Hepatitis: Viola C

Gentile I, Viola C, Borgia F, Castaldo G, Borgia G. · Dipartimento di Medicina Pubblica e Sicurezza Sociale - Sezione di Malattie Infettive, Universită di Napoli "Federico II", Italy. · Curr Med Chem. · Pubmed #19275615 No free full text.

Abstract: Chronic hepatitis C affects 130,000,000 people worldwide. Hepatitis C virus (HCV) is a single-strand RNA virus responsible for most cases of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) in the Western world. The gold standard for the treatment of chronic hepatitis C (combination of pegylated-interferon alpha and ribavirin) results in a sustained virological response (namely, clearance of serum HCV RNA 6 months after therapy withdrawal) in only about half treated patients. Therefore, there is a race to develop new drugs for the treatment of HCV infection. One of the most promising approaches is to use protease inhibitors, i.e. drugs inhibiting NS3/NS4A HCV protease, which plays a crucial role in the viral life cycle. Telaprevir (VX-950) is the protease inhibitor in the most advanced phase of clinical testing. Telaprevir is orally available and when used in monotherapy it induced a median decline of 4 logs of HCV RNA after two weeks of therapy. However, mutants with a lower sensitivity to telaprevir have been demonstrated in a high proportion of patients within 14 days of monotherapy. The drug has been used in clinical trials in combination with pegylated-interferon and ribavirin. This triple combination resulted in a higher rate of SVR but also in a higher rate of side effects (rash, gastrointestinal disorders, and anemia) than standard treatment. This review focuses on the mechanism of action, pharmacokinetics, clinical efficacy, and tolerability of telaprevir, and on possible use of this drug in combination with other drugs for the treatment of HCV infection.

Borgia G, Gentile I, Fortunato G, Borrelli F, Borelli S, de Caterina M, Di Taranto MD, Simone M, Borgia F, Viola C, Reynaud L, Cerini R, Sacchetti L. · Dipartimento di Medicina Pubblica e Sicurezza Sociale - Sezione di Malattie Infettive, Università di Napoli Federico II, Napoli, Italy. · Liver Int. · Pubmed #18662278 No free full text.

Abstract: BACKGROUND: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) alpha plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate. AIMS: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment. METHODS: Patients were treated with pegylated interferon alpha-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B(12), folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination. RESULTS: Homocysteine levels were deranged (>16 micromol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 micromol/L in SVR patients and 15.5 micromol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390-44.837, P=0.0001), homocysteine <16 micromol/L (odds ratio: 3.397, 95% confidence interval: 1.033-11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125-9.458, P=0.029) were independent predictors of SVR. CONCLUSIONS: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFNalpha plus ribavirin treatment, while polymorphisms of MTHFR are not.

Viola C, Asselah T, Samuel D, Durand F, Boudjema H, Valla D, Marcellin P. · Service d'Hépatologie, INSERM CRB3, University of Paris VII, Hôpital, Beaujon, Clichy 92 110, France. · World J Gastroenterol. · Pubmed #16937481 links to  free full text

Abstract: We described a 59-year-old male patient who underwent liver transplantation in 1989 for hepatocellular carcinoma (HCC) complicating hepatitis B virus (HBV) cirrhosis. In 2001 (12 years after liver transplantation), he developed a lung metastasis of HCC without intrahepatic recurrence and the resection was done. In July 2003, he was symptom free without any recurrence. HCC metastasis can develop even after a very long time of liver transplantation. Many HCCs grow slowly, and the growth rate of recurrent tumors in patients receiving immunosuppressive therapy is significantly greater than that of those who do not receive immunosuppressive therapy.

Perrella A, Borgia G, Guida GM, Graf M, Gnarini RM, Viola C, Atripaldi L, Sbreglia C, Perrella O. · No affiliation provided · J Gastroenterol Hepatol. · Pubmed #16048590 No free full text.

This publication has no abstract.

Gentile I, Viola C, Reynaud L, Borrelli F, Cerini R, Ciampi R, Piazza M, Borgia G. · Department of Public Medicine and Social Security, Institute of Infectious Diseases( Ed. 18), University of Naples Federico II, Naples, Italy. · J Interferon Cytokine Res. · Pubmed #15871666 No free full text.

Abstract: A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.

Perrella A, Borgia G, Borrelli F, Di Sirio S, Gnarini M, Grattacaso S, Graf M, Guida M, Viola C, Guarnaccia M, Perrella O. · Department of Public Medicine and Social Security, Institute for Infectious Diseases, Federico II Medical School University of Naples, Italy. · Int J Immunopathol Pharmacol. · Pubmed #15698524 No free full text.

This publication has no abstract.