Hepatitis research and treatment最新文献

A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop liver cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation, however, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or preemptive therapy is limited to mildly decompensated patients due to poor tolerance. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic hepatitis C. Combined pegylated interferon and ribavirin therapy is the current standard treatment with sustained viral response rates of 25% to 45%. The rate is lower than that in the immunocompetent population, partly due to the high prevalence of intolerability. To date, there is no general consensus regarding the antiviral treatment modality, timing, or dosing for HCV in patients with advanced liver disease and after liver transplantation. New anti-HCV drugs to delay disease progression or to enhance viral clearance are necessary.

HCV-Ag-specific TH17 cells secrete IL17, a cytokine involved in autoimmune diseases and regulated by IL10 and TGF-b. 5-12% of patients with chronic HCV infection have hypothyroidism. We evaluated the role of these cytokines in this patients by determining serum concentration of TsH, T3, free T4, IL2, IL10, IL12, IL17, TGF-b, anti-TG, TPO, CCP, GBM, and cardiolipin antibodies in 87 chronically noninterferon treated HCV-infected patients. 20 patients (group A) had elevated TsH values (>5 μUI/ml) whereas the remaining 67 (group B) had normal values. The percentage of anti-TPO, TG, GBM, and cardiolipin antibodies in group A patients (33%, 41%, 5% and 5%, resp.) as well as IL17, IL2 and TGF-b concentrations (25 ± 23 pg/ml, 643 ± 572 pg/ml, and 618 ± 221 pg/ml, resp.) were significantly higher than group B. Abnormal Th17 regulation mediated by IL-2 and low TGF-b concentrations is associated with hypothyroidism in chronically-infected HCV patients.

A combination therapy with pegylated interferon (PEG-IFN) plus ribavirin (RBV) has made it possible to achieve a sustained virological response (SVR) of 50% in refractory cases with genotype 1b and high levels of plasma HCVRNA. Several factors including virus mutation and host factors such as age, gender, fibrosis of the liver, lipid metabolism, innate immunity, and single nucleotide polymorphism (SNPs) are reported to be correlated to therapeutic effects. However, it is difficult to determine which factor is the most important predictor for an individual patient. Data mining analysis is useful for combining all these together to predict the therapeutic effects. It is important to analyze blood tests and to predict therapeutic effects prior to initiating treatment. Since new anti-HCV agents are under development, it will be necessary in the future to select the patients who have a high possibility of achieving SVR if treatment is performed with standard regimen.

Interferons were first described in 1957, but it was not until 34 years after their discovery that sufficient quantities of it were available for treatment of hepatitis C virus (HCV) infections, Clinicians now have an excellent understanding of the basis for the effectiveness of interferon alpha (IFN-α) in the therapy of this disease. Treatment with IFN-α is more efficient when it complemented by the antiviral ribavirin and the IFN-α is conjugated with polyethylene glycol to form peginterferon. In the near future treatment of HCV with IFN-α may involve new anti-HCV agents that are currently under development.

Multiple extrahepatic manifestations have been associated with chronic hepatitis C, the most important among them being cryoglobulinemia, glomerulonephritis, porphyria cutanea tarda, lichen planus, seronegative arthritis, and lymphoproliferative disorders as in the sudies of Bonkovsky and Mehta (2001) and El-Serag et al. (2002). We will discuss in this paper chronic hepatitis C- related kidney disease and course and management of patients with chronic hepatitis C in special circumstances like hemodialysis and kidney transplantation.

Since 1986, interferon-alfa (IFN-α) monotherapy has been administered for patients with chronic hepatitis C (CHC). However, sustained response rate is only about 8% to 9%. Subsequent introduction of ribavirin in combination with IFN-α was a major breakthrough in the treatment of CHC. Sustained virological responses (SVRs) rate is about 30% in hepatitis C virus genotype 1 (HCV-1) patients, and is about 65% in HCV-2 or -3 patients. After 2000, pegylated interferon (PegIFN) much improved the rates of SVR. Presently, PegIFN-α-ribavirin combination therapy has been current standard of care for patients infected with HCV. In patients with HCV-1, treatment for 48 weeks is optimal, but 24 weeks of treatment is sufficient in HCV-2 or -3 infected patients. Clinical factors have been identified as predictors for the efficacy of the IFN-based therapy. The baseline factor most strongly predictive of an SVR is the presence of HCV-2 or -3 infections. Rapid virological response (RVR) is the single best predictor of an SVR to PegIFN-ribavirin therapy. If patients can't achieve a RVR but achieve a complete early virological response (cEVR), treatment with current standard of care can provide more than 90% SVR rate. HCV-1 patients who do not achieve an EVR should discontinue the therapy. Recent advances of protease inhibitor may contribute the development of a novel triple combination therapy.