Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To compare two interferon (IFN) schedules for the treatment of chronic hepatitis C, we followed 211 patients who received 3 million units IFN-alpha2b thrice weekly for either 6 months (group 1; 85 patients) or 12 months (group 2; 126 patients), with a median follow-up of 3.4 (0.1-8.4) and 4.2 (0.7-8.7) years, respectively. The biochemical and virological responses at the end of treatment were 34.1% and 16.5% versus 62.7% and 41.2% for the 6- and the 12-month regimens, respectively. Late biochemical responses (after the third month of treatment) occurred in 30.6% of responding patients, and they were not particularly associated with an adverse long-term treatment outcome. In a multivariate analysis, patients with a primary response were significantly more frequently infected with a non-1b HCV genotype (relative risk [RR]: 14.4), had been treated for 12 months (RR: 6.0), and had an early stage of liver fibrosis (RR: 5.2). Baseline serum HCV-RNA and ferritin levels also bore a significant, though weaker, association with a primary response. Using a set of pretreatment variables in a model of discriminant analysis, we could correctly predict the long-term virological outcome in 86.6% of the individual cases. At the end of follow-up, a biochemical and virological sustained response was observed in 14.1% and 11.8% versus 40.5% and 31% of groups 1 and 2, respectively. Significant predictors of a virological sustained response were a virological primary response (RR: 41.2) and the pretreatment level of serum HCV-RNA (RR: 10.3 per each 10(6)-Eq/mL decrease). Patients with a "good treatment profile," including an early stage of liver fibrosis, a non-1b genotype and serum HCV-RNA <0.35 x 10(6) Eq/mL, had a 66.7% rate of observed virological SR, compared with a zero response for those with the opposite, a "bad treatment profile." We conclude that a 12-month IFN treatment, along with a non-1b genotype and the absence of advanced stage of fibrosis, are the main determinants for the induction of a virological primary response in chronic hepatitis C. Such response, along with a low pretreatment serum HCV-RNA level, are the main predictors for a 4-year virological response to IFN.
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PMID:Biochemical and virological outcome of patients with chronic hepatitis C treated with interferon alfa-2b for 6 or 12 months: a 4-year follow-up of 211 patients. 930 5

Because the majority of patients with chronic hepatitis C do not respond to interferon, alternative treatments need to be established. Several lines of evidence suggest that iron depletion is beneficial for such patients. Thus, gastrectomized patients with a reduced capacity for iron absorption might have an advantage in treatment of their liver damage over patients with intact gastrointestinal tracts. Four male gastrectomized patients had post-transfusion chronic hepatitis C. The iron load in three patients was adjusted below 10 ng/ml of serum ferritin level by phlebotomy. Subsequent interferon treatment for the four patients without iron load cleared circulating hepatitis C virus RNA in one patient only. However, serum ferritin concentrations were stabilized at low levels without maintenance phlebotomy, and sustained normalization of serum liver enzyme activities was obtained in all four patients. Similar treatments were done for 10 male patients with intact gastrointestinal tracts. The amount of removed iron from these patients was more than that from gastrectomized patients. Interferon also failed to clear circulating hepatitis C virus RNA except in one case. Low ferritin levels and sustained normalization of liver enzymes were seen in three patients. A transient elevation of ferritin levels with low enzyme activities was seen in two patients. Relapsing hepatitis was seen in five of the seven patients who needed maintenance phlebotomy due to a rebound in serum ferritin levels, probably because of active iron absorption from the intestine. Our data suggest that depletion of cytotoxic iron is a key to managing patients with chronic hepatitis C.
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PMID:The advantage of gastrectomized patients in management of their chronic hepatitis C. 948 Oct 91

The efficacy of a high-dose de-escalating treatment regimen versus the standard, fixed-treatment regimen of interferon-alpha2a (IFN; Roferon-A) in chronic hepatitis C was evaluated in 291 patients who had elevated alanine aminotransferase (ALT) levels, for at least 6 months prior to the study, and histologically proven chronic hepatitis. Patients were randomized into two groups: 142 patients received IFN at a fixed dose (3 million international units (MIU) three times a week for 6 months) and 149 patients received 6 MIU three times a week for 3 months followed by 3 MIU three times a week for the next 3 months. The groups did not differ significantly with respect to age, gender or percentage of patients with cirrhosis. Response was evaluated by monitoring ALT levels monthly during treatment and during the 6 months post-treatment follow-up. Sixty-one per cent and 66% of the patients in the fixed and de-escalating treatment groups had a primary response (serum ALT normalization) during the treatment period; sustained-response rates at the end of follow-up were 20% and 29%, respectively (not significant). In non-cirrhotic patients, a primary response was recorded in 65% and 70% of the patients in the fixed and de-escalating groups; sustained-response rates were 22% and 33%, respectively. Overall, 62% of patients with a sustained response showed histological improvement. In univariate analysis, patients with sustained response tended to be non-cirrhotic and had lower initial serum gamma-glutamyl transpeptidase and ferritin levels. Multivariate analysis indicated that only ALT activity assessed at month 1 (P < 0.01) was a significant predictor of sustained response. These findings suggest that although the difference in the response rates between the de-escalating (6 MIU three times a week for 3 months; 3 MIU three times a week for 3 months) and fixed (3 MIU three times a week for 6 months) treatment regimens did not reach statistical significance, there was a clear trend towards higher response with the 6 MIU induction dose in patients without cirrhosis.
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PMID:Comparison of high initial and fixed-dose regimens of interferon-alpha2a in chronic hepatitis C: a randomized controlled trial. French Multicenter Interferon Study Group. 949 17

Hepatic iron has been associated with more aggressive liver disease in chronic viral hepatitis. We evaluated whether the recently described C282Y mutation of the hemochromatosis gene, designated HFE (responsible for at least 83% of hereditary hemochromatosis), was associated with more advanced liver disease in chronic hepatitis C. One hundred thirty-seven patients with biopsy-proven chronic hepatitis C were studied and liver biopsies scored for necroinflammation (grade 0-18) and fibrosis (stage 0-6). Genomic DNA was amplified by polymerase chain reaction and the C282Y mutation identified by restriction with RsaI and electrophoretic separation of restriction fragments. Ten (7.3%) patients had the C282Y mutation. No C282Y homozygous patients were identified. Age, sex distribution, and estimated weekly alcohol consumption were not significantly different between those with and without the mutation. Serum ferritin was higher in the heterozygotes (mean, 339 microg/L) compared with homozygous wild types (153 microg/L; P = .0005). In the majority of patients, liver iron was graded 0 out of 4, but hepatocyte iron staining was more commonly present in heterozygotes compared with homozygous normals (30% compared with 4% [P = .02]). Liver disease was more advanced in those with the mutant allele (mean fibrosis stage: 3.6, compared with wild type: 1.5 [P = .01]). Cirrhosis was found more often in those with the mutation (40%) compared with those without (8.7%) (P = .01; odds ratio: 7.6 [1.9-31.2]). There was no significant difference in inflammation scores between heterozygotes and wild type (mean, 5.4 compared with 4.1). Hepatitis C virus (HCV)-RNA titers were measured by branched DNA assay (HCV RNA 2.0-Chiron), and there was no difference between heterozygous and homozygous normal patients. Thus, despite relatively minor increases in iron stores, individuals who are heterozygous for hemochromatosis appear to develop more fibrosis in chronic hepatitis C. Venesection may be useful therapy in this subgroup.
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PMID:Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C. 1033 38

After successful marrow transplantation (BMT) iron overload remains an important cause of morbidity in Thalassemia. After BMT, patients have normal erythropoiesis capable of producing a hyperplastic response to phlebotomy so that this procedure can be contemplated as a method of mobilizing iron from overloaded tissues. Forty-one patients (mean age 16 +/- 2.9 years) with prolonged follow-up (range 2-7 years) after BMT were submitted to a moderate intensity phlebotomy program (6 ml/kg blood withdrawal at 14-day intervals) to reduce iron overload. Values are expressed as mean +/- SD or as median with a range (25th-75th percentile). Serum ferritin decreased from 2,587 (2,129-4,817) to 280 (132-920) micrograms/l (p < 0.0001), total transferrin increased from 2.34 +/- 0.37 to 2.9 +/- 0.66 g/l (p = 0.0001), transferrin saturation decreased from 90% +/- 14% to 39% +/- 34% (p < 0.0001). Liver iron concentration evaluated on liver biopsy specimens decreased from 20.8 (15.5-28.1) to 3 (0.9-14.6) mg/g dry weight (p < 0.0001). Alanine amino-transaminase from 5.2 +/- 3.4 to 1.6 +/- 1.2 (p < 0.0001) times the upper level of normality. The histological grading for chronic hepatitis (Histology Activity Index) decreased from 4.2 +/- 2.4 to 2.3 +/- 1.8 (p < 0.0001). Phlebotomy is a safe, efficient, and widely applicable method to decrease iron overload in "ex-thalassemic."
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PMID:Treatment of iron overload in the "ex-thalassemic". Report from the phlebotomy program. 966 50

Vibrio vulnificus causes severe wound infections and sepsis, mostly in persons with chronic liver diseases. Survival of this organism in the whole blood collected from healthy volunteers and patients with chronic hepatitis, liver cirrhosis, and hepatoma was analyzed as an indication of susceptibility. The bacterial numbers in the blood after 5 h of incubation tended to increase with the severity of the liver disease and differed significantly between hepatoma patients and healthy volunteers (P<.05). Survival of V. vulnificus in the whole blood correlated positively with serum ferritin concentration (r=.266; P<.05) and percentage of transferrin iron saturation (r=. 200; P<.05) and correlated negatively with serum C4 concentration (r=-.198; P<.05) and phagocytosis by neutrophils (r=-.204; P<.05). Among these parameters, low phagocytosis activity (P<.01) and high ferritin level (P<.01) in the blood were the independent predictors.
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PMID:Survival of Vibrio vulnificus in whole blood from patients with chronic liver diseases: association with phagocytosis by neutrophils and serum ferritin levels. 984 54

Recent reports suggest the hepatic iron concentration (HIC) may influence the activity of hepatitis and the response to interferon (IFN) therapy in patients with chronic hepatitis C (CH-C). We have evaluated iron status in 28 patients with CH-C and determined if pretreatment iron status can predict the response to IFN-alpha therapy in these patients. Increased serum iron, transferrin saturation, and ferritin levels were observed in 3 (11%), 11 (39%), and 5 (18%) patients, respectively. Hepatic iron deposits were histologically detected in 17 (61%) patients, and 14 of them had stainable hepatocytic iron. However, all HIC values were within the normal range (203-1279 microg/g). Seven of 17 patients treated with IFN-alpha for 6 mo had normalization of serum transaminases and disappearance of serum HCV-RNA (responders). Nonresponders had a significantly higher median HIC compared with responders (710 vs 343 microg/g, respectively; p < 0.05). There was no significant difference in other pretreatment iron parameters, serum HCV-RNA level, or HCV-genotype between responders and nonresponders. In conclusion, mild hepatic iron accumulation occurs in patients with CH-C. Increased hepatic iron stores are associated with poor response to IFN therapy. Pretreatment HIC may be an additional host-specific parameter with a predictive value for responsiveness to IFN therapy, in addition to well-known predictive viral factors.
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PMID:Failure to respond to interferon-alpha 2a therapy is associated with increased hepatic iron levels in patients with chronic hepatitis C. 984 73

Interferon (IFN) is the only drug that has been approved by the FDA for therapy of chronic hepatitis C. However, optimal dose and duration of therapy are still controversial. This study compares the effectiveness of treatment of chronic hepatitis C patients with 3 vs. 5 million units (MU) of recombinant alpha-interferon 2-b three times per week. We also evaluated the relapse rate with a shorter 12 week-course of therapy in those patients who had normalization of aminotransferases by week 12. Seventy-five patients were randomized to receive either 3 vs. 5 MU of IFN; seventy-two completed the study. A complete response was seen in 11/35 (31%) of those treated with 5 MU vs. 13/37 (35%) in the 3 MU dose (p = 0.74). Patients were followed after IFN was withdrawn and only 2 had persistently normal aminotransferases. Analysis of multiple variables was done to predict response to IFN and only elevations of GGT, ferritin and alkaline phosphatase were found to be predictors of a poor response. Therefore, we recommend initial therapy with 3 MU of IFN for a longer period than 12 weeks in patients who show a response.
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PMID:Chronic hepatitis C: treatment comparison between 3 and 5 million units of interferon alpha-2b. 988 67

Elevated iron levels have been associated with raised serum alanine transaminase (ALT) levels in hepatitis C virus (HCV)-infected humans. However, it is not clear if HCV infection causes increased iron accumulation by the liver or if the severity of HCV infection is actually worsened by higher iron levels in the host. To better understand the relationship between iron and persistent HCV infections, we examined the effect of excess dietary iron on disease severity in HCV-infected chimpanzees. Iron was supplemented in the diets of four HCV-infected and two uninfected chimpanzees for 29 weeks to achieve iron loading. Iron loading was confirmed by increases in serum iron levels, percentages of transferrin saturation, ferritin levels, elevations in hepatic iron concentration (HIC), and by histological examination. The majority of HCV-infected chimpanzees had higher iron levels before iron feeding than the uninfected animals. Although various degrees of iron loading occurred in all chimpanzees, HCV-infected animals exhibited increased loading in comparison with uninfected animals. The effects of iron loading on HCV disease expression was determined by comparing disease parameters during an extended baseline period before iron loading with the period during iron loading and immediately following iron loading. Iron loading did not influence the viral load, but did exacerbate liver injury in HCV-infected chimpanzees, as evidenced by elevated ALT and histological changes. Because all chimpanzees on high iron diets experienced iron loading, but pathological effects were only observed in HCV-infected chimpanzees, HCV infection appears to increase the susceptibility of the liver to injury following iron loading. These results confirm and extend previous observations made in human populations and serve to further validate the chimpanzee model of chronic hepatitis C.
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PMID:Effects of iron loading on pathogenicity in hepatitis C virus-infected chimpanzees. 1034 34

Approximately one third of patients with chronic hepatitis C virus (HCV) infection have normal alanine transaminase (ALT) levels. We studied the clinical, biochemical, virological, and histological features in patients with persistently normal ALT. A case-control study was conducted on 275 patients with chronic HCV infection, including 75 patients with persistently normal ALT and 200 patients with abnormal ALT. Persistently normal ALT was defined as 4 consecutive ALT values in each patient within a period of 12 months. The average age of the patients was 44 years (range 18 to 69 years). More non-Hispanic whites had persistently normal ALT. The mean serum ferritin level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (128 +/- 92 ng/mL and 224 +/- 128 ng/mL), respectively (P =.017). The mean HCV-RNA level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (12 x 10(5) +/- 2.8 x 10(6) copies/mL and 33 x 10(5) +/- 8.0 x 10(6)), respectively (P =.02). Histologically, patients with persistently normal ALT had less severe portal inflammation (P <.05), lobular inflammation (P =.003), piecemeal necrosis (P =.002), fibrosis (P <.05), lower prevalence of cirrhosis (P =.007), as well as a slower fibrosis progression rate (P <.001). Chronic hepatitis C patients with persistently normal ALT have low-activity grade and stage on liver biopsy. In these patients the hepatitis C RNA level was lower compared with abnormal ALT patients, which may explain the slower fibrosis progression rate.
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PMID:Clinical features of hepatitis C-infected patients with persistently normal alanine transaminase levels in the Southwestern United States. 1053 55


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