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)

Hepatitis delta virus (HDV) is a human pathogen causing fulminant hepatitis and liver cirrhosis. HDV has a circular single-stranded RNA genome, which encodes only a single protein, hepatitis delta antigen (HDAg), from the antigenomic strand. Although the functional roles of HDAg have been extensively studied, the molecular mechanism of persistent infection and pathogenesis of HDV are not yet understood. Here we report that overexpressed HDAg protects cells from death in baculovirus-infected insect cells. Using both wild-type and recombinant baculovirus-infected insect cells, we have demonstrated that HDAg inhibited wild-type baculovirus-induced cytolysis and thus extended the survival of virus-infected insect cells. By deletion analysis, we show that N-terminal 25 amino acids are essential for this function. From these data, we suggest that HDAg may play a major role in persistent infection of HDV.
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PMID:Overexpression of hepatitis delta antigen protects insect cells from baculovirus-induced cytolysis. 953 20

The main problem of children with HBeAg positive hepatitis B and associated hepatitis D is progression to liver cirrhosis with decompensation of liver function and need for liver replacement therapy within 15-20 years after infection. To determine whether interferon-alpha (IFN-alpha) therapy has a positive effect on HBV replication and inflammatory activity, we evaluated clinical and serological data of 8 children treated with IFN-alpha and 6 historic control patients without treatment. 4 of the nontreated patients seroconverted from HBeAg to anti-HBe between 7 to 17 years after initial diagnosis and showed decreased inflammatory activity in the liver. In the treatment group, the rate of seroconversion to anti-HBe (3 early, 2 late seroconverters) corresponded well to former trial results obtained in patients exclusively infected by HBV. Serum aminotransferase levels decreased or normalized in seroconverted children. In chronic HBV infection with associated hepatitis D (HDV) infection--compared to the spontaneous course of the disease--IFN-alpha therapy reduced inflammatory activity by earlier seroconversion to anti-HBe in responding patients. Moreover, viral replication and infectivity of hepatitis B was markedly reduced, but no effect on replication of HDV could be documented. Although long-term effects cannot be exactly estimated, at present IFN-alpha remains the only available treatment for HBeAg and anti-HDV positive children and seems to be of benefit for responding patients.
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PMID:Alpha-interferon treatment in HBeAg positive children with chronic hepatitis B and associated hepatitis D. 978 81

A 69-year-old Japanese man with hepatocellular carcinoma (HCC) associated with triple hepatitis viruses [hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV)] infection is reported. The patient had a past history of intravenous drug abuse and a tattoo on his back. A liver biopsy, performed in November 1989, showed HCC associated with cirrhosis. HBsAg and anti-HD antibody had been detected repeatedly starting in August 1984 and anti-HCV antibody was detected in 1990. By indirect immunoperoxidase staining the HD antigen was detected in the nuclei of hepatocytes of biopsy specimens and noncancerous liver cells obtained from autopsy specimens. Liver cirrhosis associated with triple hepatitis virus infection developed to hepatocellular carcinoma, and transcatheter arterial embolization treatment for HCC was effective. Despite having HCC and cirrhosis, the patient lived well beyond the expected time.
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PMID:Long-term follow-up of a patient with hepatocellular carcinoma associated with triple hepatitis virus (HBV, HDV, HCV) infection. 988 4

Acute and severe impairment of liver function with jaundice and ascites occurred in two out of seven patients with chronic hepatitis D during interferon alpha administration (10 MU three times a week). Both of them were young women with histological diagnoses of moderate to severe chronic hepatitis and cirrhosis with no signs of portal hypertension. Only a slow and partial recovery was observed after interferon withdrawal. Autoantibodies against basal cell layer tested positive in these two patients. In the remaining five patients with hepatitis D who did not experience liver impairment during interferon administration, basal cell layer antibodies were found only in one case. We conclude that severe decompensation of liver cirrhosis related to hepatitis D may occur during interferon administration. Positivity of basal cell layer antibodies may be associated with the risk of developing such an adverse event but our data are not sufficient to prove this association.
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PMID:Exacerbation of chronic hepatitis D during interferon alpha administration. 1009 Nov 6

The aim of this study was to assess the long-term outcome in hepatitis B virus (HBV)-infected patients according to HBV, hepatitis C virus (HCV), and hepatitis D virus (HDV) replication, focusing on survival, liver failure, and hepatocellular carcinoma (HCC). A cohort of 302 hepatitis B surface antigen (HBsAg)-positive subjects (mean age, 34 +/- 15.3 years; male/female 214/88; 39 subjects under 14 years) with biopsy-proven chronic hepatitis (86 with cirrhosis) was prospectively assessed, with a median follow-up of 94 +/- 37.6 months. One hundred nine patients received interferon alfa (IFN). At baseline, 86 subjects (28.5%) were hepatitis B e antigen (HBeAg)-positive (wild-type HBV), 80 (26.5%) were HBeAg-negative, HBV-DNA-positive, 76 (25.2%) had HDV infection, 43 (14.2%) had dual HBV/HCV infection, and 17 (5.6%) were negative for HBV-DNA, anti-HCV, and anti-HDV. During follow-up, decompensation of disease occurred in 46 subjects: 8 developed HCC, 36 developed ascites, and 2 developed jaundice. Five patients underwent transplantation. Thirty-five subjects died: 33 of hepatic and 2 of nonhepatic causes. Overall mortality was 5.2-fold that of the general population (95% CI: 3.6-7.3; 35 deaths observed, 6.7 expected; P <.0001). By Cox regression analysis, survival was independently predicted by young age, absence of cirrhosis at baseline, and sustained normalization of aminotransferases during follow-up. Survival without decompensation was independently predicted by the same factors and by IFN treatment. Chronic hepatitis B infection increases mortality in comparison with the general population in our area regardless of specific virological profiles at presentation. Presence of cirrhosis and persistent necroinflammation markedly increase the risk of death.
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PMID:The long-term course of chronic hepatitis B. 1038 64

The hepatitis D virus (HDV) relies on the helper hepatitis B virus (HBV) for the provision of its envelope, which consists of hepatitis B surface antigen (HBsAg). The RNA genome of HDV is a circular rod-like structure due to its extensive intramolecular base-pairing. HDV-RNA has ribozyme activity which includes autocatalytic cleavage and self-ligation properties, essential in virus replication via the rolling circle mechanism. Replication of the RNA is thought to be effected by cellular RNA polymerase II. Hepatitis D antigen (HDAg) is the only protein encoded by HDV-RNA and its long and short forms have a regulatory role in the replication and morphogenesis of the virus. Superinfected HBV carriers who become chronically infected with HDV are at increased risk of developing cirrhosis. Attempts to treat such carriers with interferon have not been particularly successful. In recent years the epidemiology of HDV has changed primarily due to the impact of HBV vaccination in preventing an increase in the pool of susceptible individuals. Copyright 1998 John Wiley & Sons, Ltd.
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PMID:Hepatitis D virus. 1039 91

Chronic delta hepatitis is a severe form of chronic liver disease caused by hepatitis delta virus (HDV) infection superimposed on chronic hepatitis B or the hepatitis B surface antigen (HBsAg) carrier state. Therapy of delta hepatitis is currently unsatisfactory. We have evaluated lamivudine (3-thiacytidine), an oral nucleoside analogue with marked effects against hepatitis B, as therapy in 5 patients with chronic hepatitis D. Five men, ages 38 to 65 years, were treated. All had HBsAg, antibody to HDV, and HDV RNA in serum, as well as persistent elevations in alanine aminotransferase (ALT) levels and liver histology showing severe chronic hepatitis with fibrosis or cirrhosis. Lamivudine was given in a dose of 100 mg orally daily for 12 months. Patients were monitored carefully and tested for HBsAg, HBV-DNA and HDV-RNA levels serially during the year of treatment and for 6 months thereafter. Liver biopsies were performed before therapy and repeated after 1 year. Serum levels of HBV DNA fell rapidly in all 5 patients, becoming undetectable even by polymerase chain reaction (PCR) in 4. However, all 5 patients remained HBsAg- and HDV-RNA-positive, and serum ALT levels and liver histology did not improve. All patients tolerated therapy well. When lamivudine was stopped, HBV-DNA levels returned to pretreatment values without a change in disease activity. Lamivudine is a potent inhibitor of HBV-DNA replication, but does not improve disease activity or lower HDV-RNA levels in patients with chronic delta hepatitis.
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PMID:Lamivudine for chronic delta hepatitis. 1042 73

Chronic delta hepatitis is an uncommon but severe form of chronic viral hepatitis for which there is currently no satisfactory therapy. A patient with chronic delta hepatitis was treated with interferon alfa, 5 million units daily for 12 years. Serial serum samples were tested for routine liver tests and selected samples for quantitative levels of hepatitis B surface antigen (HBsAg) and hepatitis delta virus RNA. Liver biopsies were performed before, during, and after an initial 1-year course of therapy and again after 3 and 10 years of continuous therapy. With initiation of interferon therapy, serum aminotransferase levels decreased to normal range, became abnormal again when the dose was reduced, and increased to pretreatment levels when therapy was stopped. With reinstitution and prolonged therapy, aminotransferase levels became persistently normal; after several years, both hepatitis delta virus RNA and serum HBsAg became undetectable. Liver biopsy, which initially revealed cirrhosis, showed gradual improvement in inflammatory and fibrosis scores and, after 10 years, no abnormalities or fibrosis. Therapy was stopped, and the patient remained free of evidence of infection. In conclusion, long-term therapy with interferon alfa in high doses led to resolution of chronic delta hepatitis, disappearance of hepatitis delta and B virus markers, and improvement in fibrosis.
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PMID:Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy. 1053 87

In patients with multiple hepatotropic viral infections (B and C, or B, C and D), the reciprocal influence of each virus remains controversial. The aims of this study were twofold: first, to determine the impact of multiple infection on the replication status of B, C and D viruses and on histological features; and second, to compare patients with multiple infection to patients infected only with the hepatitis C virus (HCV). We retrospectively included 50 patients with multiple infection and 50 control HCV patients, who were matched on independent factors associated with fibrosis, such as age, gender, alcohol consumption and duration of infection. The replication status of hepatitis B virus (HBV), HCV and hepatitis D virus (HDV), and histological lesions, were determined. In patients with multiple infection, HCV RNA was present less frequently (44% vs 98%, P < 0.001) and the prevalence of cirrhosis was higher (35% vs 8%, P < 0.001). Among patients with triple infection (n = 16), HBV replication was observed in 25%, HCV RNA was detectable in only two (P < 0.0001) and HCV viremia was significantly lower than in the matched HCV patients (0 vs 54.7, P < 0.0001). Among patients with dual infection (n = 34), HCV RNA was present less frequently in those with serological markers of active HBV infection than in those without (30% vs 79%, P = 0.01). Hence, multiple infection is associated with a decrease of HCV replication. Cirrhosis seems to be more frequently observed in patients with multiple infection. In patients with triple infection, serum HCV RNA and markers of HBV replication were absent in 80%, suggesting that HDV acts as a dominant virus. In patients with dual infection, HBV and HCV exert an alternative, dominant replication.
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PMID:Replication status and histological features of patients with triple (B, C, D) and dual (B, C) hepatic infections. 1071 38

Hepatitis D (delta) virus (HDV) is an infectious agent that propagates in hepatocytes only in the presence of hepatitis B virus, causing fulminant or chronic hepatitis with liver cirrhosis. HDV is a 36 nm particle that includes a circular RNA genome of 1.7 kilobases with an extensive internal complementary that allows it to fold into a rod-like structure. The relationships among genotypes, sequence variability, geographical distribution and disease severity of HDV remain unknown. Consequently, in the present study, the complete nucleotide sequence of an HDV isolated from a Canadian patient was determined. The viral RNA from serum was amplified using reverse transcription coupled to polymerase chain reaction amplification. The resulting complementary DNA was cloned and sequenced. Sequence analysis revealed that this new isolate contained 1672 nucleotides corresponding to genotype 1, which has a worldwide distribution. Sequencing of four independent clones revealed 17 substitutions, corresponding to an overall sequence variability of 1%. Surprisingly, seven mutations were found in the 48-nucleotide region located between the two highly conserved self-catalytic motifs. This is the first demonstration that many substitutions are identified in this region of HDV, and prompts the present authors to define it as a hypervariable region.
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PMID:A Canadian isolate of hepatitis D (delta) virus. 1093 3


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