State of the iron metabolism in patients with chronic hepatitis C type C does not influence antiviral treatment with interferon and ribavirin

BACKGROUND/AIMS: Comparison of the iron status in patients who responded and did not respond to combination treatment with interferon alpha and ribavirin in chronic hepatitis C. METHODOLOGY: The study group comprised of 61 patients with chronic hepatitis C (genotype 1) treated with alpha 2b interferon and ribavirin. The iron metabolism was evaluated based on serum iron level, total iron binding capacity, transferrin saturation, serum ferritin concentration and hepatic iron concentration. In the evaluation of antiviral treatment efficacy biochemical and virological responses were taken into account. RESULTS: End of treatment response was observed in 38 patients (62%). Significant differences in iron parameters were not observed between responders and non-responders. Also, sustained viral response, 6 months after treatment completion, was reached in 32 patients (52.5%). Iron metabolism parameters did not differ significantly in the group of sustained responders versus non- responders. Finally, ALT normalization was observed in 42 patients (68.9%). Again, no significant differences in iron status were observed between patients with and without biochemical response excluding significantly higher serum ferritin concentration in non-responders. CONCLUSIONS: Results of this study show that iron status does not significantly influence the efficacy of treatment with interferon and ribavirin in patients with chronic hepatitis C.     

Hepatic iron concentration does not predict response to standard and pegylated-IFN/ribavirin therapy in patients with chronic hepatitis C

BACKGROUND/AIMS: Iron overload is common among patients with chronic hepatitis C (CHC). In this study the role of hepatic iron concentration (HIC) and serum iron parameters was assessed to determine response to standard and pegylated interferon (IFN)/ribavirin combination therapy in patients with CHC. METHODS: Liver biopsies were obtained from 169 IFN-na?ve patients (m=115, f=54, age: 40.8+/-10.7) with CHC. 140 patients were treated with standard IFN/ribavirin, 29 patients with pegylated-IFN/ribavirin. Biopsy specimens were evaluated according to the DiBisceglie scoring system and iron grading. HIC was determined by atomic absorption spectroscopy. Ferritin and transferrin saturation and presence of HFE-C282Y and H63D gene mutations were determined at baseline. RESULTS: Nonresponders to combination therapy had higher serum ferritin levels at baseline (p<0.01). There was no difference of HIC, transferrin saturation levels, and the HFE-mutation status between responders and nonresponders. Logistic regression analysis revealed serum ferritin as an independent predictor of response. HIC correlated with the DiBisceglie score (r=0.352, p<0.001), iron grading (r=0.352, p<0.001) and serum ferritin (r=0.335, P<0.001). CONCLUSIONS: Pretreatment liver iron concentration does not predict response to combination therapy in patients with CHC. In contrast, high baseline serum ferritin levels are predictors of poor response to antiviral therapy.     

Iron depletion and response to interferon in chronic hepatitis C

BACKGROUND/AIMS: Chronic viral hepatitis is associated with elevated serum iron indexes, and iron accumulation in the liver may contribute to liver injury and fibrosis due to hepatitis as well as increased risk of developing hepatocellular carcinoma. We studied the effect of iron depletion on the response to subsequent interferon therapy in chronic hepatitis C. METHODOLOGY: A population of 83 patients affected by chronic hepatitis C who had not previously undergone any specific therapy and who had laboratory confirmation of iron overload (serum ferritin > 400 ng/mL in the males and > 300 ng/mL in the females) was divided into two homogeneous groups. The 43 patients in Group A underwent phlebotomy (300 mL every 10-15 days for an average total of 8 sessions) until their serum ferritin levels were < 100 ng/mL. The 40 patients in Group B were treated with interferon without prior iron depletion. RESULTS: In Group A, iron depletion alone induced a highly significant (p < 0.01) reduction of alanine aminotransferase serum values: from 165 U/L (range: 60-370 U/L). Seventy-six patients completed therapy and follow-up: a complete and sustained response was obtained in 12/39 cases in Group A and in 6/37 cases in group B (p < 0.05). CONCLUSIONS: Iron depletion carried out in patients with chronic hepatitis C who have elevated serum ferritin values induces a significant reduction in necro-inflammatory activity (notable decrease in average alanine aminotransferase values) and improves their response to subsequent treatment with interferon, although it does not modify the viral load.     

Effect of iron depletion on serum markers of fibrogenesis, oxidative stress and serum liver enzymes in chronic hepatitis C: results of a pilot study.

BACKGROUND: Hepatic iron deposition has been associated with decreased response to interferon-alpha monotherapy, and has been speculated to contribute to disease progression in chronic hepatitis C (CHC). We performed this study to evaluate the effect of iron depletion on biochemical and virologic markers, and markers of lipid peroxidation and fibrogenesis. MATERIALS AND METHODS: Eighteen patients with CHC who did not have a virologic response to interferon monotherapy underwent weekly phlebotomies until iron depletion (serum ferritin <50 ng/ml). Serum levels of alanine transaminase (ALT), hepatitis C virus-RNA, transferrin saturation, ferritin, 8-isoprostane, hyaluronic acid, amino-terminal procollagen III peptide and YKL-40 were measured before and after iron depletion. RESULTS: There was a statistically significant reduction of serum ALT, transferrin saturation and serum ferritin after iron depletion (range 4-11 phlebotomies). Serum ALT returned to normal after iron depletion in four (22%) patients. There was a significant reduction in serum procollagen III peptide level among patients who achieved biochemical response. No significant reduction was noted in serum levels of other markers. CONCLUSIONS: Iron depletion was associated with a biochemical response in 22% of patients who did not respond to interferon monotherapy. There was a significant reduction in a key marker of fibrogenesis among patients with biochemical response. These data support longer-term studies of iron depletion in CHC.     

Effect of iron depletion on long-term response to interferon in patients with chronic hepatitis C with increased plasma iron without accumulation of liver iron

We studied the effect of iron depletion on the response to subsequent interferon therapy in a population of 83 patients affected by chronic hepatitis C who had not previously undergone any specific therapy and who had laboratory confirmation of iron overload (serum ferritin > 400 ng/mL in the males and > 300 ng/mL in the females). The population was divided into two homogeneous groups. Group A consisted of 43 patients who underwent phlebotomy (300 mL every 10-15 days for an average total of 8 sessions) until serum ferritin levels of < 100 ng/mL were obtained. The 40 patients in Group B were treated with interferon without prior iron depletion. Iron depletion alone, induced in Group A, brought about a highly significant (p < 0.01) reduction of alanine aminotransferase serum values: from 165 U/L (range 60-370 U/L) to 67 U/L (range 27-158 U/L). Seventy-six patients completed therapy and follow-up: a complete and sustained response was obtained in 12/39 cases in Group A and in 6/37 cases in Group B (p < 0.05). Iron depletion carried out in patients with chronic hepatitis C, who have elevated base values of serum ferritin, induces a significant reduction in necro-inflammatory activity (notable decrease in average alanine aminotransferase values) and improves the response to subsequent treatment with interferon, although it does not modify the viral load.     

Iron depletion is not effective in inducing a virologic response in patients with chronic hepatitis C who failed to respond to interferon therapy

OBJECTIVE: Some studies have suggested that increased iron stores may impact negatively on the response to interferon in patients with chronic hepatitis C infection. We performed this prospective trial to determine the effects of iron depletion on ALT and HCV-RNA levels in patients with chronic hepatitis C infection and to assess whether the response to interferon in patients who had previously failed to respond to interferon was enhanced by iron depletion. METHODS: Patients with chronic hepatitis C resistant to interferon therapy and no evidence of iron overload underwent weekly phlebotomies until the serum ferritin level was below lower limits of normal for the subject's age and sex. Patients were then started on interferon-alpha2b, 3 million units subcutaneously three times per week for a period of 24 weeks. Iron studies, ALT, and HCV-RNA levels were monitored at baseline, after phlebotomy and at 12 and 24 weeks of interferon therapy. RESULTS: Thirty-three patients were enrolled, 28 completed the study. A mean of 7.2 units of blood were removed to achieve iron depletion. ALT levels decreased significantly with phlebotomy (142 IU/L before phlebotomy vs 82 IU/L after phlebotomy; p < 0.001), but log HCV-RNA levels remained unchanged (6.49 before phlebotomy vs 6.51 after phlebotomy). Interferon therapy did not improve ALT levels further. HCV-RNA levels were minimally reduced during interferon therapy (log HCV-RNA 6.49 before interferon vs 6.00 after 24 weeks of interferon therapy). Two patients achieved a virologic end of treatment response, both relapsed within 3 months after discontinuation of interferon. No patient achieved a sustained virologic response. CONCLUSIONS: In patients who previously failed treatment with interferon, iron depletion induced by phlebotomy improves ALT levels but is ineffective in achieving viral eradication in patients retreated with interferon 3 million units three times per week.     

Iron metabolism in patients with the anaemia of end-stage renal disease during treatment with recombinant human erythropoietin

Iron metabolism was studied in 21 patients with the anaemia of end-stage renal disease during 40 weeks of treatment with recombinant human erythropoietin (rhEPO). Oral iron was prescribed to all patients. Initial serum iron concentrations and transferrin saturation levels were subnormal, decreased during the correction period of treatment, and increased thereafter. In 81% of patients in whom pretreatment transferrin saturation was below 0.25, transferrin saturation decreased below 0.16, despite sufficiently high serum ferritin levels. Serum ferritin concentrations decreased significantly. There was no correlation between serum ferritin levels and serum iron or transferrin saturation. Ferrokinetic studies, performed before and during treatment, showed an increase in plasma iron turnover, in erythron transferrin uptake, and in the flux of iron binding sites through the plasma. The rhEPO dose needed to keep the haematocrit at the target level during the maintenance period of treatment was significantly correlated with transferrin saturation, and iron binding capacity, but not with serum ferritin concentrations. This suggests that the functional availability of iron in plasma, rather than the size of body iron stores, is a major factor in the determination of the response to rhEPO treatment in end-stage renal disease.     

Effect of iron therapy on serum ferritin levels in iron-deficiency anemia

The level of serum ferritin is a reliable indicator of body iron stores. Exceptions include liver disease, malignant diseases, and treatment of iron-deficiency anemia. The latter was noted in iron- deficient infants who showed a rise of serum ferritin to normal levels in the first week of treatment. To evaluate this in adults, 14 patients with iron-deficiency anemia were studied prior to and after beginning treatment with oral ferrous sulfate in standard dose, 300 mg t.i.d., or double dose, 600 mg t.i.d. Serum ferritin was assayed by radioimmunoassay. No rise occurred in the first 3 wk in 5 patients treated with standard dose, although hematologic response occurred. With double dose, 7 of 9 showed a ferritin rise in 2 days with return to subnormal levels within 6 days of discontinuing iron. This study indicates that standard treatment of iron deficiency anemia in adults does not cause a rise in serum ferritin until hemoglobin levels are normal. The early rise seen with double dose is most likely due to absorption of iron in excess of utilization for erythropoiesis resulting in temporary storage. When iron is discontinued, stores are rapidly depleted as reflected by the prompt decrease in serum ferritin.     

Role of iron load on fibrogenesis in chronic hepatitis C

BACKGROUND/AIMS: In chronic viral hepatitis, an enhanced iron load is related to lower response to interferon. Furthermore, iron, through the production of oxygen radicals, may stimulate hepatocyte necrosis and the activation of cells responsible for synthesis and deposition of extracellular matrix. We investigated the relationship between iron load, evaluated by serum assays, and liver fibrogenesis in chronic active viral hepatitis. METHODOLOGY: Serum iron, ferritin, transferrin saturation and serum markers of hepatic fibrogenesis (Laminin and the amino-terminal peptide of procollagen III-NPIIIP-) were assayed in 102 patients (47 females, 55 males, mean age 42.48 years) affected by chronic hepatitis C virus and in 81 healthy controls (47 males, 34 females). In hepatitis C virus patients (studied before alpha-interferon treatment) a semiquantitative score for portal inflammation, necrosis and fibrosis was applied to liver biopsy. RESULTS: Serum indices of iron load were higher in hepatitis C virus patients than in controls, and were higher in cirrhotic than in chronic hepatitis cases. Ferritin and serum iron were positively correlated with NPIIIP and laminin; moreover cases with ferritin levels over the normal limit for sex and age had higher levels of NPIIIP and laminin than cases with normal or poor iron status. CONCLUSIONS: Our data suggest that even a mild increase of iron load stimulates hepatic fibrogenesis, probably adding oxygen free radical injury to the damage of viral infection.     

Usefulness of combined measurement of serum bile acids and ferritin as additional prognostic markers to predict failure to reach sustained response to antiviral treatment in chronic hepatitis C

AIM: To investigate the relationship between serum levels of ferritin and bile acids (BA) and the response to antiviral treatment in chronic hepatitis C (HCV). METHODS: A retrospective study was carried out on 35 control volunteers and 50 patients receiving interferon alpha-2b alone or plus ribavirin for 48 weeks. These were classified as sustained responders (SR) for >6 months after therapy (n = 17), non-responders (NR) (n = 27) and relapsers (RL) (n = 6). Before treatment, serum ferritin levels were determined by immunoturbidometry, 3alpha-hydroxyl-BA levels (S-3alpha-OH-BA) were assayed enzymatically and total (desulfated, deglucuronidated and deamidated) BA concentrations (STBA) by gas chromatography-mass spectrometry. RESULTS: STBA were lower in controls than in patients (SR < NR + RL). The highest levels of cholic acid and chenodeoxycholic acid families were found in NR + RL. Levels of cholic acid family were similar in controls and SR, whereas those of chenodeoxycholic acid family were higher in SR than in controls. A significant correlation between STBA (but not S-3alpha-OH-BA) and ferritin was found. Apparent value to predict the absence of a sustained response was calculated by combining elevated ferritin (>300 microg/mL) and STBA or individual BA species at different cut-off values. The best degree of certainty (100% specificity) was obtained using STBA >15 microM. CONCLUSION: These results recommend that larger prospective trials should be performed in chronic HCV patients to evaluate the usefulness of combined measuring of STBA and ferritin as additional prognostic markers to predict the existence of a very low probability of a sustained response to the current standard treatment, i.e. pegylated interferon in combination with ribavirin.     

The Role of Iron in Hepatitis C Infection

Iron overload of varying degrees is common among patients with chronic hepatitis C. The clinical significance of this iron overload is uncertain. Studies that have evaluated the effect of hepatic iron stores on the response to anti-viral treatment or on the natural history of chronic hepatitis C have found variable results depending on the technique used to measure hepatic iron stores and the degree of iron overload present among the study population. We have tried to comprehensively analyze the literature regarding the clinical interaction between iron overload and the natural history of chronic hepatitis C. The one clear relationship that emerges is that pre treatment serum ferritin inversely correlates with the odds of achieving sustained virological(SVR) response after combination interferon ribavirin treatment. We have also reviewed the limited literature that reports the effect of therapeutic phlebotomy to reverse iron overload among patients with chronic hepatitis C. A small meta-analysis of 6 prospective randomized trials and a subsequent seventh trial do suggest that phlebotomy to induce iron depletion enhances the likelihood of achieving (SVR) after anti-viral therapy. However, these studies are primarily in patients receiving interferon monotherapy, which is of course now obsolete. Finally, a few small studies suggest that therapeutic phlebotomy to induce iron depletion reduces liver transaminase levels and may improve histology, and perhaps even reduce the risk of hepato-cellular carcinoma. Prospective randomized controlled trials of phlebotomy among patients with advanced hepatitis C and iron overload are needed.     

Elevated serum iron predicts poor response to interferon treatment in patients with chronic HCV infection

To date, there are no firm clinical, demographic, biochemical, serologic, or histologic features predicting which patients with chronic hepatitis C are more likely to respond to therapy with interferon-. Serum iron, total iron-binding capacity, transferrin saturation, and ferritin were measured in the fasting state. The amount of stainable iron in liver biopsy specimens was evaluated histochemically as well. All patients received subcutaneous recombinant human IFN-2a three million units thrice weekly by self-administration. Eleven of 13 (84%) responders had low to normal serum iron levels as compared to one of 26 (4%) nonresponders (P<0.001). The serum transferrin was similar in both groups, but iron saturation was significantly lower in responders (30±10%) than in nonresponders (53±12%) (P<0.001). Serum ferritin and hepatic iron content were higher in nonresponders (NS). It is suggested that increased serum iron and transferrin saturation blunt the action of interferon, as they have opposite effects on the immune system. Iron overload can thus lead to a poor response to interferon. It remains to be seen whether reducing iron overload will improve the response to interferon therapy.     

The use of deferoxamine infusions to enhance the response rate to interferon-α treatment of chronic viral hepatitis B

Summary An individual's iron status may affect the response rate achieved with the use of interferon (IFN) as therapy for chronic viral hepatitis. A total of 27 patients with chronic hepatitis B viral infection, who had elevated serum ferritin levels, were randomized to receive either IFN 5 MU, three times weekly by subcutaneous injection alone ( n = 14) or in combination with cycles of deferoxamine at a dose of 80 mg kg^-1 per cycle ( n = 13) administered over 3 consecutive days, to reduce their iron and maintain a serum ferritin level less than 250 ng ml^-1. All deferoxamine-treated patients were on a low iron-containing diet. An IFN response was defined as a normalization of the serum alanine aminotransferase (ALT) level and seroconversion from hepatitis B e antigen (HBeAg) positivity to hepatitis B e antibody (HBeAb) positivity. The deferoxamine-treated group experienced a reduction in their serum ferritin level to 226 ± 73 ng ml^-1 as a result of the deferoxamine treatment. Six of the 13 (46%) deferoxamine-treated patients and two of the 14 (14%) control patients normalized their ALT levels. Seven of the 13 (54%) deferoxamine but only 14% of the IFN-treated group seroconverted to HBeAb positivity. A greater rate of histological improvement and loss of hepatitis B virus (HBV) DNA was seen in the deferoxamine-treated group. Two of the deferoxamine-treated patients were treated only once, two were treated twice, seven were treated three times and two were treated four times to achieve a ferritin level below 250 ng ml^-1.     

Iron in hepatitis C: villain or innocent bystander?

Elevations in serum transferrin-iron saturation and ferritin are common in patients with chronic hepatitis C infection, especially if they have concomitant elevations in serum aminotransferases. However, serum markers of iron stores do not accurately reflect hepatic iron content, or predict clinically important endpoints such as response to interferon and disease progression. In contrast, hepatic iron concentration, which is usually normal or only mildly elevated in chronic hepatitis C infection in the absence of cirrhosis, is one of the strongest predictors of response to interferon monotherapy. Iron depletion by phlebotomy consistently reduces serum aminotransferases and in combination with interferon may have improved antiviral efficacy compared to interferon alone. Unfortunately, no data are available on the role, if any, of iron depletion therapy, as an adjunct to interferon and ribavirin combination treatment. Future studies should focus on the efficacy of combining iron depletion with pegylated interferon and ribavirin and on the effect of long-term iron depletion on histologic progression of chronic hepatitis C infection.     

Relationship between the serum alanine aminotransferase level at the end of interferon treatment and histologic changes in wild-type and precore mutant hepatitis B virus infections

Summary Unravelling the role of interferon (IFN) in the treatment of chronic hepatitis B is complicated by many factors. Several mutant forms of hepatitis B virus (HBV) have recently been discovered; the most common of these is the precore mutant, characterized by hepatitis Be antigen (HBeAg) negativity and hepatitis Be antibody (HBeAb) positivity in an individual with an active HBV infection. The aim of this study was to compare the response rate to IFN therapy in patients with wild-type HBV infection and in individuals infected with the precore mutant. A second aim was to evaluate the role of an increased serum ferritin in terms of the IFN response rate in these two different types of HBV infection.
Therapy ministered at a dose of 5 MU subcutaneously three times weekly for 6 months to 41 individuals with a chronic wild-type hepatitis B infection and 16 individuals with a precore mutant chronic HBV infection. An IFN response was defined as normalization of the serum alanine aminotransferase (ALT) level and an HBeAg to HBeAb seroconversion (in wild-type hepatitis infection), and a normalization of the serum ALT in individuals infected with a precore mutant infection.
Ntrywo groups were matched for age, gender, serum ALT, serum iron, total iron binding capacity (TIBC), serum ferritin and liver histology. Forty-six per cent of the subjects with wild-type disease responded to IFN therapy. By contrast, only four of the 16 cases (25%) of the precore mutant cases responded ( P < 0.05). Ferritin levels correlated well with the type of IFN response; as the serum ferritin level increased, the response rate to IFN declined. Hapatic infection caused by a precore HBV mutant is more resistant to IFN therapy than wild-type infection. The serum ferritin level appears to influence the type of IFN response achieved. Individuals with a serum ferritin level greater than 300 ng ml^-1 failed to respond to IFN in 93% of the cases studied.     

Lower serum prohepcidin levels associated with lower iron and erythropoietn requirements in hemodialysis patients with chronic hepatitis C

ABSTRACT: BACKGROUND: Patients with chronic HCV infection have increased liver iron. Recently identified protein hepcidin synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. It was previously reported lower erythropoietin and iron supplementation requirement in HD patients with HCV infection. We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection. METHODS: Sixty patients (27 male, 33 female, mean age 50 +/-15 years) on chronic HD were included. Parameters related to iron metabolism (ferritin, serum iron and total iron binding capacity (TIBC)), inflammation (hs-CRP, TNF-alpha and IL-6) and prohepcidin levels were measured. The response to treatment (erythropoiesis-stimulating agent (ESA) resistance index) was assessed from the ratio of the weekly erythropoietin (rhuEPO) dose to hemoglobin (Hb) per unit weight. RESULTS: Serum prohepcidin levels of HCV positive patients (135+/-25 ng/mL) were significantly lower than HCV negative patients [148+/-18 ng/mL, (p=0.025)]. Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients (p=0.016). Serum prohepcidin levels was positively correlated with ferritin (r=0.405, p=0.001) and IL-6 (r=0.271, p=0.050) levels in HD patients. In the HCV positive group, serum prohepcidin levels significantly correlated with ferritin levels (r=0.514 p=0.004). In the HCV negative group, serum prohepcidin levels significantly correlated with serum IL-6 levels (r=0.418, p=0.027). In multiple regression analysis performed to predict prohepcidin in HCV positive patients, serum ferritin was found to be an independent variable (r=0.28, p=0.008). CONCLUSIONS: HCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation and/or lower iron and rhuEPO requirement in these patients.     

Measurements of iron status in patients with chronic hepatitis.

Eighty patients with chronic viral hepatitis were screened for evidence of iron overload. Elevated serum iron values were noted in 36% of cases; serum ferritin values were above normal in 30% of men and 8% of women. Twenty-eight additional patients with chronic hepatitis for whom liver tissue was available for determination of iron content were evaluated to study the significance of iron overload in association with chronic hepatitis. Although 46% had elevated serum iron, ferritin, or transferrin-saturation levels, the hepatic iron concentration was elevated in only four cases, and the hepatic iron index was in the range for hereditary hemochromatosis (greater than 2.0) in only two of these. Serum aspartate aminotransferase activities correlated with serum ferritin levels in these patients, suggesting that ferritin and iron levels were increased in serum because of their release from hepatocellular stores associated with necrosis. Thus, in patients with chronic hepatitis in whom hereditary hemochromatosis is suspected, a liver biopsy should be performed with quantitation of hepatic iron and calculation of the hepatic iron index to confirm the diagnosis.     

Serum thioredoxin levels as an indicator of oxidative stress in patients with hepatitis C virus infection

BACKGROUND/AIM: It has recently been suggested that oxidative stress may be associated with hepatitis C virus (HCV) infection. Thioredoxin (TRX) is a stress-inducible thiol-containing protein. The aim of this study was to evaluate the clinical significance of serum TRX levels in patients with HCV-related chronic liver diseases. METHODS: Serum TRX levels were determined with a sandwich enzyme-linked immunosorbent assay kit in 174 serum HCV-RNA positive patients, including 6 asymptomatic carriers, 124 chronic hepatitis, 20 liver cirrhosis, and 24 hepatocellular carcinoma, and in 15 healthy volunteers. RESULTS: The serum TRX levels (medians and [ranges], ng/ml) were significantly elevated in the HCV-infected patients; 30.9 [20.7-37.7] in asymptomatic carriers, 34.5 [8.6-135.6]* in chronic hepatitis, 42.5 [21.4-97.2]* in liver cirrhosis, and 43.9 [11.7-180.3]** in hepatocellular carcinoma (*p<0.05, **p<0.001, vs. 24.9 [1.3-50.7] in healthy controls). Serum TRX levels were significantly correlated with the serum levels of ferritin and fibrogenesis markers, and with the histological stage of hepatic fibrosis. The serum TRX levels before interferon treatment of patients whose serum HCV-RNA was still positive on day 14 following interferon treatment (42.6 [20.1-90.0]) were significantly higher than those of patients whose serum HCV-RNA was negative on day 14 following interferon treatment (25.8 [7.4-59.8], p<0.05). CONCLUSIONS: The serum TRX levels of patients with HCV infection increased with their serum ferritin levels and the progression of liver fibrosis. Patients with higher serum TRX levels exhibited resistance to interferon therapy. Oxidative stress may therefore be responsible for the pathological mechanism of HCV-related liver diseases and be one of the impediments to eradication of HCV during interferon treatment.     

Serum iron and iron stores in non-anemic patients with fibromyalgia

The aim of the study was to assess iron serum levels and markers of iron stores in non-anemic fibromyalgia (FM) patients and to evaluate their impact on the prevalence and clinical manifestations of FM patients. Eighty-four patients with primary FM and 87 controls were investigated. Demographic and clinical data were collected from all participants. All patients completed the fibromyalgia impact questionnaire (FIQ). Patients evaluated the effect of the disease on their daily activity (DA) and judged the severity (DS) of the disease on a 0–10 scale. Venous blood was tested for serum iron, transferrin, ferritin, and soluble transferrin receptors (sTfR). Iron deficiency was defined if any of the following were present: serum iron <40 μg/dL, serum ferritin levels <10 ng/mL, or sTfR levels >28.1 nmol/L. Analysis at a cutoff level of serum ferritin levels ≤30 ng/mL and sTfR/ferritin ratio was also performed. Hemoglobin, iron, transferrin, sTfR, ferritin levels, and sTfR/ferritin ratios did not differ between the groups. The mean FIQ score was 57.13 ± 20.21 and the DA and DS scores were 6.79 ± 2.97 and 6.74 ± 3.09, respectively. No correlations were found between the parameters studied and the FIQ or its ten individual items. Thirty-eight controls (43.7%) and 23 FM patients (27.4%) had ferritin levels of ≤30 (p < 0.04). Within the FM group, lower levels were associated with lower total FIQ score and FIQ subscale scores. Patients with FM do not have reduced serum levels of iron or surrogate markers of iron stores. At present, there is no evidence to support iron supplementation in the treatment of FM.     

Hepatic iron contents and response to interferon-α in patients with chronic hepatitis C

Recent reports have shown that response to interferon treatment is influenced by hepatic iron contents in patients with chronic hepatitis C. In those reports, however, hepatitis C virus (HCV) genotypes and serum HCV-RNA levels were not examined. The aim of the present study was to investigate whether hepatic iron contents influence the response to interferon in patients with chronic hepatitis C and whether HCV genotypes and serum HCV-RNA levels play a role in this relationship. Among 65 patients with chronic hepatitis C, hepatic iron contents were significantly high in patients with a history of excess drinking of alcohol (more than 80 g/day) compared to those without, and significantly low in female patients before menopause. Having excluded these patients, hepatic iron contents were significantly higher in patients with genotype 1b infection than those with genotype 2a and 2b infection. There was no significant correlation between hepatic iron contents and plasma HCV-RNA levels. Among the patients with genotype 1b infection, hepatic iron contents were significantly lower in the responders to interferon than those in the nonresponders (429 ± 100 vs 875 ± 110 µg/g liver,P<0.05). From these results, it is concluded that response to interferon is mainly influenced by HCV genotypes, while hepatic iron contents may play an important role in response to interferon in patients with genotype 1b infection.