Hepatitis C

Description: Viral hepatitis type C (HC) is a disease caused by hepatitis C virus (HCV) infection, mainly through blood-borne transmission. Clinical manifestations include fever, gastrointestinal symptoms and abnormal liver function. Similar to hepatitis B, but lighter. Most cases are subclinical and chronic, which can lead to fulminant hepatic failure. More common in people infected with other viruses. (A) the cause of the disease HCV is a type of hepatitis virus transmitted by blood. In 1989, Chiron Corporation of the United States applied molecular cloning technology to successfully clone (HCV) cDNA. HCV is the first human virus discovered using molecular biology techniques. HCV belongs to the family of togavirus, its biological traits, and its genetic structure is similar to that of flavivirus and prion. It has been confirmed that HCV is a spherical particle containing a lipid outer shell and has a diameter of 30 to 60 nm. The HCV genome is a long positive-strand, single-stranded RNA of approximately 9.5 Kb in length. The HCV genome has a large open reading frame (ORF) encoding a 3010 or 3011 amino acid polyprotein. The encoded polyprotein bodies have a distinct common structure with flaviviruses: structural proteins (including core and envelope proteins) and non-structural proteins (NS1-NS5). HCV is an RNA virus, which is relatively easy to mutate. Only 68.1% to 91.8% of the nucleotides in different regions are identical, and can be divided into different genotypes according to the difference in HCV gene sequence. At present, there is no uniform standard and uniform method for HCV genotyping. Okamoto divides HCV into four genotypes I, II, III and IV. According to its classification, most North American and European HCV strains belong to type I. Japan is mainly type II, and there are also type III and type IV. According to Wang Yu's report in China, the northern cities are mainly type II and III, while the southern cities are more than 90% type II. (B) pathogenesis 1. Direct pathogenesis of HCV infection Many studies have shown that the severity of liver tissue inflammation in HCV-infected patients is related to viremia. The correlation between the severity of liver tissue inflammation and the level of HCV RNA in hepatocytes in patients with chronic hepatitis C is more strongly correlated with serum HCV RNA levels. After treatment with interferon, serum ALT levels gradually decreased with the decrease of serum HCV RNA content. The above results suggest that HCV may have direct pathogenic effects. However, immunohistochemical studies have not fully demonstrated that the expression of HCV antigen in liver tissue is associated with inflammatory activity in liver disease. Groff and other studies have found that the presence of HCV antigen in hepatocytes does not necessarily indicate the presence of hepatocytes. HCV granules, liver disease inflammatory activity is not necessarily related to hepatocyte HCV antigen expression, and liver tissue inflammation is associated with the presence of HCV virions in hepatocytes, indicating that HCV has a direct cytopathic effect. The direct pathogenic effect of HCV may be related to the replication of HCV in hepatocytes, causing changes in the structure and function of hepatocytes, or interfering with hepatocyte degeneration and necrosis caused by protein synthesis in hepatocytes. The presence of HCV asymptomatic carriers seems to imply HCV. No direct pathogenic effects. However, most of the "chronic HCV carriers" liver tissues with normal ALTs have been reported to have different degrees of lesions and inflammation. The degree of liver tissue inflammation is related to the level of HCV replication, indicating that asymptomatic carriers are rare and further support HCV has a direct pathogenic effect. 2. Cell-mediated immune damage may be the main cause of liver disease caused by HCV. One of the important features of hepatitis C liver histopathology is the accumulation of lymphocytes in the portal area, sometimes forming lymphoid follicles. Hepatitis is obvious, and lymphocyte infiltration is undoubtedly related to immune response. Some scholars have shown that the lymphocytes infiltrated in chronic hepatitis C are mainly CD8+ cells, many of which have active epitopes, which are shown to be activated. Under the electron microscope, lymphocytes were observed to be in close contact with hepatocytes, suggesting that it is toxic to hepatocytes. In vitro tests by Mondelli et al have confirmed that cytotoxic T cells of chronic non-A, non-B hepatitis have increased toxicity to autologous hepatocytes. In chronic hepatitis C, cytotoxicity is mainly caused by T cells. In contrast, in patients with autoimmune hepatitis, immune effector cells are restricted to non-T lymphocytes. In chronic HBV infection, both non-T and T lymphocytes are involved in hepatocyte injury. HCV-specific antigens activate CD8+ and CD56+ cells, suggesting that CD56+ cells also play an important role in the pathogenesis of chronic hepatitis C. Intrahepatic T cells of patients with chronic hepatitis C can recognize multiple antigenic determinants of protein C, E1 and E2/NS1 proteins of HCV. This recognition is restricted by HLA class I and also indicates the pathogenesis of Tc cells in chronic hepatitis C. It plays a role. Other studies have shown that most of the chronic HCV-infected patients with peripheral blood and liver tissue restricted by HLA-II molecules CD4+ cells (TH-1 cells) can attack HCV-specific immune antigenic determinants, CD4+ cells to HCV core antigen The response is related to liver inflammatory activity, and TH-1 cells play a key role in chronic hepatitis C. The HCV-specific TH cell surface antigenic determinant enhances the specific response of Tc cells to HCV antigen, suggesting that TH cells can assist and enhance Tc cell attack to destroy HCV-infected hepatocytes. The E1 and E2/NS of HCV RNA are hypervariable regions, which are easily mutated in vivo and can cause changes in the target antigen (E1, E2/NS protein) of the hepatocyte membrane of HCV-infected patients, and Tc cells will be recognized again. Emerging antigenic determinants attack and destroy liver cells, which is why the higher the HCV RNA mutation rate, the more serious the liver tissue inflammation. It also suggests that immune-mediated mechanisms play an important role in hepatocyte injury in chronic HCV-infected individuals. 3. Autoimmune HCV infection is often accompanied by the following characteristics: 1 non-specific immune disorder, such as mixed condensed globulinemia, Sjogren's syndrome and thyroiditis; 2 serum can detect non-specific autoantibodies, such as rheumatoid factor , anti-nuclear antibody and anti-smooth muscle antibody; 3 part of type II autoimmune hepatitis [anti-liver kidney microsomal type I antibody (anti-C-LKM-1 antibody) positive] may appear anti-HCV positive; 4 may appear anti-GOR 5 liver histological changes are similar to autoimmune liver disease, so it is speculated that the pathogenesis of HCV infection may involve autoimmune factors. However, the relationship between anti-HCV, anti-LKM-1 and anti-GOR, and its pathogenic significance need to be further studied. 4. Significance of apoptosis in the pathogenesis of hepatitis C Apoptosis is mediated by Fas antigen on the surface of cell membrane, and Hiramatsu et al. confirmed that Fas antigen is not expressed in normal liver tissue. When infected with HCV, Fas antigen is more common in Liver tissue with active lesions, especially around the portal area. The expression of Fas antigen in HCV-infected patients is closely related to the degree of liver tissue necrosis and inflammation, and the expression of hepatocyte HCV core antigen. This indicates that Fas-mediated apoptosis is one of the forms of HCV-infected hepatocyte death. The pathogenesis of HCV infection is complex, and many factors and their interrelationships need further study and clarification. Compared with other types of hepatitis, hepatitis C has its characteristic pathological changes, mainly including the following: 1 lymphocyte agglomeration in the portal area and Poulsen-Christoffersen type cholangitis (biliary epithelial cell degeneration, surrounded by a large number of lymphocytic infiltration) ) is an important feature and has diagnostic value. 2 Early cases showed sinusoidal cell infiltration, but did not affect the liver cells around the sinus is the important difference between acute hepatitis B. 3 Hepatocyte necrosis is lighter, the range is limited, and it appears later. 4 sinus and hepatocyte interstitial fibrosis is more obvious than hepatitis B, and appears earlier, which may be one of the reasons for the development of cirrhosis. 5 Hepatocyte steatosis is more common, fat vacuoles can be macrobubble or vesicular. 6 Hepatocyte eosinophilic changes are flaky and appear in the non-inflammatory response zone. Symptoms: [clinical manifestations] 1. Incubation period The incubation period of this disease is 2 to 26 weeks, with an average of 7.4 weeks. Hepatitis C caused by blood products has a short incubation period of 7 to 33 days, with an average of 19 days. 2. Clinical clinical manifestations are generally lighter than hepatitis B, mostly subclinical without jaundice, common single ALT is elevated, long-term persistence does not drop or repeated fluctuations, the average ALT and serum bilirubin are lower, jaundice persists The time is short. However, there are also serious illnesses, and the clinical difficulty is different from hepatitis B. Hepatitis C virus infection is more chronic than hepatitis B virus infection. It has been observed that about 40% to 50% develop into chronic hepatitis, 25% develop into cirrhosis, and the rest is self-limiting. Most patients with acute hepatitis C develop chronically without jaundice. The long-term fluctuation of ALT does not decrease, and serum anti-HCV continues to be high titer positive. Therefore, clinical attention should be paid to the observation of changes in ALT and anti-HCV. Although the clinical manifestations of hepatitis C are mild, the incidence of severe hepatitis can also be seen. Five hepatitis viruses, HAV, HBV, HCV, HDV and HEV, can cause severe hepatitis, but the background and frequency of occurrence are different. Statistics from Europe and the United States indicate that the causes of acute and subacute severe hepatitis are: HBV is the most common, and Japan is mostly HCV. It is speculated that the reason may be that the HCV infection rate in Japanese population is much higher than that in Europe and America, and the HCV genotype in Europe and America is different from that in Japan. There is no detailed information in China. Most of the reports are mostly HBV. HCV-induced severe hepatitis is mostly caused by chronic hepatitis B and HCV infection. 3. Pattern of viremia A follow-up study of patients with hepatitis C after transfusion showed that HCVemia has the following patterns: (1) Acute self-limiting hepatitis with transient viremia. (2) Acute self-limiting hepatitis with persistent viremia. (3) persistent viremia but no hepatitis, as a symptomatic carrier of HCV. (4) Chronic hepatitis C with intermittent viremia. (5) Chronic hepatitis C with persistent viremia. 4. Overlap infection of HBV and HCV Because HCV has a similar transmission route to HBV, the possibility of infecting both viruses is present, but it is more common to infect HCV on the basis of persistent HBV infection. The 302 Hospital of the People's Liberation Army found that the anti-HCV positive rate in the serum of patients with HBsAg-positive chronic liver disease was 0 (0/14) in mild chronic hepatitis (slow-moving liver); 24.24% (8/33) in chronic active hepatitis; chronic heavy Hepatitis was 33.33% (3/9). It shows that the positive rate increases with the progress and evolution of hepatitis B. It is speculated that the reason may be due to the increased chance of receiving iatrogenic infections such as blood transfusion during the progression of chronic hepatitis B. On the other hand, there are reports that there is a significant difference between the severe hepatitis with HBV/HCV overlap infection and the severe hepatitis with HBV infection alone, and the bilirubin, AST/ALT and mortality rates of the two groups. It indicated that hepatocyte necrosis in the overlapping infection group was much more serious than that in severe hepatitis with HBV infection alone. It has been observed that HBV DNA and HCV RNA in HBV and HCV overlap cases are only 19% positive, and most of them are HCV RNA or HBV DNA single positive. In addition, almost all HCV RNA positive patients are e antigen negative cases, suggesting that the virus overlaps. The infection is proliferating and interfering. 5. HCV infection and hepatocellular carcinoma (HCC) Read more...

Disease Name: Introduction to Hepatitis C: Viral hepatitis type C (HC is referred to as hepatitis C), a disease caused by hepatitis C virus (HCV) infection, mainly through blood-borne transmission. Clinical manifestations include fever, gastrointestinal symptoms and abnormal liver function. Similar to hepatitis B, but lighter. Most cases are subclinical and chronic, which can lead to fulminant hepatic failure. More common in people infected with other viruses. Causes: (1) Causes of the disease HCV is a type of hepatitis virus that is transmitted by blood. In 1989, Chiron Corporation of the United States applied molecular cloning technology to successfully clone (HCV) cDNA. HCV is the first human virus discovered using molecular biology techniques. HCV belongs to the family of togavirus, its biological traits, and its genetic structure is similar to that of flavivirus and prion. It has been confirmed that HCV is a spherical particle containing a lipid outer shell and has a diameter of 30 to 60 nm. The HCV genome is a long positive-strand, single-stranded RNA of approximately 9.5 Kb in length. The HCV genome has a large open reading frame (ORF) encoding a 3010 or 3011 amino acid polyprotein. The encoded polyprotein bodies have a distinct common structure with flaviviruses: structural proteins (including core and envelope proteins) and non-structural proteins (NS1-NS5). HCV is an RNA virus, which is relatively easy to mutate. Only 68.1% to 91.8% of the nucleotides in different regions are identical, and can be divided into different genotypes according to the difference in HCV gene sequence. At present, there is no uniform standard and uniform method for HCV genotyping. Okamoto divides HCV into four genotypes I, II, III and IV. According to its classification, most North American and European HCV strains belong to type I. Japan is mainly type II, and there are also type III and type IV. According to Wang Yu's report in China, the northern cities are mainly type II and III, while the southern cities are more than 90% type II. (B) pathogenesis 1. Direct pathogenesis of HCV infection Many studies have shown that the severity of liver tissue inflammation in HCV-infected patients is related to viremia. The correlation between the severity of liver tissue inflammation and the level of HCV RNA in hepatocytes in patients with chronic hepatitis C is more strongly correlated with serum HCV RNA levels. After treatment with interferon, serum ALT levels gradually decreased with the decrease of serum HCV RNA content. The above results suggest that HCV may have direct pathogenic effects. However, immunohistochemical studies have not fully demonstrated that the expression of HCV antigen in liver tissue is associated with inflammatory activity in liver disease. Groff and other studies have found that the presence of HCV antigen in hepatocytes does not necessarily indicate the presence of hepatocytes. HCV granules, liver disease inflammatory activity is not necessarily related to hepatocyte HCV antigen expression, and liver tissue inflammation is associated with the presence of HCV virions in hepatocytes, indicating that HCV has a direct cytopathic effect. The direct pathogenic effect of HCV may be related to the replication of HCV in hepatocytes, causing changes in the structure and function of hepatocytes, or interfering with hepatocyte degeneration and necrosis caused by protein synthesis in hepatocytes. The presence of HCV asymptomatic carriers seems to imply HCV. No direct pathogenic effects. However, most of the "chronic HCV carriers" liver tissues with normal ALTs have been reported to have different degrees of lesions and inflammation. The degree of liver tissue inflammation is related to the level of HCV replication, indicating that asymptomatic carriers are rare and further support HCV has a direct pathogenic effect. 2. Cell-mediated immune damage may be the main cause of liver disease caused by HCV. One of the important features of hepatitis C liver histopathology is the accumulation of lymphocytes in the portal area, sometimes forming lymphoid follicles. Hepatitis is obvious, and lymphocyte infiltration is undoubtedly related to immune response. Some scholars have shown that the lymphocytes infiltrated in chronic hepatitis C are mainly CD8+ cells, many of which have active epitopes, which are shown to be activated. Under the electron microscope, lymphocytes were observed to be in close contact with hepatocytes, suggesting that it is toxic to hepatocytes. In vitro tests by Mondelli et al have confirmed that cytotoxic T cells of chronic non-A, non-B hepatitis have increased toxicity to autologous hepatocytes. In chronic hepatitis C, cytotoxicity is mainly caused by T cells. In contrast, in patients with autoimmune hepatitis, immune effector cells are restricted to non-T lymphocytes. In chronic HBV infection, both non-T and T lymphocytes are involved in hepatocyte injury. HCV-specific antigens activate CD8+ and CD56+ cells, suggesting that CD56+ cells also play an important role in the pathogenesis of chronic hepatitis C. Intrahepatic T cells of patients with chronic hepatitis C can recognize multiple antigenic determinants of protein C, E1 and E2/NS1 proteins of HCV. This recognition is restricted by HLA class I and also indicates the pathogenesis of Tc cells in chronic hepatitis C. It plays a role. Other studies have shown that most of the chronic HCV-infected patients with peripheral blood and liver tissue restricted by HLA-II molecules CD4+ cells (TH-1 cells) can attack HCV-specific immune antigenic determinants, CD4+ cells to HCV core antigen The response is related to liver inflammatory activity, and TH-1 cells play a key role in chronic hepatitis C. The HCV-specific TH cell surface antigenic determinant enhances the specific response of Tc cells to HCV antigen, suggesting that TH cells can assist and enhance Tc cell attack to destroy HCV-infected hepatocytes. The E1 and E2/NS of HCV RNA are hypervariable regions, which are easily mutated in vivo and can cause changes in the target antigen (E1, E2/NS protein) of the hepatocyte membrane of HCV-infected patients, and Tc cells will be recognized again. Emerging antigenic determinants attack and destroy liver cells, which is why the higher the HCV RNA mutation rate, the more serious the liver tissue inflammation. It also suggests that immune-mediated mechanisms play an important role in hepatocyte injury in chronic HCV-infected individuals. 3. Autoimmune HCV infection is often accompanied by the following characteristics: 1 non-specific immune disorder, such as mixed condensed globulinemia, Sjogren's syndrome and thyroiditis 2 serum can detect non-specific autoantibodies, such as rheumatoid factor, Anti-nuclear antibody and anti-smooth muscle antibody 3 part type II autoimmune hepatitis [anti-liver kidney microsomal type I antibody (anti-C-LKM-1 antibody) positive] may appear anti-HCV positive 4 may appear anti-GOR; 5 liver Histological changes are similar to autoimmune liver disease, so it is speculated that the pathogenesis of HCV infection may involve autoimmune factors. However, the relationship between anti-HCV, anti-LKM-1 and anti-GOR, and its pathogenic significance need to be further studied. 4. Significance of apoptosis in the pathogenesis of hepatitis C Apoptosis is mediated by Fas antigen on the surface of cell membrane, and Hiramatsu et al. confirmed that Fas antigen is not expressed in normal liver tissue. When infected with HCV, Fas antigen is more common in Liver tissue with active lesions, especially around the portal area. The expression of Fas antigen in HCV-infected patients is closely related to the degree of liver tissue necrosis and inflammation, and the expression of hepatocyte HCV core antigen. This indicates that Fas-mediated apoptosis is one of the forms of HCV-infected hepatocyte death. The pathogenesis of HCV infection is complex, and many factors and their interrelationships need further study and clarification. Compared with other types of hepatitis, hepatitis C has its characteristic pathological changes, mainly the following: 1 Lymphocyte cluster accumulation in the portal area and Poulsen-Christoffersen type cholangitis (biliary epithelial cell degeneration, surrounded by a large number of lymphocytic infiltration ) is an important feature and has diagnostic value. 2 Early cases showed sinusoidal cell infiltration, but did not affect the liver cells around the sinus is the important difference between acute hepatitis B. 3 Hepatocyte necrosis is lighter, the range is limited, and it appears later. 4 sinus and hepatocyte interstitial fibrosis is more obvious than hepatitis B, and appears earlier, which may be one of the reasons for the development of cirrhosis. 5 Hepatocyte steatosis is more common, fat vacuoles can be macrobubble or vesicular. 6 Hepatocyte eosinophilic changes are flaky and appear in the non-inflammatory response zone. Symptoms: [clinical manifestations] 1. Incubation period The incubation period of this disease is 2 to 26 weeks, with an average of 7.4 weeks. Hepatitis C caused by blood products has a short incubation period of 7 to 33 days, with an average of 19 days. 2. Clinical clinical manifestations are generally lighter than hepatitis B, mostly subclinical without jaundice, common single ALT is elevated, long-term persistence does not drop or repeated fluctuations, the average ALT and serum bilirubin are lower, jaundice persists The time is short. However, there are also serious illnesses, and the clinical difficulty is different from hepatitis B. Hepatitis C virus infection is more chronic than hepatitis B virus infection. It has been observed that about 40% to 50% develop into chronic hepatitis, 25% develop into cirrhosis, and the rest is self-limiting. Most patients with acute hepatitis C develop chronically without jaundice. The long-term fluctuation of ALT does not decrease, and serum anti-HCV continues to be high titer positive. Therefore, clinical attention should be paid to the observation of changes in ALT and anti-HCV. Although the clinical manifestations of hepatitis C are mild, the incidence of severe hepatitis can also be seen. Five hepatitis viruses, HAV, HBV, HCV, HDV and HEV, can cause severe hepatitis, but the background and frequency of occurrence are different. Statistics from Europe and the United States indicate that the causes of acute and subacute severe hepatitis are: HBV is the most common, and Japan is mostly HCV. It is speculated that the reason may be that the HCV infection rate in Japanese population is much higher than that in Europe and America, and the HCV genotype in Europe and America is different from that in Japan. There is no detailed information in China. Most of the reports are mostly HBV. HCV-induced severe hepatitis is mostly caused by chronic hepatitis B and HCV infection. 3. Pattern of viremia A follow-up study of patients with hepatitis C after transfusion showed that HCVemia has the following patterns: (1) Acute self-limiting hepatitis with transient viremia. (2) Acute self-limiting hepatitis with persistent viremia. (3) persistent viremia but no hepatitis, as a symptomatic carrier of HCV. Read more...