Cases reported "Hepatitis C, Chronic"

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1/427. liver transplantation for endstage hepatitis c cirrhosis in a patient with primary hypogammaglobulinaemia.

    liver transplantation was performed in a patient with primary hypogammaglobulinaemia, chronic hepatitis c and hepatic failure. The immediate posttransplant period was uncomplicated. Owing to a stricture of the choledochojejunostomy the patient was reoperated with construction of a hepaticojejunostomy 11 months posttransplant. The patient remained hepatitis c virus (HCV) RNA-positive, with high and increasing levels of HCV. Liver biopsies demonstrated the recurrence of HCV. 14 months after the transplantation the patient developed severe diarrhoea caused by cryptosporidium parvum. The infection did not respond to available therapeutic measures. He deteriorated with development of liver failure and died 18 months after the transplantation. The present case report illustrates the difficulties associated with organ transplantation in patients with primary hypogammaglobulinaemia.
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2/427. Ontogeny of hepatitis c virus (HCV) hypervariable region 1 (HVR1) heterogeneity and HVR1 antibody responses over a 3 year period in a patient infected with HCV type 2b.

    Hypervariable region 1 (HVR1) sequences of 96 clones at six time-points representing 27 variants in two major and one minor group were identified in a patient with chronic hepatitis c virus (HCV) infection over 3 years. Major and selected minor variants were used to design synthetic peptides corresponding to the HVR1 C terminus. Peptide ELISA reactivity with IgG was plotted against the corresponding clone frequency, and three patterns emerged: (1) three peptides were unreactive; (2) antibodies against two peptides followed emergence of the corresponding variant, suggesting isolate-specificity; (3) antibodies against four peptides preceded the appearance of the corresponding variant, indicating cross-reactivity or previous exposure. Cross-reactivity was investigated further: sera from six time-points were tested against 11 unrelated HVR1 peptides, seven of which (63.6%) showed cross-reactivity at all time-points. Cross-reactivity of nine patient-specific peptides tested against a panel of 45 heterologous sera from chronic HCV carriers ranged between 0 and 20%. Only three of 27 variants appeared at more than one time-point and in two cases specific and/or cross-reactive HVR1 antibodies coexisted with the corresponding variant, consistent with emergence of escape mutants. In addition, analysis of HVR1 IgG reactivity within a group of closely related patient-specific peptides revealed a loss of reactivity in one peptide attributable to a single amino acid substitution. interferon-alpha treatment considerably reduced viral RNA but, paradoxically, heterogeneity increased.
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3/427. sarcoidosis with selective involvement of a second liver allograft: report of a case and review of the literature.

    A case of sarcoidosis recurrent in a patient's second liver allograft is described. There was no granulomatous disease seen in the patient's first liver allograft. After the second orthotopic liver transplantation (OLT), the patient was successfully treated for acute rejection, aspergillus infection, and cytomegalovirus viremia. Approximately 2 months after the second OLT, the patient was treated with long-term interferon-alpha for recurrent hepatitis c. Five years after the operation, he experienced liver failure secondary to recurrent hepatitis and underwent a third OLT. This is only the second reported case of sarcoidosis recurrent in the liver parenchyma of a transplanted organ and the first in which interferon-alpha might have played a role.
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4/427. Triggering of acute alcoholic hepatitis by alpha-interferon therapy.

    BACKGROUND/AIMS: Alcohol may induce autoimmunity by recognition of acetaldehyde-modified proteins which may be implicated in the pathogenicity of acute alcoholic hepatitis. We report here the potential role of alpha-interferon, a potent inducer of the autoimmunity process, in inducing alcoholic hepatitis. methods: We analyzed clinical, biological, virological and histological features in two cases where alpha-interferon treatment for HCV-related hepatitis led to a marked increase in aminotransferase activities. RESULTS: alpha-interferon as treatment of HCV-related hepatitis seemed to exacerbate acute alcoholic hepatitis despite moderate alcohol consumption. In Case 1, moderate daily alcohol intake of 40 g during therapy led to biopsy-proven acute alcoholic hepatitis, while the same consumption before therapy did not. In Case 2, before treatment, the liver biopsy showed mild acute alcoholic hepatitis; aminotransferases increased during alpha-interferon therapy, although no increase in alcohol intake was observed. CONCLUSION: alpha-interferon therapy by its immunomodulatory properties could be implicated in alteration of the course of acute alcoholic hepatitis. These observations emphasize that the decision to treat with alpha-interferon when there is even moderate alcohol consumption should be carefully weighted in HCV-infected patients.
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5/427. Sudden hearing loss in a patient hepatitis c virus (HCV) positive on therapy with alpha-interferon: a possible autoimmune-microvascular pathogenesis.

    Alpha interferon (alpha-IFN) is used for the treatment of various systemic disorders. Side-effects of alpha-IFN therapy can involve numerous organ systems, but sudden hearing loss has only once been recorded. We report a case of sudden hearing loss occurring in a patient with chronic hepatitis c treated with alpha-IFN and recovered five days after the discontinuation of this agent. This is the first record of anti-endothelial cell antibodies detection in a patient with sudden hearing loss. The finding of anti-endothelial cell antibodies suggests an association between sudden hearing loss and microvascular damage during interferon therapy.
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6/427. Disappearance of serum HCV-RNA after short-term prednisolone therapy in a patient with chronic hepatitis c associated with autoimmune hepatitis-like serological manifestations.

    We report a 70-year-old woman with chronic hepatitis c associated with autoimmune hepatitis (AIH)-like serological manifestations, in whom elimination of hepatitis c virus (HCV) was observed after corticosteroid treatment. The patient was infected with HCV, genotype Ib, but had several laboratory findings, such as markedly elevated serum gamma-globulin and IgG, characteristic of AIH, as well as a high titer of an anti-nuclear antibody. An ultrasound (US)-guided liver biopsy disclosed chronic active hepatitis F3. Corticosteroid worsened her liver function test results and raised amounts of HCV-RNA in the serum. Withdrawal of the corticosteroid led to prompt normalization of transaminase levels and the disappearance of serum HCV-RNA, determined by reverse transcription-polymerase chain reaction (RT-PCR). For 4 years, up to the time of this study, her transaminase values have been normal and HCV viremia was not detected by repeated RT-PCR. We believe this to be the first reported case in which eradication of HCV was achieved by corticosteroid therapy alone, without the introduction of interferon.
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7/427. Successful treatment of decompensated chronic viral hepatitis by bursal disease virus vaccine.

    Three cases of women with chronic liver inflammation caused by hepatitis b (two) and C (one) viral infections, were followed up to twelve years after diagnosis. As conventional therapy was ineffective and the patients progressed into decompensated liver disease, they were superinfected with massive doses of an attenuated variant (MTH-68/B) of the apathogenic avian Bursal Disease virus (a double-stranded RNA virus from the birnaviridae family). Clinical symptoms and biochemical abnormalities were resolved in two patients following few months of virus treatment. Cirrhosis was stabilized and significant clinical improvement was achieved in the third patient--who before the virus therapy was moribund with recurring, diuretic-resistant ascites, variceal bleedings, portal encephalopathy and renal failure. To our knowledge, these are the first recorded cases of decompensated chronic viral hepatitis which went to long-lasting remission or were stabilized by superinfection with an apathogenic virus.
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8/427. Rapid evolution of chronic viral hepatitis into hepatocellular carcinoma after beta-interferon treatment.

    A 62-year-old man, affected by Chronic Active Hepatitis (discovered in 1993) and treated with interferon, referred to our department with increased abdominal volume, persistent abdominal pain, continuous-remittent fever and jaundice. CT scan of the liver revealed a hypodense, not capsulated, infiltrative, solid formation in the right lobe. US guided biopsy showed multinucleated giant cells, with eosinophilic cytoplasm and pleomorphism of the nuclei, arranged in several thick trabecula lined by endothelial cells or formed bile containing acini. In our case, the rapid evolution of chronic viral hepatitis towards HCC calls for a careful evaluation of the role of IFN therapy, since this drug is widely used in chronic liver diseases.
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9/427. Secondary hyperparathyroidism exacerbation: a rare side-effect of interferon-alpha?

    Recombinant human interferon alpha (alpha IFN) is the only treatment with proven benefit for chronic hepatitis c virus (HCV) infection. Nevertheless its use in some susceptible individuals has led to the development or aggravation of different autoimmune conditions. We report the case of a 20 year old woman on peritoneal dialysis with chronic lobular hepatitis secondary to HCV infection who developed de novo psoriasis 9 months after starting treatment with alpha-IFN. In addition to psoriasis, alpha-IFN prescription was also concurrent with an unexpected and refractory secondary hyperparathyroidism exacerbation initially characterized by a marked reduction of serum calcium levels and a consequential increase of PTH. Both complications disappeared after drug withdrawal. The clinical sequence makes an alpha-IFN-induced autoimmune side effect the most plausible hypothesis. The case is discussed and some possible etiopathogenic factors are briefly reviewed.
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10/427. Response to treatment with interferon-alfa in patients with chronic hepatitis c and high titers of -M2, -M4 and -M8 antimitochondrial antibodies.

    The prevalence of antimitochondrial antibodies (AMA) in chronic hepatitis c is 2%; titers of AMA are usually low (< 1:40). The prevalence decreases to 0.5% when the results are verified by determination of the M2 subtype (anti-M2, ELISA). In patients in whom both hepatitis c virus (HCV) and AMA are present, the therapeutic decision to give interferon-alfa is complicated, because AMA may be 'real', and if it reflects primary biliary cirrhosis, cholestasis can be triggered or exacerbated. This does not occur when AMA positivity results from induction by hepatotropic C virus; however, this is rarely the case when AMA titers are high (> 1:160). OBJECTIVE: to undertake a preliminary analysis of the submitochondrial profile of AMA in three patients with chronic hepatitis c and positive AMA titers (> 1:160). methods: we determined antibodies to submitochondrial particles (subtypes) -M2, -M4 and -M8 by ELISA, complement binding (CB) and western immunoblotting with Immunoblot-M2 or WIB-M2 (immunoreactive bands). RESULTS: two patients were positive for mitochondrial subtypes by ELISA (IgG/IgM subclass) and CB (ELISA M2 470/365 in patient 1 and 600/1370 in patient 2; M4 490/1200 in patient 2. CB M2 1:128, M4 1:64, M8 1:64 in patient 1, M2 1:128 in patient 2). Immunoreactive epitopes (bands) were detected with WIB-M2 for 70, 56, 51, 45 and 36-kDa molecules. Interferon-alfa treatment was unsuccessful, with biochemical exacerbation of cholestasis. In contrast, the patient with no submitochondrial particles according to ELISA, CB and WIB-M2 results responded favorable to this drug. CONCLUSION: these preliminary results suggest that analyses to detect antibodies to submitochondrial particles (-M2, -M4 and -M8 subtypes) and -M2-immunoreactive epitopes in patients with chronic hepatitis c and AMA titers > 1:160 facilitates the diagnosis of primary biliary cirrhosis, and establishes a contraindication for treatment with interferon-alfa despite the presence of HCV infection.
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