patients with prolonged acute hepatitis A, the plasma HAV RNA, which was positive on the day of admission to hospital, was found to be negative from day 62, 46, 84, and 105, respectively, after the onset of the symptoms. In patients with relapsing hepatitis, HAV viremia paralleled the clinical and biochemical course of disease. In all patients with a typical self-limiting course, clearance of plasma HAV RNA was observed within 20 days of the onset of symptoms. In most patients, plasma HAV viremia became undetectable before the normalization of serum aminotransferases, underlining the importance of the immune reaction in the pathogenesis of acute hepatitis A. The data also suggest that the detection of plasma HAV RNA after 20 days of illness may predict a prolonged course of the disease, but relapsing hepatitis remains unpredictable on the basis of plasma HAV determination.
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PMID:HAV replication in acute hepatitis with typical and atypical clinical course. 1285 2

Pathogenic molecular pathways in cirrhotic liver diseases such as hepatitis C virus (HCV), autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly characterized. Differentially expressed genes are often important in disease pathogenesis. Suppression subtractive hybridization (SSH) is a genome-wide approach that enriches for differentially expressed mRNA transcripts. We aimed to make novel observations of differential gene expression in cirrhosis using SSH combined with quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Liver transcriptomes in HCV cirrhosis, AIH cirrhosis, PBC, and nondiseased liver tissue were examined by SSH. Resulting complementary DNA (cDNA) clones were rescreened for differential expression by dot-blot hybridization and then sequenced. Selected gene expression was quantified by real-time RT-PCR. Following SSH, 694 clones were rescreened for differential gene expression, of which 145 were sequenced and found to derive from 89 different genes. Seven clones were homologous only with expressed sequence tag (EST) sequences encoding genes having no known function. Up-regulated expression of four genes was confirmed by real-time RT-PCR: transmembrane 4 superfamily member 3 (tetraspanin CO-029) in all forms of cirrhosis, hedgehog interacting protein (HIP) in AIH cirrhosis and chitinase 3-like-1 (HC gp-39 or ykl-40) and arginine-glutamic acid repeat (RERE) in HCV cirrhosis. RERE gene polymorphisms and splice variants were observed in all tissues examined. Tetraspanin CO-029 up-regulation was primarily localized to bile ductular cells. In conclusion, novel observations of differential gene expression in human cirrhosis were made using SSH as the primary discovery tool. In particular, further studies of the RERE gene and its products in HCV associated liver disease are warranted.
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PMID:Novel differential gene expression in human cirrhosis detected by suppression subtractive hybridization. 1293 84

Breakthroughs during lamivudine therapy were assessed according to hepatitis flares and mutational polymorphism of hepatitis B virus (HBV) infecting patients. Of 42 patients with chronic hepatitis B and positive for hepatitis B e antigen in serum, 13 (30%) harbored HBV mutants with lamivudine resistance after a mean duration of 29 months on lamivudine. The virological breakthrough occurred 14.5 months after the start of lamivudine treatment, and all the patients with it developed breakthrough hepatitis 3 months later. The clinical course of breakthrough hepatitis was self-limited except in one patient who had already developed cirrhosis at the baseline. One year after breakthrough hepatitis, serum ALT, albumin, prothrombin time and platelet counts were maintained well on conventional treatments without resorting to interferon. Major HBV mutants during breakthrough hepatitis were those with M552I in the YMDD motif of viral DNA polymerase/reverse transcriptase in 7 patients (54%), M552I/L528M in 4 patients (31%) and M552V/L528M in 2 patients (15%). There were no patients in whom mutations at nucleotide 529 occurred including the 2 who later developed hepatocellular carcinoma. There was no clear relationship between distinct mutational patterns and clinical courses. Further studies are needed for making out the effects of lamivudine-resistant mutants on clinical outcomes, taking into considerations genotypes of HBV.
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PMID:Subclones of drug-resistant hepatitis B virus mutants and the outcome of breakthrough hepatitis in patients treated with lamivudine. 1468 51

Although it seems to be rather unlikely, it still remains unclear whether hepatitis G virus (HGV) is involved in post-transfusion hepatitis. Prevalence of HGV viremia and persistence in blood donors was determined. ALT and AST values of viremic and non-viremic donations of the donors were compared. 25,006 blood donations were tested for the presence of HGV RNA by reverse transcriptase polymerase chain reaction. ALT and AST were determined for every donation. Sequential serum samples of 105 HGV RNA-positive donors were tested for both HGV RNA and antibodies to the HGV-E2 antigen (anti-E2) by enzyme-linked immunosorbent assay. Stored serum samples of 66 patients from before and after transfusion of HGV RNA-positive units were also tested. 1.6% of the 25,006 blood donations were HGV RNA-positive. One of 105 HGV RNA-positive blood donors showed viremia for more than 6 years. Three donors showed viremia and HGV antibody at the same time. There is no significant difference in ALT and AST activity in HGV RNA-positive donors compared to a control group of healthy donors and also before and after seroconversion to HGV RNA-negative (p > 0.05). Transmission of HGV by blood components has been shown in transfused patients. The prevalence of HGV infection in patients (n = 66) is 17%. Transmission of HGV by blood components does occur. Patients have a significantly higher prevalence of HGV viremia compared to blood donors. In blood donors no liver affection by means of ALT or AST elevation can be seen. Long persistence of HGV viremia is common and the presence of anti-E2 does not exclude viremia.
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PMID:Prevalence, persistence and liver enzyme levels of HGV RNA-positive blood donors determined by large-scale screening and transmission by blood components. 1500 Feb 18

Hepatocellular carcinoma (HCC), the major manifestation of primary liver cancer, is one of the most frequent and malignant diseases worldwide. Among other environmental factors, hepatitis viruses, as the hepatitis B (HBV) and hepatitis C (HCV) viruses, are to be listed in the etiology of HCC. Both of these viruses cause a wide spectrum of clinical manifestations, ranging from healthy carrier state to acute and chronic hepatitis, cirrhosis and HCC. HBV and HCV are different viruses in structure: HBV contains a DNA genome which replicates through an RNA intermediate and requires an active viral reverse transcriptase (RT) polymerase enzyme, while HCV is an RNA virus which has no RT activity and replicates on the cellular membrane by RNA replication. In this review we discuss how these two biologically diverse viruses use common pathways to induce hepatocarcinogenesis despite their significant structural and viral cycle differences. A summary is also given of several observable common and different features. Direct integration of HBV viral sequences into the host genome increases the genomic instability, which does not occur in HCV infection. However, viral proteins may directly play a significant role in the induction of carcinogenesis by both viruses.
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PMID:Similarities and differences in hepatitis B and C virus induced hepatocarcinogenesis. 1502 54

During a natural outbreak of mouse hepatitis virus (MHV) infection in an animal facility in Rome, 6-week-old, outbred, immunocompetent Hsd:ICR (CD-1) and immunodeficient Hsd:athymic nude-nu sentinel mice (barrier maintained) were exposed to MHV in order to study tissue distribution and duration of the virus in naturally infected mice. Infection was diagnosed by serology and by reverse transcriptase-polymerase chain reaction (RT-PCR) using primers directed to two separate but highly conserved regions of the MHV genome. Faeces, colons, spleens, lungs, brains, livers, epididymides, testes, uteri and ovaries from sentinels were tested by RT-PCR after 1, 2, 4, 6, 8 and 12 weeks. A second round of amplification with nested primers was performed to increase the sensitivity of detection. The results indicated that all the organs tested became infected with the virus at various times. Furthermore, male and female reproductive organs were infected within 6 weeks of the beginning of exposure. Investigation of MHV transmission by ovarian transplantation and by in vitro fertilization (IVF) revealed that MHV was transmitted by infected ovaries transplanted into both immunocompetent and immunodeficient mouse strains but transmission was not observed when sperm from infected testes were used for IVF. These results suggest that sperm do not transmit infection from actively infected animals and that IVF could be considered a cleansing procedure.
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PMID:Tissue distribution and duration of mouse hepatitis virus in naturally infected immunocompetent ICR (CD-1) and immunodeficient athymic nude-nu mouse strains used for ovarian transplantation and in vitro fertilization. 1507 Apr 59

Our aim was to evaluate the antiviral effect of a combination of two nucleoside reverse transcriptase inhibitors, emtricitabine (FTC) and clevudine (L-FMAU), with the addition of an adenovirus-driven delivery of recombinant gamma interferon (IFN-gamma) in the woodchuck model of hepatitis B virus infection. Six woodchuck hepatitis virus (WHV)-infected woodchucks received L-FMAU (10 mg/kg) plus FTC (30 mg/kg) intraperitoneally for 8 weeks; six other animals received in addition an intravenous injection of a recombinant adenovirus vector expressing woodchuck IFN-gamma (Ad-IFN) at weeks 4 and 8. In the control group, two animals received Ad-IFN alone, two received adenovirus vector expressing the green fluorescent protein reporter gene, and one remained untreated. In less than 2 weeks, all woodchucks that received L-FMAU plus FTC showed a rapid and marked inhibition of viral replication, with a 4-log(10) drop in serum WHV DNA. In two animals, viremia remained suppressed for several months after the end of treatment. Similarly, a dramatic decrease in intrahepatic replicative intermediates of viral DNA was observed in the L-FMAU/FTC-treated groups. The additional administration of Ad-IFN led to increased inflammation in the liver but did not enhance the antiviral effect of the L-FMAU/FTC combination. In conclusion, therapies combining L-FMAU and FTC in WHV-infected woodchucks resulted in a potent and sustained antihepadnaviral effect both in the liver and in the blood circulation. However, no extra benefit of adding IFN-gamma gene transduction to the L-FMAU/FTC combination could be detected.
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PMID:Effect of a combination of clevudine and emtricitabine with adenovirus-mediated delivery of gamma interferon in the woodchuck model of hepatitis B virus infection. 1521 26

In spite of indisputable benefits, the use of antiretroviral therapy is associated with multiple metabolic complications. Switching to simpler regimens might maintain viral suppression, improve metabolic side effects, and provide insight into the pathogenesis of these complications. Our objective was to carefully characterize the virological and metabolic effects of switching from a successful protease inhibitor (PI)-based antiretroviral regimen to a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with nevirapine (NVP). Forty patients, taking their first successful (less than 40 HIV RNA copies/ml) PI-based regimen, switched their PI to NVP. If patients did not tolerate NVP, substitution with efavirenz was allowed. The duration of the study was 48 weeks. At 12 weeks intervals subjects had multiple virological and metabolic parameters including glucose, insulin, C-peptide, glucagon, proinsulin, blood lipids, and lipoproteins. A subgroup of 18 patients also had body composition evaluations with DEXA scans and MRIs of the abdomen and the thighs as well as insulin tolerance tests. Ninety-five percent of the patients maintained viral suppression (95% CI 88-100%); only one patient failed and another developed hepatitis. There were improvements in glucose (decreased fasting glucose, insulin, and improved insulin tolerance) and lipid metabolism (decreased triglycerides and increased HDL), but no changes in body composition and bone mineral density. Our study supports a pathogenic role for PIs in the development of hypertriglyceridemia and insulin resistance, but a more limited role in the fat redistribution syndrome.
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PMID:Evaluation of the virological and metabolic effects of switching protease inhibitor combination antiretroviral therapy to nevirapine-based therapy for the treatment of HIV infection. 1524 34

The main transmission route of TT virus (Transfusion-Transmitted Virus, TTV) and hepatitis G virus (HGV) is by parenteral route of blood and blood-products. Since they form the same risk group, some of TTV or HGV positive patients may also be infected by hepatitis B virus (HBV) and/or hepatitis C virus (HCV). In this study, the presence of TTV and HGV has been investigated by reverse transcriptase-polymerase chain reaction (RT-PCR, GeneAmp 5700 Sequence Detection System, AB), in 40 hepatitis B, 30 hepatitis C and 5 hepatitis B and C co-infected patients, 50 HBV and HCV negative hemodialysis patients, and 50 randomly selected healthy blood donors. As a result, 37 (21.1%) TTV and 11 (6.3%) HGV positivity were detected, out of a total 175 cases. The positivity rates for TTV and HGV were found as 40% and 5% in HBV-positive, 23.3% and 20% in HCV-positive, 20% and 20% in HBV+HCV co-infected patients, 20% and 4% in hemodialysis patients, and 6% and 0% in healthy blood donors, respectively. In conclusion, as the positivity rates were not low for these viruses, their role on the hepatitis pathogenesis should be further investigated by detailed studies.
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PMID:[TT virus and hepatitis G virus in different risk groups in Afyon]. 1529 3


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