MTHFR C677T mutations in liver cirrhosis with and without portal vein thrombosis.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C Fabiano
Publications and source records attributed to C Fabiano.
Polyamines biosynthesis and oxidation in free-living amoebae.
In this paper we describe the polyamine biosynthesis and oxidation processes, giving an overview about recent results in free-living Amoebae. The protozoa polyamine levels are different in comparison with mammalian cells. Also, the polyamine levels in protozoa cells change if these species are pathological or not for the human beings. All the amoeba strains show high concentrations of 1,3-diaminopropane (DAP), spermidine and acetylspermidine while spermine is absent. In these amoeba a considerable polyamine oxidase activity has been found, which acts on N8-acetylspermidine, but not on free polyamines. This enzyme is responsible, together with polyamine acetylase, of DAP synthesis whose function is not well known.
Amoeba↗
HCV NS5A mutations in Europeans infected by genotype 1b.
Explore the source record for details and available documents.
Genotype↗
Long-term course of interferon-treated chronic hepatitis C.
BACKGROUND/AIMS: To evaluate whether sustained response to a-interferon improves clinical outcome in patients with chronic hepatitis C. METHODS: A cohort of 410 consecutive patients (65% with chronic hepatitis, 35% with cirrhosis) were treated with a-interferon in two trials (mean follow-up 62.1 months, range 7-109 months). All were serum HCV RNA positive before therapy and received first 10 then 5 million units of a-2b or a-nl interferon three times weekly for 6 to 12 months. Sustained response was defined as normal aminotransferases 12 months after stopping interferon. RESULTS: Sixty-two patients (15.1%: 54 with chronic hepatitis, eight with cirrhosis) were sustained responders. At the end of follow-up, 56 out of 62 sustained responders (90.3%) were serum HCV RNA negative. No biochemical relapse after 12 months was seen in sustained responders, regardless of initial histology, HCV genotype or persistence of HCV RNA. Although three died of non-hepatic causes, no liver-related events were observed among sustained responders. Complications of liver disease occurred in 34 relapsers/non-responders: nine hepatocellular carcinomas, 21 ascites and four portal hypertensive bleedings. Eleven relapsers/nonresponders died: eight of hepatic and three of non-hepatic causes. Event-free survival was significantly longer in sustained responders than in all the remaining patients. In a regression analysis, sustained response to interferon, low age and absence of cirrhosis were independent predictors of event-free survival. CONCLUSIONS: Hepatitis C virus is probably eradicated and progression of liver disease is prevented in most patients who remain HCV RNA negative with normal transaminases for more than 1 year after stopping treatment.
Adult↗
Nitric oxide mediates NMDA-evoked [3H]GABA release from chick retina cells.
The stimulation of NMDA receptor increased [3H]GABA release from preloaded cultured retina cells. This effect appears to be mediated by NO production, since addition of L-NA reduces NMDA-evoked [3H]GABA release. Spermine/NO complex, an NO donor, mimics the effect produced by NMDA. The addition of zaprinast, a phosphodiesterase inhibitor, as well as 8-Br-cGMP enhances the NMDA-evoked [3H]GABA release. These results agree with the existence in chick retina cells of NO/cGMP pathways and support a role for NO in NMDA-evoked events. The activation of this receptor complex through maturative stages of the retina together with the NO-mediated increase in GABA release may account for NMDA differentiative effect in culturing retina cells.
1-Methyl-3-isobutylxanthine↗
Long-term efficacy of alpha-interferon in beta-thalassemics with chronic hepatitis C.
Hepatitis C virus (HCV) infection is a common cause of liver disease among polytransfused thalassemics. We treated a cohort of subjects with beta-thalassemia major and chronic hepatitis C with alpha-interferon. The aims of the study were to assess the long-term biochemical and virologic efficacy of alpha-interferon and to evaluate the influence of HCV type and liver siderosis on the outcome of therapy. Seventy subjects (mean age, 14.1 years) with chronic HCV infection and abnormal aminotransferases received recombinant alpha-interferon for 12 months and were observed after therapy for at least 24 months. Sixty-three subjects (90%) were HCV-RNA positive at the start of therapy. HCV type 1b was found in 41 subjects (65.1%), non-1b types in 13 (20.6%), and mixed HCV types in 9 (14.3%). Liver biopsy showed cirrhosis in 11 subjects (15.7%) and siderosis grade 3-4 in 24 patients (34.2%). Three patients stopped therapy due to adverse events. Twenty-eight subjects (40%) had normal aminotransferases and had cleared HCV-RNA when last observed (mean follow-up, 36.5 months; range, 25 to 49 months). Of 41 patients who did not normalize aminotransferases, 9 had become HCV-RNA negative at the end of follow-up. The absence of cirrhosis, low liver iron content, and infection with non-1b HCV type were independently associated to complete sustained response upon multivariable analysis. In conclusion, alpha-interferon may induce a sustained virologic and biochemical remission of hepatitis in beta-thalassemic patients with chronic HCV infection and nonadvanced liver disease.
Adolescent↗
A randomized controlled trial of high-dose maintenance interferon therapy in chronic hepatitis C.
In chronic hepatitis C virus (HCV) infection, the rate of sustained response to interferon is low. We evaluated, in patients responding to a 26-week course of interferon, the effect of high-dose maintenance therapy in preventing relapse. Three hundred and ten patients with chronic HCV infection (38.3% with cirrhosis, 80.6% with HCV type 1) received interferon alfa-2b for 26 weeks (10 MU tiw for 8 weeks, then 5 MU tiw for 18 weeks). One hundred and twenty-four subjects (40%) normalized aminotransferases, and were allocated randomly either to continue on 5 MU tiw for a further 26 weeks (prolonged therapy group: 60 patients) or to stop interferon (brief therapy group: 64 patients). Fifty-two weeks after stopping interferon the overall sustained biochemical response rate was 13.2% (41/310). The number of patients with normal aminotransferases was comparable between the prolonged and brief therapy groups (30% vs. 35.9%, P = n.s.), and the rate of HCV-RNA clearance was similar (48.8% vs. 42.4%, P = n.s.). The timing of posttreatment relapse was not influenced by the duration of therapy. Fifty-nine patients (19%) did not complete therapy due to adverse effects. Multivariate analysis identified four features predicting sustained biochemical response in subjects normalizing aminotransferases under therapy: negative HCV-RNA at end of therapy, normal aminotransferases at 4 weeks of therapy, high baseline aminotransferases, and high baseline platelets. Infection with HCV type 1 was not a significant predictor of response, due to its high prevalence in our population (80.6%). It is concluded that in patients with chronic hepatitis C mostly infected by HCV type 1, a prolonged high-dose interferon course (900 MU over 52 weeks) did not increase the rate of sustained biochemical response and of HCV-RNA clearance in comparison to a brief course (510 MU over 26 weeks).
Adolescent↗
HCV viraemia is more important than genotype as a predictor of response to interferon in Sicily (southern Italy).
BACKGROUND/AIMS: To investigate host- and virus-related factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent. METHODS: We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of the 5' non-coding region. RESULTS: Mean pre-treatment HCV-RNA level (x 10(3) genome equivalents/ml +/- SD) was lower in sustained responders (3854 +/- 7142) than in relapsers (9587 +/- 10163) or in non-responders (5709 +/- 6618). HCV subtype 1b was highly prevalent (82%), while types 1a, 2a, 3 and 4 were rare (about 5% each). However, the prevalence of 1b was much lower (31%) under 40 years of age. The prevalence of subtype 1b among sustained responders (74%) was similar to that observed among relapsers (82%) or non-responders (84%), but some nucleotide substitutions in the putative RNA loop of the 5' non-coding region were seen only among relapsers or non-responders. Multiple logistic regression model showed that early response to interferon was predicted by absence of cirrhosis and a pre-treatment HCV-RNA level below 350. Sustained response to interferon was predicted by pre-treatment HCV-RNA level below 350 and a low fibrosis score. CONCLUSIONS: Among patients with hepatitis C from an area where subtype 1b is highly prevalent, absence of cirrhosis and low pre-treatment serum HCV-RNA level are the most important predictors of response to IFN. Some nucleotide substitutions found in the 5' non-coding region of subtype 1b are associated with non-response or relapse.
Adult↗
Interferon and steroid treatment in patients with chronic hepatitis C and antinuclear or anti-liver-kidney microsomal antibodies.
Treatment of HCV-related chronic hepatitis is controversial when non-organ specific autoantibodies are present, due to potential severe autoimmune reactions under interferon. We evaluated, in an open study, a sequential approach (steroid->interferon) in 20 consecutive patients with biopsy-proven chronic hepatitis, anti-HCV positive (EIA2/RIBA2) and autoantibody positive at a titre > or = 1/80 (18 antinuclear and 2 anti-liver-kidney microsomal antibodies). Nine patients responded to steroids (ALT reduced by > or = 50% at 12 weeks) and continued on prednisone up to one year. Notably, ALT did not return to normal and steroid treatment was ineffective in controlling necroinflammation on follow-up biopsies. After stopping prednisone, ALT rebounded to pre-treatment levels in 6/9 cases. Four of these 6 then received interferon: 3 of them had a complete response (e.g. normal ALT at end of therapy), in 2 with loss of HCV RNA. Eleven patients were, instead, steroid resistant and after wash-out were switched to lymphoblastoid alfa-interferon (6 MU t.i.w. for 8 weeks, 3 MU t.i.w. for 16 weeks). Four cases had a complete response to interferon (3 with loss of HCV RNA) with follow-up biopsies showing definite reduction of necroinflammation. None of the 15 receiving interferon in the present study experienced ALT peaks, deterioration of liver disease, autoimmune-like phenomena. We suggest that antiviral treatment with alfa-interferon could be the first choice in chronic hepatitis C, even in autoantibody positive cases.
Adult↗
Hepatitis C virus infection as a determinant of behavior in type 1 autoimmune hepatitis.
To determine if hepatitis C virus infection influences the behavior of type 1 autoimmune hepatitis and to assess the performance parameters of third-generation immunoassays for viral infection in this disease, 64 patients with different patterns of disease behavior were assessed retrospectively for antibodies to hepatitis C virus by third-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay and for HCV RNA by polymerase chain reaction. Hepatitis C virus RNA was detected in seven patients (11%) and antibodies to hepatitis C virus were found in five (8%). All patients who had an acute onset of illness or who sustained remission after therapy lacked HCV RNA in serum. In contrast, four of 31 patients who relapsed (13%) and three of 17 patients who failed treatment (18%) had HCV RNA in serum. Patients with HCV RNA were indistinguishable from those without HCV RNA; in three patients, infection was recognized only by testing for HCV RNA. Four of seven patients with HCV RNA responded fully to corticosteroids, although each relapsed after drug withdrawal. Smooth muscle antibodies (43% versus 91%, P = 0.006) and concurrent smooth muscle and antinuclear antibodies (0% versus 60%, P = 0.003) occurred less frequently in patients with HCV RNA than in counterparts without HCV RNA. The specificity of the third-generation enzyme immunoassay was 98% and its overall predictability was 94%. Its sensitivity, however, was 57% and false positive results occurred in 20%. Hepatitis C virus infection is an uncommon determinant of disease behavior in type 1 autoimmune hepatitis, but it may be present in relapse or treatment failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Third-generation hepatitis C virus tests in asymptomatic anti-HCV-positive blood donors.
This study evaluated the performance of third-generation anti-HCV assays in blood donors who were positive by second-generation anti-HCV, and assessed any possible relationship between antibody patterns, HCV replication and liver damage. Fifty-two second-generation enzyme immunoassay-positive asymptomatic Italian blood donors were retested for anti-HCV by third-generation enzyme immunoassay and recombinant immunoblot assay (Ortho third-generation enzyme immunoassay, third-generation recombinant immunoblot assay), utilising recombinant C33c and NS5 and synthetic peptide C100 and C22 antigens, and for HCV-RNA by "nested" polymerase chain reaction with 5' region primers. Alanine aminotransferases were tested monthly for 6 months. Two out of 52 second-generation enzyme immunoassay-positive donors were third-generation enzyme immunoassay, third-generation recombinant immunoblot assay and HCV-RNA negative. Among 50 third-generation enzyme immunoassay-positive cases, two had a third-generation enzyme immunoassay optical density < or = 1: one was third-generation recombinant immunoblot assay and HCV-RNA negative, and the other was third-generation recombinant immunoblot assay "indeterminate" and HCV-RNA-positive. The remaining 48 cases had third-generation enzyme immunoassay optical density > 1: six were third-generation recombinant immunoblot assay negative (one HCV-RNA+ve), eight "indeterminate" (two HCV-RNA+ve) and 34 positive (22 HCV-RNA+ve). All "indeterminate" subjects reacted only to C22. HCV-RNA was positive in 22/34 cases with positive third-generation recombinant immunoblot assay (two or more Ags), 3/9 "indeterminate" and 1/11 negative. Alanine amino-transferases were abnormal in 13 cases with positive third-generation recombinant immunoblot assay, one was "indeterminate" and three were negative.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hepatitis C viremia in chronic liver disease: relationship to interferon-alpha or corticosteroid treatment.
We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody-positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p < 0.001). Mean viremia level (x 10(3) genome equivalents/ml +/- S.D.), as assessed with the branched-DNA test, was 5,700 +/- 7,618 in the 48 patients with chronic hepatitis, 3,340 +/- 3,633 in the 21 patients with cirrhosis and 1,768 +/- 2,770 in the 31 patients with hepatocellular carcinoma (p < 0.02). We also analyzed retrospectively the relationship between viremia and treatment. Fifty-five patients (41 chronic hepatitis, 14 cirrhosis) underwent interferon-alpha treatment. Mean viremia level was comparable among the 30 responders (5,644 +/- 8,207) and the 25 nonresponders (5,519 +/- 6,208) to interferon, but it was significantly lower (1,841 +/- 1,864) in the 12 of 30 responders (11 chronic hepatitis, 1 cirrhosis) who maintained remission up to 1 yr after cessation of interferon treatment. Fourteen patients (7 chronic hepatitis, 7 cirrhosis) with autoantibodies (12 antinuclear, 2 anti-liver-kidney microsomal) were treated with prednisone. The mean viremia level significantly increased after 3 mo of treatment, even in face of ALT decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
IgM and IgG antibodies to hepatitis C virus in patients with mixed cryoglobulinaemia.
To assess the relationship between hepatitis C virus (HCV) infection and essential mixed cryoglobulinaemia (EMC), sera from 23 patients with EMC were tested for IgG and IgM antibodies to HCV antigens and for HCV RNA. Quantitative HCV antibody studies were performed on serum and purified cryoglobulin fractions. HCV antibodies of both IgG and IgM class were found in 22 (96%) patients. Ten of these were also HCV-RNA positives. Higher titres of anti-HCV IgM were present in the 11 patients with evidence of liver damage. Anti-HCV IgG antibodies were shown to be concentrated in the IgG fraction of cryoglobulins in all eight patients studied. These results strongly suggest a role for HCV in the pathogenesis of EMC.
Adult↗
The natural history of chronic HDV infection.
Explore the source record for details and available documents.
Adolescent↗
Serum hepatitis C virus (HCV)-RNA and response to alpha-interferon in anti-HCV positive chronic hepatitis.
Hepatitis C virus (HCV) replication was assessed before and during alpha-interferon (IFN) treatment in 22 anti-HCV positive patients with posttransfusion or sporadic chronic hepatitis (CH). Eleven patients were "responders" and 11 patients "non-responders" to IFN. Thirteen anti-HCV negative healthy subjects and five anti-HCV negative patients with autoimmune CH served as controls. Serum HCV-RNA was detected by the polymerase chain reaction (PCR) in all untreated anti-HCV positive patients but in none of the anti-HCV negative subjects. PCR primers from the 5'-noncoding (NC) region were more sensitive than primers from a non-structural (NS5) region in detecting HCV-RNA (21/22, 95% vs. 7/22, 32%, respectively). Positive strand HCV-RNA titre and positivity rate for the negative strand were similar in responders and non-responders before IFN treatment, as well as anti-c100-3 titre by enzyme-linked immunosorbent assay (ELISA), and anti-5-1-1, anti-c33c, anti-c22 positivity rate by immunoblot assay (RIBA). HCV-RNA positivity by both NC and NS primers was more frequent before IFN among responders. During IFN treatment, serum HCV-RNA was detectable, mostly at low titres, in 1 (NC positive) of the 11 responders and in 9 (4 NS positive and 5 NC positive) of the 11 non-responders. Among the four non-responders who were NS positive during IFN, three were NC positive before IFN. Serum HCV-RNA was always found in our post-transfusion or sporadic anti-HCV positive patients with CH. Viraemia generally decreased during IFN treatment, but no available HCV markers clearly distinguished responders from non-responders before IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Polyamines are involved in retinoic acid-mediated induction of tissue transglutaminase in human peripheral blood monocytes.
The differentiation of human peripheral blood monocytes (HPBM) into macrophages, when cultured in vitro, has been associated with an increase in the expression of tissue transglutaminase (TGc). Retinoic acid (RA) addition to 5-day-old cultured monocytes, 36 h later induced about 5-folds increase of TGc content. The preliminary exposure of cultured monocytes to alpha-difluoromethylornithine (DFMO) significantly reduced TGc induction caused by RA. DFMO alone does not induce significant changes in the time-course of TGc activity. In cultured monocytes exposed to DFMO, putrescine and spermidine, but not spermine were significantly depleted. The supplementation of putrescine (1 mM) or spermidine (0.5 mM) to culture medium reversed the inhibiting effect of DFMO on RA-mediated induction of TGc. However, the addition of polyamines in the absence of RA or DFMO did not mimic the induction of TGc by RA. We conclude that TGc induction by RA during in vitro maturation of monocytes to macrophages may be modulated by polyamine availability.
Cell Differentiation↗
Hepatitis delta superinfection during alpha-interferon treatment for hepatitis B.
Alpha-interferon (IFN) has been used to treat hepatitis B virus carriers with chronic hepatitis Delta virus superinfection. Although the drug inhibits hepatitis Delta virus replication during administration, long-term clearance of the virus has not been obtained in most patients. The effectiveness of alpha-interferon on chronic HDV infection is therefore questionable. No data are available on acute infection. We report the case of a young, immunocompetent HBsAg carrier in whom hepatitis Delta virus superinfection occurred while he was receiving alpha-interferon in order to reduce high level HBV replication, and followed a peculiar course.
Acute Disease↗
Hepatitis C virus replication in chronic liver disease.
Explore the source record for details and available documents.
Female↗