Correlation between serum levels of alanine aminotransferase and ferritin in male blood donors with antibody to hepatitis C virus

Chronic hepatitis C has been demonstrated to be associated with hepatic iron overload, and the hypothesis that the disease activity of hepatitis C is associated with iron cytotoxicity was tested in male volunteer blood donors. Sera with either antibody to hepatitis C virus or hepatitis B surface antigen were selected for determination of ferritin concentration and alanine aminotransferase activity. A correlation between serum ferritin concentration (Y; μg/l) and alanine aminotransferase activity (X; IU/l) was found in donors with antibody to hepatitis C (logY=0.65 × logX+0.98,r=0.53, andP<0.01). The correlation was lower in donors with hepatitis B surface antigen (r=0.37;P<0.01). Hepatitis C virus infection probably induces time-dependent iron accumulation associated with the progression of disease activity, while hepatitis B virus infection results in a variety of iron loads with different clinical features. The high disease activity related to hyperferritinemia suggests the presence of iron-induced liver damage in donors with hepatitis C.     

Reduced glutathione concentration in erythrocytes of patients with acute and chronic viral hepatitis

SUMMARY. Reduced glutathione (GSH), the main intracellular mechanism that protects against oxidative stress, is the subject of considerable interest in viral hepatitis. In patients with chronic hepatitis C, results reported from different centres are controversial, demonstrating either a reduction or an elevation of GSH concentration. The aim of this study was to evaluate the glutathione concentration in erythrocytes (normal range 2.45 ± 0.15 mmol l^?1) in patients with acute and chronic viral hepatitis. In 52 patients with acute viral hepatitis (hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection) there was marked reduction of GSH at the beginning of the disease (0.79 ± 0.43 mmol l^?1. P < 0.001) with high alanine aminotransferase (ALT) activity (1549 ± 772.9 IU l^?1). In 37 patients with chronic HCV infection the mean value of GSH was below the normal range (1.92 ± 0.62 mmol l^?1. P < 0.001). In 60% of patients (n = 22), depletion of GSH was observed and 40% (n = 15) presented with a normal concentration of GSH. In 10 patients with chronic HBV infection the mean value of GSH was also below the normal range (1.93 ± 0.32 mmol l^?1, P < 0.001); in 80% of cases (n = 8) depletion of GSH was observed and 20% of patients (n = 2) had normal GSH concentrations. The ALT activity was not significantly different in patients with depleted and normal GSH concentrations (P > 0.05) in groups with chronic HBV and HCV infection.     

Prediction of sustained virological response in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) and ribavirin

Objective. Patient- and virus-related factors influence the response of patients with chronic hepatitis C to interferon-based therapy. The purpose of this study was to model the probability of achieving a sustained virological response in individual patients, taking into consideration various predictive factors. Material and methods. We combined data from two randomized, multinational trials in which patients received peginterferon alfa-2a (40KD) plus ribavirin. The logistic regression model for patients infected with hepatitis C virus genotype 1 included age, viral load, histology, alanine aminotransferase quotient, body mass index, treatment duration, ribavirin dose and adherence. Results. In the genotype 1 model, varying baseline factors had a striking effect on the probability of sustained virological response. A dramatic difference in the probability of sustained virological response was seen in a series of hypothetical patients in whom five factors were varied to represent best and worst case scenarios. The best case scenario (age 20 years; no cirrhosis/bridging fibrosis; alanine aminotransferase quotient =7; body mass index 20 kg/m²; viral load 40,000 IU/mL) was associated with a 97% probability of sustained virological response, compared with 7% in the worst case scenario (age 60 years; cirrhosis/bridging fibrosis; alanine aminotransferase quotient =1; body mass index 30 kg/m²; viral load 9,000,000 IU/mL). Both adherence to treatment and achieving an early virological response increased the probability of sustained virological response. Conclusions. In treatment-naïve patients with chronic hepatitis C, host factors play a major role in determining treatment outcome and the logistic regression model is useful for predicting the probability of sustained virological response in individual patients.     

APRI as a predictor of early viral response in chronic hepatitis C patients

AIM: To evaluate the aspartate aminotransferase (AST) to platelet ratio index (APRI) as a predictive factor of early viral response in chronic hepatitis C naive patients.METHODS: We performed an ambispective casecontrol study. We enrolled chronic hepatitis C naive patients who were evaluated to start therapy with PEGylated interferon a-2b (1.5 mg/kg per week) and ribavirin (> 75 kg: 1200 mg and < 75 kg: 1000 mg). Patients were allocated into two groups, group 1: Hepatitis C patients with early viral response (EVR), group 2: Patients without EVR. Odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the relationship between each risk factor and the EVR in both groups.RESULTS: During the study, 80 patients were analyzed, 45 retrospectively and 35 prospectively. The mean ± SD age of our subjects was 42.9 ± 12 years; weight 70 kg (± 11.19), AST 64.6 IU/mL (± 48.74), alanine aminotransferase (ALT) 76.3 IU/mL (± 63.08) and platelets 209 000 mill/mm3 (± 84 429). Fifty-five (68.8%) were genotype 1 and 25 (31.3%) were genotype 2 or 3; the mean hepatitis C virus RNA viral load was 2 269 061 IU/mL (± 7 220 266). In the univariate analysis, APRI was not associated with EVR [OR 0.61 (95% CI 0.229-1.655, P = 0.33)], and the absence of EVR was only associated with genotype 1 [OR 0.28 (95% CI 0.08-0.94, P = 0.034)]. After adjustment in a logistic regression model, genotype 1 remains significant.CONCLUSION: APRI was not a predictor of EVR in chronic hepatitis C; Genotype 1 was the only predictive factor associated with the absence of EVR in our patients.     

Improvement of the course of hepatitis C following cytosine arabinoside as conditioning treatment prior to bone marrow transplantation

To investigate the effect of high doses of cytosine arabinoside (AraC) on liver function in non-A, non-B hepatitis, we prospectively followed 11 leukemic patients with posttransfusion hepatitis at the time of conditioning before bone marrow transplantation. Diagnosis of non-A, non-B hepatitis was based on a sustained elevation of serum alanine aminotransferase (ALT) (≥ 2.5 times the upper limit of normal), negative serology for hepatitis A and B viruses, cytomegalovirus and Epstein-Barr virus and, in eight out of nine surviving patients, on antihepatitis C sero-conversion. Conditioning included high dose AraC (3 g/m²/12 h) on day −6 and day −5, cyclophosphamide (60 mg/kg) on day −4 and day −3 and total body irradiation (day −1, 800 cGy). Ten out of 11 patients exhibited a striking reduction in ALT level already apparent within 24 h following AraC administration and sustained until day +29. Mean ( ± SD) ALT level on day −6 was 242 ( ± 138) IU/l; on day −3, 161 ( ± 100) IU/l (P < 0.001); and on day + 4, 60 ( ± 27) IU/l. After day + 29, a progressive rise in ALT concentrations was again observed in all patients. High doses of AraC might thus exert a potent inhibitory effect on HCV replication in vivo which warrants further investigation.     

High levels of immunoglobulin A anti-tissue transglutaminase antibodies at diagnosis are a predictive factor for celiac hepatitis

Introduction: Celiac hepatitis is characterized by the presence of liver injury in patients with celiac disease that resolves after gluten-free diet.

Aim: To evaluate predictive factors of celiac hepatitis at celiac disease diagnosis.

Methods: Retrospective study including 46 adult patients with the diagnosis of celiac disease.

Results: Eighty-seven percent were women, with a mean age of 33?±?11 years, 87% had a Marsh 3 and 46% (n?=?21) had celiac hepatitis. These patients had a median Immunoglobulin A anti-tissue transglutaminase antibody (TTG-IgA) level of 208.0?U/ml (p25–p75: 89–1316?U/ml), a mean aspartate aminotransferase of 42?±?24?U/L, alanine aminotransferase 50?±?28?U/L, alkaline phosphatase 111?±?64?U/L, at the time of diagnosis. Median TTG-IgA one year after diagnosis was 9U/ml (p25–p75: 4.5–30.5?U/ml) and 33% of the patients had normal values. At diagnosis, patients without celiac hepatitis had a median TTG-IgA of 77U/ml (p25–p75: 24–288?U/ml), mean aspartate aminotransferase of 23?±?4?U/L, alanine aminotransferase 20?±?6?U/L, alkaline phosphatase 69?±?17?U/L. Median of TTG-IgA one year after diagnosis was 6?U/ml (p25–p75: 3–19?U/ml) and 48% had normal values. The celiac hepatitis group patients had higher values of TTG-IgA (p?=?0.007) at diagnosis. There was a statistically significant positive correlation between TTG-IgA and alanine aminotransferase (r?=?0.324, p?=?0.028) at diagnosis. The odds of having celiac hepatitis was almost 5-fold higher in patients with a TTG-IgA level higher than 310?U/ml (OR?=?4.8, 95%CI?=?1.213–18.781, p?=?0.025).

Conclusions: Higher TTG-IgA levels are a predictive factor for celiac hepatitis in adult patients with celiac disease at diagnosis.     

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.     

Combined lamivudine and famciclovir therapy for patients with chronic hepatitis B

OBJECTIVE: No single antiviral drug is able to eradicate hepatitis B virus (HBV) infection. It has been shown in vitro that lamivudine and panciclovir (the active metabolite of famciclovir) act synergistically to inhibit HBV replication. To study the therapeutic efficacy of combined lamivudine and famciclovir therapy in patients with chronic hepatitis B. METHODS: Twenty‐one patients with chronic hepatitis B, who had been given lamivudine monotherapy for more than 6 months without improve­ment, had increased serum alanine aminotransferase (ALT) and HBV‐DNA levels, and were positive for hepatitis B surface antigen (HBsAg); 17 were positive for HBeAg. The diagnosis was verified by histology in 12 HBeAg‐positive cases. All patients were given combined therapy with lami­vudine (100 mg q.d.) and famciclovir (500 mg t.i.d.) orally for 4 months, and then with lamivudine alone for 5?10 months. RESULTS: Serum HBV‐DNA levels were initially 1 × 10^{8.19 ± 1.18} copies/mL, then decreased to 1 × 10^{5.25 ± 1.18} copies/mL at the end of the combined treatment and 1 × 10^{5.25 ± 1.82} copies/mL in the follow‐up period (P < 0.01). Serum ALT decreased from 225 ± 110 U/L before the trial to 79 ± 50 U/L at the end of the combined treatment and 81 ± 48 U/L in the follow‐up period (P < 0.01). In 17 HBeAg‐positive patients, eight (47.1%) had HBeAg/anti‐hepatitis B e antigen (HBeAg) seroconversion with a significant decrease of HBV‐DNA (<1 × 10⁴ copies/mL) and normal ALT (P < 0.01). Of four HBeAg‐negative patients, three had decreased levels of HBV‐DNA, to below 1 × 10⁴ copies/mL, which was associated with a significant decrease in ALT. Two patients had recurrent flare‐ups in the follow‐up period, but both HBV‐DNA and ALT were lower than the pretreatment levels. In 10 patients who underwent a second liver biopsy, improvements in inflammatory activity and fibrosis were seen in eight (80%) and four (40%) cases, respectively (P < 0.05). CONCLUSIONS: The combination treatment of lamivudine and famciclovir has synergistic or additive anti‐HBV effects, and may be an alternative therapy for patients with active chronic hepatitis B.     

Cold activation of complement in sera from patients with persistent hepatitis C virus infection on interferon therapy

The loss of haemolytic activity in sera during storage at low temperature (the cold activation of complement) was observed in 136 of 184 (74%) patients with chronic liver disease associated with hepatitis C virus (HCV) infection. This was more frequent than observed in the three of 40 (8%) patients with chronic hepatitis B (P < 0.001) or none in 43 normal controls (P < 0.001). Of 103 patients with chronic hepatitis C who had completed a full course of recombinant interferon-α2a therapy (total dose: 516×10⁶U), 40 responded completely and 21 responded partially, as judged by the normalization or decrease of alanine aminotransferase levels 6 months after the completion of therapy; 42 patients did not respond at all. The cold activation of complement persisted in five (13%) complete responders, less often than in 33 (79%) non-responders (P < 0.001). At the completion of interferon therapy, the cold activation of complement persisted in 12 of 54 patients despite the normalization of alanine aminotransferase. Spontaneous exacerbation of hepatitis occurred in seven of 12 (58%) patients with cold activation, which was more frequent than in the four of 42 patients (10%) without it (P < 0.01). The cold activation of complement disappeared along with the loss of HCV-RNA in five of six responders during the 6 month period after the completion of interferon therapy, while both cold activation and HCV-RNA persisted in all eight non-responders. These results indicate that the cold activation of complement may be useful as a marker of HCV viraemia for monitoring the response to interferon in patients with HCV infection.     

Deferasirox for iron chelation in multitransfused children with sickle cell disease; long‐term experience in the East London clinical haemoglobinopathy network

Deferasirox (DFX) has been licensed for iron chelation in patients with sickle cell disease (SCD), but there is limited data on its long‐term efficacy and safety in children. This retrospective study included 62 regularly transfused children managed in the East London and Essex Clinical Haemoglobinopathy Network (mean age 9.2 ± 3.2 yr). Efficacy measurements consisted of monthly serum ferritin (SF) and annual R2 MRI‐estimated liver iron concentration (LIC), and safety markers included serum creatinine and alanine aminotransferase (ALT). The mean duration of DFX treatment was 2.5 ± 1.4 yr, and mean dose at 36 months was 25 mg/kg/d. Mean SF at initiation of treatment was 2542 ± 952 ng/mL and increased to 4691 ± 2255 ng/mL at 36 months (P = 0.05). Mean LIC on first scan was 10.3 mg/g dry weight and did not decrease significantly on follow‐up scans. There was a significant correlation between relative change in LIC and in SF (R² = 0.66, P < 0.001). Reversible transaminitis episodes, probably due to drug‐induced hepatitis, were noted in 53% of patients. Responses to an adherence and acceptability questionnaire indicated that more than 50% of children had difficulties in taking DFX, commonly because of unpleasant taste. Our results show that more than 50% of children with SCD have inadequate control of iron overload with DFX. It is not clear whether this is because of frequent dose interruptions, poor tolerability and adherence, or poor efficacy of the drug. We recommend further studies to confirm these findings and to optimise iron chelation in this population.     

"Normal" liver stiffness values differ between men and women: a prospective study for healthy living liver and kidney donors in a native Korean population

Background and Aim: Liver stiffness (LS) measurement can distinguish individuals with potential liver disease (LD) from the general population. However, if LS is sex‐sensitive, prevalence of LD may be incorrectly estimated when the same reference LS value is applied irrespective of sex. Here, we evaluated whether normal ranges of LS differ between healthy men and women. Methods: LS was measured in a cohort of healthy living liver and kidney donors, none of whom suffered from diabetes mellitus, hypertension, hepatitis B or C virus infection, heart or liver dysfunction, or metabolic syndrome. Patients with abnormal laboratory findings related to potential LD (platelet count < 150 × 10³/µL; aspartate aminotransferase > 40 IU/L; alanine aminotransferase [ALT] > 40 IU/L; albumin < 3.3 g/dL; total bilirubin > 1.2 mg/dL; gamma‐glutamyl transpeptidase > 54 IU/L; alkaline phosphatase > 115 IU/L) were excluded. Results: Among 242 patients analyzed, the mean age was 34.1 for men (n = 121) and 40.5 years for women (n = 121) (P < 0.001). Men had a higher mean LS value than women (5.2 ± 1.2 vs 4.8 ± 1.1 kPa/P < 0.001). Multivariate‐linear regression analysis identified sex as the only independent factor for LS values (β = 0.361/P = 0.021). Using the 5th–95th percentiles, we determined normal LS ranges of 3.7–7.0 kPa in men and 3.3–6.8 kPa in women. In subgroups with ALT < 30 IU/L (subgroup‐1, n = 216) and ALT < 20 IU/L (subgroup‐2, n = 163), men had significantly higher LS values than women (5.2 ± 1.3 vs 4.7 ± 1.1 kPa/P = 0.003 and 5.1 ± 1.2 vs 4.7 ± 1.1 kPa/P = 0.030, respectively), demonstrating an independent sex effect (β = 0.483/P = 0.003 and β = 0.389/P = 0.030, respectively). Conclusions: An independent sex effect on LS values was confirmed. Thus, sex‐specific references should be used for effective screening based on LS measurements.     

Telbivudine therapy for chronic hepatitis B: A journey to identify super‐responders and to optimize treatment using the roadmap model

Hepatitis B virus (HBV) infection is one of the most serious health problems worldwide with a high risk for cirrhosis and liver cancer. Several antiviral agents have been approved for the treatment of chronic hepatitis B, leading to a rapid reduction in HBV DNA and normalization of serum alanine aminotransferase levels. Telbivudine, a potent inhibitor of HBV replication, has been shown to be well tolerated. Because of the emergence of drug resistance, optimization strategies for telbivudine therapy have been shown to improve patient responses. Optimal baseline characteristics in so‐called super‐responders have been used to predict the virological response. Baseline HBV DNA levels < 9 log₁₀ copies/mL (2 × 10⁸ IU/mL) or alanine aminotransferase levels of more than or equal to twofold the upper limit of normal in HBeAg‐positive patients and HBV DNA < 7 log₁₀ copies/mL (2 × 10⁶ IU/mL) in HBeAg‐negative patients were strong predictors for virological response. In addition, the roadmap model, based on early virological response at week 24 of therapy, is considered as a powerful tool to identify patients at risk of treatment failure (HBV DNA ≥ 300 copies/mL, i.e. 60 IU/mL) and to reduce the risk of antiviral resistance. When considering pre‐treatment characteristics and on‐treatment responses, telbivudine may provide physicians with a wide choice of options to effectively treat patients with chronic hepatitis B, especially those with or at risk of renal impairment, or women of childbearing age.     

Effect of antiviral therapy on circulating cytokeratin‐18 fragments in patients with chronic hepatitis C

Summary. Hepatocellular apoptosis plays a major role in the pathogenesis of chronic hepatitis C. It can be measured noninvasively by determining the circulating levels of cytokeratin‐18 fragments. We hypothesized that the effect of antiviral therapy on this parameter will be different in patients with a sustained virological response, relapse (REL) and nonresponse (NR). We quantified cytokeratin‐18 fragments in plasma of patients participating in the Swiss Hepatitis C cohort, who received antiviral therapy without stopping because of sides effects. A total of 315 patients were included, 183 with a sustained response, 64 with NR and 68 who relapsed. Mean levels ±SD of circulating cytokeratin‐18 fragments before therapy were 174 ± 172 U/L for responsders, 188 ± 145 for nonresponders and 269 ± 158 U/L for patients who relapsed. The values were significantly higher in the REL group (ANOVA P < 0.006). A sustained response was associated with a significant improvement of the plasma levels (94 ± 92 U/L, paired test P < 0.000001), whereas there was no improvement in the nonresponder group (183 ± 158 U/L) and in the relapser group (158 ± 148 U/L). There was a weak correlation between alanine aminotransferase (ALT) and cytokeratin‐18 fragment levels (r² = 0.35, P < 0.000001) before therapy but not after therapy and none with hepatitis C virus (HCV) viremia. Successful antiviral therapy results in a significant decrease in circulating levels of cytokeratin‐18 fragments arguing for a reduction in hepatocellular apoptosis after clearance of the HCV. Baseline cytokeratin‐18 fragment levels are higher in relapsers. Correlations with ALT are weak, suggesting that these two tests measure different but related processes.     

Individuals Homozygous for the H63D Mutation Have Significantly Elevated Iron Indexes

Our objective was to assess the iron indexes of patients with one or more mutations of the HFE gene with a specific interest in studying the effect of the H63D/H63D genotype. Eight hundred twenty subjects who underwent HFE mutational testing for C282Y and H63D mutations were retrospectively identified. Data collected included age, gender, HFE genotype, and values for serum ferritin, iron saturation, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Compared to the Wild/Wild genotype (0.34 ± 0.17), genotypes H63D/C282Y (0.44 ± 0.14 P < 0.01), H63D/H63D (0.51 ± 0.21 P < 0.01), and C282Y/C282Y (0.64 ± 0.20 P < 0.01) had significantly higher transferrin saturation levels and were independent predictors of higher iron saturation in multivariate regression analysis. Compared to the Wild/Wild genotype, no abnormal HFE genotypes had significantly higher ferritin levels, although the genotype H63D/H63D was an independent predictor of higher serum ferritin (P = 0.02) in regression analysis. There was no significant difference in the proportion of patients with abnormally elevated AST (P = 0.64) or ALT (P = 0.80) between groups. H63D homozygotes have elevated transferrin saturation compared to the Wild genotype, comparable to that of C282Y homozygotes and compound heterozygotes. The clinical significance of this finding is unclear but warrants further study.     

Interferon‐α treatment in children and young adults with chronic hepatitis B: a long‐term follow‐up study in Taiwan

Background/Aims: The short‐ and long‐term benefits of interferon (IFN)‐α therapy in young patients with chronic hepatitis B (CHB) acquiring infection perinatally or during early childhood have been questioned. Methods: Twenty‐one Taiwanese hepatitis B envelope antigen (HBeAg)‐positive CHB patients aged 1.8–21.8 years (median 14.0 years) with alanine aminotransferase (ALT)>80 IU/L at entry were enrolled for IFN‐α therapy. They received IFN‐α therapy with a dose of 3 MU/m²/day three times a week for 24 weeks. A control group included untreated 21 CHB patients closely matched for gender, age, duration of ALT >80 IU/L and HBeAg status. All 42 patients were prospectively followed for 6.5–12.5 years after the end of therapy. Results: The cumulative rate of virological response [anti‐HBe seroconversion and serum hepatitis B virus (HBV)‐DNA <10⁵ copies/ml] was not different between the IFN‐treated patients and control patients at 1 year (41 vs 44%) and at 6 years (88 vs 89%) after stopping treatment. Serum hepatitis B surface antigen loss occurred in two (9.5%) treated patients and in one (4.8%) control patient. Patients with a successful treatment response (anti‐HBe seroconversion, HBV‐DNA <10² copies/ml and ALT normalization at 1 year after stopping treatment) were younger than those without a successful response (P=0.03). A lower pretreatment serum HBV‐DNA level (<2 × 10⁸ copies/ml) is not only a significant factor to predict successful treatment response (P=0.008) but also has a beneficial effect on the long‐term cumulative rate of virological response in IFN‐treated patients (P=0.021), but not in control patients. Genotype difference or emergence of a precore stop codon mutant before treatment was not predictive for HBeAg clearance. Conclusion: For young CHB patients in Taiwan with infection occurring perinatally or in early childhood, the real advantage of IFN‐α therapy was not observed. IFN‐α therapy showed a beneficial effect on short‐ and long‐term virological outcomes only in those with a lower pretreatment serum HBV‐DNA level.     

Serum hepcidin levels are related to the severity of liver histological lesions in chronic hepatitis C

Summary. Hepcidin is synthesized in the liver and has a crucial role in iron homoeostasis. Its synthesis is up‐regulated in chronic inflammation and iron excess. We examined the determinants of serum hepcidin and liver hepcidin mRNA levels and their association with histological lesions in patients with chronic hepatitis C (CHC) and healthy controls. We studied 96 patients with CHC and 30 controls. Serum hepcidin levels were measured by an in‐house competitive ELISA. Hepcidin mRNA levels were determined by a one‐step qRT‐PCR in total RNA extracted from liver biopsy specimens of 27 patients with CHC and six disease controls. Histological lesions were evaluated according to Ishak’s classification. Serum hepcidin was significantly lower in patients with CHC than healthy controls (14.6 ± 7.3 vs 34.6 ± 17.3 ng/mL, P < 0.001). In patients with CHC, serum hepcidin correlated positively with aspartate aminotransferase (r = 0.334, P = 0.001) and insulin resistance (r = 0.27, P = 0.016) and had a trend for correlation with alanine aminotransferase (r = 0.197, P = 0.057) and serum haemoglobin (r = 0.188, P = 0.067) but not with ferritin. A significant positive correlation was also found between serum hepcidin levels and both necroinflammation (r = 0.259, P = 0.011) and fibrosis (r = 0.214, P = 0.036). Serum hepcidin was among others an independent predictor of cirrhosis (odds ratio: 1.145, P = 0.039). Liver hepcidin mRNA levels did not differ between patients and controls and were relatively lower in patients with than without cirrhosis (19.3 ± 21.7 vs 38.3 ± 26.0, P = 0.067). Patients with CHC have reduced serum hepcidin levels, which correlate with worse necroinflammation and fibrosis. The previously mentioned observations suggest a viral effect on hepatic hepcidin production, but might also support its involvement in the inflammatory process.     

Efficacy of preoperative recombinant human erythropoietin administration for reducing transfusion requirements in patients undergoing surgery for hip fracture repair. An observational cohort study

Background Preoperative anaemia is a major risk factor for allogeneic blood transfusion (ABT) in patients undergoing hip fracture repair. We investigated the efficacy of preoperative recombinant human erythropoietin (rHuEPO) administration for reducing ABT requirements in a series of consecutive hip fracture patients presenting with haemoglobin (Hb) between 10 g/dl and 13 g/dl. Methods The blood conservation protocol consisted of the application of a restrictive transfusion trigger (Hb < 8 g/dl) and the perioperative administration of intravenous iron sucrose (3 × 200 mg/48 h) (group 1, n = 115). Additionally, some patients received preoperative rHuEPO (40 000 IU sc) on admission to the orthopaedic ward (group 2, n = 81). Results Overall, 103 of 196 patients (52·5%) received at least one ABT unit (2·1 ± 1·0 U/patient). However, there were significant differences in perioperative ABT rates between groups (60% vs. 42%, for groups 1 and 2, respectively; P = 0·013). Postoperative Hb on postoperative days 7 and 30 was higher in group 2 than in group 1. In addition, in group 2, Hb levels were higher on postoperative day 30 than on admission (12·7 ± 1·0 g/dl vs. 11·9 ± 0·8 g/dl, respectively; P = 0·030). Administration of rHuEPO did not increase postoperative complications or 30‐day mortality rate. Only three mild intravenous iron adverse effects were witnessed. Conclusions In anaemic hip fracture patients managed with perioperative intravenous iron and restrictive transfusion protocol, preoperative administration of rHuEPO is associated with reduced ABT requirements. However, appropriate training, education and awareness are needed to avoid protocol violations and to limit further exposure to ABT and ABT‐related risks.     

Development of hepatocellular carcinoma in elderly patients with chronic hepatitis C with or without elevated aspartate and alanine aminotransferase levels

Objective. Hepatocellular carcinoma (HCC) in the elderly infected with hepatitis C virus (HCV) is expected to increase globally within the next two decades. The purpose of the study was to define the natural history of elderly patients with chronic hepatitis C needs in order to prevent HCC from arising in these patients. Material and methods. Treatment-naive patients aged ≥65 years with platelet counts >120×10³/mm³ were classified as 120 with aspartate and alanine aminotransferase (ASAT and ALAT) levels ≦40 IU/l (group A) and 212 with either or both levels ≥41 (group B) and followed-up for 3 years or longer without antiviral treatment. Results. Cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 for both). In particular, of the patients aged 65–69 years at entry, cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 and p=0.001, respectively). Liver-related causes of death were more common in group B than in group A (20/34 (59%) versus 1/9 (11%), p=0.021). HCC developed more frequently in men than in women (p=0.033). Conclusions. In elderly patients with chronic hepatitis C, cirrhosis and HCC develop more frequently in those with elevated transaminase levels than in those without elevated transaminase levels. Therefore, transaminase levels need to be suppressed below ≦40 IU/l, using antiviral treatments or other agents, in order to prevent cirrhosis and HCC arising in these patients. In view of rare liver-related deaths, aggressive antiviral treatment would not be necessary in the elderly with chronic hepatitis C who have normal transaminase levels.     

Effect of Deferiprone on Liver Iron Overload and Fibrosis in Hepatitis C Virus-Infected Thalassemia

To assess the effects of liver iron overload and fibrosis after treatment with a chelating agent in hepatitis C virus (HCV)-infected thalassemia, from April 1999 to July 2004, 45 patients with thalassemia major (age range 9–33 years, mean 19.3) received daily deferiprone (L1) for 23–60 months (75 mg/kg). The patients were divided into two groups on the basis of their hepatitis status (27 with, 18 without). Their serum was analyzed for alanine aminotransferase (GPT), aspartate aminotransferase (GOT), bilirubin (total/direct), r-glutamyl transpeptidase (r-GT), alkaline phosphatase (Alk-P), and ferritin. Liver iron overload and fibrosis were defined by a senior pathologist. No significant differences were demonstrated in serum levels of GPT, GOT, bilirubin, r-GT, Alk-P or ferritin; comparison was made for each group before and after L1 treatment. Iron scores were 2.3 ± 0.9 and 2.8 ± 0.9 for the hepatitis C negative and positive groups, respectively (p = 0.07), with liver fibrosis scores of 1.0 ± 0.5 and 0.4 ± 0.52 (p = 0.56). The two scores were not higher for the positive group. There was no evidence of: 1) greater iron overload and fibrosis in the HCV-infected thalassemic patients; 2) L1 inducing progressive hepatic fibrosis or worsening iron overload in HCV-infected thalassemic patients after long-term therapy; 3) further damage to liver cells associated with L1 treatment.