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.     

Influence of iron on the severity of hepatic fibrosis in patients with chronic hepatitis C

AIM: To evaluate the association among hepatic fibrosis, serum iron indices, and hepatic iron stores in patients with Chronic Hepatitis C (CMC). METHODS: Thirty-two CHC patients were included in our study. The histological degree of fibrosis and inflammation activity was assessed according to the Metavir system. The serum iron indices including ferritin, iron and transferrin saturation were measured. Hepatic iron deposition was graded by Perls' stain. RESULTS: The CHC patients with severe hepatic fibrosis (n = 16) were significantly older than CHC patients with mild fibrosis (n = 16) (P = 0.024). The serum iron indices, increased serum iron store and positive hepatic iron stain were not significantly different between the two groups. In multivariate logistic regression analysis, the age at biopsy was an independent predictor of severe hepatic fibrosis (Odds ratio = 1.312; P = 0.035). The positive hepatic iron stain was significantly associated with the values of alanine aminotransferase (ALT) (P = 0.017), ferritin (P = 0.008), serum iron (P - 0.019) and transferrin saturation (P = 0.003). The ferritin level showed significant correlation with the value of ALT (r = 0.531; P = 0.003), iron (r = 0.467; P = 0.011) and transferrin saturation (r = 0.556; P = 0.002). CONCLUSION: Our findings suggest that the severity of hepatitis C virus (HCV)-related liver injury is associated with patient age at biopsy. Both serum iron indices and hepatic iron deposition show correlation with serum indices of chronic liver disease but are not related to grade and stage of liver histology.     

Increased Oxidative Stress,Decreased Total Antioxidant Capacity,and Iron Overload in Untreated Patients with Chronic Hepatitis C

The aim of this study was to determine oxidative stress in patients with untreated chronic hepatitis C (CHC), relating the obtained results with iron status and disease activity markers. Two groups (CHC patients and controls) were studied. CHC patients presented significantly higher values than the control group in some parameters: ALT, AST, GGT, iron, ferritin, and transferrin saturation, and also in tert-butyl hydroperoxide initiate chemiluminescence and thiobarbituric acid-reactive substances (TBARS) as well as lower values in total radical-trapping antioxidant parameter (TRAP). TBARS showed a significant correlation with serum AST and with transferrin saturation, whereas TRAP correlated inversely with serum albumin. Serum ferritin correlated with ALT and GGT, whereas serum iron did so with GGT. In conclusion, lower antioxidant capacity, higher levels of pro-oxidants activity, and iron overload occur in untreated patients with CHC. This greater oxidative activity could play an important role in pathogenesis and evolution of hepatitis C and thus further investigations.     

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.     

Influence of iron on the severity of hepatic fibrosis in patients with chronic hepatitis C

AIM: To evaluate the association among hepatic fibrosis, serum iron indices, and hepatic iron stores in patients with Chronic Hepatitis C (CHC). METHODS: Thirty-two CHC patients were included in our study. The histological degree of fibrosis and inflammation activity was assessed according to the Metavir system. The serum iron indices including ferritin, iron and transferrin saturation were measured. Hepatic iron deposition was graded by Peris' stain. RESULTS: The CHC patients with severe hepatic fibrosis (n = 16) were significantly older than CHC patientswith mild fibrosis (n = 16) (P = 0.024). The serum iron indices, increased serum iron store and positive hepatic iron stain were not significantly different between the two groups. In multivariate logistic regression analysis, the age at biopsy was an independent predictor of severe hepatic fibrosis (Odds ratio = 1.312; P = 0.035). The positive hepatic iron stain was significantly associated with the values of alanine aminotransferase (ALT) (P = 0.017), ferritin (P = 0.008), serum iron (P= 0.019) and transferrin saturation (P = 0.003). The ferritin level showed significant correlation with the value of ALT (r = 0.531; P = 0.003), iron (r = 0.467; P = 0.011) and transferrin saturation (r = 0.556; P = 0.002). CONCLUSION: Our findings suggest that the severity of hepatitis C virus (HCV)-related liver injury is associated with patient age at biopsy. Both serum iron indices and hepatic iron deposition show correlation with serum indices of chronic liver disease but are not related to grade and stage of liver histology.     

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.     

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 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.     

Randomized placebo-controlled trial of interferon alpha-2b plus ribavirin with and without lactoferrin for chronic hepatitis C.

Lactoferrin (LF), an iron-binding glycoprotein, exhibits several biological activities, including anti-viral activity and immunomodulatory functions. LF has been reported to inhibit hepatitis C virus (HCV) infection in cultured human hepatocytes and HCV viremia in low pretreatment HCV RNA titers of patients with chronic hepatitis C (CHC). However, the combination of interferon (IFN) alpha-2b plus ribavirin with LF for CHC has not been previously investigated. Thirty-six CHC patients, who were positive for HCV RNA with high serum levels of HCV RNA or who did not respond to or relapsed after interferon monotherapy, were randomly assigned to two groups: IFN alpha-2b and ribavirin plus LF for 24 weeks (18 patients), and IFN alpha-2b and ribavirin plus placebo (18 patients). Treatment was discontinued in three patients (17%) in the LF group and eight patients (44%) in the placebo group. For the 25 patients who finished the 24 weeks of treatment, virological sustained response was seen in 6 (40%) patients in the LF group and in 5 (50%) patients in the placebo group and there was no statistically significant difference between the two groups (p=0.7). Serum alanine aminotransferase concentrations remained normal throughout the follow-up period in nine patients (60%) in the LF group as compared with five patients (50%) in the placebo group (p=0.7). The proportion of patients with a virological or biochemical response at the end of the treatment period did not differ between the two groups. Furthermore, there were no statistically significant differences between the two groups in hemoglobin concentration, serum iron, ferritin, Th1/Th2 ratio or ribavirin concentration throughout the treatment and follow-up periods. In conclusion, we could not demonstrate that LF in combination with IFN alpha-2b and ribavirin increases the virological and biochemical response rate for CHC patients with high serum levels of HCV RNA or for CHC patients who do not response to or relapse after IFN monotherapy.     

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.     

Iron deficiency due to excessive therapeutic phlebotomy in hemochromatosis

Thirteen adults (eight men, five women) with hemochromatosis had undergone routine iron depletion therapy but while on maintenance phlebotomies developed iron deficiency which persisted for 25 +/- 13 (mean +/- 1 SD) months before diagnosis. All had symptoms and signs of iron deficiency. Levels of transferrin saturation were 10% +/- 5% (1 SD), and serum ferritin concentrations were 8 +/- 3 ng/mL. Eleven had anemia; eight had hypochromia and microcytosis. Bone marrow specimens obtained in five patients revealed no stainable iron. Medical records indicated that parameters of body iron status were infrequently or incorrectly used for adjusting the frequency of phlebotomies. Two patients developed iron deficiency due to additional blood loss from esophageal varices and bilateral hip replacement, respectively. Ten of the patients were treated with ferrous sulfate, 325 mg daily, for 2-6 weeks when anemia was corrected. In patients who were not given iron, anemia and microcytosis recovered in 8-24 months. We conclude that (i) sustained iron deficiency in hemochromatosis patients should be prevented by monitoring hemoglobin levels and serum ferritin; and (ii) hemoglobin concentrations and values of mean corpuscular hemoglobin may be higher in iron-deficient persons with hemochromatosis than in individuals without hemochromatosis. Symptomatic iron deficiency in hemochromatosis patients may be treated safely with a brief course of ferrous sulfate. Recovery is slower when iron is not given. However, iron supplementation is unnecessary and not recommended for the mild, self-limited anemia and decreased serum iron and ferritin concentrations encountered after initial iron depletion therapy for hemochromatosis.     

Serum transferrin receptor: a quantitative measure of tissue iron deficiency

This study was undertaken to evaluate the role of serum transferrin receptor measurements in the assessment of iron status. Repeated phlebotomies were performed in 14 normal volunteer subjects to obtain varying degrees of iron deficiency. Serial measurements of serum iron, total iron-binding capacity, mean cell volume (MCV), free erythrocyte protoporphyrin (FEP), red cell mean index, serum ferritin, and serum transferrin receptor were performed throughout the phlebotomy program. There was no change in receptor levels during the phase of storage iron depletion. When the serum ferritin level reached subnormal values there was an increase in serum receptor levels, which continued throughout the phlebotomy program. Functional iron deficiency was defined as a reduction in body iron beyond the point of depleted iron stores. The serum receptor level was a more sensitive and reliable guide to the degree of functional iron deficiency than either the FEP or MCV. Our studies indicate that the serum receptor measurement is of particular value in identifying mild iron deficiency of recent onset. The iron status of a population can be fully assessed by using serum ferritin as a measure of iron stores, serum receptor as a measure of mild tissue iron deficiency, and hemoglobin concentration as a measure of advanced iron deficiency.     

Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C

Background We have previously demonstrated that in patients with chronic hepatitis C (CHC), iron depletion improves serum alanine aminotransferase (ALT) levels as well as hepatic oxidative DNA damage. However, it has not been determined whether continuation of iron depletion therapy for CHC favorably influences its progression to hepatocellular carcinoma (HCC). Methods We conducted a cohort study on biopsy-proven CHC patients with moderate or severe liver fibrosis who failed to respond to previous interferon (IFN) therapy or had conditions for which IFN is contradicted. Patients were divided into two groups: subjects in group A (n = 35) underwent weekly phlebotomy (200 g) until they reached a state of mild iron deficiency, followed by monthly maintenance phlebotomy for 44–144 months (median, 107 months), and they were advised to consume a low-iron diet (5–7 mg iron/day); group B (n = 40) comprised CHC patients who declined to receive iron depletion therapy. Results In group A, during the maintenance phase, serum ALT levels decreased to less than 60 IU/l in all patients and normalized (<40 IU/l) in 24 patients (69%), whereas in group B no spontaneous decrease in serum ALT occurred. Hepatocarcinogenesis rates in groups A and B were 5.7% and 17.5% at the end of the fifth year, and 8.6% and 39% in the tenth year, respectively. Multivariate analysis revealed that iron depletion therapy significantly lowered the risk of HCC (odds ratio, 0.57) compared with that of untreated patients (P = 0.0337). Conclusions Long-term iron depletion for CHC patients is a promising modality for lowering the risk of progression to HCC.     

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.     

Erythropoiesis: Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

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.     

Use of erythropoiesis stimulating agents and intravenous iron for cancer and treatment-related anaemia: the need for predictors and indicators of effectiveness has not abated

Cancer and treatment-related anaemia is a significant clinical problem. Erythropoiesis stimulating agents (ESA) improve anaemia and ultimately enhance patients' quality of life. However, about one-third of patients do not respond to ESA administration, mostly because of the impaired supply of iron to the erythroid marrow (functional iron deficiency). Concomitant administration of intravenous (IV) iron may improve responsiveness. The use of baseline predictors of response to ESA and of indicators of appropriateness of response and iron availability should allow targeted therapeutic interventions with both ESA and IV iron. Several biochemical and haematological indicators of response and of iron balance have been studied, but firm criteria for their use have not yet been rigorously established. The commonly used early predictive markers of response to ESA, such as baseline endogenous erythropoietin levels and an increase in haemoglobin, reticulocytes, and soluble transferrin receptor levels during ESA treatment, have not proved reliable due to their low sensitivity and specificity. Traditional markers of iron availability, such as serum ferritin and transferrin saturation display interpretation pitfalls. The need for predictors and indicators of responsiveness to ESA and IV iron is still current and clinically relevant.     

应用艾尔巴韦/格拉瑞韦治疗基因1b型慢性丙型肝炎初治和经治患者效果对比研究

目的 观察应用艾尔巴韦/格拉瑞韦治疗基因1b型慢性丙型肝炎(CHC)初治和经治患者的效果.方法 2019年1月～2020年3月我院收治的初治CHC患者59例和经治CHC患者56例,均接受艾尔巴韦/格拉瑞韦治疗12 w,随访24 w.采用实时荧光定量RT-PCR法检测血清HCV RNA载量,常规检测血清层黏蛋白(LN)、...     

Serum Iron Markers in Patients With Chronic Hepatitis C Infection

Background

Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.

Objectives

The aim of this study was to investigate the possible correlations between iron metabolism serum markers, HCV viral load, and liver disease severity in treatment-naive patients with chronic hepatitis C infection.

Patients and Methods

Eighty five patients with untreated hepatitis C chronic infection were investigated.

Results

Twenty one patients (24.7%) had elevated serum iron levels, and 29 subjects (34.1%) had severe liver fibrosis. Significantly elevated levels of serum iron (P < 0.05) and ferritin (P < 0.001), associated with lower levels of TIBC (P < 0.05) were detected in patients with severe fibrosis compared to no/mild fibrosis. Severe necroinflammatory activity was also significantly correlated with serum iron (P < 0.001), TIBC (P < 0.05), and ferritin levels (P < 0.001). Using multiple linear regression analysis, serum levels of ferritin and transferrin were the independent variables selected as being good predictors for advanced fibrosis and severe necroinflammatory activity. No significant correlations were detected between HCV viral load and iron markers.

Conclusions

This study revealed that serum iron markers (especially ferritin and transferrin) might be used as surrogate markers for both liver fibrosis and necroinflammatory activity.Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.     

Hepatic iron influences responses to combination therapy with peginterferon alfa and ribavirin in chronic hepatitis C

BACKGROUND/AIMS: Mild to moderate iron overload is common in chronic hepatitis C (CHC) and may influence the response to antiviral therapy. The aim of this study was to assess the association among serum iron indices, hepatic iron stores and sustained virological response (SVR) rates of combination therapy with peginterferon alfa and ribavirin in patients with CHC. METHODOLOGY: A total of 36 CHC patients were treated with peginterferon and ribavirin for 6 months. The SVR was defined as undetectable hepatitis C virus RNA by qualitative assay 6 months after the end of therapy. The serum iron indices including ferritin, iron and transferrin saturation were measured. The hepatic iron deposition was graded on Perls' stain. RESULTS: The SVR was obtained in 25/36 (69.44%) patients. The serum iron indices including transferrin saturation and ferritin were not significantly different between patients with the SVR and without. In multivariate logistic regression analysis, cirrhosis (P = 0.010, odds ratio = 0.020) and a positive hepatic iron stain (P = 0.046, odds ratio = 0.065) were both significantly independent predictors of non-SVR. CONCLUSIONS: The findings suggest that the positive hepatic iron stain is an independent predictor of non-response to combination therapy with peginterferon alfa and ribavirin for patients with CHC. Liver cirrhosis also predicts non-responses to the combination therapy.