Hepatitis: Puoti M

Rockstroh JK, Bhagani S, Benhamou Y, Bruno R, Mauss S, Peters L, Puoti M, Soriano V, Tural C, Anonymous00076. · Department of Medicine I, University of Bonn, Bonn, Germany. · HIV Med. · Pubmed #18257771 No free full text.

Abstract: OBJECTIVES: With the decline in HIV-associated morbidity and mortality following the introduction of highly active antiretroviral therapy (HAART), liver disease has emerged as a major cause of death in HIV/hepatitis B virus (HBV) and HIV/hepatitis C virus (HCV) coinfected persons. Therefore, screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease. With the introduction of new agents for the treatment of hepatitis B and increased knowledge of how best to manage hepatitis C, an update of current guidelines for management of HBV and HCV coinfection with HIV is warranted. SUMMARY: Clearly, all HIV-infected patients should be screened for hepatitis A, B and C, taking into account shared pathways of transmission. Patients who are seronegative for hepatitis A and B should be considered for vaccination. In HIV-infected patients with chronic hepatitis B, the first important differentiation is whether HAART is required or not. In the setting of stable HIV infection, with no need for HAART, several treatment options are available, namely treatment with interferon, early initiation of HAART, or selective non-HIV active anti-HBV nucleoside therapy, with the aim of achieving undetectable HBV DNA levels. In most cases, undetectable HBV DNA can only be achieved with combination therapy. With regard to hepatitis C, individualized tailoring of the duration of HCV therapy is advisable, taking into account rapid or delayed virological response. In patients who do not achieve at least a 2 log drop in HCV RNA at week 12, treatment can be terminated because of the low probability of achieving sustained virological response. Overall, with the currently available treatment algorithms, HCV can be eradicated in over 50% of patients. Therefore, HCV therapy should be considered and discussed with the patient if an indication for HCV therapy (elevated liver enzymes, positive HCV RNA and >F1 fibrosis) is present. CONCLUSIONS: Management of underlying hepatitis B and/or C in patients with HIV infection is of great importance in preventing liver disease-associated morbidity and mortality.

Soriano V, Puoti M, Garcia-Gascó P, Rockstroh JK, Benhamou Y, Barreiro P, McGovern B. · No affiliation provided · AIDS. · Pubmed #18090386 No free full text.

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Soriano V, Puoti M, Sulkowski M, Mauss S, Cacoub P, Cargnel A, Dieterich D, Hatzakis A, Rockstroh J. · No affiliation provided · AIDS. · Pubmed #15090824 No free full text.

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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.

Soriano V, Puoti M, Peters M, Benhamou Y, Sulkowski M, Zoulim F, Mauss S, Rockstroh J. · Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · AIDS. · Pubmed #18614862 No free full text.

Abstract: Nearly 10% of the estimated 36 million people having HIV worldwide suffer from chronic hepatitis B virus (HBV) infection. The advent of new antiviral agents against HBV and the recent availability of improved molecular diagnostic tools have revolutioned the management of HIV/HBV coinfected patients. The present study represents an update of the current knowledge about HBV/HIV coinfection and an intent to provide practical advise about how to give the best care to HIV-infected persons with chronic hepatitis B.

Antonelli A, Ferri C, Galeazzi M, Giannitti C, Manno D, Mieli-Vergani G, Menegatti E, Olivieri I, Puoti M, Palazzi C, Roccatello D, Vergani D, Sarzi-Puttini P, Atzeni F. · University of Pisa School of Medicine, Pisa, Italy. · Clin Exp Rheumatol. · Pubmed #18570753 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is a worldwide public health problem with a global prevalence of 2-3%. It is believed that about 170 million people are currently infected (about 3% of the world's population), and a further 3-4 million are infected each year. HCV is the main reason for liver transplantation in the developed world, and the main cause of liver-related morbidity and mortality in a number of countries, including Italy. It is not only a frequent cause of chronic liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma, but is also involved in the pathogenesis of various autoimmune and rheumatic disorders (arthritis, vasculitis, sicca syndrome, porphyria cutanea tarda, lichen planus, nephropathies, thyroid diseases, and lung fibrosis), as well as in the development of B-cell lymphoproliferative diseases. Furthermore, patients suffering from C hepatitis tend to produce rheumatoid factor, cryoglobulins and a large series of autoantibodies (ANA, anti-SSA/SSB, SAM, ATG, aCL). The use of glucocorticoids or immuno-suppressant agents in HCV infected individuals, which are needed to treat autoimmune and rheumatic disorders, leads to a risk of worsening the clinical outcome of HCV. Under these conditions, the viral infection often needs to be treated with antiviral agents, mainly pegylated interferon combined with ribavirin. However, cyclosporine A seems to be safe and effective in patients with autoimmune disease (AD) and concomitant chronic HCV infection as is documented by the reduction in viremia and transaminases, particularly in patients with high baseline levels. Finally, HCV is the main trigger of mixed cryoglobulinemia. An attempt at viral eradication is therefore indicated in most patients, and is particularly effective in the case of mild or moderate manifestations. In severe cases, rituximab is an apparently safe and effective alternative to conventional immunosuppression and, specifically, it controls B-cell proliferation.

Bruno R, Sacchi P, Puoti M, Maiocchi L, Patruno SF, Cima S, Filice G. · Division of infectious and Tropical Diseases, Fondazione IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy. · AIDS Rev. · Pubmed #18385777 No free full text.

Abstract: The coinfection of HIV and HCV has become a pathology with several distinctive characteristics. Pathogenesis of liver damage in patients with HIV and HCV coinfection is complex and multifactorial. It derives from a balance of factors which interact among themselves in a dynamic way. The reasons for the accelerated course of HIV/HCV coinfection are mainly related to two principal causes: the persistence of HCV, which depends upon alterations of cell-mediated immunity, and the activation of the immune system towards secretion of proinflammatory and profibrotic cytokines. This review will first focus on the characteristics of both these immune-mediated mechanisms, and then their implication on fibrogenesis as well as on other pathogenetic mechanisms, such as interactions between viruses and the deficit of protective mechanisms. A better knowledge of adaptive immune mechanisms, cytokine alteration, interference with host defense mechanisms, and the "cross-talk" among the viruses will improve the understanding of the pathogenetic mechanism and provide the opportunity to cure this disease.

Soriano V, Puoti M, Sulkowski M, Cargnel A, Benhamou Y, Peters M, Mauss S, Bräu N, Hatzakis A, Pol S, Rockstroh J. · Department of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, 28029 Madrid, Spain. · AIDS. · Pubmed #17502718 No free full text.

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Gatti F, Nasta P, Matti A, Manno D, Mendeni M, Puoti M, Carosi G. · Department of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. · AIDS Rev. · Pubmed #17474310 No free full text.

Abstract: Hepatitis C virus-related long-term complications are nowadays a leading cause of morbidity and mortality in HIV-infected persons. According to international guidelines, all HIV/HCV-coinfected patients should be evaluated and, if eligible, treated with pegylated interferon plus ribavirin. The management of anti-HCV treatment side effects, which may be even more serious in HIV patients, is very important to minimize treatment early discontinuations. The purpose of this review is to supply clinicians with an update, provided by the most recent and relevant literature, of underlying mechanisms, incidence, and advice about the management of pegylated interferon and ribavirin side effects in HCV/HIV-coinfected patients.

Marzano A, Angelucci E, Andreone P, Brunetto M, Bruno R, Burra P, Caraceni P, Daniele B, Di Marco V, Fabrizi F, Fagiuoli S, Grossi P, Lampertico P, Meliconi R, Mangia A, Puoti M, Raimondo G, Smedile A, Anonymous00107. · Division of Gastroenterology and Hepatology, AO San Giovanni Battista, Torino, Italy. · Dig Liver Dis. · Pubmed #17382608 No free full text.

Abstract: The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and referred mainly to the pre-antivirals era. Today a rational approach to the problem of hepatitis B in these patients provides for: (a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), (b) the treatment with antivirals (therapy) of active carriers, (c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if they are undergoing immunosuppressive therapies judged to be at high risk, (d) the biochemical and hepatitis B surface antigen (HBsAg) monitoring (or universal prophylaxis, in case of high risk immunosuppression) in subjects with markers of previous contact with HBV (HBsAg negative and anti-HBc positive), in order to prevent reverse seroconversion. Moreover it is suggested a strict adherence to criteria of allocation based on the virological characteristics of both recipients and donors in the general setting of transplants and in liver transplantation the universal prophylaxis with nucleos(t)ides analogues (frequently combined with specific anti-HBV immunoglobulins) in HBsAg positive candidates and in HBsAg negative recipients of anti-HBc positive grafts.

Bruno R, Puoti M, Sacchi P, Filice C, Carosi G, Filice G. · Division of Infectious and Tropical Diseases, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy. · J Hepatol. · Pubmed #16356582 No free full text.

Abstract: Hepatocellular carcinoma (HCC) resulting from chronic infection with hepatitis B or C virus (HBV, HCV) is a significant health problem. Concurrent infection with human immunodeficiency virus (HIV) may accelerate the progression from cirrhosis to HCC. Current guidelines advise screening patients with cirrhosis at 6-month intervals using ultrasonography and measurement of alpha-fetoprotein levels. In early-stage HCC, resection and liver transplantation are curative, as is percutaneous ethanol injection for small tumours in patients who are not candidates for surgery. HIV-infected patients do not qualify for liver transplantation. For late-stage HCC, chemoembolization can improve survival. Prevention of hepatitis and cirrhosis are key goals in reducing the impact of HCC. Numerous issues in HCC prevention, diagnosis, and management still remain to be resolved through large-scale, randomized clinical trials.

Puoti M, Torti C, Bruno R, Filice G, Carosi G. · Clinica di Malattie Infettive e Tropicali, AO Spedali Civili, Università di Brescia, P.zzle Spedali Civili 1, I 25123 Brescia, Italy. · J Hepatol. · Pubmed #16338021 No free full text.

Abstract: HIV co-infection influences the course and natural history of hepatitis B virus (HBV) infection by impairing the quantity and quality of the innate and adaptive immune response. The rates of spontaneous resolution after acute infection and spontaneous anti-HBe and anti-HBs seroconversions are decreased, and levels of HBV replication are increased in HIV-infected patients. A more rapid progression of liver fibrosis and a higher rate of cirrhosis decompensation (but not hepatocellular carcinoma) have been demonstrated in co-infected patients. The risk of HBV-associated end-stage liver disease and liver-related mortality may be increased by HIV co-infection. Antiretroviral therapy may trigger spontaneous anti-HBe and anti-HBs seroconversion and/or a better immune control of HBV replication by restoring adaptive immunity, but can also increase hepatitis flares. Reactivation of chronic hepatitis B has been observed after suspension of anti-retrovirals with anti-HBV activity or after occurrence of HBV resistance to lamivudine. Future research should focus on: the impact of HIV-induced changes in innate and adaptive immune response and modifications induced by anti-retroviral therapy that may impact on progression of advanced chronic hepatitis B; the association between HBV genotype and clinical course of disease; and the role of occult HBV infection as a co-factor with other causes of liver injury.

Soriano V, Puoti M, Bonacini M, Brook G, Cargnel A, Rockstroh J, Thio C, Benhamou Y. · Department of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, 28029 Madrid, Spain. · AIDS. · Pubmed #15718833 No free full text.

This publication has no abstract.

Puoti M, Prestini K, Putzolu V, Zanini B, Baiguera C, Antonini MG, Pagani P, Airoldi M, Carosi G. · Department of Infectious and Tropical Diseases, University of Brescia and AO Spedali Civili, Brescia, Italy. · J Biol Regul Homeost Agents. · Pubmed #14518713 No free full text.

Abstract: HIV and HCV share common transmission pathways, but HCV is more efficiently transmitted through blood than with sexual exposure. Thus HCV coinfection is frequent in HIV seropositives, mainly in those with history of injection drug use and/or transfusion. HIV coinfection increases HCV replication rate, the rate of HCV vertical transmission and accelerates the course of hepatitis C towards cirrhosis and hepatocellular carcinoma. The evidence of an effect of HCV on HIV disease progression is less convincing. The results of several studies suggest that HCV coinfection does not hasten the progression of HIV infection towards AIDS. However two recent studies showed that HCV coinfection is independently associated with a lower restoration of CD4 counts during combination antiretroviral treatment. However this finding should be confirmed by additional studies.

Puoti M, Zanini B, Bruno R, Airoldi M, Rossi S, Quiros Roldan E, El Hamad I, Moretti F, Castelli F, Sacchi P, Filice G, Carosi G. · Clinica di Malattie Infettive e Tropicali Università degli Studi di Brescia - AO Spedali Civili, Brescia, Italy. · HIV Clin Trials. · Pubmed #12187507 links to  free full text

Abstract: Human immunodeficiency virus (HIV) co-infection accelerates progression of hepatitis C virus (HCV) toward cirrhosis. Thus, with the increase of life expectancy observed after introduction of combination antiretroviral treatment, liver disease is becoming an increasing cause of morbidity and mortality in HIV-infected patients. In addition, HCV co-infection blunts CD4 restoration induced by HAART and increases HAART hepatotoxicity. For all these reasons, anti-HCV treatment is mandatory in HIV seropositives. The perfect treatment of hepatitis C should not only be safe and effective, but it should not have any adverse impact on HIV diseases and concurrent anti-HIV therapy. Two drugs are currently licensed for treatment of HCV: interferon alfa (IFNalpha) and ribavirin. Three hundred and thirty-eight patients have been included in pilot studies on the efficacy and tolerability of IFNalpha monotherapy: 16% showed sustained response and 10% dropped out. No significant adverse impact of IFNalpha monotherapy on HIV diseases or antiretroviral treatment has been observed. IFNalpha and ribavirin in combination have been introduced more recently: only 88 patients were included in pilot studies published as full papers with a 25% sustained response and an 11% rate of drop outs. Anemia and cumulative toxicity with didanosine were the most important side effects of combination treatment, but it did not affect HIV disease progression. Higher rates of sustained response (33%) without increase of side effects have been observed in preliminary experiences with the new long-acting pegylated interferons in combination with ribavirin. The search for the perfect treatment continues.

Bruno R, Sacchi P, Puoti M, Soriano V, Filice G. · Division of Infectious and Tropical Disease, IRCCS S. Matteo Hospital, University of Pavia, Italy. · Am J Gastroenterol. · Pubmed #12135007 No free full text.

Abstract: HIV-hepatitis C virus (HCV) coinfection is common and affects more than one-third of all HIV infected persons worldwide. Prevalence among risk categories varies according to shared risk factors for transmission, mainly intravenous drug use (IDU) and hemophiliacs. Chronic HCV infection seems to accelerate the course of HIV disease, resulting in a worsened clinical and immunological progression. At the same time, several studies suggest that HIV disease modifies the natural history of HCV infection, leading to a faster course of progression from active hepatitis to cirrhosis, to end stage liver disease and death. HCV infection mimics opportunistic diseases because its natural history is significantly accelerated in HIV patients. Since highly active antiretroviral therapy (HAART) has slowed the progression of HIV disease and decreased the rate of HIV associated mortality, the prognosis of HIV disease has been modified, and the need to treat HCV coinfection become a significant issue. Because of the poor response rate obtained by either interferon alone or interferon thrice weekly plus ribavirin, the combination of pegylated interferon and ribavirin will probably become the standard of care, although the clinicians should be aware of the overlapping toxicity of nucleoside analogues and ribavirin. Many selected categories of patients pose particular challenges to physicians treating HCV infection: nonresponders to interferon, cirrhotic patients, and patients infected with both HCV and HBV. Liver transplantation in HIV patients is currently under evaluation, but should become the rescue therapy for HIV patients with end stage liver disease.

Bruno R, Puoti M, Sacchi P, Carosi G, Filice G. · Division of Infectious and Tropical Diseases, IRCCS S. Matteo Hospital, University of Pavia, Italy. · Dig Liver Dis. · Pubmed #12132794 No free full text.

Abstract: Hepatitis C virus-related liver disease and its associated complications are steadily emerging health concerns in persons co-infected with human immunodeficiency virus. The increasing number of liver-related deaths in human immunodeficiency virus-hepatitis C virus co-infected individuals supports the compelling argument for more aggressive treatment in these patients. The safety and efficacy of interferon/ribavirin in human immunodeficiency virus/hepatitis C virus co-infected patients is currently under evaluation. Despite well-documented concern over highly active antiretroviral therapy-associated hepatotoxicity human immunodeficiency virus/hepatitis C virus co-infected patients should be offered antiretroviral therapy. Since management of co-infected patients is complex a multidisciplinary approach is needed in order to facilitate care and help patients to achieve a positive outcome.

Puoti M, Airoldi M, Bruno R, Zanini B, Spinetti A, Pezzoli C, Patroni A, Castelli F, Sacchi P, Filice G, Carosi G. · Clinica di Malattie Infecttive e Tropicali, Università degli studi de Brescia, AO Spedali Civili dei Brescia. · AIDS Rev. · Pubmed #11998781 No free full text.

Abstract: Shared epidemiological risks have resulted in HIV-infected populations having a high prevalence of hepatitis B virus (HBV) co-infection. Several prospective studies have investigated the impact of HBV co-infection on HIV disease progression; most of them were negative. On the contrary, there is evidence that HIV may modify the natural history of HBV infection. HIV positive subjects have higher rates of HBV chronification, higher HBV replication, lower ALT levels and lower rates of seroconversion to anti-HBe and anti-HBs. The impact of HIV co-infection on the outcome of HBV infection is still controversial, even if some studies have shown an accelerated progression towards decompensated cirrhosis in HIV co-infected subjects. HBV co-infection is a risk factor for severe hepatotoxicity during HAART. Vaccination for HBV is mandatory in nonimmune HIV subjects, however its efficacy in immunosuppressed patients is still controversial. HIV co-infection decreases the effectiveness of Interferon in the treatment of HBV infection. Because of its activity against both HBV and HIV, lamivudine is used in HIV-HBV co-infected patients at doses of 300 mg/daily and as part of an antiretroviral regimen, but the rate of sustained response is poor and HBV strains with mutations associated with lamivudine resistance occur at a rate of 20% per year. Trials of new drugs with activity against HBV, some of them with activity also against HIV, and some of them without cross-resistance with lamivudine, are now underway. Highly Active Anti-Hepatitis B Therapy will probably soon come of age.

Puoti M, Zanini B, Baiguera C, Bella D, Prestini K, Milesi L, Antonini MG, Carosi G. · Clinica di Malattie Infettive e Tropicali, Università, e Azienda Ospedaliera Spedali Civili, Brescia. · Recenti Prog Med. · Pubmed #11695308 No free full text.

Abstract: Treatment of HCV infection in HIV seropositives is becoming a management priority because of: the increasing HCV and stage liver disease mortality and the unfavourable impact of HCV infection on efficacy and toxicity of antiretroviral combination treatment. Treatment end points are: eradication of HCV or suppression of HCV replication in order to slow HCV disease progression and to increase efficacy and to reduce hepatotoxicity of antiretrovirals. Interferon as monotherapy and in combination with ribavirin induces eradication of HCV in respectively 17 and 28% and suppression of viral replication in 26 and 36% of treated HIV infected subjects. The impact of these drugs on HIV disease evolution and on antiretroviral treatment efficacy, toxicity and compliance needs to be established. Then the cost-effectiveness of anti HCV therapy in anti HIV infected patients still needs to be defined.

Bonacini M, Puoti M. · Keck School of Medicine at the University of Southern California, Hoffman Medical Research Bldg 101, 2011 Zonal Ave, Los Angeles, CA 90033, USA. · Arch Intern Med. · Pubmed #11112228 links to  free full text

Abstract: Hepatitis C (HCV) infection occurs in as many as 33% of the patients with human immunodeficiency virus (HIV) infection. In view of their improved survival, liver disease will become more clinically significant in patients coinfected with HIV/HCV. Several studies in patients with hemophilia have shown that coinfected patients develop earlier and more severe liver disease, including hepatocellular carcinoma. In nonhemophilic cohorts, lower CD4 counts are associated with an increased prevalence of cirrhosis. However, HCV infection does not seem to alter the natural history of HIV infection in most cases. Human immunodeficiency virus coinfection in pregnant women increases the risk of perinatal HCV transmission 2-fold, with more than 25% of occurrences involving transmission of both viruses: cesarean delivery significantly decreases this risk. The expanded use of highly active antiretroviral therapy may lead to further improvement in morbidity and mortality from HIV infection. Thus, the management of coexistent HCV liver disease will need to be formulated. We suggest that alcohol be disallowed. Interferon and ribavirin in combination are likely to become the therapy of choice, particularly in coinfected patients with higher CD4 counts, lower HCV viremia, and non-1 genotype. During treatment, complete blood cell counts need to be closely monitored. Future controlled trials will determine the efficacy and safety of long-acting interferon preparations. Administration of highly active antiretroviral therapy, with the intent to prevent decreases in CD4 counts, seems crucial in stemming liver disease progression. However, some drugs have clear-cut hepatotoxic potential and patients with known liver disease should be closely monitored. Arch Intern Med. 2000;160:3365-3373.

Martín-Carbonero L, Puoti M, García-Samaniego J, De Luca A, Losada E, Quinzan G, Bruno R, Mariño A, González M, Núñez M, Soriano V. · Department of InfectiousDiseases, Hospital Carlos III, Madrid, Spain. · J Viral Hepat. · Pubmed #18637070 No free full text.

Abstract: SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.

Quiros-Roldan E, Calabresi A, Lapadula G, Tirelli V, Costarelli S, Cologni G, Zaltron S, Puoti M, Carosi G, Torti C. · Institute for Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. · Antivir Ther. · Pubmed #18572746 No free full text.

Abstract: BACKGROUND: The efficacy of long-term hepatitis B virus (HBV) treatment with tenofovir (TDF) in relation to lamivudine (LMV) resistance in HIV patients failing on LMV deserves further investigations. METHODS: HIV-HBV coinfected patients were selected, provided that LMV was included in the first highly active antiretroviral therapy regimen and TDF was subsequently introduced. RESULTS: Forty HIV-HBV patients were included, 25 had undetectable HBV DNA on LMV and 15 were failing on LMV treatment. Three cases of triple 173V + 180M + 204V HBV reverse transcriptase (rt) mutants were identified, as well as several mutations or polymorphisms in the surface antigen gene at positions possibly correlating with vaccine escape. A new mutation (rtl233V) was found in one adefovir-naive patient. In 10 patients, uninterrupted TDF treatment led to a sustained treatment response for a median of 160 (interquartile range 111-189) weeks. Two patients underwent intermittent treatment with TDF and LMV, responding any time TDF was reintroduced. In one patient, TDF without LMV provided treatment response. One patient did not respond to TDF because of low treatment adherence. One patient infected with the triple rt mutant did not respond to entecavir, but TDF was successful as rescue. CONCLUSIONS: Combination therapy with TDF was effective against HBV mutant viruses resistant to LMV and provided sustained control of HBV replication over long-term follow-up, even after entecavir failure. Moreover, suppression of HBV vaccine escape variants could provide important benefits from a public health perspective.

Antonini MG, Babudieri S, Maida I, Baiguera C, Zanini B, Fenu L, Dettori G, Manno D, Mura MS, Carosi G, Puoti M. · Dept. of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. · Infection. · Pubmed #18458815 No free full text.

Abstract: BACKGROUND: Combination therapy with pegylated interferon (peginterferon) plus ribavirin is associated with several side effects, including neutropenia and infection. AIMS: To evaluate the incidence of neutropenia and infection between all consecutive patients with hepatitis C who were treated in two centers with peginterferon-alfa-2a and peginterferon-alfa-2b, in combination with ribavirin and actively monitored for occurrence of any infection. METHODS: A total of 319 consecutive patients with chronic hepatitis C received once-weekly peginterferon alfa-2b at a weight-adjusted dose (n=162) or peginterferon alfa-2a at a flat dose (n=157), plus ribavirin. RESULTS: Neutropenia was observed in 53 patients overall (17%). There were 73 infections in 73 subjects (23% of the treated population); 4/73 required hospitalization. Infections included respiratory infections (n=23), cellulitis (n=17), dental abscesses (n=13), gastroenteric infections (n=2), and other types of infections (n=18). The incidence of all infections was significantly associated with age, especially over 60 years (p<0.01) but not with neutropenia or type of pegylated interferon. CONCLUSIONS: During the treatment with pegylated interferons and ribavirin, we did not find a correlation between neutropenia and infections. This result provides a support for the notion that current guidelines for pegylated interferons dose reduction in the treatment of chronic hepatitis C for hematologic toxicity could be overly strict.

Lapadula G, Torti C, Paraninfo G, Castelnuovo F, Uccelli MC, Costarelli S, Ladisa N, Maserati R, Di Pietro M, De Silvestri A, Tinelli C, Puoti M, Carosi G, Anonymous00036. · Istituto per le Malattie Infettive e Tropicali, Università di Brescia, Brescia, Italy. · Antivir Ther. · Pubmed #16856626 No free full text.

Abstract: BACKGROUND: The independent role of HCV genotype 3 (HCV-3) in dyslipidaemia following highly active antiretroviral therapy (HAART) is still unexplored. METHODS: Analysis of data from a cohort of 307 HIV/HCV-coinfected patients and 415 HIV-monoinfected controls was conducted. Patients with available lipid levels at baseline and minimum 3-month follow-up were ranked into three groups by HCV status (HCV-3, other HCV genotypes or HCV negative). Univariate and multivariate GEE models were performed to assess factors correlated with lipid serum levels as coefficient (Coef., defined as mean difference [mg/dl] across the follow-up). Univariate and multivariate logistic regression analyses were performed for prediction of relevant hypertriglyceridaemia (> or = 500 mg/dl) and relevant hypercholesterolaemia (> or = 240mg/dl) at 3 months of follow-up. RESULTS: HCV-3 correlated with lower triglyceridaemia (Coef.=-38.22; P=0.001), independently from the other considered variables, including age, gender and use of stavudine or lopinavir. Even though HCV infection per se appeared to be protective, HCV-3 in particular was also independently associated with lower cholesterolaemia (Coef.=-46.35; P<0.001). At logistic regression analyses, HCV-3, but not HCV-non-3, was associated with lower risk of relevant hypercholesterolaemia (odds ratio [OR] 0.06; P=0.01) and relevant hypertriglyceridaemia (OR 0.11; P=0.05), independently from other considered variables. CONCLUSIONS: Our data confirm that HCV coinfection per se is associated with lower risk of hypercholesterolaemia after HAART. This effect was particularly attributed to HCV-3, which was the only genotype associated with lower triglyceridaemia during HAART.

Puoti M, Cozzi-Lepri A, Ancarani F, Bruno R, Ambu S, Ferraro T, Tundo P, Santantonio T, Toti M, Bonasso M, d'Arminio Monforte A, Anonymous00217, Anonymous00218. · Institute of Infectious and Tropical Diseases, Spedali Civili, University of Brescia, Brescia, Italy. · Antivir Ther. · Pubmed #15535419 No free full text.

Abstract: We examined the impact of a lamivudine-containing highly active antiretroviral therapy (HAART) regimen on 164 hepatitis B virus/HIV co-infected individuals starting their first HAART. Lamivudine-treated patients (accounting for 73% of the study population) showed a significantly lower level of alanine aminotransferase over follow-up [-81.1 mU/ml mean difference; 95% confidence intervals (95% CI): -30.3; -131.7, P=0.003] and a significantly reduced risk of liver-related morbidity/mortality [Relative hazard (RH)=0.07; 95% CI: 0.01-0.38, P=0.002] than those starting a lamivudine sparing-regimen.