1. What is hepatitis C? How are people infected with hepatitis C?
Answer: Hepatitis C is caused by the infection of hepatitis C viruses (HCV). In the past, it was called non-B hepatitis transmitted through intestinal tract because it belongs neither to scope of hepatitis A nor to the scope of hepatitis B. At Tokyo Meeting held in September 1989, the non-b hepatitis transmitted out side of intestinal tract was formally named hepatitis C. The major infection sources are hepatitis C patients and HC carriers. All people, mainly adults, are susceptible to the infection of hepatitis C, and the main routes of transmission are: (1) blood transmission: As the major transmission route, transfusion of blood and blood products, such as blood components, factor v a, albumins and gamma globulins, may cause hepatitis C infection, and HCV is the major protomer of hepatitis after transmission. Besides, dialysis and ntravenous drug injection as swell as tattooing and ear piercing also may infect hepatitis C. Lately, the incidence of hepatitis C begin to lower because measures have been adopted to compare specialty and screen blood donators with reagent. (2) Mother-to-child transmission: Vertical transmission of HCV through placenta in the gestational period and close contact transmission from infected mothers to babies during and after delivery have been reported. However, compared with HBV, the infection rate of hepatitis C is lower, and is mainly during delivery and in the breast feeding period. (3) Sexual contact transmission: Sexual contact is also a infection route of hepatitis C. At present, most scholars think that the sexual transmission of HCV occurs between male homosexual population and intravenous drug users, and the incidence is not high between husband and wife. (4) Daily close contact transmission: Close contact in a family inclusive of sharing comb, nail-clippers, shaver and toothbrush may be a route of hepatitis C infection.
2.What characteristics does hepatitis C£¿
Answer: HCV belongs to flavivirus of togaviridae, which has globular particles with an envelope and a diameter of 30-60nm. On the envelope, there are glycoprotein and lipid that can be killed by organic dissolvent. HCV is a recombined continental RNA virus, but its genic structure is clear. The virus is a multi-element protein of long positive chain and single strand RNA and having more than 3000 coded amino acid and contains a structural protein area (including core capsid protein and envelope protein) and some non- structural protein areas (NSI-NS5). The structural protein area is highly conservative, while the non- structural protein areas have respective functions, but are prone to give rise to variation. Compared with HBV, HCV has the following features: (1) the diameter of RNA virus particles is 36-40nm in liver cells and 36-62nm in the blood; (2) when viremia caused by HCV appears, the virus contents are lower than that caused by HBV, and the HCV RNA is difficult to be detected by common molecular biology; (3) HCV is replicated in liver cells, leading to the hyperplasia of smooth membrane and the formation of ?tubular structure, with HCV RNA not integrated on the chromosomes of host liver cells; (4) the immunogenicity of HCV antigen is lower than that of HBV antigen; (5) easy to vary and more in subtypes; (6) sensible to organic solvent and its infection can disappears after treatment with 1:1000 formalin or under 37¡æ for 96 hours, or 60¡æ for 10 hours, or under 100¡æ for 5 minutes.
3. How does HCV happen?
Answer: Now it is thought that HCV directly acts on the damage to the liver of acute hepatitis C patients, and the immune dysfunction of the organism is an important factor that causes the damage to the liver of hepatitis C, especially chronic hepatitis C patients. (1) Direct morbigenous action of HCV: the HCV RNA contents and the appearance of HCV antigen (HCAg) in the serum of hepatitis C patient are directly correlated with the ALT level; the replication of HCV is often accompanied with liver damage; after treatment by taking interferon, the ALT level in the serum is gradually lowered with HCV RNA contents; as observed from the pathological section of the liver tissue of acute hepatitis C patient, the liver cells have wide oxyphilous change, while adjacent area is deficient in lymphocytes, and thus it can be speculated the virus itself has a cell killing function. (2) Immune pathogenesis of hepatitis C: the immune factor, especially cell dysimmunity may play an important role in the onset of hepatitis C. The special pathologic changes of hepatitis C (Lymphoid cell concentration or follicle formation in the liver portal area) also indicate that the immune pathogenesis has something to do with the attack of hepatitis C.
4. What are the clinical features of hepatitis C?
Answer: (1) Compared with hepatitis B, the peak value of alanine aminotransferase (called transaminase for short) in the serum of hepatitis C patients is low, more cases are without jaundice and other symptoms, and most patients are difficult to be discovered and diagnosed except periodical test of liver functions. (2) The lift of transaminase is of three specific types, e.g. single phase type, double phase type and smooth type, with incubation period 2-26 weeks, averaging 7.8 weeks, much shorter that of hepatitis B which averages 11.8 weeks after blood transfusion. It is reported that hepatitis C in the incubation period occurs for the most part in hemophilia patients, with the shortest incubation period of 4 days to 2 weeks and the most cases 1-4 weeks. The Incubation period of sporadic hepatitis C (without transfusion history) is difficult to determine, and someone has analyzed the sporadic cases in families and think the incubation period is 12 weeks. Different incubation period may be caused by different factors of hepatitis C or different dosage of the same factor. (4) Hepatitis C with short incubation period is often a severe illness with more symptoms and jaundice, but only a few can develop into chronic disease. (5) Hepatitis C of mild type and with long incubation period or without jaundice is prone to develop into chronic disease, particularly females and those transmitted through skin. (6) 2-3 years after recovery through biochemical and histological treatment, transaminase often increase slowly or intermittently. (7) Blood donator without symptoms may transmit hepatitis C to blood receiver and the blood collected from the same donator continuously for 6 years is still infectious to chimpanzee indicate the donator is a chronic HCV carrier, and the carrying rate is higher than that of Hepatitis B patient. (8) The clinical manifestations and natural development after infected with HCV are similar in all counties, and the general law is: 1/4 patients have significant symptoms and 3/4 have not; clinically, 1/3 patients have jaundice and 2/3 have not; among the total Hepatitis C cases admitted, about 1.5% patients will develop into eruptive hepatitis and more than half develop into chronic hepatitis; the acute (sub-clinical) infection of Hepatitis C needs about 10 years in average to develop into chronic Hepatitis C, about 20 years into cirrhosis of the liver, and for a few patients about 30 years into primary hepatocellular carcinoma. (9) Serious hepatitis C is seldom seen among sporadic cases, and those that have developed into eruptive hepatitis are most caused by overlapping infections.
5.What are the specific diagnosis methods of hepatitis C?
Answer: The specific diagnosis methods of hepatitis C established in recent years are an important breakthrough, and they are: (1) Hepatitis C (anti-HCV) test inclusive of radio-immuno-assay (RIA) and Enzyme linked immunosorbent assay (ELLSA). The second generation of anti-HCV widely adopted at present in clinical test enjoys good sensibility and specificity and is helpful in diagnosing hepatitis C and simple in operation. But it has also its disadvantage, namely, the ratios of false positive and false negative are rather high and the diagnosis rate is rather low, with G type immune globulin (IgG) unable to show whether the disease is acute or chronic, whether a person is a HCV carrier and whether there are memory reaction and infectivity. It is reported that the third generation of Enzyme linked immune reagent for anti-HCV test will be soon developed. (2) Recombined immune blot assay (RIBA): it is in nature equal to simultaneous test of 2-4 anti-HCV, and its significance lies in the confirmation of HCV infection and so it is called confirmation test by some people. Now the applied in clinical test is the second generation of RIBA, the major disadvantage of which is still unable to distinguish between stages of infection and complicated. (3) Polymerase chain reaction (PCR) test of HCV Ribonucleic acid (HCVRNA). The above-mentioned anti-HCV test is easy to operated, but it has disadvantage, therefore, it is essential to test directly causative agent. Compared with anti-HCV test, HCVRNA test with PCR has the following advantages: ¢Ù It is possible to obtain a reliable index whether there is infection, and test positive means there are viruses and infection; ¢Ú with good specificity and high sensibility, it can detect HCV infection of HCV positive and hepatitis C patient of anti-HCV negative; ¢Û wide in use, it can be applied to evaluate curative effect but also with limitation. (4) Others: HCV antibody M type immune globulin (HCV IgM) test, HCV antigen test, reversed passive hemagglutination test and its neutralization test, all of them have certain diagnosis significance.?
6.What are the pathologic features and pathogenesis of hepatitis C?
Answer: Hepatitis C has many specific changes in pathology. (1) Lymphocyte concentration in portal area, leading to the formation of lymphoid follicle; denaturalization of bile duct epithelial cell with large area of lymphocyte infiltration. This serious portal area inflammation and bile duct injury are important marks of chronicity of hepatitis C. (2) The infiltration of liver mid-sinus inflammation cells does not involve the peri-sinus liver cells. This is a feature that distinguishes hepatitis C from hepatitis B, which is often accompanied with peri-sinus cell acidophilic degeneration and necrosis. (3) The liver cell degeneration and necrosis are mild in the lobulus pulmonis. (4) The fibrosis of peri-sinus and liver cell intervals is more distinct and appears earlier than hepatitis B. This is perhaps one of the reasons why hepatitis C is more prone to develop into hepatocirrhosis. (5) Liver cell fat degeneration is commonly seen. Hepatitis C is a disease with a predominance of liver cell injury, and the mechanism of liver cell damage is ¢Ù HCV directly damages liver cells. The virus, in the course of its replication, directly damages the cell organ of liver cells, promoting the permeability of transaminase in the cell membrane. ¢Ú Experimentation shows that immunity if a major cause in liver cell injury, and especially, cell immunity may be an important factor that leads to the injury of liver cells by HCV. The liver cell death caused by HCV takes two forms, e.g. necrosis and withering. In addition, the tumor necrosis factor (TNF) of hepatitis C patients is always high and this can also promote further injury of liver cells. In short, the mechanism of liver cells being damaged by HCV is not a simple, but a complicated one, including the change of penetration and physiological function of liver cells.
7. What is the meaning of hepatitis C antibody (anti-HCV) positive while HCV Ribonucleic acid (HCV-RNA) negative of the serum?
Answer: When anti-HCV positive while HCV RNA negative appears in serologic test, the false negative in anti-HCV test should be first excluded in connection with clinical manifestations, and then consider the following possibilities: (1) The recovery stage of acute hepatitis C: in this period, HCV stops replicating and so HCV RNA turns negative while HCV can exist for a period of time. (2) Chronic Hepatitis C: High titer anti-HCV is closely correlated with HCV RNA and often means the replication of HCV is infectious. But it is also possible that HCV continues present in the liver, while viremia is in a fluctuating state, namely, HCV RNA in the serum rises and falls as a wave, and when the HCV RNA is at the trough (concentration is very low), HCV RNA can be tested negative. Therefore, HCV RNA should be followed and re-examined.
8. What is the meaning of hepatitis C antibody (anti-HCV) negative while HCV Ribonucleic acid (HCV-RNA) positive of the serum?
Answer: When anti-HCV negative while HCV RNA positive appears in serologic test, the following possibilities should be considered: (1) The early stage of acute hepatitis C: in this period, although the viremia appears and HCV RNA is positive, the anti-HCV in the serum usually doesn¡¯t appear or is of low titer, and the HCV in the serum is tested negative. (2) HCV infection of persons with low immune response: taking the patients of liver transplant or kidney transplant for example, because they have taken immuno-inhibitor for a long time, their immune response to hepatitis c antigen is low and serum anti-HCV is often negative, while viremia is present. Therefore, the serum anti-HCV is negative, but HCV RNA is positive. This situation can be found in mother-to-child-transmission of HCV with active antibody response being lowered or delayed after the disappearance of antibodies input passively. This situation can also be found in about 1/4 patients who have suffered from chronic nephrasthenia after hemodialysis and infected with HCV.??
9. What can be done if serum anti-HCV is positive while liver function is normal?
Answer: For the persons whose serum anti-HCV is tested positive but liver function is normal, they should be further examined and observed because simple anti-HCV positive might be false positive or hepatitis C has already been recovered. It has been reported that for a few hepatitis C patients, their anti-HCV remains as long as 9 years. Therefore, it is advisable to have HCV RNA in the blood of the patient tested with PCR and the liver function continuously observed. If the liver function continues to be normal, it is not necessary to be treated, but if the liver function is abnormal (such as ALT continuous to be high and those having history of blood transfusion and operation), anti-virus treatment should be considered, and especially HCV RNA is tested positive.
10. What is the similarity between hepatitis C and hepatitis B?
Answer: (1) The clinical manifestations of hepatitis C are similar to that of hepatitis B, but the cases without symptom and jaundice are more than that of hepatitis B. Some patients are not easy to be found and diagnosed except that liver function is periodically tested. (2) The transmission forms of hepatitis C are similar to that of hepatitis B, and both can be transmitted through transfusion of blood and blood products, hemodialysis and intravenous drug injection. (3) Similar to hepatitis B, HCV carriers without symptoms are also can be seen. Study shows that blood donators who carry HCV but without symptoms can transmit hepatitis C to blood receivers, and the blood collected continuously from a blood donator for 6 years can infect chimpanzee, indicating that chronic HCV can also be carried for a long time, and its carrying rate is even higher than that of hepatitis B. (4) Both hepatitis C and hepatitis B can develop into chronic hepatitis and liver cirrhosis, and the incidence of hepatitis C is higher than that of hepatitis B. (5) Similar to hepatitis B, hepatitis C can also develop into primary liver cancer. (6) Hepatitis C can also be transmitted through sexual contact and from an infected woman to her child, but the probability is lower than hepatitis B.
11. How to prevent hepatitis C?
Answer: At present, hepatitis C in our country is mainly caused by the transfusion of blood and blood products. Therefore, it is important to strengthen the management of blood products for the prevention of Hepatitis C. For the screening of blood donators, hepatitis C antibody test and ALT test must be conducted; single serum sampling and blood returning cell method adopted by blood stations should be controlled, which was populated in 1993 in Nanjing, and since then, the incidence of Hepatitis C has been declined; Someone claims that the blood of donators with the activity of imidoxanthin deoxydation enzymes of 5.0 ISU/L AND HBc positive should not be put into another person¡¯s blood; Before transfusion, re-examination of anti-HCV can lower the incidence of Hepatitis C; Patients should reduce blood transfusion as much as possible, and if possible, should use the blood of voluntary donator instead of professional donator; The patient who shall be operated on schedule should consider to use ¡°self-deposited blood¡±, e.g. drawing his own blood and refrigerating it a month before operation for his own use later; When injection is necessary either for prevention or for treatment, aseptic technique should be strictly adopted with a tube and a needle only for a single person and disposable injector used. According to the experiences of Gu¡¯an County in Hebei Province, blood station should adopt disposable serum sampling and blood returning apparatus.? Because hepatitis C can be transmitted vertically, blocking mother-child transmission is also a measure in preventing Hepatitis C. At present, Hepatitis C vaccine has been successfully developed, and should be used to inoculation. If the husband or the wife is a Hepatitis C patient, they should avoid saliva exchange, and in sexual life, condom should be adopted. But they should not be excessive nervous about it, because heterosexual contact is not the major route of HCV transmission. Besides, strictly checking intravenous injection and paying attention to hygiene is also one of the measures in prevention of Hepatitis C.