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Objectives: Patients with chronic hepatitis C virus (HCV) infection have a genuine risk of developing liver fibrosis and cirrhosis, potentially resulting in hepatocellular carcinoma (HCC), a risk that remains even after sustained viral response (SVR). Glycomics-based biomarkers are an attractive tool to closely monitor these patients during and after antiviral treatment, as alterations in the abundance of N-glycans reflect an altered state of the liver. This study assessed serum glycomics for the evaluation of inflammation-related fibrosis regression during and after treatment of HCV with DAAs., Methods: The GlycoFibroTest and GlycoCirrhoTest were analyzed in the sera 36 HCV-infected patients with advanced fibrosis (F3) or established cirrhosis (F4), before (week 0), during (week 12) and after (week 24) a twelve-week oral administration of DAAs therapy - using an optimized glycomic technology on a DNA sequencer., Results: All patients achieved SVR after treatment and two of them developed HCC in the subsequent five years. A significant decrease of the GlycoFibroTest (p < 0.0001) was seen after 12 weeks, consistent with other measured biomarkers (APRI, FIB-4, FibroTest). Statistical analysis was performed in IBM SPSS Statistics version 28.0, using the non-parametric Friedman's test with a statistical significance α level of 0.05., Conclusion: This study suggests that the GlycoFibroTest is a serum biomarker for viral response in HCV patients. The rapid decrease of the glycomics-based biomarker probably reflects the amelioration of liver inflammation as underlying process, rather than the improvement of liver fibrosis itself.

Hepatitis C virus (HCV) is highly variable and transmits through infected blood to establish a chronic liver infection in the majority of patients. Our knowledge on the infectivity of clinical HCV strains is hampered by the lack of in vitro cell culture systems that support efficient viral replication. We and others have reported that HCV can associate with and infect immune cells and may thereby evade host immune surveillance and elimination. To evaluate whether B cells play a role in HCV transmission, we assessed the ability of B cells and sera from recent (<2 years) or chronic (≥ 2 years) HCV patients to infect humanized liver chimeric mice. HCV was transmitted by B cells from chronic infected patients whereas the sera were non-infectious. In contrast, B cells from recently infected patients failed to transmit HCV to the mice, whereas all serum samples were infectious. We observed an association between circulating anti-glycoprotein E1E2 antibodies and B cell HCV transmission. Taken together, our studies provide evidence for HCV transmission by B cells, findings that have clinical implications for prophylactic and therapeutic antibody-based vaccine design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Desombere, Van Houtte, Farhoudi, Verhoye, Buysschaert, Gijbels, Couvent, Swinnen, Van Vlierberghe, Elewaut, Magri, Stamataki, Meuleman, McKeating and Leroux-Roels.)

Objectives : Hepatitis C virus (HCV) is a major cause of acute and chronic liver disease (e.g. cirrhosis and hepatocellular carcinoma). In Belgium, screening recommendations focus on risk groups. However, it is estimated that 50% of the infected patients are undiagnosed. This study assessed the prevalence of HCV in patients visiting two general practices in Flanders, Belgium. We revealed the associated risk factors and explored whether the current recommendations for HCV screening need to be reconsidered. Methods : A cross-sectional study in a non-urban practice in Lendelede and an urban community health center in Ghent, Belgium was performed. Patients for whom a blood test was required, were recruited for HCV screening. A patient survey assessed the associated risk factors. Results : There were 1112 patients included in the study. Nineteen patients were HCV Ab positive (1.71%) and eight were HCV RNA positive (0.72%). Five patients were unaware of their status. Using IV drugs, being born in the baby boom cohort and originating from a non-Belgian low-endemic country are significantly associated with HCV Ab positivity. Four of the 19 HCV Ab positive patients didn't meet any of the registered risk factors. Conclusions : This study confirms the problem of underdiagnosis of HCV, which is both related to the fact that not all risk groups are being screened and to the fact that patients are identified beyond the risk groups. These results, as well as the current changes in treatment options and their reimbursement, justify a reconsideration of the current recommendations for screening of HCV. To develop the most effective screening strategy in Flanders, further research is necessary.

Background: Prevalence data on viral hepatitis B (HBV), hepatitis C (HCV), and HIV infection in prison are often scarce or outdated. There is currently no systematic screening for these blood-borne viral infections (BBV) in Belgian prisons. There is an urgency to assess the prevalence of these BBV to inform policymakers and public healthcare., Methods: This was a multicentre, interventional study to assess the prevalence of BBV using opt-in screening in prisons across Belgium, April 2019 - March 2020. Prisoners were tested using a finger prick and BBV risk factors were assessed using a questionnaire. A generalized linear mixed model was used to investigate the association between the various risk factors and HCV., Results: In total, 886 prisoners from 11 Belgian prisons were screened. Study uptake ranged from 16.9 to 35.4% in long-term facilities. The prevalence of HCV antibodies (Ab), hepatitis B surface antigen (Ag) and HIV Ab/Ag was 5.0% (44/886), 0.8% (7/886), and 0.2% (2/886). The adjusted odds for HCV Ab were highest in prisoners who ever injected (p < 0.001; AOR 24.6 CI 95% (5.5-215.2). The prevalence of detectable HCV RNA in the total cohort was 2.1% (19/886). Thirteen (68.4%) prisoners were redirected for follow-up of their HCV infection., Conclusions: Opt-in testing for viral hepatitis B, C and HIV was relatively well-accepted in prisons. Compared with the general population, prisoners have a higher prevalence of infection with BBV, especially for HCV. Systematic screening for these BBV should be recommended in all prisons, preferably using opt-out to optimize screening uptake., Trial Registration: Retrospectively registered at clinical trials NCT04366492 April 29, 2020., (© 2021. The Author(s).)

Background and Study Aims: Although multiple HCV prevalence studies were recently performed in the general population from Belgium, they suffer from a lack of geographical representativeness, an insufficient number of participants or a lack of inclusion of high prevalence groups. The aim of this study is to provide robust information on the HCV burden., Methods: Recently performed HCV prevalence studies in the general, adult population were included in this study, based on well-defined selection criteria. A meta-analysis was performed to estimate the seroprevalence, the prevalence of participants with viremia and the prevalence estimation for people with viremia which were unaware of their status., Results: Eight studies fulfilled the criteria for inclusion of the quantitative prevalence estimation. Based on the meta-analysis on these 8 studies, we estimated an HCV seroprevalence of 1.01% [95% CI : 0.66-1.42%], representing a total of 90,722 adult, HCV seropositives of which 64,412 individuals (0.71%) were confirmed seropositive. Based on the RNA presence, an estimated viremic prevalence of 0.33% [95% CI : 0.21-0.47 %] was determined, corresponding with 29,642 individuals. This is 46,0% of the true HCV seropositive residents. Further, based on the availability of patient information in 5 out of the 8 studies, a prevalence of 0.18% [95% CI : 0.07-0.33] representing 16,168 individuals from the adult Belgian population are unaware of their HCV status., Conclusions: We believe that the quantitative measurement by the meta-analysis will be more reliable for their use in the design of a screening strategy or in the development of prevention campaigns as compared to the prevalence estimations performed at local level., (© Acta Gastro-Enterologica Belgica.)

Background and Study Aims: Hepatitis C virus (HCV) infection often causes asymptomatic disease and patients are frequently diagnosed at an advanced stage. Oral direct acting antivirals (DAAs) are successful in treating HCV with high sustained virologic response (SVR) and excellent tolerability. The aim of this study is to evaluate cost-effectiveness of a broad screening strategy proposing screening to all undiagnosed members of a population (comprehensive HCV screening), in the general adult population, emergency department (ED) attendees, men who have sex with men (MSM) and people who inject drugs (PWID)., Patients and Methods: We populated a theoretical model with Belgian data. A decision tree model simulating HCV screening and diagnosis was combined with a Markov state transition model simulating treatment. There was one screening round per year during five years. In the ED population only one screening round was considered., Results: The model calculated that more HCV patients could be detected and treated with comprehensive screening compared to the current situation. Incremental cost per incremental quality adjusted life years (QALY) gained was lower than 10.000€/QALY for one and for five screening rounds in the general population (5.139 and 5.200 respectively), in ED attendees (one screening round 5.967), in MSMs (4.292 and 4.302 respectively) and in PWIDs (3.504 and 3.524 respectively)., Conclusion: A broad screening strategy combined with treatment is likely to be a cost-effective strategy to detect and treat HCV infected patients and diminish the HCV burden in Belgium., (© Acta Gastro-Enterologica Belgica.)

Recently, concerns were raised of high rates of HCC recurrence in patients treated with direct-acting antivirals (DAA) for hepatitis C infection. We investigated the HCC occurrence and recurrence rates within 6 months after treatment with DAA with or without pegylated interferon (PEG-IFN) in real life. This is a retrospective, multicenter cohort trial, executed in 15 hospitals distributed across Belgium. Populations were matched based on fibrosis score (Metavir F3-F4). Patients with a Child-Pugh score ≥ B were excluded. In total, 567 patients were included, of whom 77 were treated with PEG-IFN+DAA between 2008 and 2013 and 490 with DAA without PEG-IFN between 2013 and 2015. Patients treated with PEG-IFN+DAA (53±9y) were younger than patients treated with DAA without PEG-IFN (59±12y) (P=.001). 47% of patients treated with PEG-IFN+DAA were in the F4 stage vs 67% of patients treated with DAA without PEG-IFN (P=.001). Screening was inadequate in 20% of both patient groups (P=.664). The early occurrence rate of HCC was 1.7% and 1.1% in patients treated with DAA with and without PEG-IFN, respectively (P=.540). The early recurrence rate was 0% in patients treated with PEG-IFN+DAA and 15.0% in patients treated with DAA without PEG-IFN (P=.857). There is no difference in early occurrence of new HCC between patients treated with DAA with and without PEG-IFN. We did observe a high early recurrence rate of HCC in patients treated with DAA without PEG-IFN. However, these patients were at baseline more at risk for HCC. Finally, in 20%, screening for HCC was inadequate., (© 2017 John Wiley & Sons Ltd.)

Background and Aim: Hepatitis C viral infection (HCV) has become a curable disease due to the development of direct acting antivirals (DAA). The WHO has set a target to eliminate HCV completely. Therefore, people who inject drugs (PWID) also need to be treated. In this study, we compared the real-life uptake and outcome of DAA treatment for HCV in PWID and non-PWID., Methods: We performed a nation-wide, retrospective cohort study in 15 hospitals. All patients who were treated with simeprevir-sofosbuvir, daclatasvir-sofosbuvir, or ombitasvir/paritaprevir ritonavir-dasabuvir between December 2013 and November 2015 were included., Results: The study population consisted of 579 patients: 115 PWID (19.9%) and 464 non-PWID (80.1%). Of the PWID 18 were active PWID (15.6%), 35 still received opiate substitution therapy (OST) (30.4%) and 62 were former PWID without OST (53.9%). PWID were more infected with genotype 1a and 3 (p=0.001). There were equal rates of side-effects (44.7% vs. 46.6%; p=0.847), similar rates of treatment completion (95.7% vs 98.1%; p=0.244) and SVR (93.0% vs 94.8%; p=0.430) between PWID and non-PWID, respectively., Conclusion: PWID, especially active users, are underserved for DAA treatment in real life in Belgium. Reimbursement criteria based on fibrosis stage make it difficult to treat PWID. Treatment adherence is similar in PWID and the general population, even in patients with active abuse. DAA were safe and effective in PWID despite the higher prevalence of difficult-to-treat genotypes. Based on these data more efforts to treat PWID are needed and policy changes are necessary to reach the WHO targets., (Copyright © 2017 Elsevier B.V. All rights reserved.)

As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis., Competing Interests: The authors declare no conflict of interest.

Background: This manuscript serves as an update to position papers published in 2014 based on the available Belgian hepatitis C virus (HCV) epidemiological data., Methods: Building on the current standard of care (2015 : 900 ≥ F3 patients treated with 70-85% SVR), four new scenarios were developed to achieve the goals of near viral elimination and prevention of HCV associated morbidity and mortality by 2026 and 2031. Increases in treatment efficacy were assumed in 2016 (90% SVR) and 2017 (95% SVR)., Results: Scenario 1: Treating 6,670 patients annually by 2018 (≥ F0 beginning in 2017) and diagnosing 3,790 patients annually by 2020, a 90% reduction in viremic cases and advanced outcomes was observed by 2026. Scenario 2: Treating 4,300 patients annually by 2018 (≥ F0 beginning in 2020) without increasing the number diagnosed, a 90% reduction in viremic cases and 85%-95% reduction in advanced outcomes was observed by 2031. Scenario 3: Treating 5,000 ≥ F2 patients annually by 2018, and diagnosing 3,620 patients annually by 2020, a 90% reduction in advanced outcomes and 50% reduction in viremic cases was observed by 2026. Scenario 4: Treating 3,100 ≥ F2 patients annually by 2018 without increasing the number diagnosed, a 90%-95% reduction in advanced outcomes and 55% reduction in viremic cases was observed by 2031., Conclusions: Scenario 2 would provide the most favorable balance of outcomes (90% reduction in viremic prevalence and advanced outcomes) and realistic requirements for implementation (gradual increase in treatment, delayed incorporation of patients with no/mild fibrosis)., (© Acta Gastro-Enterologica Belgica.)

Background & Aims: TMC435 is an investigational, once-daily, oral NS3/4A protease inhibitor currently in phase III development for the treatment of hepatitis C virus (HCV) infection. Phase I and II studies in patients infected with HCV genotype 1 have demonstrated that TMC435 is generally well tolerated, has a pharmacokinetic profile that supports once daily dosing, and demonstrates potent antiviral activity. This phase IIa study (TMC435-C202; NCT00812331) was conducted to investigate the antiviral activity, safety, tolerability, and pharmacokinetics of TMC435 in treatment-naїve patients infected with HCV genotypes 2-6., Methods: The study consisted of 7 days of monotherapy with TMC435 (200mg once daily). Patients could begin treatment with pegylated interferon/ribavirin from day 8 with a follow-up period up to days 37-42., Results: Thirty-seven patients were enrolled in Germany, Belgium and Thailand. For the primary end point at day 8, the mean (± standard error) change in plasma HCV ribonucleic acid (log(10)IU/ml) from baseline was the greatest for genotypes 6 (-4.35 ± 0.29) and 4 (-3.52 ± 0.43), followed by genotypes 2 (-2.73 ± 0.71) and 5 (-2.19 ± 0.39). No antiviral activity was evident for genotype 3. Viral breakthrough occurred in six patients during the monotherapy phase and in six additional patients during PegIFN/RBV-only period. All adverse events were mild or moderate and there were no discontinuations during the TMC435 monotherapy period., Conclusions: The results of this phase IIa proof-of-concept trial provide evidence that TMC435 has a spectrum of activity against multiple HCV genotypes, except for genotype 3. In this study, TMC435 was generally safe and well tolerated., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Mixed cryoglobulinemia and hepatitis C virus infection are strongly connected and the therapeutic approach is standardized according to the severity of the symptoms. We report the difficult management of 59 year old female HCV patient presenting cutaneous lesions and arthralgia due to mixed cryoglobulinemia. No therapy was able to achieve a complete remission and during the six years of active disease we observed several clinical recurrences. The intensive plasmapheresis regimen led to a complete remission of the symptoms but it was associated with severe complications. In this case report we describe an episode of acute necrotizing pancreatitis due to intravascular haemolysis following therapeutic plasmapheresis. To the best of our knowledge the association between plasmapheresis and acute pancreatitis has not been previously described.

Background: Early detection of nonresponders to hepatitis C therapy limits unnecessary exposure to treatment and its side-effects. A recent algorithm combining baseline anti-NS4a antibodies and on-treatment quantitative PCR identified nonresponders to a combination of interferon and ribavirin after 1 week of treatment., Aim: To validate a stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1 chronic hepatitis C patients treated with the current standard pegylated interferon and ribavirin combination therapy., Methods: Eighty-nine genotype 1 patients from the Dynamically Individualized Treatment of hepatitis C Infection and Correlates of Viral/Host dynamics Study treated for 48 weeks with standard 180 μg pegylated interferon (PEG-IFN)-α-2a (weekly) and ribavirin 1000-1200 mg (daily) were analysed. Baseline anti-NS4a antibody enzyme-linked immunosorbent assay (NS4a AA 1687-1718) was performed on pretreatment serum. Hepatitis C virus-RNA was assessed at days 0, 1, 4, 7, 8, 15, 22, 29, weeks 6, 7, 8, 10, 12 and 6 weekly thereafter until end of treatment. Multiple regression logistic analysis was performed., Results: Overall 54 of 89 (61%) patients achieved sustained virological response. A baseline anti-NS4a antibody titre less than 1/1250 correlated with absence of favourable initial viral decline according to variable response types (P = 0.015). The optimal algorithm was developed using the combination of the absence of anti-NS4a Ab (<1/1250) at baseline and the presence of a viral load ≥ 100.000 IU/ml at week 4. This algorithm has a specificity of 43% and negative predictive value of 100% to detect nonresponse to standard PEG-IFN-α-2a and ribavirin therapy at fourth week of therapy (intention-to-treat analysis)., Conclusion: The decision to stop the therapy in genotype 1 chronic hepatitis C patients treated with PEG-IFN-α-2a and ribavirin can be confidently made after 4 weeks of treatment based on the absence of baseline anti-NS4a Ab and a week-4 hepatitis C virus-RNA above 100.000 IU/ml.

Aim: To evaluate the efficacy of early interferon alpha-2b in non-post-transfusion acute hepatitis C virus: a prospective study with historical comparison., Patients: Group A: 28 patients prospectively treated for acute hepatitis C virus with daily regimen of interferon 5 million units for 2 months. Group B: historical series of 16 patients with untreated acute hepatitis C virus., Results: There was no significant difference between the two groups with regard to gender, age, icterus, alanine aminotransferase, or genotypes. In group B, hepatitis spontaneously resolved in three of 16 (19%) patients (follow-up 1-7 years). In group A, 21 of 25 patients became sustained viral responders (75%; P = 0.0003 vs. group B). Factors include not predictive of sustained viral response: age, gender, sources of infection, presence of icterus, alanine aminotransferase peak, bilirubin peak, incubation period, presence of hepatitis C virus antibodies at presentation, or genotypes. The time from presentation to the start of therapy was, however, significantly shorter in sustained viral responders (43 +/- 31 days) than in relapsers or non-responders (88 +/- 52 days) (P = 0.016)., Conclusions: Early treatment of acute hepatitis C virus with interferon prevents chronicity. A short waiting time from presentation to treatment appears as the most relevant predictive factor for sustained response.

Background: Preliminary data demonstrate that the recurrence of hepatitis C is more severe in patients undergoing adult-to-adult living liver (AAL) transplantation (Tx) in comparison with cadaveric liver (CL) Tx. The authors report on the 1-year follow-up of their cohort of hepatitis C virus (HCV) patients undergoing AALTx or CLTx., Methods: Twenty-six patients with HCV end-stage liver cirrhosis underwent CLTx and 17 underwent AALTx. The diagnosis of recurrent HCV was made on the basis of increased transaminases, detectable HCV RNA levels, and histologic findings on liver biopsy. Liver biopsies were performed on the basis of clinical indications. Bilirubin concentration, partial thromboplastin time, and alanine aminotransferase activity were compared between the two groups at different time intervals., Results: HCV recurrence was seen in 10 of 26 CLTx patients versus 6 of 17 AALTx patients (P=0.1). Time until recurrence was longer in AALTx patients (158+/-114 days vs. 227+/-154 days, P=0.4). Of the biochemical parameters, only bilirubin concentration at week 4 was significantly different between AALTx and CLTx patients (3.1+/-4.3 mg/dL vs. 1.26+/-0.83 mg/dL, P=0.04). Overall survival and the number of patients needing retransplantation were similar in both groups., Conclusions: At a follow-up period of 1 year, there is no difference in outcome between end-stage HCV patients undergoing AALTx or CLTx.

Background/aims: To analyze the kinetics of the hepatitis C virus and the patterns of resistance to interferon alpha, we assessed HCV RNA levels early during retreatment with high-dose interferon in patients who did not respond to standard treatment., Methods: Eleven non-responders to previous therapy with 3-6 MU interferon three times a week were retreated with daily 10 MU. Plasma was sampled at days 0, 1, 2, 3, 14 and 28; all samples were prepared within 2 h and stored at -70 degrees C without thawing until analysis. The quantitative HCV RNA level was assessed by the Superquant assay (NGI, USA). The Eurohep reference panel, tested blindly, confirmed the linearity of the assay with a detection limit for genotypes 1 and 3 between 10(2) and 10(3) copies/ml., Results: All patients showed a fall in viral load between week 0 and week 2 (2.6 log, i.e. 99.7%, range 1.3-4.7 log), whereas no fall was detected after week 2. Closer examination in nine patients revealed that all had a dramatic fall in the first 2 days (first day 1.8 log, 0.8-3.5; second day 0.8 log, -0.2-1.3), without any significant fall thereafter. The calculated half-life of viral decay in plasma was 5 (2-8.9) h, corresponding to a clearance of 2.4 (0.2-13.7) x 10(11) virions per day. Sustained responders showed a significantly greater fall in viral load in the first day (3.2 log, 2.8-3.5) than those who did not respond (1.4 log, 0.8-2.1, p=0.001). All three sustained responders had undetectable plasma HCV RNA at day 14., Conclusion: In patients without a response to standard interferon, the hepatitis C virus has a high daily turnover rate similar to that reported in naive patients. Our findings suggest that an early clearance of HCV RNA from the circulation is the key to a sustained response, which might be induced in about 25% of these patients by treatment with high (10 MU) daily doses of interferon. These findings have important implications for the concept of treatment of hepatitis C, which should shift its focus from long-term mild treatment towards aggressive therapy aiming at a fast viral disappearance within the first few days.

The number of hepatitis C virus ( HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical. [ABSTRACT FROM AUTHOR]

Background The combination therapy of pegylated-interferon-α2a plus ribavirin is considered as the standard of care for patients with chronic hepatitis C. A sustained viral response is obtained in 40–50% of naïve patients with genotype 1 and in around 80% of naïve patients with genotype 2 or 3. Aim To assess whether amantadine, added to the conventional combination therapy, could improve the treatment efficacy. Methods In all, 630 patients (intent-to-treat population) with chronic hepatitis C were randomized into two groups: 316 patients (treatment group) received pegylated-interferon-α2a (180 μg once weekly) plus ribavirin (1000–1200 mg/daily) with amantadine (200 mg/daily); 314 patients (control group) received pegylated-interferon-α2a (180 μg once weekly) plus ribavirin (1000–1200 mg/daily) without amantadine. The duration of the treatment was 48 weeks for genotypes 1, 4, 5 and 6, and 24 weeks for genotypes 2 and 3. Results There was no statistically significant difference between treatments groups for any of the variables tested for. Subgroups of patients likely to take advantage of the addition of amantadine were not identified. Conclusions This large study definitely excludes the role of amantadine in addition of conventional combination therapy in the treatment of chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

: To evaluate the efficacy of early interferon α-2b in non-post-transfusion acute hepatitis C virus: a prospective study with historical comparison. : Group A: 28 patients prospectively treated for acute hepatitis C virus with daily regimen of interferon 5 million units for 2 months. Group B: historical series of 16 patients with untreated acute hepatitis C virus. : There was no significant difference between the two groups with regard to gender, age, icterus, alanine aminotransferase, or genotypes. In group B, hepatitis spontaneously resolved in three of 16 (19%) patients (follow-up 1–7 years). In group A, 21 of 25 patients became sustained viral responders (75%; P = 0.0003 vs. group B). Factors include not predictive of sustained viral response: age, gender, sources of infection, presence of icterus, alanine aminotransferase peak, bilirubin peak, incubation period, presence of hepatitis C virus antibodies at presentation, or genotypes. The time from presentation to the start of therapy was, however, significantly shorter in sustained viral responders (43 ± 31 days) than in relapsers or non-responders (88 ± 52 days) ( P = 0.016). : Early treatment of acute hepatitis C virus with interferon prevents chronicity. A short waiting time from presentation to treatment appears as the most relevant predictive factor for sustained response. [ABSTRACT FROM AUTHOR]

The standard treatment for patients with chronic hepatitis C is a 6–12-month combination therapy with interferon alpha and ribavirin. Induction treatment could result in a faster early decline of the hepatitis C virus (HCV) load and a better response rate. Naive chronically infected HCV patients ( n = 454) were randomized into two arms to receive either induction treatment with interferon alpha 2b 5 million units (MU) subcutaneously (s.c.) daily during a period of 8 weeks (arm A); or treatment with interferon alpha 2b 5 MU s.c. three times a week (TIW) for a period of 8 weeks (arm B). After week 8, interferon treatment in both arms was 3 MU s.c. TIW for a total period of 12 months. In both arms, ribavirin (1000–1200 mg orally per day) was added at week 4. Induction treatment resulted in a higher virological response at week 8 of treatment (66% vs 47%; P < 0.01). However, response at the end of treatment and at 6 months follow-up was not different (53% vs 50%, 41% vs 33%). The occurrence of adverse events and the drop-out rate were similar in both arms. Although an early virological response is observed more frequently in the induction treatment, end of treatment response and sustained responses did not differ. [ABSTRACT FROM AUTHOR]

Summary Background : In patients with chronic hepatitis C, elevations in serum iron levels, hepatic iron content and oxidative stress-related molecules have been reported. Treatment with ribavirin induces an increase in hepatic iron concentration. In situations of iron overload, non-transferrin-bound iron can appear. Therefore, we determined non-transferrin-bound iron levels in untreated chronic hepatitis C patients and in patients during interferon–ribavirin treatment. Materials and methods : In 10 untreated and 19 interferon–ribavirin-treated chronic hepatitis C patients, we examined non-transferrin-bound iron levels by a colorimetric method using nitrilotriacetic acid as a ligand and sodium triscarbonatecobalt(iii) to block free iron binding sites on transferrin. Results : Despite the presence of high serum iron saturation and ferritin levels, non-transferrin-bound iron was absent in the majority of hepatitis C virus patients (25/29, 86%). There was no difference in non-transferrin-bound iron levels between untreated and treated patients. Four patients with high non-transferrin-bound iron levels were distinguished by higher serum iron levels. In two of these patients, hepatocytic iron was present on liver biopsy. Conclusions : In the majority of chronic hepatitis C patients, non-transferrin-bound iron levels are normal. Treatment with ribavirin does not induce high non-transferrin-bound iron levels. Non-transferrin-bound iron levels are only higher than normal in hepatitis C patients with higher serum iron levels. [ABSTRACT FROM AUTHOR]