Hepatitis: Esteban R

Buti M, Esteban R. · No affiliation provided · Ann Hepatol. · Pubmed #18007558 No free full text.

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Esteban R. · No affiliation provided · Hepatology. · Pubmed #12883472 No free full text.

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Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R. · Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. · J Hepatol. · Pubmed #18433919 No free full text.

Abstract: Thrombocytopenia (platelet count <150,000/microL) is a common complication in patients with chronic liver disease (CLD) that has been observed in up to 76% of patients. Moderate thrombocytopenia (platelet count, 50,000/microL-75,000/microL) occurs in approximately 13% of patients with cirrhosis. Multiple factors can contribute to the development of thrombocytopenia, including splenic platelet sequestration, bone marrow suppression by chronic hepatitis C infection, and antiviral treatment with interferon-based therapy. Reductions in the level or activity of the hematopoietic growth factor thrombopoietin (TPO) may also play a role. Thrombocytopenia can impact routine care of patients with CLD, potentially postponing or interfering with diagnostic and therapeutic procedures including liver biopsy, antiviral therapy, and medically indicated or elective surgery. Therapeutic options to safely and effectively raise platelet levels could have a significant effect on care of these patients. Several promising novel agents that stimulate TPO and increase platelet levels, such as the oral platelet growth factor eltrombopag, are currently in development for the prevention and/or treatment of thrombocytopenia. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease.

Idris BI, Brosa M, Richardus JH, Esteban R, Schalm SW, Buti M. · Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. · Eur J Gastroenterol Hepatol. · Pubmed #18334876 No free full text.

Abstract: BACKGROUND: Chronic hepatitis B virus (HBV) infection can lead to fatal complications and death. Only a relatively small proportion of patients actually receive medication, and the majority requires long-term antiviral therapy that can result in the emergence of resistant strains of HBV. The study aimed to estimate the future burden of chronic hepatitis B in Spain over the next 20 years, the impact of current lamivudine treatment and the emergence of drug-resistant HBV. METHODS: We constructed a hypothetical cohort of people with active chronic HBV infection in Spain in 2005, and 'followed' the cohort for 20 years. The cohort was stratified with respect to factors that affect prognosis (i.e. hepatitis B e-antigen and histology-defined status). To estimate the burden, Markov mathematical simulation was performed based on three scenarios: natural history, treatment with antiviral drug (lamivudine) and treatment with a hypothetical drug with identical profiles to lamivudine but to which there is no resistance. RESULTS: We estimated that in 2005 there were around 111,000 individuals suffering from active chronic HBV infection. If the cohort is not treated, by the year 2025 there will be about 60,000 events of morbidity and 40,000 cases of liver-related deaths, with 1.84 billion euro expected to be consumed in providing care for the cohort. Treating 35% of the cohort with lamivudine will reduce the morbidity and mortality by 19 and 15%, respectively; whereas the hypothetical drug will reduce the morbidity and mortality by 27 and 24%. The cumulative cost savings resulting from the use of lamivudine and the hypothetical drug, respectively, are 160 and 300 million euro. Antiviral resistance accounts for a reduction of about one-third in the potential benefit of treatment, and almost a half of the potential cost saving. CONCLUSION: Chronic hepatitis B will pose a great burden in the future if the individuals with active disease are left untreated. Effective antiviral therapy and treatment coverage have substantial impact in reducing the future burden; however, antiviral resistance decreases treatment benefit considerably.

Bruguera M, Torres M, Campins M, Bayas JM, Segura A, Barrio JL, Esteban R, Gatell JM, Martínez M, Monés J, Plans A, Planas R, Serra C, Tural C, Villalbí JR. · Servicio de Hepatología, Hospital Clínic, Barcelona, España. · Med Clin (Barc). · Pubmed #17878027 No free full text.

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Buti M, Rodriguez-Frias F, Jardi R, Esteban R. · Liner Unit, Hospital General Universitari Pall d'Hebron, Barcelona, Spain. · J Clin Virol. · Pubmed #16461229 No free full text.

Abstract: The hepatitis B virus (HBV), a member of the Hepadnaviridae family, is prone to mutations due to its asymmetric replication via reverse transcription of an RNA intermediate. The estimated mutation rate of the hepadnavirus genome is 2 x 10(4) base substitutions/site/year. This mutation rate is approximately 100 times higher than that of other DNA viruses but between 100 and 1000 times lower than that of RNA viruses. Analyses of both naturally occurring viral variants and in vitro mutagenesis studies have identified some mutations that have a role in viral latency, pathogenesis of liver disease, immune escape, and resistance to antiviral therapy.

Buti M, Casado MA, Fosbrook L, Esteban R. · Department of Hepatology, Hospital Vall d'Hebrón, Barcelona, Spain. · Pharmacoeconomics. · Pubmed #16235977 No free full text.

Abstract: BACKGROUND: Patients infected with chronic hepatitis C virus (HCV) genotype 1 are the least responsive to peginterferon (pegIFN) and ribavirin therapy. The monitoring of early virological response (EVR) is therefore an important tool for quickly identifying non-responders, permitting therapy discontinuation and avoiding adverse effects and costs. OBJECTIVE: To analyse the financial impact, in treatment-naive patients infected with HCV genotype 1, of two different measurement techniques for evaluating the EVR during pegIFN-alpha-2b plus ribavirin therapy, and to compare the results of a 48-week standard course of therapy with pegIFN-alpha-2b plus ribavirin without measuring EVR. METHODS: A budget impact model was constructed using a decision-tree analysis. EVR was defined as a >2 log decline in HCV RNA levels at week 12 either tested with two quantitative HCV RNA tests or undetectable HCV core antigen (HCV core Ag) protein levels at week 12 (one HCV core Ag test). Clinical data were taken from multicentre trials and costs from the published literature (euro, 2003 values). The analysis was carried out from the perspective of the Spanish healthcare system and therefore only direct costs were considered. The base-case scenario assumed that a potential study population of 18,504 people in Spain with chronic HCV genotype 1 would be eligible for treatment with pegIFN-alpha-2b plus ribavirin. RESULTS: In the base case, the most effective strategy was testing EVR by HCV core Ag. This resulted in 12,745 patients reaching a sustained virological response (SVR) at an overall cost of 243.98 million euro (19,142 euro per SVR). Conversely, quantitative HCV RNA testing resulted in 11,776 patients with an SVR at a cost of 232.73 million euro ( 19,763 euro per SVR). The incremental cost per successfully treated patient with HCV core Ag testing versus quantitative HCV RNA testing was 11,597 euro. One-way sensitivity analyses demonstrated that changes in the study parameters did not modify the outcomes, except when increasing the EVR or SVR of strategy 2 or when decreasing the EVR or SVR of strategy 3. CONCLUSION: This model suggests, with its underlying assumptions and data, that the assessment of EVR at week 12 by HCV core Ag testing in chronic HCV patients infected with genotype 1 permits identification of those patients expected to achieve an SVR with pegIFN-alpha-2b and ribavirin, resulting in a lower overall cost to the Spanish healthcare system than HCV RNA testing or no testing at all.

Buti M, Esteban R. · Liver Unit, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. · Drugs. · Pubmed #16033287 No free full text.

Abstract: The management of chronic hepatitis B (CHB) has improved dramatically over the last decade with the development of new drugs such as lamivudine and adefovir dipivoxil, in addition to the now standard interferon (IFN)-alpha therapy. These new drugs can achieve a significant reduction or inhibit replication of hepatitis B virus (HBV) DNA during therapy. However, in the majority of patients, particularly in those who are hepatitis B e antigen (HBeAg)-negative, the sustained off-therapy suppression of HBV DNA is rare. For this reason, several new antiviral and immunomodulatory agents are currently being evaluated. Among the immunomodulatory agents, pegylated IFNalpha (peginterferon-alpha) has been shown to be more effective for HBeAg-positive CHB than either lamivudine or standard IFNalpha monotherapy, particularly in those patients infected by HBV genotypes A and B. The new antivirals entecavir, tenofovir disoproxil fumarate and telbivudine exhibit a more potent viral inhibitory effect than the currently approved drugs (IFNs, lamivudine and adefovir dipivoxil). However, the emergence of viral resistance has been witnessed and this could be one of the major limitations to the clinical use of these new drugs, particularly during prolonged therapy. In HBeAg-negative patients it is more and more common for oral antiviral therapy to be administered for prolonged periods, as the sustained off-therapy response rates of short-term therapy are very low. Different studies are currently evaluating combination therapy, using lamivudine with adefovir dipivoxil or peginterferon-alpha with lamivudine; the preliminary results show virological responses no better than those achieved by monotherapy. However, as combination therapy is associated with a low likelihood of developing HBV drug resistance, this could result in a higher virological response during prolonged therapy. In the near future the most realistic therapeutic option for the majority of patients with CHB will be long-term use of these new, more potent antiviral drugs, if they can achieve good safety profiles while maintaining low resistance rates at affordable costs.

Buti M, Esteban R. · Liver Unit, Hospital General Universitari Vall d'Hebron, Paseo Valle de Hebron 119, Barcelona 08035, Spain. · J Hepatol. · Pubmed #14708692 No free full text.

Abstract: To summarize, the future of chronic hepatitis B therapy seems to be the combination of different drugs. Ideally, the optimal drugs to combine would meet the following criteria: they should be orally applicable, they should have an excellent safety profile and the duration of therapy should limited. Currently, the drugs most likely to fulfill these criteria are the nucleoside analogs.

Buti M, Esteban R. · Liver Unit, Hospital General Universitari Vall d' Hebron, Barcelona, Spain. · Drugs Today (Barc). · Pubmed #12698207 No free full text.

Abstract: In chronic hepatitis B therapy there are new and exciting developments in antivirals such as nucleotide analogues. Adefovir is the latest drug approved for therapy of chronic hepatitis B. This agent has a potent in vitro and in vivo effect against herpes virus, retroviruses and hepadnaviruses. In the hepatitis B virus setting, adefovir dipivoxil inhibits both the wild type and HBV lamivudine-resistant strains. Adefovir is an oral drug and the recommended dose for chronic hepatitis B is 10 mg daily. The safety profile of this dose is excellent but higher doses can produce renal tubular damage, particularly when the drug is used for prolonged therapy. Up to now, no evidence of HBV resistance to adefovir dipivoxil has been detected, and this constitutes one of its main advantages as it permits longer duration of therapy. Adefovir is an important new addition to current first-line treatments for HBeAg and anti-HBe-positive chronic hepatitis B, as well as being rescue therapy for lamivudine-resistant HBV strains.

Esteban R. · Servei de Medicina Interna-Hepatologia, Hospital Vall d'Hebron, Barcelona, Spain. · Semin Liver Dis. · Pubmed #12447723 No free full text.

Abstract: Approximately 400 million individuals worldwide have developed chronic hepatitis B after exposure to the hepatitis B virus (HBV). Up to 40% of these will eventually develop serious hepatic complications. Although widespread immunization, improved blood supply testing, and emphasis on safe sex have significantly decreased new HBV infections, the large reservoir of infected individuals (400 million) remains a serious health problem. At present, only two agents are available for the treatment of chronic hepatitis B: interferon alfa and lamivudine. Both are associated with important limitations of efficacy or safety, or both. These limitations and other problems associated with the evaluation of current and investigational therapies for chronic hepatitis B give rise to several key issues in management of HBV: duration of therapy, goals of therapy, need for standardization of the measurement of clinical responses, and definitions of response to therapy. The last two of these key issues are of particular concern. The lack of similarity in study designs, the use of inconsistent definitions of and criteria for therapeutic response, and the lack of uniformity in assays to detect HBV DNA titers hamper consistent evaluations of treatment. Therefore, there is a need for the scientific community to standardize the measures of performance and methods of analysis and reporting of clinical trials for current and new drugs.

Casado MA, Buti M, Fosbrook L, Esteban R. · Schering-Plough, S.A. Paseo de la Castellana, 143, 28046 Madrid. · Gastroenterol Hepatol. · Pubmed #11968346 No free full text.

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Olive G, Buti M, Esteban R. · Servicio de Hepatología, Hospital Universitario Vall d'Hebron, Barcelona. · Rev Clin Esp. · Pubmed #11387827 No free full text.

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Castells L, Esteban R. · Liver Unit, Hospital General Vall d'Hebron, Passeig Vall d'Hebron 129, 08035 Barcelona, Catalonia, Spain. · Eur J Gastroenterol Hepatol. · Pubmed #11338062 No free full text.

Abstract: Liver transplantation has become the treatment of choice for patients with end-stage liver disease. De novo hepatitis B infection after liver transplantation is a rare event and usually runs a mild clinical and histological course. Despite the favourable outcome, a wide spectrum of hepatitis B virus (HBV)-associated liver disease may develop, ranging from asymptomatic carriage to severe chronic active hepatitis or cirrhosis and even fulminant hepatic failure. The achievement of protective titres of anti-HBs through vaccination has been suggested to be protective against the development of de novo HBV infection. The results of vaccination in cirrhotic patients awaiting for liver transplant have been very disappointing. High-dose/short-term schedules have been tried in transplant candidates in order to increase the response rate. New and more immunogenic formulations (containing new adjuvants or additional pre-S1/pre-S2 recombinant antigens), and, more importantly, early vaccination of potential transplant candidates at earlier stages of their liver disease should further prevent de novo hepatitis B in transplant recipients.

Buti M, Esteban R. · University General Hospital Valle de Hebron, Barcelona, Spain. · Forum (Genova). · Pubmed #10717258 No free full text.

Abstract: An important group of patients with chronic hepatitis C do not respond to interferon (IFN) therapy. Compared with untreated patients with chronic hepatitis C, non-responders have a higher percentage of cirrhosis, are more frequently infected by genotype 1 and usually have a viral load above 2 x 106 copies/ml. Also, patients with cirrhosis have lower life expectancy and higher risk of clinical complications, and therefore, are most in need of effective treatment strategies. There is no evidence that the re-treatment of non-responders with a standard regimen of IFN or more prolonged IFN therapy achieves a sustained biochemical or virological response. Between 20% and 40% of non-responder patients treated with IFN therapy for more than two years had an hepatic improvement in liver histology associated with a decrease in hepatitis C virus-ribonucleic acid levels. In contrast, combination therapy with IFN and ribavirin for six months now results in sustained response rates between 6% and 29% depending on the viral genotype and the presence or absence of cirrhosis. Patients infected with genotype 2 and 3 have a higher probability of achieving a sustained virological response than those infected by genotype 1. Currently, different studies are underway to determine whether high-dose IFN and/or induction therapy combined with ribavirin for more prolonged periods of time could increase the sustained response rate in non-responders. No other drugs appear to be efficacious in these patients, except the combination of IFN, ribavirin and amantadine which has shown interesting results in a preliminary trial but they need to be confirmed in further studies. These findings suggest that combination therapy is beneficial and can be recommended for some non-responder patients until other new therapies are available.

Buti M, Esteban R. · Hospital General Universitario Valle Hebron, Barcelona, Spain. · J Hepatol. · Pubmed #10622582 No free full text.

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Buti M, Rodríguez Frías F, Calleja JL, Jardí R, Pons F, Crespo J, Casanovas T, Enríquez J, Carnicer F, Romero M, García Bengoechea M, Prieto M, García Samaniego J, Miras M, Pérez Roldán F, Rueda M, Esteban R. · Servicio de Hepatología, Hospital Universitari Vall d'Hebron, Barcelona, España. · Med Clin (Barc). · Pubmed #17988612 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine. PATIENTS AND METHOD: One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied. RESULTS: At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected. CONCLUSIONS: Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%.

Castells L, Esteban JI, Bilbao I, Vargas V, Allende H, Ribera E, Piron M, Sauleda S, Len O, Pahissa A, Esteban R, Guardia J, Margarit C. · Liver Unit, Department of Medicine, Hospital Universitari Vail d'Hebron, Barcelona, Spain. · Antivir Ther. · Pubmed #17302376 No free full text.

Abstract: OBJECTIVE: To investigate the efficacy of early antiviral treatment for hepatitis C virus (HCV) recurrence in HIV/HCV-coinfected patients undergoing liver transplantation for end-stage liver disease. METHODS: Open prospective trial of early treatment of HCV recurrence in consecutive HIV/HCV-coinfected patients transplanted at a tertiary hospital in Barcelona between 2002 and 2004. All patients had indication for liver transplantation, no previous CDC class C HIV-associated opportunistic events, a CD4+ T-cell count >100cells/microl, and undetectable plasma HIV RNA on highly active antiretroviral therapy. Treatment with pegylated interferon-alpha2b (1.5 microg/kg/week) and ribavirin (800-1000 mg/day) was given for 24 to 48 weeks, as soon as HCV recurrence was histologically documented. RESULTS: Of six patients who underwent transplant, five patients surviving the early post-transplantation period developed HCV recurrence, presenting as severe cholestatic hepatitis in three, and were started on antiviral treatment a median of 12 weeks (range: 5-31) after transplantation. After a median follow-up of 24 months all treated patients were alive. Biochemical response was achieved in all patients, although only one achieved a sustained virological response. Mild rejection before HCV recurrence occurred in two cases. Treatment was well tolerated with no episodes of rejection or mitochondrial toxicity. No patient required modification of the antiretroviral regimen. Liver biopsies performed in patients without virological response, 12-34 months after transplantation, showed cirrhosis in two and moderate chronic active hepatitis in the remainder. CONCLUSIONS: Despite early antiviral treatment, severe HCV recurrence after liver transplantation may compromise long-term survival in HIV-infected patients. Improved treatment strategies for these patients are urgently required.

Castells L, Vargas V, Allende H, Bilbao I, Luis Lázaro J, Margarit C, Esteban R, Guardia J. · Liver Unit, Internal Medicine Department, Hospital General Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Ps Vall d'hebron 119-129, 08035 Barcelona, Spain. · J Hepatol. · Pubmed #15876467 No free full text.

Abstract: BACKGROUND/AIMS: The efficacy and safety of treatment with pegylated interferon alpha-2b (Peg-Intron, 1.5 microg/kg) and ribavirin (400-800 mg) in the acute phase of recurrent HCV after LT is presented. METHODS: Twenty-four patients (17 men) transplanted for HCV-associated cirrhosis (genotype 1b) were treated for at least 6 months and compared with 24 consecutive transplant patients (16 men) without antiviral therapy (controls). RESULTS: At completion of treatment, 14/24 treated patients (58%) achieved HCV-RNA negativity, compared to none of controls (P<0.0001). Sustained virological response (SVR) occurred in 8/23 treated patients (34.7%) who reached week 24 after treatment and none of controls (P<0.005). At 12 weeks after treatment, 15/24 patients (62.5%) had an early virological response (EVR) (seven tested HCV-RNA negative). SVR was associated with absence of corticosteroid bolus administration (P=0.01), presence of EVR (P=0.002) and absence of cytomegalovirus infection (P=0.001). Haematological adverse effects included anaemia, 17/24 cases (71%) and leukopenia, 23/24 cases (96%). One patient presented mild acute rejection that resolved by adjusting immunosuppressive dose. CONCLUSIONS: Treatment with pegylated interferon alpha-2b plus ribavirin in the acute phase of HCV reinfection yielded an EVR of 62.5% and a SVR of 34.7%. The combination was safe, with a low rate of therapy withdrawal.

Rizzetto M, Tassopoulos NC, Goldin RD, Esteban R, Santantonio T, Heathcote EJ, Lagget M, Taak NK, Woessner MA, Gardner SD. · Experimental Department of Gastroenterology, San Giovanni Battista Hospital C.So Bramante, 88 10126 Turin, Italy. · J Hepatol. · Pubmed #15664241 No free full text.

Abstract: BACKGROUND/AIMS: The histological and clinical outcome of lamivudine 100mg/day was assessed in 76 HBeAg-negative chronic hepatitis B patients previously randomised to a double-blind comparison study of lamivudine and placebo. METHODS: Paired liver biopsies were available before 1 year of randomised lamivudine treatment and after 2 years of further open-label treatment for 48 patients. Serum samples were analysed for hepatitis B markers and ALT levels (n=74). RESULTS: The histological activity index improved, remained unchanged and worsened in 64, 32 and 5%, respectively, for patients without YMDD-variant HBV compared to 15, 54 and 31% with the variant. None of the 42/48 patients without cirrhosis at baseline progressed to cirrhosis. Of 24/48 patients without bridging fibrosis at pre-treatment, 83% (20/24) did not progress to bridging fibrosis. Median HBV DNA remained below the lower limit of detection and ALT < or =1 times the ULN for patients without the variant whereas levels gradually increased to 11.3Meq/ml (bDNA assay) and 2 times the upper limit of normal by month 24 for patients with variant. CONCLUSIONS: The clinical benefit of lamivudine is greatest for patients without YMDD variants over 2 years of extended treatment. Additional therapies should be considered for patients with YMDD variants.

Buti M, Valdés A, Sánchez-Avila F, Esteban R, Lurie Y. · No affiliation provided · Hepatology. · Pubmed #12717407 No free full text.

This publication has no abstract.

Buti M, Sanchez-Avila F, Lurie Y, Stalgis C, Valdés A, Martell M, Esteban R. · Liver Unit, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. · Hepatology. · Pubmed #11915041 No free full text.

Abstract: Pegylated interferon (peginterferon) alfa-2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa-2b and ribavirin in 55 patients. Twenty-eight patients were randomized to receive a high once-weekly dose of peginterferon alfa-2b (3 microg/kg for 1 week, 1.5 microg/kg for 3 weeks, and 1.0 microg/kg for 44 weeks), and 27 patients were randomized to receive a low dose (0.5 microg/kg) for 48 weeks. Both groups also received 800 mg ribavirin daily. Mean baseline HCV RNA load, measured by reverse-transcription polymerase chain reaction, was similar in both groups (5.32 +/- 0.86 log vs. 5.15 +/- 1.04 log). The 3-microg/kg dose of peginterferon alfa-2b inhibited HCV RNA more significantly than the 0.5-microg/kg dose during the first 48 hours (2.08 +/- 0.93 log vs. 1.09 +/- 0.80 log; P <.001) and both increased at 72 hours (0.54 +/- 0.73 log vs. 0.03 +/- 0.36 log; P = not significant [NS]), but the high dose showed a greater reduction at the end of the week (1.07 +/- 0.99 log vs. 0.72 +/- 0.73 log). Both doses showed a progressive, slower viral decrease throughout therapy; however, HCV RNA became undetectable faster and in more patients with the high dose (22% vs. 7% at week 4, 56% vs. 44% at week 12, 69% vs. 63% at week 24, and 71% vs. 61.5% at the end of therapy). In conclusion, peginterferon alfa-2b/ribavirin produces an initial rapid decline in HCV RNA levels, followed by a slower, progressive decrease, similar to the biphasic kinetic profile of standard combination therapy. Higher doses of peginterferon alfa-2b also accelerate viral clearance.

Sauleda S, Juárez A, Esteban JI, Altisent C, Ruiz I, Puig L, Esteban R, Guardia J. · Centre de Transfusió i Banc de Teixits, Servei Català de la Salut, Hospital Universtari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. · Hepatology. · Pubmed #11679976 No free full text.

Abstract: We have conducted an open, prospective trial to assess the safety and efficacy of interferon alfa-2b and ribavirin in combination for the treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected hemophiliacs. Twenty hemophiliacs coinfected with HIV and hepatitis C virus (HCV), 18 of them under highly active antiretroviral therapy (HAART), with a mean CD4(+) cell count of 490 +/- 176 cells/mm(3) and undetectable (n = 9) or low-level HIV RNA (<10,000 copies/mL; n = 11), were treated with interferon-alfa2b (3 MU thrice weekly) and ribavirin (800 mg/d) for 6 or 12 months according to virologic response. Patients were monitored for tolerance and response at 4, 8, 12, 24, 36, and 48 weeks during treatment and every other month thereafter. All 20 patients enrolled completed at least 6 months of treatment with no major side effect requiring treatment withdrawal, dose reduction, or modification of HAART. Overall, 8 patients (40%) achieved a sustained virologic response at the end of the 6-month post-treatment follow-up. Sustained responders had lower baseline HCV-RNA levels (5.7 +/- 0.8 vs. 6.3 +/- 0.4 log10 IU/mL, P =.041) but were otherwise similar to nonresponders. All sustained responders had a decrease in HCV-RNA level of at least 1 log per month during the first 2 months and undetectable levels at 6 months. In conclusion, our results provide evidence that combination therapy with interferon and ribavirin is safe in HIV-infected hemophiliacs with stable CD4 cell count and undetectable or low-level HIV replication, and leads to eradication of HCV in 40% of these patients.

Buti M, Sánchez F, Cotrina M, Jardi R, Rodríguez F, Esteban R, Guardia J. · Unidad de Hepatologia, Hospital General Universitario Valle de Hebron, Paseo Valle Hebron s/n, Barcelona 08035, Spain. · J Infect Dis. · Pubmed #11262212 No free full text.

Abstract: To determine whether a dramatic decrease in hepatitis B virus (HBV) DNA levels within the first months of lamivudine therapy can predict the emergence of YMDD variants in patients with chronic hepatitis B, quantitative testing was done every 3 months on serum samples from 35 patients who were treated with lamivudine for >1 year. The decline in HBV DNA levels from baseline to month 3 was higher in 22 responders than in 13 nonresponders (mean+/-SD, 4.16+/-1.06 vs. 2.88+/-1.77 log(10) copies; P=.002), whereas no differences were observed in patients with and without YMDD variants at 1 year of therapy. At 3 months, HBV DNA was undetectable in 77% of the responders, whereas, after 1 year, it was undetectable in 23% of nonresponders, 40% of patients with YMDD variants, and 74% of those without variants. Therefore, quantitative HBV DNA testing is very useful in deciding whether to continue therapy, because of the low likelihood of response in patients who remain HBV DNA positive at month 3 of treatment.

Buti M, Cotrina M, Cruz de Castro E, Jardí R, Rodríguez F, Esteban R, Guardia J. · Servicio de Hepatología, Hospital Universitario Valle de Hebrón, Barcelona. · Gastroenterol Hepatol. · Pubmed #10228320 No free full text.

Abstract: BACKGROUND: Three month administration of lamivudine in patients with chronic hepatitis B produces a transitory inhibition of the DNA of the hepatitis B virus (HBV). AIM: The aim of this study was to evaluate the efficacy and safety of one year treatment with lamivudine in patients with chronic hepatitis B and liver transplantation (LTx) with recurrence of HBV infection. PATIENTS AND METHODS: Sixteen patients with chronic hepatitis B, 4 patients with decompensated hepatic cirrhosis and 4 patients having undergone LTx with recurrence of HVB infection were treated with the oral administration of 100 mg/day of lamivudine for one year. RESULTS: At 3 months of treatment, the HBV-DNA became negative in 94% of the cases of chronic hepatitis B, in 10% of those with decompensated hepatic cirrhosis and in 100% of the cases of LTx. At one year of treatment, the HBV-DNA was negative in 81% of the chronic hepatitis B, in 100% of the decompensated cirrhotics and in 100% of the LTX cases which survived. The tolerance to treatment was excellent in all the cases. In 34% of the cases, mutations were observed in the gene of the polymerase DNA at one year of treatment. CONCLUSIONS: Lamivudine produces intense, rapid inhibition in viral replication not only in chronic hepatitis B but also in cases of decompensated cirrhosis or recurrence following liver transplantation. Around 30% of the patients undergoing one year of treatment with lamivudine developed gene mutations of the HBV polymerase.