Poly(ethylene terephthalate), Poly(butylene terephthalate), and Polystyrene Oligomers: Occurrence and Analysis in Food Contact Materials and Food.

Polyesters (PES) and polystyrene (PS) are among the most used plastics in the production of food contact materials (FCM). The existence of compounds that could migrate from these materials into food requires a constant analytical control to ensure the safety of consumers due to consumption. It also implies a significant research challenge for their identification and quantification. One of the most important groups of known FCM migrants are the substances known as oligomers. PES and PS oligomers have long been suspected to possess some toxicological effects. The International Agency for Research on Cancer and the European Food Safety Authority alerted recently to the potential carcinogenicity of styrene, with its oligomers consequently being also in the spotlight. At the same time, PES cyclic oligomers are categorized as having Cramer III toxicity. Many recent works on the occurrence of poly(ethylene terephthalate) (PET), poly(butylene terephthalate) (PBT), and PS oligomers in FCM and food have been published. The oligomeric chemical analysis requires the use of demanding analytical strategies to address their different physicochemical characteristics (melting points, octanol/water partition coefficients, and solubility properties). Chromatographic methods are normally preferred due to the intrinsic complexity of the target matrices, but the reduced amount of reliable analytical standards still hinders the widespread screening analysis of oligomers in food. This work presents the most relevant recent studies and analytical methodologies used in the analysis of PET, PBT, and PS oligomers in food and FCM, as well as current and future challenges.

Cellular lipids and protein alteration during biodegradation of expanded polystyrene by mealworm larvae under different feeding conditions.

The present study reports the biodegradation of polystyrene (PS) by mealworm (Tenebrio molitor) following different feeding regimes. Changes in lipids and protein were studied to evaluate possible differences in the growth and metabolic pathways of the insects depending on the diets. Thermo-gravimetric analysis of the excretions (frass) revealed a decrease in the molecular mass of the PS polymers. The insects' biomass contained less protein when PS was part of the diet, suggesting that the insects undergo a certain level of stress compared to control diets. The frass also contained lower amount of nitrogen content compared to that from insects fed a control diet. NH4+ and other cations involved in biochemical processes were also measured in insects' frass, including potassium, sodium, magnesium, and calcium, combined with a small pH change. The decrease in the mineral content of the frass was attributed to increased cellular activity in PS-fed insects. A higher amount of ceramides and cardiolipins, biomarkers of apoptosis, were also found in association with PS consumption. It was concluded that the insects could metabolize PS, but this caused an increase in its stress levels.

Biodegradation of expanded polystyrene by mealworm larvae under different feeding strategies evaluated by metabolic profiling using GC-TOF-MS.

The present study investigated the biodegradation of polystyrene (PS) plastic by mealworm (Tenebrio molitor) on different diets followed by untargeted screening of larvae gut intestine tissue and frass (manure and feed residuals) to investigate the existence of polymer-generated organic residues. Three different diets, consisting of PS, rolled barley and water were tested. PS degradation rates ranged from 16% to 23% within 15 days, with no statistical differences in survival rates. The larvae fed with ad libitum barley:PS (20:1 w/w) and water had the highest growth rate, while higher PS consumption was observed for barley:PS of 4:1 w/w. A GC-TOF-MS analysis revealed no contaminating substances in the gut intestine tissue, nor styrene or PS oligomers, whilst several bioactive compounds and traces of alkanes, mostly with small carbon chains, were present. Metabolomics analysis on the collected frass, either on the lipophilic (CHCl3) or the polar fraction (MeOH-H2O) was performed. Styrene and PS oligomers (dimers, trimers) were identified, though in a relatively low total amount, up to a total of 346.0 ng/mg 2,4 di-tert butylphenol was identified in both frass and tissue, coming from the PS polymer (Non-intentionally added substances; NIAS). Finally, in the polar fraction of frass, bioactive molecules (fatty acids, amides) were identified, together with several hydrocarbons, mostly with longer carbon chains. The formation of these substances indicated enzymatic and biochemical activity in the larvae-gut intestine. It was shown that degrading and contaminating organic compounds occur at low levels, in both gut intestine and frass, during bio-degradation of PS.

[Glucocorticosteroids for people with alcoholic hepatitis (Cochrane review)].

Alcoholic hepatitis (AH) is a form of alcoholic liver disease. Glucocorticosteroids (GCS) are used as anti - inflammatory drugs for people with alcoholic hepatitis. AIM: To assess the benefits and harms of GCS in people with AH. MATERIAL AND METHODS: We identified trials through electronic searches in Cochrane Hepato-Biliary's (CHB) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, and Science Citation Index Expanded. We considered for inclusion randomised clinical trials (RCTs) assessing GCS versus placebo/no intervention in adult participants with AH. We allowed co - interventions in the trial groups if they were similar. We followed Cochrane methodology, CHB Group methodology using Review Manager 5 and Trial Sequential Analysis(TSA) to perform meta - analysis (M-A), assessed bias risk of the trials, certainty of evidence using GRADE. RESULTS AND DISCUSSION: Sixteen trials fulfilled the inclusion criteria. Fifteen trials provided data for analysis (927 participants received GCS, 934 - placebo/no intervention). The GCS were administered to adult participants at different stages of AH orally or parenterally for a median of 28 days. There was no evidence of effect of GCCs on our primary outcomes all - cause mortality up to 3 months following randomisation (RR 0.90, 95% CI 0.70-1.15; n=1861), on health - related quality of life (MD - 0.04 points; 95% CI -0.11-0.03; n=377; trial = 1) (EQ-5D-3L scale), on the occurrence of serious adverse events during treatment (RR 1.05, 95% CI 0.85-1.29; n=1861). We found no evidence of a difference between the intervention groups. The risk of bias was high in all the trials except one. The certainty of evidence was very low or low. One of the trials seems to be not industry - funded. CONCLUSION: We found no evidence of a difference between GCS and placebo or no intervention on all - cause mortality, health - related quality of life, and serious adverse events during treatment. We cannot exclude increases in adverse events and cannot rule out significant benefits and harms of GCSs. Future trials ought to report depersonalised individual participant data.

The Royal Free Hospital 'hub-and-spoke network model' delivers effective care and increased access to liver transplantation.

OBJECTIVES: 'Hub-and-spoke' networks may be one solution to reduce the geographical inequality in access to liver transplantation (LT) and the growing demands on, and saturation of, LT centres. It is not clear if such networks improve equity of access, deliver comparable patient outcomes or effect patient satisfaction. STUDY DESIGN: Retrospective evaluation of outcomes and patient satisfaction within the Royal Free liver transplant 'hub-and-spoke' network. METHODS: Patient outcomes in those assessed for LT between September 2011 and 2014 at spoke centres (n = 4) were compared retrospectively with those assessed at the LT hub centre. Patient satisfaction questionnaires were completed and changes in LT referral patterns were explored with data obtained directly from NHS Blood and Transplant (NHSBT). RESULTS: A total of 655 patients (180 spoke; 475 hub) were assessed for LT. Patients referred from spoke centres were more likely to have viral hepatitis as an underlying aetiology (72/180 vs 110/475; P < 0.001), or hepatocellular carcinoma (48/180 vs 60/475; P < 0.001) as an indication for LT and were more likely to be listed for LT when compared with hub patients (139/180 vs 312/475, P = 0.005). Mortality on the waiting list (9/123 vs 25/269, P = 0.57), waiting time to LT (64-days vs 78-days, P = 0.91) and Model for End-Stage liver disease (MELD)/United Kingdom End-Stage Liver Disease (UKELD) score (P = 0.24/0.26) in listed patients were equivalent as were 1- and 3-year patient and graft survival rates. Patient satisfaction rates were high at both types of centre, with significantly more patients preferring 'locally delivered care' at spoke vs hub (11/50 vs 70/73, P≤0.0001). Since the development of formal hub-and-spoke networks data from NHSBT based on postcode confirmed a significant increase in patients undergoing LT (153%) from spoke centres, whereas numbers assessed and transplanted from the hub centre have remained static. CONCLUSION: Hub-and-spoke LT networks are effective in offering equivalent clinical outcomes, high patient satisfaction and alleviate clinical pressure on the hub centre. They have to potential to help eliminate the geographical disparity in mortality rates from chronic liver disease.

Systematic review with meta-analysis: diagnostic accuracy of transient elastography for staging of fibrosis in people with alcoholic liver disease.

BACKGROUND: The progression of hepatic fibrosis into cirrhosis is a main prognostic factor for survival in people with alcoholic liver disease. The range of cut-off values characterising the stage of hepatic fibrosis seems to be dependent on the aetiology of the liver disease. AIMS: To determine the diagnostic accuracy of transient elastography (the index test) for diagnosis of fibrosis in alcoholic liver disease when compared with liver biopsy (the reference standard), using the METAVIR scoring system. To establish the optimal cut-off values for the hepatic fibrosis stages. METHODS: We followed Cochrane Methodology for diagnostic test accuracy reviews. We identified 14 studies. Among the study participants with alcoholic liver disease, 834 provided numerical data for analysis (August 2014). Only half of the studies were monoaetiology studies. We used the bivariate model and estimated the summary sensitivities and summary specificities. Hence, we calculated the summary likelihood ratios (LRs) to rule in or rule out hepatic fibrosis. We investigated pre-defined sources of heterogeneity. RESULTS: Severe fibrosis (F3 or worse): summary (95% CI) sensitivity 0.92(0.89-0.96) and specificity 0.70(0.61-0.79); LR+ 3.1(2.1-4.1), LR- 0.11(95% CI 0.06-0.16). Cirrhosis (F4): summary (95% CI) sensitivity of 0.95(0.87-0.98) and specificity 0.71(0.56-0.82); LR+ 3.3(2.1-5.0); LR- 0.07(0.03-0.19). CONCLUSIONS: Transient elastography may be used as a diagnostic method to exclude cirrhosis or severe fibrosis when the test is negative. Cut-off values of around 12.5 kPa for cirrhosis may be used in clinical practice, but caution is needed, as the values reported in the review are not yet prospectively validated.

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis B in the UK: systematic review and economic evaluation.

We compared the cost-effectiveness of various noninvasive tests (NITs) in patients with chronic hepatitis B and elevated transaminases and/or viral load who would normally undergo liver biopsy to inform treatment decisions. We searched various databases until April 2012. We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes quality-adjusted-life-years (QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four decision-making strategies: testing with NITs and treating patients with fibrosis stage ≥F2, testing with liver biopsy and treating patients with ≥F2, treat none (watchful waiting) and treat all irrespective of fibrosis. Treating all patients without prior fibrosis assessment had an incremental cost-effectiveness ratio (ICER) of £28,137 per additional QALY gained for HBeAg-negative patients. For HBeAg-positive patients, using Fibroscan was the most cost-effective option with an ICER of £23,345. The base case results remained robust in the majority of sensitivity analyses, but were sensitive to changes in the ≥ F2 prevalence and the benefit of treatment in patients with F0-F1. For HBeAg-negative patients, strategies excluding NITs were the most cost-effective: treating all patients regardless of fibrosis level if the high cost-effectiveness threshold of £30,000 is accepted; watchful waiting if not. For HBeAg-positive patients, using Fibroscan to identify and treat those with ≥F2 was the most cost-effective option.

Nine scoring models for short-term mortality in alcoholic hepatitis: cross-validation in a biopsy-proven cohort.

BACKGROUND: Several prognostic models have emerged in alcoholic hepatitis (AH), but lack of external validation precludes their universal use. AIM: To validate the Maddrey Discriminant Function (DF); Glasgow Alcoholic Hepatitis Score (GAHS); Mayo End-stage Liver Disease (MELD); Age, Bilirubin, INR, Creatinine (ABIC); MELD-Na, UK End-stage Liver Disease (UKELD), and three scores of corticosteroid response at 1 week: an Early Change in Bilirubin Levels (ECBL), a 25% fall in bilirubin, and the Lille score. METHODS: Seventy-one consecutive patients with biopsy-proven AH, admitted between November 2007-September 2011, were evaluated. The clinical and biochemical parameters were analysed to assess prognostic models with respect to 30- and 90-day mortality. RESULTS: There were no significant differences in the areas under the receiver operating characteristics curve (AUROCs) relative to 30-day/90-day mortality: MELD 0.79/0.84, DF 0.71/0.74, GAHS 0.75/0.78, ABIC 0.71/0.78, MELD-Na 0.68/0.76, UKELD 0.56/0.68. One-week rescoring yielded a trend towards improved predictive accuracies (30-day/90-day AUROCs: 0.69­0.84/0.77­0.86). In patients with admission DF ≥ 32 (n = 31), response to corticosteroids according to ECBL, 25% fall in bilirubin and the Lille model yielded AUROCs of 0.73/0.73, 0.78/0.72 and 0.81/0.82 for a 30-day/90-day outcome respectively. All models showed excellent negative predictive values (NPVs; range: 86­100%), while the positive ones were low (range: 17­50%). CONCLUSIONS: MELD, DF, GAHS, ABIC and scores of corticosteroid response proved to be valid in an independent cohort of biopsy-proven alcoholic hepatitis. MELD modifications incorporating sodium did not confer any prognostic advantage over classical MELD. Based on excellent NPVs, the models are best to identify patients at low risk of death.

Biochemical criteria at 1 year are not robust indicators of response to ursodeoxycholic acid in early primary biliary cirrhosis: results from a 29-year cohort study.

BACKGROUND: In primary biliary cirrhosis (PBC), biochemical criteria at 1 year are considered surrogates of response to ursodeoxycholic acid (UDCA). However, due to the slow natural history of PBC, evaluation at 1 year may be suboptimal to assess the therapeutic response, particularly in early disease. AIM: To determine whether evaluation of biochemical criteria at 1 year is a reliable surrogate of UDCA response in early PBC. METHODS: We analysed the prospectively collected data of 215 patients (untreated = 129; UDCA-treated = 86) with early PBC (normal baseline bilirubin/albumin) and a median follow-up of 8 years (range: 1-29.1). The 1-year attainment rates of the Barcelona, Paris-I, Paris-II and Toronto definitions, and their predictive relevance for a poor outcome (death, transplantation, complications of cirrhosis), were assessed either as a result of UDCA or no treatment. Independent associations with attaining each UDCA response definition were identified by multivariate analysis. RESULTS: Untreated patients displayed 1-year biochemical features compatible with 'treatment response' at rates (Barcelona: 36.4%, Paris-I: 66.7%, Toronto: 59.7%, Paris-II: 40.3%) similar to those obtained under UDCA. Depending on the definition, baseline ALP≤3xULN (OR: 4.80-35.90), AST≤2xULN (OR: 5.63-9.34) and early histological stage (OR: 3.67-3.87) were the stronger predictors for attaining the criteria. UDCA treatment was associated with attaining Barcelona (OR = 2.16) and Paris-II (OR = 2.84), but not Paris-I, and not Toronto definition when excluding late histological cases. Paris-I criteria were significantly predictive of long-term outcomes (HR = 2.83) in untreated patients. CONCLUSIONS: In early PBC, biochemical criteria at 1 year reflect severity of the disease rather than the therapeutic response to UDCA.

Laboratory and field dissipation of penoxsulam, tricyclazole and profoxydim in rice paddy systems.

Rice cultivation relies on pesticide applications to ensure high yields. However, the regular use of pesticides seriously affects the quality of neighboring surface water systems. Thus complete knowledge of the environmental fate and dissipation of pesticides in the paddy rice environment should become available. So far only a few studies have provided comprehensive assessment of the dissipation of pesticides under the submerged cultivation conditions followed in rice. Thus, laboratory and 2-year field studies were performed to assess the dissipation of two new generation rice herbicides (penoxsulam and profoxydim) and one of the most important rice fungicides (tricyclazole). A good agreement between laboratory and field experiments was observed with a faster dissipation of penoxsulam and tricyclazole under field conditions. Profoxydim was the least persistent chemical (DT50 soil<1d; DT50 water 0.5-1.2d), followed by penoxsulam which persisted for longer particularly in the water compartment (DT50water=3.8-5.9d). Tricyclazole was the most persistent pesticide, especially in the soil compartment with DT50 values of 44.5-84.6 (field) and 197d (laboratory). These results could be utilized for the assessment of the environmental risk associated with the use of those pesticides in rice cultivation and the determination of potential mitigation measures for minimizing the risk for contamination of neighboring natural water resources.

A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolisation (TACE) has not been shown to be superior to bland embolisation (TAE) for treatment of hepatocellular carcinoma (HCC). METHODS: We conducted a randomised phase II/III trial in patients with untreated HCC. Patients were randomised to TAE with polyvinyl alcohol (PVA) particles alone or sequential TACE (sTACE) in which cisplatin 50 mg was administered intrarterially 4-6 h before PVA embolisation. Treatment was repeated 3-weekly for up to three treatments. The primary endpoint was overall survival and secondary endpoints were progression-free survival, toxicity and response. Target sample sizes for phase II and III were 80 and 322. RESULTS: The trial was terminated at phase II after 86 patients had been randomised. Patients were well matched for prognostic criteria. All three planned treatments were given to 57.1% (TAE) and 56.8% (TACE) patients. Grade 3/4 toxicity occurred in 63.5% and 83.7%, respectively (P=0.019). End-of-treatment RECIST response (CR+PR) was 13.2 and 32.6% (P=0.04) (mRECIST 47.3% and 67.4) and median overall survival and progression-free survival was 17.3 vs 16.3 (P=0.74) months and 7.2 vs 7.5 (P=0.59), respectively. CONCLUSION: Transarterial chemoembolisation according this novel schedule is feasible and associated with a higher response rate than TAE alone. The survival benefit of TACE over TAE remains unproven.

Tacrolimus trough levels, rejection and renal impairment in liver transplantation: a systematic review and meta-analysis.

We hypothesized that current trough concentrations of tacrolimus after liver transplantation are set too high, considering that clinical consequences of rejection are not severe while side effects are increased.We systematically reviewed 64 studies (32 randomized controlled trials and 32 observational studies) to determine how lower tacrolimus trough concentrations than currently recommended affect acute rejection rates and renal impairment. Among randomized trials the mean of tacrolimus trough concentration during the first month was positively correlated with renal impairment within 1 year (r = 0.73; p = 0.003), but not with acute rejection, either defined using protocol biopsies (r = -0.37; p = 0.32) or not (r = 0.11; p = 0.49). A meta-analysis of randomized trials directly comparing tacrolimus trough concentrations (five trials for acute rejection [n = 957] and two trials for renal impairment [n = 712]) showed that "reduced tacrolimus" trough concentrations (<10 ng/mL) within the first month after liver transplantation were associated with less renal impairment at 1 year (RR = 0.51 [0.38-0.69]), with no significant influence on acute rejection (RR = 0.92 [0.65-1.31]) compared to "conventional tacrolimus" trough levels (>10 ng/mL). Lower trough concentrations of tacrolimus (6-10 ng/mL during the first month) would be more appropriate after liver transplantation. Regulatory authorities and the pharmaceutical industry should allow changes of regulatory drug information.

Review article: the extra-skeletal effects of vitamin D in chronic hepatitis C infection.

BACKGROUND: Recent interest has focused on the extra-skeletal effects of vitamin D, in particular, in patients with chronic hepatitis C. AIMS: To review data in the literature regarding the extra-skeletal effects of vitamin D in patients with chronic hepatitis C, with and without liver transplantation. METHODS: A Medline search was performed for relevant studies up to August 2011 using the terms 'vitamin D' 'chronic liver disease' and 'hepatitis C'. RESULTS: Vitamin D deficiency is very frequent before liver transplantation ranging between 51% and 92%, whereas, in the liver transplantation setting, the prevalence of vitamin D deficiency is also high. Severe liver disease may increase the risk of vitamin D deficiency and vice versa, as there may be a relationship between vitamin D deficiency and fibrosis. In patients with chronic hepatitis C and those with recurrent of hepatitis C after liver transplantation, recent clinical data shows that a higher serum vitamin D level is an independent predictor of sustained virological response (SVR) following anti-viral therapy, and that a higher SVR is achieved with vitamin D supplementation. CONCLUSIONS: Larger randomised clinical studies with adequate statistical power are needed to confirm these potentially very important nonskeletal effects of vitamin D in patients with chronic hepatitis C.

Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy.

BACKGROUND & AIMS: Transient elastography is a non-invasive method, for the assessment of hepatic fibrosis, developed as an alternative to liver biopsy. We studied the performance of elastography for diagnosis of fibrosis using meta-analysis. METHODS: MEDLINE, EMBASE, SCI, Cochrane Library, conference abstracts books, and article references were searched. We included studies using biopsy as a reference standard, with the data necessary to calculate the true and false positive, true and false negative diagnostic results of elastography for a fibrosis stage, and with a 3-month maximum interval between tests. The quality of the studies was rated with the QUADAS tool. RESULTS: We identified 40 eligible studies. Summary sensitivity and specificity was 0.79 (95% CI 0.74-0.82) and 0.78 (95% CI 0.72-0.83) for F2 stage and 0.83 (95% CI 0.79-0.86) and 0.89 (95% CI 0.87-0.91) for cirrhosis. After an elastography result at/over the threshold value for F2 or cirrhosis ("positive" result), the corresponding post-test probability for their presence (if pre-test probability was 50%) was 78%, and 88% respectively, while, if values were below these thresholds ("negative" result), the post-test probability was 21% and 16%, respectively. No optimal stiffness cut-offs for individual fibrosis stages were validated in independent cohorts and cut-offs had a wide range and overlap within and between stages. CONCLUSIONS: Elastography theoretically has good sensitivity and specificity for cirrhosis (and less for lesser degrees of fibrosis); however, it should be cautiously applied to everyday clinical practice because there is no validation of the stiffness cut-offs for the various stages. Such validation is required before elastography is considered sufficiently accurate for non-invasive staging of fibrosis.

Systematic review: portal vein thrombosis in cirrhosis.

BACKGROUND: As current imaging techniques in cirrhosis allow detection of asymptomatic portal vein thrombosis during routine ultrasonography, more patients with cirrhosis are diagnosed with portal vein thrombosis. Although a consensus on noncirrhotic extra-hepatic portal vein thrombosis has been published, no such consensus exists for portal vein thrombosis with cirrhosis. AIM: To perform a systematic review of nonmalignant portal vein thrombosis in cirrhosis in terms of prevalence, pathogenesis, diagnosis, clinical course and management. METHODS: Studies were identified by a search strategy using MEDLINE and EMBASE. RESULTS: Portal vein thrombosis is encountered in 10-25% of cirrhotics. In terms of pathophysiology, cirrhosis is no longer considered a hypocoagulable state; rather than a bleeding risk in cirrhosis, various clinical studies support a thrombotic potential. Clinical findings of portal vein thrombosis in cirrhosis vary from asymptomatic disease to a life-threatening condition at first presentation. Optimal management of portal vein thrombosis in cirrhosis is currently not addressed in any consensus publication. Treatment strategies most often include the use of anticoagulation, while thrombectomy and transjugular intrahepatic portosystemic shunts are considered second-line options. CONCLUSIONS: Portal vein thrombosis in cirrhosis has many unresolved issues, which are often the critical problems clinicians encounter in their everyday practice. We propose a possible research agenda to address these unresolved issues.

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

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.