Establishment Of The Serum Specimen Repository Of HCV Infected Patients And Effect Observation Of Antiviral Therapy To Hepatitis C Patients With Liver Cirrhosis After Splenectomy Or Partial Splenic Embolization

Hepatitis C virus (hepatitis C, HCV) is an enveloped, positive single-stranded RNA virus, with the diameter of 40 ~ 60 nm. Since HCV was successfully cloned in 1989, the etiology, epidemiology, chronic mechanism of HCV has been achieved great progress. However, on account of the high variability, the treatment and prevention against HCV are still limited. Currently there are around 170 million people infected with hepatitis C virus worldwide, accounting for 3% of the total population; and each year there are three ~ four million new cases, The variances of the HCV infection rates range from 0.1% to 10% in different countries. Statistics show that there are approximately 40 million HCV-infected people in China, accounting for 3.2% of the Chinese population, and the infected population presents a trend of rising. HCV can easily lead to persistent infection and chronic hepatitis. 50% ~ 80% of HCV infection are likely to progress to chronic hepatitis, of which about 20% of the patients with chronic hepatitis could progress to liver cirrhosis in 20 years. 1% ~ 4% of the cirrhotic patients will progress to primary hepatic carcinoma each year. In the United States, 25% of liver cancer cases derived from HCV infection, HCV infection increases the social charges, and HCV treatments cost about 1.8 billion dollars in the United States in 1998 according to statistics. HCV become a serious threat to human health. The dead ages of most HCV patients are about 44 ~ 54 years old, therefore, HCV treatment is essential. It has been proved that anti-viral treatment should be carried out to reduce the occurrence of liver cancer or liver failure even if the HCV infection progress to chronic hepatitis or liver cirrhosis.At present, the standarded hepatitis C treatment should follow the guidance of treatment response (response guided therapy, RGT) principle, peg-interferon combined ribavirin is used as the treatment for 24-72 weeks. Patients infected different HCV genotypes show different sustained virological response rate to the standarded treatment, the response rates of 1,4 genotypes are only 40% ~ 50%, and 2,3 genotypes are as high as 80%. Therefore, a large number of hepatitis C patients are different to be cured. And the use of interferon and ribavirin may result in some adverse reactions, such as influenza-like symptoms, fatigue, cognitive dysfunction, depression, skin rash, gastrointestinal symptoms, thyroid dysfunction, retinopathy, hemolytic anemia and cytopenia. Many patients can not tolerate the treatment and dropped out early.Chronic hepatitis C the current standard treatment of limited efficacy, adverse reactions, and particularly for hepatitis C cirrhosis patients with hypersplenism, thrombocytopenia, leucopenia, if not for such patients properly treated with interferon on anti-virus treatment, it has high risk. 29 cases of HCV-associated cirrhosis and hypersplenism with complete clinical data from above-mentioned specimen repository were selected, treated with splenectomy or partial splenic embolization to cure the hypersplenism. And then peg-IFNα-2α135μg or 180μg per week united ribavirin ribavirin capsule 600mg/d～900mg/d was given by hypodermic injection , then observed the effect. This study offered the clinical evidences that either splenectomy or partial splenic embolization should be treated to HCV-derived cirrhosis patients complicated with hypersplenism, as well as accumulating the valuable experiences for treating these kinds of patients.Our study was as follows:1 Establishment of the serum specimen repository of HCV infected patients.We collected the serum specimen of all the patients with HCV chronic infection from January 2001 to December 2008 in our hospital. Patient specimens and clinical information were registered. Some patients'serum samples were assayed by HCV RNA quantitative detection and HCV genotyping. Investigation on the pathogenic mechanism, viral evolution and interaction between host factors and viral factors of HCV in the population would lay a solid foundation for the development of effective vaccines and drugs.2 Effect observation of antiviral therapy to hepatitis C patients with liver cirrhosis after splenectomy or partial splenic embolization.29 cases of HCV-associated cirrhosis and hypersplenism with complete clinical data from above-mentioned specimen repository were selected, treated with splenectomy or partial splenic embolization to cure the hypersplenism. And then peg-IFNα-2α135μg or 180μg per week united ribavirin ribavirin capsule 600mg/d～900mg/d was given by hypodermic injection , then observed the effect. This study offered the clinical evidences that either splenectomy or partial splenic embolization should be treated to HCV-derived cirrhosis patients complicated with hypersplenism, as well as accumulating the valuable experiences for treating these kinds of patients.Results:1 Successfully established HCV specimen repository of HCV infectious patients in our hospital, and laid a solid foundation of investigation on the pathogenic mechanism, viral evolution and interaction between host factors and viral factors of HCV and development of effective vaccines and drugs.2 Our Study revealed that blood transmission is the main route for HCV infecting in our country. With the rapid economical development and standardization of the use of blood products, we could ignore the transmission via drug abuse. We also found that genotype 1b HCV was still dominated HCV genotype in Chinese patients, while 2a,1b/2a shared the rest parts respectively. Due to limit of sample size, the associativity between difference of genotypes and severity of liver disease were still unclear, which should be investigated in the future work.3 Among the in-patients in the established specimen repository of HCV, 29 patients with cirrhosis of hepatitis C and hypersplenism were choosed for anti-viral therapy. After settled the hypersplenism with splenectomy or partial splenic embolization, these patients were treated with Peg-IFNα-2αunited with ribavirin capsule. The efficacy was superior to those with hypersplenism. The results indicated that the rate of sustained virological response (SVR) is 62.07%(18/29), the rate of HCV continuing negative is 68.97%(20/29), and ALT normalization rate for continuing is 72.41% (21/29). None of the patients with good compliance had a serious adverse reaction.Conclusions:1 HCV specimen repository of human was successfully established in this study. The specimen repository will lay the foundation for the pathogenesis of HCV, virus evolution, interplay between the host and HCV, and development of vaccine and drug. However, there are some disadvantages needed to be optimized in further study. First, the number of cases collected was less, which was enslaved to the economic condition and out-of-date concept of patients. Second, the number of patients that had detected genotype was also less, and the peripheral blood mononuclear cell had not been collected completely.2 In this study, after eliminating hypersplenism, the patients with hepatitis C cirrhosis combined with hypersplenism were treated with Peg-IFN-2αunited with ribavirin for anti-viral therapy. The results demonstrated that the untoward reaction was slight, the rate of sustained therapy response was better, and the incidence of liver failure and liver cancer was decreased.