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.     

Clinical significance of hepatic iron deposition and serum iron values in patients with chronic hepatitis C infection

OBJECTIVES: To assess the potential association between hepatic iron deposition or serum iron values and hepatic fibrosis and inflammatory activity in patients with chronic hepatitis C virus infection. METHODS: In 100 consecutive patients with hepatitis C virus infection, tissue iron deposition was assessed by quantifying iron stain on liver biopsy specimens. Serum iron, ferritin, and transferrin saturation were determined by standard laboratory procedures. Statistical analyses incorporated potential confounders associated with hepatic fibrosis. RESULTS: Twenty-one patients had no fibrosis (stage 0), 13 had portal fibrosis (stage 1), 31 had periportal fibrosis (stage II), 10 had bridging fibrosis (stage III), and 25 had cirrhosis (stage IV). Positive iron stain found in liver biopsy specimens of 19 patients was associated with stage III or IV fibrosis (p = 0.004). No significant difference was found between the iron concentration or the hepatic iron index in patients with stage III or IV fibrosis compared with patients with stage I or II fibrosis. At least 1 of 3 serum iron values assessed was abnormal in 55 patients. In univariate analysis, elevated serum iron (p = 0.01), serum ferritin (p < 0.001), and transferrin saturation (p = 0.002) were associated with stage III or IV fibrosis. In multivariate analysis, the only independent predictive factor of severe hepatic fibrosis was serum ferritin (p < 0.02; odds ratio = 11.35). The serum ferritin value and tissue iron stain had a significant positive correlation (p < 0.001). CONCLUSIONS: Increased hepatic iron deposition may be associated with more advanced hepatic fibrosis in patients with chronic hepatitis C virus infection. The serum ferritin value, an independent predictor of severe hepatic fibrosis in patients with chronic hepatitis C virus infection, may predict hepatic iron deposition and severity of fibrosis.     

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.     

Regulatory failure of serum prohepcidin levels in patients with hepatitis C

BACKGROUND/AIMS: Elevated serum ferritin and hepatic iron concentrations are frequently observed in chronic hepatitis C (CHC), which may be related to hepcidin. Because the role of hepcidin in CHC patients remains unknown, we aimed in this study to generate some information about hepcidin in CHC. METHODS: To determine whether serum hepcidin correlates with markers of iron status in patients with viral hepatitis, we measured serum prohepcidin levels in patients with hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and in healthy controls. RESULTS: Serum prohepcidin and ferritin levels were negatively correlated (r=-0.182, P=0.037) in HCV patients and positively correlated in HBV patients and in healthy controls. The total iron scores in liver specimens from HCV patients were also negatively correlated (r=-0.403, P=0.013). Serum prohepcidin levels in patients with liver cirrhosis (LC) were significantly lower than in patients with chronic hepatitis (CH). In both CH and LC patients, serum prohepcidin levels were significantly lower in HCV patients than in HBV patients. CONCLUSION: Failure of homeostatic regulation of serum prohepcidin concentrations may be induced by HCV infection, resulting in elevation of serum ferritin levels, which leads to the progression of liver injury by iron overload in CHC patients.     

Hepatic iron, liver steatosis and viral genotypes in patients with chronic hepatitis C

Hepatic iron has been described in hepatitis C virus (HCV) infection as an important cofactor of disease outcome. The mechanisms leading to hepatic iron deposits (HIDs) in HCV patients are partially understood. We investigated HIDs in the liver biopsies of a consecutive series of 242 HCV-infected patients with well-compensated liver disease. Serum ferritin was elevated in 20.7% and transferrin saturation in 19.0%, while 38.8% had stainable HIDs indicating that serum markers of systemic iron overload have low sensitivity in predicting HIDs in hepatitis C. A cut-off value of serum ferritin (350 microg/L in females and 450 microg/L in males) had good negative predictive value in excluding presence of mild-moderate HIDs (grade II-III). Hepatic iron deposits correlated by multivariate analysis with serum ferritin [odds ratio (OR) 1.008, 95% confidence interval (CI) 1.005-1.011] and albumin (OR 1.15, 95% CI 1.02-1.297). Hepatic iron deposits were more frequent in HCV-3-infected cases than in other genotypes (P = 0.027) while raised serum iron indices were more frequent in non-HCV-3 genotypes (P = 0.02). Furthermore, advanced fibrosis (F3-F4 by METAVIR) was more frequent in non-HCV-3 genotypes (P = 0.04). In HCV-3 cases there was a close association between HIDs and severe (grade II-III) steatosis (P < 0.00001). These results indicate that in well-compensated chronic hepatitis C HIDs are strongly associated with HCV-3 and viral-induced hepatic steatosis, while in the presence of other genotypes they might merely reflect a more advanced stage of liver disease and/or a systemic iron overload. Serum ferritin could identify a subgroup of patients in which the need of venesection could be excluded without liver biopsy.     

Hepatic iron overload does not prevent a sustained virological response to interferon-alpha therapy: a long term follow-up study in hepatitis C-infected patients with beta thalassemia major

OBJECTIVES: Transfusion-acquired chronic hepatitis C infection and systemic iron overload are common in patients with beta thalassemia major. The magnitude of hepatic iron overload has been associated with a poor response to interferon-based antiviral therapy for hepatitis C. The aim of this study was to evaluate the effect of hepatic iron concentration (HIC) on response to interferon monotherapy in patients with massive hepatic iron overload. METHODS: Twenty-eight patients with beta thalassemia major, transfusion-acquired iron overload, and chronic hepatitis C infection were prospectively treated with interferon for 6 months. HIC was measured by atomic absorption spectroscopy before treatment. Serum iron, ferritin, hepatitis C virus genotype, viral load, and liver histology were analyzed. RESULTS: Eight patients (28%) achieved a sustained virological response that has been durable after a mean of 66 months of follow-up. The median HIC was 2583 microg/g dry weight. There was no difference in HIC between responders and nonresponders to therapy. Serum hepatitis C virus RNA was lower in responders than in nonresponders. Genotype 1 was more frequent in nonresponders, and non-1 genotypes were more frequent in responders, although this did not reach statistical significance because of patient numbers. CONCLUSIONS: A long term response to interferon is unrelated to HIC in this patient group, and a durable response can occur despite massive iron overload. HIC may be a factor in liver cell injury, but it does not reliably predict a response to interferon therapy.     

Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C

PURPOSE: Liver iron is frequently elevated in chronic hepatitis C and may contribute to liver injury. The pathophysiology behind this phenomenon may involve hepcidin, a gene that is up-regulated in the liver by inflammation and iron. Inappropriately low hepcidin is important to the pathophysiology of hereditary hemochromatosis. However, the role of hepcidin in the iron loading of patients with hepatitis C is unknown. SUBJECTS AND METHODS: To determine whether liver hepcidin mRNA correlates with markers of hepatic inflammation and iron status in patients with hepatitis C, we extracted total RNA from liver biopsy specimens of patients with chronic hepatitis C and quantified hepcidin mRNA. Liver hepcidin mRNA levels were then correlated with aspartate aminotransferase, alanine aminotransferase, ferritin, viral load, fibrosis, hepatic iron concentration, and Hepatic Activity Index (HAI). RESULTS: Among patients with hepatitis C, there was a significant correlation of hepcidin mRNA expression in the liver with hepatic iron concentration and serum ferritin (r = 0.72, P = 0.006, and r = 0.60, P = 0.01, respectively). Hepcidin mRNA expression in the liver did not correlate with aspartate aminotransferase, alanine aminotransferase, HAI, or viral load. No differences in hepcidin mRNA were found based on viral genotype or the presence of fibrosis. CONCLUSION: In contrast to other inflammatory states, hepcidin mRNA expression in the liver was independent of markers of inflammation in hepatitis C. Instead, our results suggest that iron stores in patients with hepatitis C regulate hepcidin expression and that iron loading in chronic hepatitis C is not due to inappropriate hepcidin expression.     

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.     

Serum Iron Levels and Hepatic Iron Overload in Nonalcoholic Steatohepatitis and Chronic Viral Hepatitis

Our objective was to determine the effect of serum iron levels and hepatic iron overload on hepatocellular damage in nonalcoholic steatohepatitis (NASH) and to compare this with chronic viral hepatitis. Twenty-five patients who had elevated transaminase levels on at least two occasions, without any evidence of viral and autoimmune hepatitis and diabetes, without a history of significant alcohol use, and with a liver biopsy consistent with NASH were enrolled in the study. Twenty-five patients with chronic viral hepatitis (13 patients with chronic hepatitis C and 12 with chronic hepatitis B) who were not under any antiviral treatment were taken as controls. Metabolic factors were studied in the NASH and chronic hepatitis groups. Biopsy specimens were stained with hematoxylin–eosin, and the grade of steatosis and the stage of fibrosis were evaluated as I, II, or III, I being mild and III being severe. Iron overload in the hepatic tissue was studied by Prussian blue staining. Serum ALT, AST, ALP, GGT, globulin, and ferritin levels were comparable in both steatohepatitis and chronic viral hepatitis groups. However, patients with chronic hepatitis had a lower albumin level and a higher serum iron level, with higher transferrin saturation. Among patients with NASH, mild, moderate, and severe steatosis was found in 7, 10, and 8 patients, respectively. Inflammatory infiltration was grade I in 24 patients and grade III in 1 patient. Fibrosis was mild in 12 patients and 13 patients had no fibrosis. Among patients with chronic viral hepatitis, inflammatory infiltration of grade I was seen in 11 patients, grade II in 11 patients, and grade III in 3 patients. Fibrosis was mild in 9 patients, moderate in 13 patients, and severe in 2 patients; 1 patient had no fibrosis. Compared to patients with NASH, those with chronic viral hepatitis cases had more severe inflammatory infiltration and fibrosis (P < 0.01). While five patients with chronic viral hepatitis had mild iron overload, patients with NASH had no hepatic paranchymal iron overload. Neither NASH nor chronic viral hepatitis revealed a relationship between hepatic iron overload and disease activity. This suggests that the iron overload actually may be a result of hemachromatosis gene mutation. The absence of hepatic parenchymal iron overload in the NASH group and only mild iron accumulation in the chronic hepatitis group may be explained by a lower frequency of the gene mutation in our country.     

Liver iron accumulation in chronic hepatitis C patients without HFE mutations: relationships with histological damage, viral load and genotype and alpha-glutathione S-transferase levels.

BACKGROUND: Host and viral factors have been suggested as possible causative factors for the presence of liver iron accumulation in chronic hepatitis C. However, there is no agreement regarding the influence of liver iron accumulation on the biochemical and histological severity of chronic hepatitis C. Moreover, data concerning the relationships between both viral load and genotype and liver iron accumulation are scanty. AIMS: To evaluate the biochemical, histological and virological assessment of a group of chronic hepatitis C patients without risk factors for iron overload, on the basis of the presence, degree and distribution of liver iron accumulation. METHODS: Fifty-three chronic hepatitis C patients (34 men, 19 women; age 44 +/- 11 years) with no risk factors for liver iron accumulation and showing no HFE mutations were chosen from a broader cohort of chronic hepatitis C patients. The presence, degree and distribution of liver iron accumulation were assessed using Deugnier's score. Relationships between the presence of liver iron accumulation and grading and staging were carried out separately. Hepatitis C virus RNA serum levels and viral genotype were compared in patients with or without liver iron accumulation. Alpha glutathione S-transferase serum levels were assessed in all patients. RESULTS: Overall, liver iron accumulation was mild and was present in 19 patients (36%). It was associated with male gender (P = 0.0358), and was reflected by high serum iron levels (P = 0.001) and high ferritin levels (P < 0.0001). Hepatitis C virus RNA levels and genotype were not associated with the presence of liver iron accumulation. In multivariate analysis, ferritin was the only variable significantly associated with liver iron accumulation (P < 0.0001). Grading was higher in patients with liver iron accumulation regardless of the site of iron deposition. Fibrosis was present in all patients with iron overload; these patients were more frequently cirrhotic. Moreover, patients with mesenchymal or mixed deposition had higher staging than patients with hepatocytic or no iron deposition. This feature was reflected by higher alpha-glutathione S-transferase levels. CONCLUSIONS: Liver iron accumulation is mild in chronic hepatitis C patients without HFE mutations and is mainly reflected by serum ferritin levels. Viral characteristics do not seem to play a role in iron deposition. Liver iron accumulation is associated with higher grading, advanced fibrosis and cirrhosis. Moreover, higher staging is associated with mesenchymal or mixed iron deposition. In these patients, higher alpha-glutathione S-transferase levels seem to reflect more complex damage.     

Hepatic iron overload is common in chronic hepatitis B and is more severe in patients coinfected with hepatitis D virus

Hepatic iron overload has been described in chronic hepatitis C as a cofactor affecting fibrosis progression. Data in patients with chronic hepatitis B infection are scarce. We investigated hepatic iron deposits and serum iron indices in 205 consecutive patients with hepatitis B and compensated liver disease. Mean age of the patients was 42.4 ± 12.4 years and 72.5% were males. Coinfection with hepatitis delta virus (HDV) was present in 8.8%. At least one of the serum iron indices was elevated in 41.5% of cases. Hepatic iron deposits were detected in 35.1% of patients, most of them being minimal (grade I) (59.7%) or mild (grade II) (27.8%). Variables significantly associated with hepatic iron deposits were male gender (P = 0.001), serum ferritin (P = 0.008), γGT (P = 0.05) and alkaline phosphatase (P = 0.05) levels. By multivariate analysis hepatic iron deposits correlated with serum ferritin [odds ratio (OR) 1.2, 95% confidence interval (CI) 1.05-1.4, P = 0.002]. Presence of mild-moderate (grades II and III) hepatic iron deposits could be excluded with high negative predictive value (90%) when serum ferritin was within normal values. A significant correlation between coinfection with HDV and hepatic iron deposits was also found (OR 4.23, 95% CI 1.52-11.82, P = 0.003). When compared to monoinfected cases, HDV positive patients had more elevated γGT (P = 0.03), more advanced fibrosis and more severe iron deposits (P < 0.0001). In conclusion, in well-compensated chronic hepatitis B infection, hepatic iron deposits and elevation of serum iron indices are common, especially in male gender and in patients coinfected with HDV. As HBV/HDV liver disease is generally more rapidly progressive than that caused by HBV monoinfection, we speculate that iron overload may be one of the factors contributing to the severity of liver disease.     

Hepatitis C,iron status,and disease severity: relationship with HFE mutations

BACKGROUND & AIMS: Mild to moderate hepatic iron loading is common in patients with chronic hepatitis C. We sought to determine whether mutations in the hemochromatosis gene, HFE, are associated with iron overload and acceleration of disease progression in hepatitis C patients. METHODS: A total of 316 patients with chronic hepatitis C were studied: 198 consecutive patients undergoing liver biopsy for compensated liver disease and 118 who underwent liver transplantation for end-stage liver disease. Serum iron studies, quantitative hepatic iron concentration, histologic activity index, and HFE genotype were determined. RESULTS: Among patients with compensated liver disease, the presence of HFE mutations was independently associated with elevations in serum iron level, serum transferrin-iron saturation, serum ferritin level, and hepatic iron index (P < 0.05). After adjustment for duration of infection with hepatitis C virus, HFE mutations were also independently associated with the presence of bridging fibrosis or cirrhosis (odds ratio, 18; 95% confidence interval, 1.7-193). HFE mutations were not independently associated with iron loading in patients with end-stage liver disease. There was no significant difference in the prevalence of HFE mutations between patients with compensated and end-stage liver disease (42% vs. 33%, respectively; P = 0.67). CONCLUSIONS: The presence of HFE mutations is independently associated with iron loading and advanced fibrosis in patients with compensated liver disease from chronic hepatitis C, especially after controlling for duration of disease. These results suggest that HFE mutations accelerate hepatic fibrosis in hepatitis C but may not be responsible for progression to end-stage liver disease.     

Serum ferritin and hepatic glutathione concentrations in chronic hepatitis C patients related to the hepatitis C virus genotype.

BACKGROUND/AIMS: Increased serum ferritin is thought to be responsible for activation of glutathione turnover in patients with chronic hepatitis C. The aim of the study was to evaluate a possible correlation between levels of serum ferritin and concentrations of hepatic, plasmatic and lymphocytic glutathione in a selected cohort of chronic hepatitis C patients in relation to the hepatitis C virus genotype. METHODS: The study considered 130 chronic hepatitis C patients and 23 control subjects. Hepatic glutathione was determined from biopsy liver specimens by high performance liquid chromatography. Total Iron Score was assessed by scoring iron separately within hepatocytes, sinusoidal cells and portal tracts. Blood samples were tested for determination of serum ferritin, and plasmatic and lymphocytic glutathione levels. Hepatic and erythocyte malonyldialdehyde were also determined along with peripheral blood mononuclear cell cytotoxic assay. RESULTS: Patients with genotype 1b showed higher levels of serum ferritin compared to patients with genotype 2a/2c and 3a and to controls, along with a significant reduction of the concentrations of hepatic, plasmatic and lymphocytic glutathione and peripheral blood mononuclear cell cytotoxic activity. The levels of serum ferritin correlated significantly to Total Iron Score, to hepatic, plasmatic and lymphocytic glutathione, to hepatic and erythrocyte malonyldialdehyde and to peripheral blood mononuclear cell cytotoxic activity. CONCLUSIONS: The levels of serum ferritin correlate significantly to lipoperoxidation markers in chronic hepatitis C patients. The increased production of free radicals with a reduced peripheral blood mononuclear cell cytotoxic activity may represent, especially in patients with genotype 1b, a factor underlying the resistance to interferon therapy and may influence the evolution of the liver disease by enhancement of the cytopathic effect of hepatitis C virus.     

Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following alpha-interferon therapy

BACKGROUND: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with alpha-interferon (IFN-alpha) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. METHODS AND RESULTS: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. CONCLUSIONS: These findings suggest that IFN-alpha treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C.     

Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection

Aim: We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection. Methods: Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls. Results: Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0-84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade. Conclusion: Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.     

Hepatic iron accumulation may be associated with insulin resistance in patients with chronic hepatitis C

Background/Aim: Insulin resistance and hepatic iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases. We investigated the relationship between insulin resistance and hepatic iron deposition in patients with chronic HCV infection. Methods: Insulin resistance was evaluated using the homeostasis model assessments for insulin resistance (HOMA-IR) in 56 non-diabetic non-obese patients with biopsy proven chronic hepatitis C. The relationship between insulin resistance and serum ferritin levels or the grade of hepatic iron deposition was assessed. Results: The levels of plasma immunoreactive insulin (IRI) and HOMA-IR were significantly correlated with serum ferritin levels and the grade of hepatic iron deposition (P = 0.003).Although IRI and HOMA-IR increased in parallel with the development of hepatic fibrosis, insulin resistance (HOMA-IR > 2) was observed in 11 (26.2%) of 42 patients even without severe fibrosis (F0-2). Among patients without severe fibrosis, IRI and HOMA-IR were significantly higher in patients with iron deposits than in those without iron deposits. Conclusion: Hepatic iron overload may be associated with insulin resistance in patients with chronic hepatitis C, especially in patients with mild to moderate fibrosis.     

慢性病毒性肝炎患者血清铁检测与肝脏生化及病理的关系

目的探讨血清铁与慢性肝炎血生化指标及病理炎症分级(G)、纤维化分期(S)及分度(S)的相关性及血清铁的检测意义。方法对455例慢性肝炎患者血清铁检测,并与肝脏生化指标、肝炎炎症分级、纤维化分期和分度做直线相关分析,同时分析轻、中、重度慢性肝炎血清铁是否存在差异。结果血清铁与ALT、AST、BIL呈正相关;而与CHE呈负相关;与肝脏病理指标中的G、S、D均呈正相关。血清铁均值随慢性肝炎程度的加重而增高。结论血清铁能一定程度上反映肝脏病变程度,但特异性较差。     

Chronic hepatitis C is mild in menstruating women

BACKGROUND AND AIMS: Women with chronic hepatitis C may have a slower rate of disease progression than men. We have previously demonstrated a relationship between hepatic iron concentration and liver fibrosis in patients with chronic hepatitis C. Our aim was to compare hepatic histologic findings, iron status and other factors putatively capable of determining the severity of chronic hepatitis between menstruating women and men of comparable age. METHODS: We studied 21 consecutive hepatitis C virus (HCV)-RNA positive menstruating women and 24 consecutive HCV-RNA positive men of comparable age, who underwent liver biopsy for chronic hepatitis C. Alcohol intake was recorded and blood tests, HCV genotyping, serum iron, unsaturated iron binding capacity, serum ferritin, hepatic iron concentration, and liver histology were evaluated. RESULTS: Menstruating women showed lower grading (2.7 +/- 1.5 vs 3.6 +/- 2, P = 0.09) and significantly lower staging (1.38 +/- 1.11 vs 2.42 +/- 1.64, P = 0.037) scores than men of comparable age. Among the factors putatively capable of determining the severity of chronic hepatitis, only the hepatic iron concentration correlated with the hepatic histologic staging in a multivariate analysis. Iron-depleted women (transferrin saturation < 20% and/or serum ferritin < 9 micrograms/L) showed significant lower hepatic histologic grading (1.75 +/- 0.7 vs 3.23 +/- 1.55, P = 0.027) and staging (0.75 +/- 1.03 vs 1.77 +/- 1.01, P = 0.026) scores than women with normal iron status. CONCLUSIONS: Menstruating women with chronic hepatitis C may have a milder disease compared to men of comparable age, possibly because of menstrual blood loss and lower hepatic iron concentration. Women with chronic hepatitis C and iron deficiency have a milder disease compared to women with normal iron status, suggesting that iron deficiency results in a slower rate of disease progression.     

Influence of Helicobacter pylori infection on iron accumulation in hepatitis C.

GOAL: Iron may play a role in the pathogenesis of chronic hepatitis C. Helicobacter pylori (Hp) infection was recently associated with iron-deficiency anemia. We examined the influence of Hp infection on hepatic iron accumulation in hepatitis C. METHODS: Ninety-five hepatitis C virus (HCV)-RNA-positive patients, including 60 chronic hepatitis, 17 cirrhosis and 18 hepatocellular carcinoma as well as 95 age- and sex-matched normal subjects without HCV infection as control, were studied. Liver biopsies were also obtained from 44 HCV-infected patients. Serum Hp antibodies were measured by an enzyme-linked immunosorbent assay and clinical data, including iron parameters and histological findings, were compared between Hp-positive and -negative HCV-infected patients. RESULTS: The percentage of serum Hp antibodies was lower in HCV-infected patients than in controls (52/95 (54.7%) vs. 68/95 (71.6%); P<0.05). HCV-infected patients had higher serum ferritin levels than controls (120 [2.8-1700] vs. 58 [2.2-420] ng/ml; P<0.0001). In HCV-infected patients, the serum ferritin levels (medians and [ranges]) in Hp-positive patients were significantly lower than those of Hp-negative patients (99 [8.5-770] vs. 150 [2.8-1700] ng/ml; P<0.05). The grades of hepatic iron deposit in Hp-positive patients were significantly lower than those in Hp-negative patients (P<0.01). CONCLUSIONS: Hp infection may at least partly affect hepatic iron accumulation in HCV-related liver diseases.