Hepatitis: Italy

Tremolada S, Delbue S, Ferrante P. · Center for Translational Research and Laboratory of Pathology, Saint Joseph Hospital, MilanoCuore, Milano. · Pediatr Med Chir. · Pubmed #19216201 links to  free full text

Abstract: Viral infections may be vertically transmitted from mother to child at different times, ranging from in utero transmission, which occurs during pregnancy, perinatal transmission, which takes place during delivery and postnatal transmission, which is usually the consequence of breastfeeding. Mother-to-child transmission, which may occur after primary, recurrent or chronic maternal infection, is potentially harmful to the fetus or the newborn since it may result in miscarriage, fetal death, congenital anomalies, intrauterine growth restriction, or severe neonatal disease. Some risk factors are thought to affect the rate of mother-to-child transmission, such as the presence of other viral infections, maternal viral load, type of infection (primary versus recurrent), obstetrical procedures (prolonged rupture of membranes, mode of delivery), social-economical conditions and breastfeeding. For some of the vertically transmitted viruses, interventions are nowadays available to prevent mother-to-child transmission, such as vaccines, passive immunization, antiviral drugs. Moreover, perinatal and postnatal infections may be prevented by the use of elective caesarean delivery and avoidance of breastfeeding.

Puoti M, Nasta P, Gatti F, Matti A, Prestini K, Biasi L, Carosi G. · Department of Infectious and Tropical Diseases, University of Brescia, AO Spedali Civili, Brescia, Italy. · J Int Assoc Physicians AIDS Care (Chic Ill). · Pubmed #19211929 No free full text.

Abstract: Highly-active antiretroviral therapy (HAART) has proven remarkably effective for prolonging the life of patients with human immunodeficiency virus (HIV). However, while most HAART agents are safe, many have the potential to cause liver toxicity. Physicians must therefore consider the possibility of drug-induced liver injury in the management of HIV-infected patients, especially those with certain risk factors such as coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV), female gender, alcohol abuse, older age, or obesity. Understanding how, when, and why drug-related liver damage occurs is key to managing these patients safely and effectively. Knowledge of HAART-related liver effects will help ensure that patients receive the most benefit with the least toxicity from any given drug regimen. As more information about the mechanisms of drug related liver injury is known, clinicians will be better able to tailor therapies to suit individual situations, resulting in greater patient safety and outcomes.

Colombo M. · A.M. & A. Migliavacca Center for Liver Diseases, 1st Division of Gastroenterology, Fondazione IRCCS Maggiore Hospital, Mangiagalli e Regina Elena, University of Milan, Milan, Italy. · Liver Int. · Pubmed #19207979 No free full text.

Abstract: Early diagnosis of hepatocellular carcinoma (HCC) is feasible because HCC develops in the background of well-known, readily identifiable and potentially avoidable environmental risk factors. According to the American Association for the Study of the Liver Diseases and the European Association for the Study of the Liver, patients with cirrhosis and carriers of chronic viral hepatitis are the target of surveillance to be investigated with abdominal ultrasounds (US) every 6 or 12 months. The diagnostic confirmation of a > or =2 cm nodule in patients with cirrhosis detected during surveillance is possible with any imaging technique among second-generation contrast US, contrast computed tomography and gadolinium-contrast magnetic resonance imaging. HCC shows an early hyperenhanced arterial vascularization, followed by enhanced hypoattenuation (wash-out) in the late phase of imaging. In patients with a < or =2 cm nodule, two imaging techniques are required for the final diagnosis, which, however, have a relatively low diagnostic sensitivity (33%). Nodules with negative imaging findings need to be investigated further with an echo-guided liver biopsy or enhanced follow-up with imaging (every 3 months) to reach a final diagnosis. The cost-effectiveness ratio of surveillance depends on multiple factors, like HCC incidence, the cost and accuracy of diagnostic tests and the costs and outcome of the therapeutic interventions.

Rizzetto M. · Department of Gastroenterology, University of Turin, Turin, Italy. · Liver Int. · Pubmed #19207978 No free full text.

Abstract: Hepatitis D virus (HDV) infection has considerably diminished in Europe since the 1970-1980s. The prevalence rates of chronic hepatitis D in HBsAg carriers in Italy have declined from 25% at the beginning of the 1980s to 8% in the 1990s. Similar declines in prevalence have been reported in Spain, Taiwan and Turkey. Better public health standards, HBV vaccination and the effect of measures to control the spread of human immunodeficiency virus have brought about a decline in the numbers of HBsAg carriers and therefore a decline in the HBV-dependent HDV. However, HDV has not declined further in Europe in the last decade, as the pool of fresh infections in migrants from HDV-endemic areas is counterbalancing the shrinking cohort of long-standing domestic infections acquired in the epidemic of the 1970-1980s. Hepatitis D remains an important health problem outside Europe, and new foci of infection continue to be identified in developing countries.

Lampertico P, Colombo M. · 1st Division of Gastroenterology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy. · Liver Int. · Pubmed #19207976 No free full text.

Abstract: Antiviral therapy is aimed to persistently suppress hepatitis B virus (HBV) to prevent liver complications and improve survival and long-term administration of nucleos(t)ide analogues represents an attractive treatment strategy. Five oral analogues are available, and all inhibit viral replication in most patients during the first year of therapy. By converse, long-term monotherapy is associated to high rates of resistance with lamivudine, and intermediate rates with Adefovir and Telbivudine. Third-generation analogues such as Entecavir and Tenofovir may efficiently inhibits viral replication in most patient for many years as they couple potency and high genetic barrier. In patients developing drug-resistance, specific rescue protocols based upon 'early add-on' have been developed to rapidly and efficiently control viral replication. In cirrhotics, long-term effective analog-based therapy prevented clinical decompensation for many years, but not liver cancer development. Long-term administration of NUCs, either as a monotherapy or as a sequential combination, inhibits HBV replication in most HBeAg-negative patients for at least 5 years, preventing clinical decompensation in cirrhotics.

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.

Alberti A. · Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy. · Liver Int. · Pubmed #19207961 No free full text.

Abstract: The natural history of chronic hepatitis C has been defined in several retrospective and prospective studies conducted in the last 20 years. These studies have clearly demonstrated that the outcome of chronic hepatitis C virus infection is profoundly influenced by a variety of cofactors and comorbidities. Many of the cofactors that affect the course of liver disease in hepatitis C also have a significant influence on the result of antiviral therapy. Unfortunately, comorbidities that have been shown to negatively influence the course and outcome of liver disease often reduce the chance of achieving a sustained virological response with pegylated interferon (PEG-IFN) and ribavirin treatment. The most important and frequent comorbidity influencing the course of chronic hepatitis C and the response to antiviral therapy is represented by the metabolic syndrome, and by the associated state of insulin resistance. Other comorbidities that have a negative influence on the progression of hepatitis C and on the response to antiviral therapy include excess alcohol intake, human immunodeficiency virus and hepatitis B virus co-infection and a number of conditions that reduce the benefit of therapy by affecting negatively compliance and/or adherence to adequate PEG-IFN or ribavirin doses.

Mazzanti G, Menniti-Ippolito F, Moro PA, Cassetti F, Raschetti R, Santuccio C, Mastrangelo S. · Department of Physiology and Pharmacology, Sapienza, University of Rome, Rome, Italy. · Eur J Clin Pharmacol. · Pubmed #19198822 No free full text.

Abstract: PURPOSE: To review the current literature on suspected green tea-related hepatic reactions and to describe two new cases reported within the framework of the Italian surveillance system of natural health products. RESULTS: A literature search of publication between 1999 and October 2008 retrieved 34 cases of hepatitis. Histological examination of the liver revealed inflammatory reactions, cholestasis, occasional steatosis, and necrosis. A positive dechallenge was reported in 29 cases. There was one reported death. A positive rechallenge occurred in seven cases (20%). In the two new cases, the causality assessment was judged as "possible" according to the RUCAM score. CONCLUSIONS: Our analysis of the published case reports suggests a causal association between green tea and liver damage. The hepatotoxicity is probably due to (-)-epigallocatechin gallate or its metabolites which, under particular conditions related to the patient's metabolism, can induce oxidative stress in the liver. In a few cases, toxicity related to concomitant medications could also be involved.

Perico N, Cattaneo D, Bikbov B, Remuzzi G. · Department of Medicine and Transplantation Ospedali Riuniti di Bergamo-Mario Negri Institute for Pharmacological Research, Bergamo, Italy. · Clin J Am Soc Nephrol. · Pubmed #19129320 No free full text.

Abstract: More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for over 1 million deaths resulting from cirrhosis and liver cancers. Extrahepatic manifestations are also relevant and include mixed cryoglobulinemia, lymphoproliferative disorders, and kidney disease. HCV infection is both a cause and a complication of chronic kidney disease, occurring largely in the context of mixed cryoglobulinemia. This infection also represents a major medical and epidemiologic challenge in patients with end-stage renal disease on renal replacement therapy with dialysis or transplantation. In these settings the presence of HCV correlates with higher rates of patient mortality than in HCV-negative subjects on dialysis or undergoing kidney transplant. The major concern is the lack of safe and effective drugs to treat HCV-infected patients with chronic kidney disease. Unfortunately, there are no large-scale clinical trials in this population, especially those receiving renal replacement therapy, so that strong evidence for treatment recommendations is scant. This review article provides the readers with the most recent insights on HCV infection both as cause and complication of chronic kidney disease, discusses pitfalls and limitations of current therapies, and reports on preliminary experience with novel therapeutic agents, as well as directions for future research.

Fabrizi F, Messa P, Martin P. · Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milano, Italy. · Int J Artif Organs. · Pubmed #19115192 No free full text.

Abstract: A variety of epidemiological data provides evidence for the occurrence of nosocomial transmission of hepatitis C virus (HCV) infection to hemodialysis (HD) patients. The most important factor implicated in HCV transmission between patients treated in the same dialysis unit is cross-contamination from supplies and surfaces as a result of failure of staff to follow infection control procedures. Parts of the HCV genome are highly variable and lend themselves to fingerprinting of each isolate using nucleic acid testing (NAT) and sequencing. This approach has permitted investigation of possible transmission routes within HD units. A systematic review of molecular virology papers revealed transmission of HCV via internal fluid pathways of the dialysis machines in a minority of reports only. Dialyzer reuse was not identified as a risk factor for HCV acquisition in multicenter databases. No randomized controlled trials exist on the impact of isolation on the risk of transmission of HCV to hemodialysis patients. A Belgian prospective multicenter study showed a reduction from 1.4% to 0% in the annual incidence of seroconversion for HCV without any isolation measures, by implementation of strict infection control procedures designed to prevent transmission of blood-borne pathogens, including HCV. However, an isolation policy for HCV-infected dialysis patients should be considered in dialysis units where nosocomial transmission of HCV persists despite reinforcement and audit of hygienic precautions for hemodialysis. Routine audit precautions (general and for dialysis machines) are recommended on a regular basis within HD units.

Cassinotti A, Birindelli S, Clerici M, Trabattoni D, Lazzaroni M, Ardizzone S, Colombo R, Rossi E, Porro GB. · Department of Clinical Science, Division of Gastroenterology, L. Sacco University Hospital, via G.B.Grassi 74, Milan, Italy. · Am J Gastroenterol. · Pubmed #19098870 No free full text.

Abstract: OBJECTIVES: The human leukocyte antigen (HLA) system includes genes involved in graft-vs-host rejection and in immune response. The discovery that HLAs are associated with several diseases led to appealing developments both in basic biomedical research and in clinical medicine, and offered the opportunity to improve the understanding of pathogenesis and classification of diseases, as well as to provide diagnostic and prognostic indicators. The aim of this article is to review the association between HLA alleles and autoimmune digestive disease and its current relationship with modern HLA nomenclature and clinical practice. METHODS: Articles dealing with the association between HLAs and autoimmune digestive disease (including celiac disease, inflammatory bowel disease, autoimmune hepatitis, sclerosing cholangitis and primary biliary cirrhosis) were searched for using Pubmed and SCOPUS databases from earliest records to January 2008. RESULTS: The review has provided two sections. In the first, we explain the basic principles of HLA structure, function, and nomenclature, as an introduction to the second section, which describes current associations between HLA alleles and digestive diseases. The clinical implications of each HLA association are critically discussed. Actually, a clinical role for HLA typing is suggested for only a few conditions, e.g., celiac disease. CONCLUSIONS: The knowledge of current HLA nomenclature and of its association with some digestive diseases such as celiac disease can be useful in clinical practice for diagnostic and prognostic purposes. This can avoid improper HLA typing as well as stressing the need for further studies on other possible clinical applications.

Albano E. · Department of Medical Science, University Amedeo Avogadro of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. · Expert Rev Gastroenterol Hepatol. · Pubmed #19090736 No free full text.

Abstract: Alcoholic liver disease still represents an important cause for death and disability in most well-developed countries and is becoming a leading cause of disease in developing countries. It is now increasingly clear that, besides the formation of acetaldehyde, alcohol effects on the liver include oxidative stress, disturbances in methionine metabolism, endoplasmic reticulum stress, inflammatory/immune responses and adipokine imbalances. This article will discuss the most recent findings on the mechanisms by which alcohol abuse causes hepatic steatosis and steatohepatitis, and now it contributes to the progression of fibrosis. Although still incomplete, these data shed new light on the multifactorial pathogenesis of alcoholic liver disease and open new possibilities in the understanding of how gender and genetic factors can influence disease progression.

Antonelli A, Ferri C, Ferrari SM, Colaci M, Sansonno D, Fallahi P. · Department of Internal Medicine, University of Pisa, Pisa, Italy. · Nat Clin Pract Endocrinol Metab. · Pubmed #19079271 No free full text.

Abstract: Chronic infection with hepatitis C virus (HCV) can result in both hepatic and extrahepatic disease and endocrine dysfunction represents an important class of HCV-related extrahepatic disease. The most frequently occurring--and clinically important--of these endocrine disorders are thyroid disease and type 2 diabetes mellitus. In this Review, we evaluate the evidence in support of a link between HCV infection and endocrine-system dysfunction, and discuss potential pathophysiological mechanisms. A meta-analysis of the literature has revealed significant associations between chronic HCV infection, thyroid autoimmunity and hypothyroidism. Furthermore, a high prevalence of thyroid cancer has been reported in HCV-positive patients. Several clinicoepidemiological studies have demonstrated that chronic HCV infection could lead to the development of type 2 diabetes mellitus, possibly as a result of HCV-induced metabolic disturbances. Some researchers have postulated that a type 1 T-helper -cell mediated immune response underpins the association of chronic HCV infection with endocrine disease. Indeed, the available data suggest that a common immunological, type 1 T-helper cell pattern of cytokine expression and activation (via interferon-gamma) could provide the pathophysiological basis for this association. Nonetheless, additional studies will be necessary to elucidate fully all the mechanisms involved in HCV-related endocrine dysfunction.

De Re V, Sansonno D, De Paoli P, Geremia S, Gatti P, Caggiari L, Simula MP, Toffoli G. · Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, Aviano, Pordenone, Italy. · Recent Pat DNA Gene Seq. · Pubmed #19075932 No free full text.

Abstract: In recent years, many pharmaceutical and biotechnology companies have shifted their drug development for infectious diseases from antibacterial to antiviral discovery. This trend reflects the large population involved in viral diseases, the need for chronic or long-term treatment, and significant unmet needs. In particular, human immunodeficiency virus, hepatitis C virus (HCV), and hepatitis B virus have been the focus of drug development, representing important areas of future growth. This report provides an overview of the most recent patents relating to HCV molecules as targets for therapeutic intervention, outlining the key drug targets and steps where pharmacological intervention can have a favorable therapeutic benefit. Historically, HCV drug development has been hampered by the lack of reliable cell culture systems and animal infection models. However, early research studies have identified new models of HCV infection, and the better acknowledgment of the viral lifecycle have allowed the identification of several highly promising targets, including protease, helicase, polymerase or inhibitors of virus attachment, which are considered drug candidates that can potentially change the treatment of HCV.

Fabrizi F, Lunghi G, Messa P, Martin P. · Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milan - Italy. · J Nephrol. · Pubmed #19034865 links to  free full text

Abstract: The most frequent kidney disease associated with chronic hepatitis C virus (HCV) infection is type I membranoproliferative glomerulonephritis (MPGN) in patients with type II mixed cryoglobulinemia. The principal clinical manifestations of glomerular disease in HCV-infected patients are the presence of proteinuria and microscopic hematuria with or without impaired kidney function. Various approaches have been tried for the treatment of HCV-associated glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents. Limited data exist regarding antiviral treatment of HCV-associated glomerulonephritis, whereas immunosuppressive agents have been suggested for cryoglobulinemic kidney disease. A recent meta-analysis of controlled clinical trials (CCTs) suggested that standard interferon (IFN) doses were more effective than immunosuppressive agents in lowering proteinuria of patients with HCV-related cryoglobulinemic glomerulonephritis (odds ratio 3.86; 95% confidence interval, 1.44-10.33; p=0.007). However, data for follow-up were not given. Two distinct approaches should be considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis according to the level of proteinuria and kidney failure. Preliminary studies with rituximab therapy of HCV-related cryoglobulinemic glomerulonephritis have given encouraging results, even if a point of caution is important, because rituximab use may be associated with activation of various infections, including HCV.

Volta U. · Department of Clinical Medicine, St.Orsola-Malpighi Polyclinic, University of Bologna, Bologna, Italy. · Minerva Med. · Pubmed #19034259 No free full text.

Abstract: Although the spectrum of liver abnormalities associated with celiac disease is particularly wide, two main forms of liver damage, namely cryptogenic and autoimmune, appear to be strictly related to gluten-sensitive enteropathy. The most frequent occurrence is a cryptogenic hypertransaminasemia, present in about a half of untreated celiac patients, as an expression of a mild liver impairment characterised by a histological picture of non specific reactive hepatitis (celiac hepatitis) reverting to normal after a few months of gluten withdrawal. In a few cases, a more severe liver injury leading to chronic hepatitis or liver cirrhosis is present. In these patients liver damage can still improve after a gluten-free diet institution. In addition, a close association between celiac disease and autoimmune liver disorders has been largely demonstrated. Indeed, 3%-7% of patients with primary biliary cirrhosis, 3%-6% with autoimmune hepatitis and 2-3% with primary sclerosing cholangitis are affected by celiac disease. Autoimmune liver dysfunction, found in celiac disease, does not usually improve after gluten-free-diet. Presently, it is difficult to establish if the two main kinds of liver injury found in celiac disease (cryptogenic and autoimmune) are discrete entities with a different pathogenesis or if they are an expression of the same disorder where genetic factors and duration of gluten exposure may determine the severity and the pattern of liver injury.

Iacobellis A, Ippolito A, Andriulli A. · "Casa Sollievo della Sofferenza" Hospital, IRCCS, viale Cappuccini 1, San Giovanni Rotondo 71013, Italy. · World J Gastroenterol. · Pubmed #19030197 links to  free full text

Abstract: The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance (SVR), halt disease progression, and prevent re-infection of the liver graft. However, while the medical need is great, the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias. We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis, due to hepatitis C virus (HCV) infection. In cases presenting with bridging fibrosis or cirrhosis, current regimens of antiviral therapy have attained a 44%-48% rate of SVR. In cirrhotic patients with portal hypertension, the SVR rate was 22% overall, 12.5% in patients with genotype 1, and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin. In patients with decompensated cirrhosis, full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall, 16% in patients with genotype 1 and 4, and 59% in those with genotype 2 and 3. Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects. Major benefits after HCV eradication were partial recovery of liver metabolic activity, prevention of hepatitis C recurrence after transplantation, and removal of some patients from the waiting list for liver transplant. Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve (Child-Pugh-Turcotte score >= 10). Although SVR rates are low in decompensated cirrhotics due to hepatitis C, these patients have the most to gain as successful antiviral therapy is potentially lifesaving.

Della Rossa A, Marchi F, Catarsi E, Tavoni A, Bombardieri S. · Rheumatic Disease Unit, University of Pisa, Pisa, Italy. · Clin Exp Rheumatol. · Pubmed #19026151 No free full text.

Abstract: Mixed cryoglobulinemia is a highly heterogeneous clinical syndrome in terms of clinical presentation, extent and severity of organ involvement, immunological abnormalities and clinical course. Modern management began with the discovery of the close association between this syndrome and hepatitis C virus (HCV) infection. In this review we examined previously published studies on mortality in different series of patients with mixed cryoglobulinemia (MC). Patients with mixed cryo-globulinemia have higher mortality rates, predicted by age, renal involvement, intestinal vasculitis, widespread vasculitis and type of cryoglobulins.

Bongiovanni M, Casana M. · Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, University of Milan, Via di Rudinì 8, 20142 Milano, Italy. · Med Chem. · Pubmed #18991734 No free full text.

Abstract: Non-invasive markers of liver fibrosis have been recently developed as a possible alternative to liver biopsy. The clinical management of hepatic diseases is dependent on the extent of liver fibrosis. Liver biopsy remains the gold standard but severe complications are found in about 0.5% of cases. Studies involving sequential liver biopsies are impractical, costly, and risky. Therefore non-invasive markers of liver fibrosis could be useful. These drawbacks justify an intensive research on non-invasive alternatives. Several serum markers are either directly involved in fibrosis remodelling or are indirectly associated with the presence of significant liver fibrosis. More recently, fibrosis scores calculated from statistical models have been described. This review describes the role of non-invasive markers in assessing hepatic fibrosis in both HCV mono-infected and HIV/HCV co-infected subjects.

Vento S, Cainelli F, Temesgen Z. · Annunziata Hospital, Infectious Diseases Unit, Via Luigi Miceli, Cosenza, Italy. · Expert Opin Investig Drugs. · Pubmed #18922100 No free full text.

Abstract: BACKGROUND: Chronic hepatitis C virus (HCV) infection is a worldwide health problem. Response rates to current standard of treatment (pegylated IFNs and ribavirin) are low in patients with the prevailing genotype 1. OBJECTIVE: To review papers published or presented at recent international meetings showing the results of trials of new anti-HCV drugs. METHODS: Literature search using the terms 'antivirals', 'interferon', 'pegylated interferon', 'ribavirin', 'polymerase inhibitors', 'protease inhibitors', 'cyclophilin inhibitors' and 'hepatitis C virus'. Search of abstracts containing the same terms in the title and presented at the American Association for the Study of Liver Diseases 2007 and at the European Association for the Study of the Liver 2008 meetings. RESULTS/CONCLUSION: Preliminary results of Phase II studies of new compounds look promising, although side effects are higher than with current standard of treatment.

Tramontano E. · Department of Sciences and Biomedical Technologies, University of Cagliari, Monserrato (Cagliari), Italy. · Mini Rev Med Chem. · Pubmed #18855743 No free full text.

Abstract: The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) is strictly essential for viral replication and it has been used as viral target for anti-HCV drug development. All small molecules which have been identified to be selective non-nucleoside inhibitors (NNI) of the HCV RdRp to date are reported.

Zanetti AR, Van Damme P, Shouval D. · Department of Public Health-Microbiology-Virology, Faculty of Medicine, University of Milan, Via C. Pascal 36, 20133 Milan, Italy. · Vaccine. · Pubmed #18848855 No free full text.

Abstract: Hepatitis B virus (HBV) infection is a world wide public health problem of major concern. HBV infection may lead to chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Vaccination is the most effective measure to control and prevent hepatitis B and its long-term serious sequelae on global scale, both in terms of cost-effectiveness and benefit-cost ratios. According to the WHO recommendations, universal vaccination has been currently implemented in 168 countries world wide with an outstanding record of safety and efficacy. The effective implementation of such programmes of vaccination has resulted in a substantial decrease in disease burden, in the carrier rate and in hepatitis B-related morbidity and mortality. A future challenge is to overcome the social and economic hurdles which still hamper the introduction of hepatitis B vaccination on a global scale.

Toniutto P, Fabris C, Bitetto D, Fumolo E, Fornasiere E, Pirisi M. · University of Udine, Internal Medicine, DPMSC, Medical Liver Transplant Unit, Piazzale Santa Maria della Misericordia 1, 33100 Udine, Italy. · IDrugs. · Pubmed #18828074 No free full text.

Abstract: Roche Holding AG is developing R-1626, an oral nucleoside inhibitor of HCV RNA polymerase. R-1626 has been demonstrated to be well absorbed and rapidly converted to the active component R-1479. The compound has demonstrated a strong capacity to inhibit HCV replication in vitro and in vivo, without the rapid development of viral resistance. After 4 weeks of treatment with R-1626 in combination with PEG-IFN plus ribavirin in treatment-naïve patients with genotype 1 HCV infection, HCV RNA could no longer be detected in approximately 74% of patients, compared with 5% of patients treated with PEG-IFN plus ribavirin alone, indicating the high potency of R-1626 to induce HCV RNA viral load reductions. R-1626 was generally well tolerated, although severe side effects of neutropenia were observed at high doses. A phase IIb clinical trial was ongoing at the time of publication to test the efficacy of R-1626 in combination with a standard or lower dose of PEG-IFN and ribavirin in HCV genotype 1-infected patients. Given its potent antiviral effect with an apparent high genetic barrier, R-1626 represents an important advancement in improving the outcome of patients with chronic HCV infection.

Molino C, Fabbian F, Cozzolino M, Longhini C. · Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy. · Int J Artif Organs. · Pubmed #18825641 No free full text.

Abstract: Chronic kidney disease (CKD) patients in dialysis (HD) show peculiar, atypical features of clinical presentation and diseases (cardiovascular, metabolic, hematologic). This is also true for viral hepatitis infections, for which CKD patients represent an important risk group. In the past, hepatitis B virus (HBV) was the major cause of viral hepatitis in end-stage renal disease (ESRD). However, the introduction of a rigorous infection-control strategy, routine screening of patients and staff for hepatitis B serologic markers, vaccination of susceptible patients and staff, use of separate rooms and dedicated machines for HD of HbsAg-positive patients have all led to a decline in the spread of HBV infection in dialysis. Despite the prevalence of the antibody-hepatitis C virus (HCV), there has been a marked decrease in HD patients; after the introduction of routine screening for HCV and the use of erythropoietin, its occurrence ranges from 5% to 25% in the United States, with a prevalence of 6.8% in Europe. In CKD and in HD patients, the presence of HBV and HCV is an independent and significant risk factor for death and this risk may be at least partially attributed to chronic liver disease with its attendant complications. Liver disease can progress with modest hepatic inflammation and prominent fibrosis; the natural history of viral hepatitis in these patients is dependent on the immune dysfunction typical of kidney disease. Despite recent advances in antiviral therapy, there are still many uncertainties in regards to the efficacy and long-term outcomes of treatment with antiviral agents.

Fabrizi F, Messa P, Martin P, Takkouche B. · Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milan, Italy. · Int J Artif Organs. · Pubmed #18825640 No free full text.

Abstract: OBJECTIVE: To examine the association between HCV infection and the occurrence of post-transplant diabetes mellitus (PTDM) among renal transplant patients. DESIGN: Meta-analysis of observational studies. DATA SOURCES: We retrieved studies published in any language by systematically searching Medline, and Embase and by manually examining the references of the original articles, reviews, and monographs retrieved. REVIEW METHODS: We included cohort and case-control studies reporting relative risk estimates and 95% confidence intervals (CIs) for PTDM occurrence with HCV after renal transplantation. Thirteen studies providing information on a total of 30,099 unique patients were included in our meta-analysis. RESULTS: Study-specific relative risks were weighted by the inverse of their variance to obtain fixed and a 95% confidence interval (CI) of 1.94; 3.83 (10 studies). In a stratified analysis including only large studies (2 studies), the pooled RR was 1.36 (95% CI, 1.21; 1.54). Egger's regression test showed some evidence of publication bias (p=0.0001), but our sensitivity analysis showed that this issue did not meaningfully change the results. CONCLUSIONS: Our study shows a marked increase of the risk of post-transplant diabetes mellitus in anti-hepatitis C virus-positive renal transplant recipients. The excess risk of death in hepatitis C virus-positive renal transplant recipients may be at least partially attributed to post-transplant diabetes mellitus with its attendant complications.