Hepatitis: Craxì A

Craxì A, Licata A. · No affiliation provided · Hepatology. · Pubmed #16440365 No free full text.

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Craxì A, Cammà C. · No affiliation provided · J Hepatol. · Pubmed #16293337 No free full text.

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Licata A, Craxì A. · No affiliation provided · Ann Ital Med Int. · Pubmed #15176703 No free full text.

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Lonardo A, Adinolfi LE, Petta S, Craxì A, Loria P. · Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy. · Expert Rev Anti Infect Ther. · Pubmed #19344243 No free full text.

Abstract: Type 2 diabetes (T2D) and HCV infection are common conditions involving, respectively, at least 170 and 130 million people worldwide. However, the distribution of such cases does not overlap in the same age groups in different geographic areas. Following pioneering reports of increased prevalence of T2D in HCV-positive cirrhosis, interest concerning the relationship between HCV and T2D has escalated. HCV is able to induce insulin resistance (IR) directly and the role of specific viral genotypes responsible for such effect is disputed. IR has consistently been found to be closely linked to fibrosis in HCV infection, although also typically associated with T2D in prefibrotic stages. HCV infection could be associated with a reduced prevalence of metabolic syndrome owing to virus-associated reduction in BMI (reported in population but not clinical studies) and hypobetaliproteinemia. A three- to ten-fold increased risk of HCV infection was reported among diabetic patients in comparison with different control groups and a meta-analysis showed a 1.8-fold excess risk of T2D among HCV-positive compared with HBV-positive patients. Moreover, HCV positivity is associated with an increased risk of T2D in patients receiving liver or kidney transplantations. T2D and IR are independent predictors of a more rapid progression of liver fibrosis and impaired response to antiviral treatment in chronic hepatitis C. Patients with cirrhosis and T2D have an increased susceptibility to hepatic encephalopathy and hepatocellular carcinoma (HCC). However, the beneficial effects of antiviral treatment on IR and T2D are controversial. Theoretically, glycemic control in chronic hepatitis C, and particularly in cirrhotic patients, could improve the prognosis and the response to antivirals, although the evidence for this is limited. Future studies should elucidate the relationship between insulin signaling, HCV and interferon signaling, entity of cardiovascular risk in patients with HCV infection, the potential role of 'metabolic' strategies added to antiviral treatment schedules, the impact of IR on liver failure, portal hypertension and HCC, particularly in patients managed in a transplant setting.

Di Marco V, Craxì A. · Dipartimento Biomedico di Medicina Interna e Specialistica, Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy. · Expert Rev Anti Infect Ther. · Pubmed #19344242 No free full text.

Abstract: The goal of antiviral therapy in patients with chronic hepatitis B is to prevent, through persistent suppression of HBV replication, cirrhosis and hepatocellular carcinoma. Currently, seven drugs are available: IFN-alpha, pegylated interferon, lamivudine, adefovir dipivoxil, entecavir, telbivudine and tenofovir. The choice of the drugs should always take into consideration the clinical features of patients, the antiviral efficacy of each drug, the risk of developing resistance, the long-term safety profile, the method of administration and the cost of therapy. Ideal candidates for treatment are hepatitis B e antigen-positive patients with a prolonged phase of immune clearance and hepatitis B e antigen-negative patients with elevated levels of serum HBV DNA, abnormal alanine aminotransferase and histologic evidence of moderate or severe liver necroinflammation and/or fibrosis. Patients with compensated or decompensated cirrhosis should be treated, even if alanine aminotransferase levels are normal and/or serum HBV DNA levels are low, in order to prevent disease flare and to improve liver function.

Tarantino G, Craxì A. · Cattedra di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Palermo, Italy. · Liver Int. · Pubmed #19207964 No free full text.

Abstract: Recently several randomized trials involving exclusively HCV 2 and 3 patients have explored the possibility of reducing the duration of therapy with PEG IFNs and ribavirin to 12-16 weeks. Among these, the largest studies (ACCELERATE, NORTH-C and NORDynamIC) have failed to demonstrate, by intention-to-treat analysis, that short treatment is non-inferior to the standard duration of 24 weeks originated by phase 3 trials. Even though obtaining univocal conclusions from these studies are difficult to obtain due to some critical differences (trial design, genotypes 2/3 ratio, rate of cirrhosis at baseline, ribavirin dose, assays to detect HCV-RNA etc), all have proved that a rapid virological response (HCV-RNA negative at 4 weeks) is the strongest predictor of SVR. Therefore, excluding risk factors for virological relapse at baseline, and identifying in the early phase of treatment, features related to a sustained response, the decision to reduce the duration of treatment to less than 24 weeks in HCV-2 and 3 patients can be response-guided appropriately. Ongoing studies will assess whether extended 48 week regimens can benefit non-RVR patients with HCV 2 or 3, especially those with more severe fibrosis.

Zignego AL, Craxì A. · Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Internal Medicine, University of Florence, Firenze, Italy. <> · Clin Liver Dis. · Pubmed #18625431 No free full text.

Abstract: Hepatitis C virus may cause hepatic and extrahepatic diseases. Extrahepatic manifestations range from disorders for which a significant association with viral infection is supported by epidemiologic and pathogenetic data, to anecdotal observations without clear proof of causality. This article describes the diagnosis and treatment of these diseases.

Craxì A, Laffi G, Zignego AL. · GI & Liver Unit, DI.BI:M.I.S., Policlinico, University of Palermo, Palermo, Italy. · Mol Aspects Med. · Pubmed #18177700 No free full text.

Abstract: Hepatitis C virus (HCV) infection is a global health problem, being the second most common chronic viral infection in the world with a global prevalence of about 3% (about 180 million people). HCV is both an hepatotropic and a lymphotropic virus; and chronic infection could cause, on one hand, chronic hepatitis, cirrhosis and hepatocellular carcinoma and on the other hand several extrahepatic diseases including, first, mixed cryoglobulinemia and lymphoma. The association between hepatic (hepatocellular carcinoma) and extrahepatic (lymphoma, thyroid cancer) malignancies has justified the inclusion of HCV among human cancer viruses. The pathogenesis of HCV-related sequelae (hepatic or extrahepatic) is not fully understood representing a challenge of prime importance in light of the optimization of clinico-therapeutic management of these patients. Combined treatment with pegylated interferon plus ribavirin is presently the first-line, gold standard treatment of most HCV-related diseases. However, mainly in the case of extrahepatic manifestations, a cautious approach to the patient, with a case to case accurate tailoring of therapy is frequently requested. The present review will outline the principal aspects of such HCV-induced systemic disease focusing on extrahepatic manifestations.

Pagliaro L, Gridelli B, Craxì A. · Università, Palermo. · Recenti Prog Med. · Pubmed #17252733 No free full text.

Abstract: Hepatology was born as a separate medical specialty around the fifties of the last century, its importance progressively grows because of the severity and high prevalence of the liver diseases. The net balance of 50 years of hepatology is definitely positive: prevention (e.g. the fall of post-transfusion HB and HC virus infections), diagnosis and better treatments have achieved better survival and quality of life in liver disease. However, deviations, errors and obsolescence of once highly credited judgements and treatments have occurred, as in any other area of medicine. This review looks back at the main pieces of the progress, and reports some previous errors and inappropriate treatments, speculating on their possible reasons.

Craxì A, Antonucci G, Cammà C. · Clinica Medica I, Cattedra di Gastroenterologia, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy. · J Hepatol. · Pubmed #16356581 No free full text.

Abstract: The available evidence on interferon-alpha (IFN) treatment for chronic hepatitis B is sufficient to conclude that in patients with HBeAg positive chronic hepatitis, standard IFN therapy significantly improves clearance of HBeAg (number needed to treat [NNT] = 4), loss of HBV-DNA (NNT = 4) and clearance of HBsAg (NNT = 18). HBeAg positive patients with normal or slightly raised ALT should be treated only if there is histological evidence of progressive disease. In patients with HBeAg negative chronic hepatitis, less than 20% of subjects who have achieved an end-of-treatment virological response after a course of standard IFN maintain a sustained virological response in the long-term. IFN treatment could help to delay or prevent disease decompensation and liver-related deaths but further large studies are needed. Lamivudine is effective at reducing, and sometimes clearing, HBV replication in heavily immunosuppressed patients and can be safely administered to patients with advanced liver disease. Lamivudine should be continued over an undefined extended period of time, with a switch from lamivudine to adefovir if there is an HBV-DNA breakthrough under therapy. Adefovir, excluding cost, is preferable to lamivudine as a first-choice because there is less chance of inducing resistance. The long-term benefit of lamivudine and adefovir and the role of combinations is under investigation.

Craxì A, Cammà C. · Cattedra di Gastroenterologia, University of Palermo, Clinica Medica I, Piazza della Cliniche 2, 90127, Italy. · Clin Liver Dis. · Pubmed #15831277 No free full text.

Abstract: The accuracy and the reliability of well-recognized clinical, virologic, histologic, and molecular risk factors for hepatocellular carcinoma are still insufficient; thus, accurate risk prediction of developing cancer in individual patients remains an elusive goal.

Cammà C, Licata A, Cabibbo G, Latteri F, Craxì A. · University of Palermo, Cattedra di Gastroenterologia, Istituto di Clinica Medica, Italy. · Expert Opin Pharmacother. · Pubmed #15794731 No free full text.

Abstract: Chronic hepatitis C virus infection is currently the most common cause of end stage liver disease worldwide. Although the conclusions of the last National Institutes of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues remain unanswered. This paper reviews the available data using an evidence-based approach. Current evidence is sufficient to recommend IFN treatment for all patients with acute hepatitis. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during month 1 is the best treatment option. The current gold standard of efficacy for treatment-naive patients with chronic hepatitis C is the combination of pegylated IFN and ribavirin. The overall sustained viral response rate to these regimens is 54 - 56% following a 48-week course of therapy. Patients with genotype 1 infection will have a 42 - 51% likelihood of response to 48weeks of therapy. Those with genotypes 2 or 3 infection will respond to 24weeks in 78 - 82% of cases. Debate continues regarding the optimal dose and duration of peginterferon (PEG-IFN), not only in patients infected with genotype 2 or 3 but also in those infected with genotype 1. The optimal dose of ribavirin has yet to be determined. Available data show the need to give the highest tolerable doses (1000-1200mg/day) to the difficult-to-treat patients (genotype 1, cirrhotics, obese), although there is a greater likelihood of intolerance. Genotypes 2 and 3 may receive 800mg/day, which is also the most appropriate lower dose for those patients who require dosage modification for anaemia or other side effects. Tolerability and compliance to therapy are still a problem, as approximately 15- 20% of patients within trials and > 25% in clinical practice withdraw from therapy. New PEG-IFNs are more effective than conventional IFN in improving liver histology. Monotherapy with PEG-IFN induces a marked reduction in staging in virological sustained responders, and to a lesser degree in relapsers, but provides no benefit to nonresponders after 24-48weeks of treatment. The use of maintenance therapy in virological nonresponders aiming to improve histology should be considered experimental and of unproven benefit. Pooling data from the literature suggests a slight preventive effect of IFN on hepatocellular carcinoma development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit may be due to spurious associations. The preventive effect is more evident among sustained responders to IFN.

Craxì A. · Istituto di Clinica Medica 1, University of Palermo, Italy. · Dig Liver Dis. · Pubmed #15645664 No free full text.

Abstract: Recently, 12-week evaluation of viral response has been recommended as a means of reducing antiviral treatment morbidity and costs. The development of early stopping rules relies on an important assumption: rules must minimise discontinuation of treatment in patients who might ultimately respond after completion of the full course of therapy. Minimising loss of potential responders is the most important clinical goal in defining an early stopping rule because it provides the most sustained virological responders. This definition of the rule relies on maximising the negative predictive value. Conversely, rules that select patients based on optimising the positive predictive value produce the highest proportion of sustained responders and may discontinue treatment in more patients, thus reducing immediate costs, but will necessarily exclude some patients who would achieve response with continued therapy and reduce the total number of sustained responders. In conclusions, in patients treated with PEG-IFN alpha-2b or alpha-2a combination therapy, the decision to continue or stop treatment can be made as early as week 12. However, individual decisions to continue antiviral treatment should also consider the variability in the accuracy of quantitative viral assays, patient preferences, and the pending results of ongoing studies of treatment maintenance in those with advanced fibrosis.

Licata A, Brucato V, Di Marco V, Barbaria F, Craxì A. · Istituto di Clinica Medica I, Università degli Studi di Palermo. · Ann Ital Med Int. · Pubmed #15529941 No free full text.

Abstract: Iron overload diseases are due to a progressive increase in total body iron stores that leads to deposition of iron in parenchymal organs and to subsequent damage to these organs. The commonest inherited form of iron overload is hereditary hemochromatosis (HH), an autosomal recessive disorder affecting the white population. Although in the western world and in northern Europe the majority of cases of HH are associated with an HFE gene mutation (C282Y and H63D), there are families with a familial iron overload disorder in whom neither the C282Y nor the H63D mutations were found. Recently, other forms of HH that are not related to HFE, but are due to mutations in genes coding iron transport proteins (ferroportin-1, TfR2, hepcidin) have been described. The clinical presentation of the disorder is highly variable, depending on the severity of iron overload. In fact, the inappropriate absorption and deposition of dietary iron may result in the development of hepatic and non-hepatic end-organ injury, leading to liver cirrhosis, hepatocellular carcinoma, diabetes, arthritis, skin pigmentation and cardiac diseases. HH and its sequelae are preventable with an early diagnosis and treatment. Patients with evidence of iron overload, a family history of HH or other risk factors should be screened by genotype testing for the HFE mutation. Nowadays, HH is recognized as being a complex genetic disease with probable significant environmental and genetic modifying factors, such as hepatitis C virus infection and alcohol abuse, and it has been shown that HFE mutations represent an independent risk factor for fibrosis and cirrhosis in chronic hepatitis C.

Cammà C, Di Bona D, Craxì A. · Ist. of Clinica Medica I, Piazza della Cliniche 2, 90100 Palermo, Italy. · Curr Pharm Des. · Pubmed #15279551 No free full text.

Abstract: Hepatitis C virus chronic infection is currently the most common cause of end-stage liver disease. The benefit of antiviral therapy on liver histology and its impact on the long-term course of the disease has been extensively studied. However, the results are still equivocal and the overall assessment of treatment effect remains difficult to evaluate. Although the conclusions of the last National Institute of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues still remain unanswered. We review the available data by an evidence-based approach and conclude that: 1) peginterferon alfa is more effective than conventional interferon in improving liver histology; 2) monotherapy with PEG-interferon induces a marked reduction in staging in virological sustained responders and to a lesser degree in relapsers, but provides no benefit to nonresponders after 24-48 weeks of treatment; 3) maintenance therapy aiming to improve histology in virological nonresponders should be considered experimental and of unproven benefit; 4) although the reduction in the number of events in sustained responders suggests a long-term benefit of IFN therapy, available evidence is still insufficient to confirm that IFN prolongs life in HCV infected patients. Data of the long-term benefit of subjects treated with IFN plus ribavirin are still not available; 5) pooling of published data suggests a slight preventive effect of IFN on HCC development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit might be due to spurious associations. The preventive effect is more evident among sustained responders to interferon.

Craxì A, Di Bona D, Cammà C. · Cattedra di Gastroenterologia, Istituto di Clinica Medica 1, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy. · J Hepatol. · Pubmed #14708686 No free full text.

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Almasio PL, Venezia G, Craxì A. · Unit of Gastroenterology, University of Palermo, Palermo, Italy. · Panminerva Med. · Pubmed #14618115 No free full text.

Abstract: AIM: Chronic hepatitis C is a progressive disease that leads to liver cirrhosis and hepatocellular carcinoma in a period ranging from 10 to 30 y. Many factors have been related to disease progression and, among them, persistent HCV replication has been advocated as one of the major determinant of hepatic deterioration. With this respect any treatment of chronic hepatitis C is mainly aimed to reduce necro-inflammation by suppressing viral activity in the long-term. We evaluated the persistence of HCV clearance after interferon therapy during follow-up in patients considered as long-term responders. Secondly, we analyzed the rate of progression from hepatitis to cirrhosis and hepatocellular carcinoma in patients with persistent viral elimination as compared to those who did not respond to treatment. METHODS: We performed a systematic review of published data as full papers on treatment of chronic hepatitis that reported data on long-term follow-up of patients with persistent HCV suppression and the rate of cirrhosis and hepatocellular carcinoma in long-term responders as compared to non-responders. Data were pooled to obtain a combined estimate of the reduced relative risk using the random effect model. RESULTS: In patients achieving a sustained virological response a relapse was observed in about 13% (range 0-86%). In subjects with a sustained viral response progression to cirrhosis is uncommon. When compared to relapsers or non-responders the calculated risk reduction in this group was -0.22 (95% C.I. - 0.36/-0.08). The calculated estimates of risk reduction of developing hepatocellular carcinoma in patients achieved sustained response were -0.097 (95% C.I. -0.13/-0.07). CONCLUSION: There is a high chance that patients in remission during the first 6 mo after antiviral treatment will remain so for the rest of their life. Cumulative data from literature showed a significant reduction in the rate of progression to cirrhosis and development of hepatocellular carcinoma in sustained viral responders as compared to non-responders or relapsers. However, since factors predictive of sustained response to interferon are independently associated with less frequent and/or later development of decompensation or HCC, the beneficial effects of antiviral therapy may be probably overestimated.

Raimondo G, Balsano C, Craxì A, Farinati F, Levrero M, Mondelli M, Pollicino T, Squadrito G, Tiribelli C. · Department of Internal Medicine, University of Messina, Italy. · Dig Liver Dis. · Pubmed #11215565 No free full text.

Abstract: Many studies have shown that hepatitis B virus infection may also occur in hepatitis B surface antigen-negative patients. This occult infection has been identified both in patients with cryptogenic liver disease and in patients with hepatitis C virus-related chronic hepatitis, and much evidence suggests that it may be a risk factor of hepatocellular carcinoma development. However several aspects of this occult infection remain unclear such as its prevalence and the factor(s) involved in the lack of circulating hepatitis B surface antigen. Moreover, it is uncertain whether the occult hepatitis B virus infection may contribute to chronic liver damage, considering that it is usually associated with a suppressed viral replication. Evidence and hypotheses concerning this fascinating field of bio-medical research are reviewed.

Cammà C, Craxì A. · Istituto Metodologie Diagnostiche Avanzate, Consiglio Nazionale delle Ricerche, Palermo, Italy. · Semin Gastrointest Dis. · Pubmed #10803635 No free full text.

Abstract: Post-treatment relapse remains a major issue in the long-term management of chronic hepatitis C. Many studies have been conducted to identify the ideal therapy that would increase the cost-effectiveness of retreatment in the individual patient. Although the conclusions of two consensus conferences for the retreatment of relapse of chronic hepatitis C have been published recently, several important issues still remain unanswered. We reviewed the available data by an evidence-based approach and conclude the following: (1) patients should be retreated with a combination of interferon (IFN) and ribavirin for 6 months if there are no contraindications to ribavirin; (2) the excellent tolerability and the lesser expense of retreatment with IFN monotherapy makes it a low-cost option for patients who have transiently cleared HCV-RNA during the first IFN course, and a primary indication for those who are contraindications to ribavirin or are likely to experience adverse events under ribavirin; (3) relapsers retreated with monotherapy must receive a high dose of IFN; and (4) patients with cirrhosis should not be retreated with IFN alone. More data, particularly on the long-term course of patients retreated with combination therapy, are needed before setting guidelines for retreatment of relapsers.

Mancini N, Carletti S, Perotti M, Romanò L, Craxì RD, Craxì A, Zanetti AR, Clementi M, Burioni R. · Laboratorio di Microbiologia, Università Vita-Salute San Raffaele, Istituto Scientifico San Raffaele, Milano, Italy. · J Med Virol. · Pubmed #16927283 No free full text.

Abstract: The dynamic features of three specific anti-hepatitis C virus (HCV) antibody subpopulations directed against different conformational epitopes of the viral E2 protein (HCV/E2) have been evaluated in patients with primary and persistent HCV infection; the three subpopulations are present in patients infected with different HCV genotypes and have shown a different activity using a pseudovirus neutralization assay (antibodies e301 and e137 exhibiting high neutralizing activity, while antibody e509 enhancement of HCV infectivity). In sequential samples from five patients with primary HCV infection and different virological outcome, all samples tested negative with the single exception of the e509 antibody in a patient not clearing the virus. In sequential samples from 28 patients with persistent infection under treatment with pegylated interferon-alpha plus ribavirin (14 sustained virological responders and 14 non-responders), the therapy did not selectively influence titers of the two neutralizing antibody subpopulations; otherwise, a net increase of the e509 antibody subpopulation related to enhancement of HCV infectivity was observed in non-responders, but not in sustained virological responders (P = 0.0156). This increase was not related to the trend of total anti-HCV/E2 response. The data indicate that a specific antibody response against these epitopes is elicited only late during the infection, thus not influencing virus clearance during primary infection, and that a selective increase of the antibody subpopulation enhancing virus infectivity is observed only in the cohort of patients not responding to antiviral therapy.

Craxì A, Yurdaydin C. · Gastroenterologia and Epatologia, University of Palermo, Palermo, Italy. · J Hepatol. · Pubmed #16618515 No free full text.

This publication has no abstract.

Ferenci P, Fried MW, Shiffman ML, Smith CI, Marinos G, Gonçales FL, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxì A, Chaneac M, Reddy KR. · Medical University of Vienna, Vienna, Austria. · J Hepatol. · Pubmed #15990196 No free full text.

Abstract: BACKGROUND/AIMS: Prediction of sustained virological response (SVR) during treatment would allow clinicians to identify patients most likely to benefit from therapy. METHODS: Retrospective analysis of data from 1121 adults with chronic hepatitis C treated for 48 weeks with peginterferon alfa-2a (40 KD) 180 microg/week plus placebo or ribavirin (1000/1200 mg/day), or interferon alfa-2b 3 MIU three times/week plus ribavirin in a randomized, multinational, study. RESULTS: 67% of patients treated with peginterferon alfa-2a (40 KD)/ribavirin with early virological responses (HCV RNA negative or > or = 2 log10 decrease) at week 12 had SVRs at week 72 (HCV RNA < 50 IU/mL). The negative predictive value (NPV) was 97%. The probability of an SVR increased with the rapidity of HCV RNA suppression. The highest SVR rates were achieved in patients with rapid virological responses at week 4, but the corresponding NPV (74%) is too low for a decision criterion. In patients with early virological responses by week 12, the SVR rate was approximately 20% lower in those who received <80% compared with patients who received > or = 80% of the planned ribavirin dose. CONCLUSIONS: Early, sustained suppression of HCV replication portends an SVR. Cessation of treatment may be contemplated in patients without a > or = 2 log10 reduction in HCV RNA after 12 weeks.

Bruno S, Cammà C, Di Marco V, Rumi M, Vinci M, Camozzi M, Rebucci C, Di Bona D, Colombo M, Craxì A, Mondelli MU, Pinzello G. · Clinica Medica, Ospedale San Paolo and Liver Unit, Ospedale Fatebenefratelli e Oftalmico, Milano, Italy. · J Hepatol. · Pubmed #15336451 No free full text.

Abstract: BACKGROUND/AIMS: We assessed the effectiveness and safety of an induction dose of peginterferon alfa-2b (PEG-IFN) plus ribavirin for initial treatment of patients with genotype 1 chronic HCV infection in a randomized, controlled, multicenter trial. METHODS: Three hundred and eleven naïve patients infected with genotype 1 and chronic hepatitis were randomly assigned to 48-week treatment with PEG-IFN once weekly (80-100 micrograms depending on body weight for 8 weeks, followed by 50 micrograms for the next 40 weeks), or standard interferon alfa-2b (IFN) 6 million units on alternate days, both in combination with ribavirin (1000-1200 mg/day). RESULTS: PEG-IFN plus ribavirin significantly increased sustained virological response (SVR) compared with IFN plus ribavirin (41.1 vs. 29.3% respectively, P=0.030). Less patients discontinued PEG-IFN than IFN (19 vs. 31%, P=0.010). By logistic regression, SVR in the PEG-IFN group was independently associated with age <50 years, and mild fibrosis at liver biopsy. CONCLUSIONS: Combination therapy with an induction dose of PEG-IFN was a more effective and better tolerated treatment for naïve patients with genotype 1 than combination therapy with high dose standard IFN. In patients aged less than 50 years with mild fibrosis this schedule achieves a very high rate of SVR.

Ferraro D, Bonura C, Giglio M, Di Stefano R, Almasio PL, Di Marco V, Craxì A, Cacciola I, Squadrito G, Raimondo G. · Department of Hygiene and Microbiology, University of Palermo, Palermo, Italy. · J Biol Regul Homeost Agents. · Pubmed #14518718 No free full text.

Abstract: BACKGROUND: Occult HBV infection in subjects with chronic hepatitis C is related to more severe disease outcome. It has been suggested that it might reduce sensitivity to antiviral treatment. AIMS: To assess in HBsAg negative subjects with chronic hepatitis C any effect of the presence of HBV genomes in the liver on the early kinetics of HCV-RNA under PEG-IFN plus ribavirin. PATIENTS AND METHODS: Twenty-two anti-HCV and HCV-RNA positive subjects, with biopsy-proven chronic hepatitis C (M/F 15/7; 50 +/- 8.6 years, 16 genotype 1b) were given PEG-IFN alpha 2b 1.0 microg qw plus ribavirin (800 to 1,200 mg daily according to body weight) for an intended 52 week period. Early virological response was assessed over the first 4 weeks of therapy by quantifying HCV-RNA. Occult HBV infection was assessed by testing for HBV-DNA in the liver before therapy. RESULTS: HBV genomes were found in the liver of 7 of 22 (31.4%) patients, unrelated to anti-HBc status. Kinetics of HCV-RNA during the first 4 weeks of antiviral treatment was unaffected by occult HBV infection, both in terms of absolute reduction of viral load and of number of cases with a reduction of > or = 2 log10 on treatment. CONCLUSIONS: Occult HBV infection does not affect the early phase of response to combination therapy. Further follow-up of patients into the maintenance phase of antiviral treatment and after stopping it will clarify if and when occult HBV has a role in reducing sustained virological response.

Abbate I, Cappiello G, Lo Iacono O, Longo R, Ferraro D, Antonucci G, Di Marco V, Di Stefano R, Craxì A, Solmone MC, Spanò A, Ippolito G, Capobianchi MR. · S. Pertini Hospital, Rome, Italy. · J Biol Regul Homeost Agents. · Pubmed #14518716 No free full text.

Abstract: ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.