Hepatitis C, Chronic

Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Treatment includes direct-acting antiviral drugs and other agents, depending on the genotype; permanent elimination of detectable viral RNA is possible.

See also causes of hepatitis, overview of chronic hepatitis, and acute hepatitis C.)

Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Treatment includes direct-acting antiviral drugs and other agents, depending on the genotype; permanent elimination of detectable viral RNA is possible. See also causes of hepatitis, overview of chronic hepatitis, and acute hepatitis C.) Hepatitis A, which is more than 6 months, is usually defined as chronic hepatitis, although this time is arbitrary. There are 6 main genotypes of the hepatitis C virus (HCV), which vary in their response to treatment. Genotype 1 is more common than genotypes 2, 3, 4, 5 and 6; it represents 70-80% of cases of chronic hepatitis C in the United States. Acute Hepatitis C becomes chronic in about 75% of patients. The Centers for Disease Control and Prevention (CDC) estimate that about 2.8 million people in the US have chronic hepatitis C infection. Chronic hepatitis C develops which often develops over decades in 20-30% of patients to cirrhosis. In HCV-infected liver hepatocellular carcinoma can develop, usually the cancer education goes cirrhosis development ahead (unlike HBV infection). Clinical Calculator: cirrhosis probability in hepatitis C symptoms and complaints, many patients are asymptomatic and have no jaundice, although some among malaise, suffer loss of appetite, fatigue and nonspecific abdominal pain. And often the first sign the chronic liver disease (eg. B. splenomegaly, spider angiomas, palmar), or complications of cirrhosis (z. B. portal hypertension, ascites, encephalopathy), respectively. Chronic hepatitis C is occasionally connected to a Lichen planus, a mucocutaneous vasculitis, glomerulonephritis, porphyria cutanea tarda, and probably a non-Hodgkin’s B-cell lymphoma. Diagnosis Serological tests The diagnosis of chronic hepatitis is suspected in patients with suspicious symptoms and signs, coincidentally noticed transaminase elevations or earlier diagnosed acute hepatitis. The diagnosis is ? 6 months after the initial infection confirmed by the finding of positive anti-HCV and positive HCV RNA (see Table: hepatitis C serology). Hepatitis C serology markers Acute HCV infection Chronic HCV infection Previous HCV infection * Anti-HCV + + + HCV RNA + + – * patients who had HCV infection and are spontaneously cured or treated successfully. Anti-HCV = Antibodies to HCV; HCV = hepatitis C virus. A liver biopsy is performed from one or more of the following reasons: To evaluate the inflammatory activity of fibrosis or progression of the disease (which can sometimes help determine which patients are treated and when) the exclusion of other causes of liver disease, but strengthened the role of liver biopsy in hepatitis C, and biopsy is replaced by non-invasive imaging (eg. as ultrasound elastography, magnetic resonance elastography) and serum markers of fibrosis as well as fibrosis scoring systems based on serological markers. The HCV genotype is determined prior to treatment because of the genotype influences the course, the duration and success of the treatment. HCV RNA detection and quantitation may be used to diagnose hepatitis C, and to evaluate the response to treatment during and after treatment. In most currently available quantitative HCV RNA analyzes, the lower limit of detection is at least <50 IU / mL. If a quantitative analysis does not have this level of sensitivity, qualitative analysis can be used. Qualitative tests can detect very low levels of HCV RNA that are often as low as <10 declare IU / ml and results as positive or negative. Qualitative tests can be used to confirm a diagnosis of hepatitis C or a sustained virologic response (SVR), defined as no detectable HCV-RNA 12 and 24 weeks after the cessation of treatment, depending on the drug regimen used. (See also the American Association for Study of Liver Disease practice guideline Diagnosis, Management, and Treatment of Hepatitis C and the US Preventive Services Task Force clinical guideline screening for hepatitis C in Adults.) Other function tests Liver function tests be determined if that was not has happened before. These include serum transaminases (ALT and AST), alkaline phosphatase and bilirubin. Other tests should be performed to assess the severity of the disease; they include serum albumin, platelet count and PT / INR. Patients should be tested for HIV and hepatitis B infection, since the transmission of these infections is similar. A high rheumatoid factor and low complement levels are suggestive of cryoglobulinemia. If symptoms or signs of cryoglobulinemia occur in the course of chronic hepatitis C, especially for HCV infection, provisions of Kryoglobulins and rheumatoid factor should be performed werden.Screening complications in patients with chronic HCV infection and advanced fibrosis or cirrhosis should every 6 months are checked for the presence of hepatocellular carcinoma by sonography and determination of alpha-fetoprotein in the serum, although the cost-effect of this approach is discussed. Prognosis The prognosis depends on whether patients have a SVR (d. E. No detectable HCV-RNA after 12 and 24 weeks after cessation of treatment, depending on the drug treatment). Patients with SVR have a> 99% chance of remaining HCV RNA negative and are typically cured. Nearly 95% of patients with SVR have improved histological findings, including fibrosis and histological activity index; Moreover, the risk of progression towards cirrhosis, liver failure and liver-related deaths has been reduced. In patients with cirrhosis and portal hypertension who were treated with interferon-based therapies has been shown that SVR reduces portal pressure and significantly reduced the risk of hepatic decompensation and for death related to liver, all-cause mortality and hepatocellular carcinoma (1) , to achieve an SVR with interferon-based therapies, is more likely if ? 1 of the following are present: Genotype other Low as genotype 1 treatment of viral load age <40 years body weight <75 kg No bridge fibrosis or cirrhosis of origin other than African American No hepatic or insulin resistance the probability to reach the occurrence of an SVR with new interferon-free regimens appears to depend mainly of the following: pre-treatment viral load degree of liver fibrosis in response to previous therapy Note to forecast 1. van der Meer AJ, veldt BJ, field JJ, et al: Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 308 (24): 2584-2593, 2012. Therapy Direct acting antivirals Sometimes with pegylated interferon (IFN) and / or ribavirin overview of HCV treatment (See also the American Association for Study of Liver Disease [AASLD] practice guidelines Recommendations . for Testing, managing, and treating hepatitis C and the AASLD / Infectious Disease Society of America guidelines when and in Whom to Initiate HCV therapy) in chronic hepatitis C treatment is a therapy appears if both of the following are present: the aminotransferase are high. Biopsy shows an active inflammatory disease with evolving fibrosis. The therapy aims to eliminate the HCV RNA permanently (known as SVR), which is associated with a permanent normalization of transaminases and a stoppage of histological damage. The treatment results are more favorable in patients with only moderate fibrosis and a viral load of <600,000 to 800,000 I.U./ml than in patients with cirrhosis and a viral load of> 800,000 I.U./ml. Until late in the year 2013, all genotypes were treated with pegylated IFN-alpha plus ribavirin. Now, most patients are treated with antiviral drugs (direct-acting antiviral drugs [DAA]), the specific HCV targets, such as proteases or polymerases affect (Hepatitis C, Chronic: HCV genotype 1 and Hepatitis C, Chronic: HCV genotypes 2, 3, 4, 5 and 6). Telaprevir and boceprevir: 1st generation protease inhibitors having activity against HCV genotype 1 Simeprevir: against a polymerase inhibitor with activity: genotype 1-specific protease inhibitor of the second generation sofosbuvir which are used to treat HCV are DAA, HCV genotypes 1 to 6 Paritaprevir: A protease inhibitor Ledipasvir: A protease inhibitor Dasabuvir: A polymerase inhibitor Ombitasvir: an inhibitor of the viral non-structural protein 5A (NS5A inhibitor) daclatasvir: a NS5A inhibitor Elbasvir: a NS5A inhibitor Grazoprevir: A protease inhibitor telaprevir, boceprevir and Simeprevir be given along with pegylated IFN and ribavirin. Sofosbuvir can be used without interferon; it may be administered (for genotypes 1 to 3) in all oral regimens with ribavirin (genotypes 1 to 6), Simeprevir (genotype 1) or Daclatasvir. Ledipasvir sofosbuvir and are available in a single pill to treat HCV genotypes 1, 4 and 6. FIG. Elbasvir / Grazoprevir in a single pill is used to treat HCV genotypes 1 and 4. FIG. The following 5-drug treatment is effective against genotypes 1 and 4: Paritaprevir / ritonavir / Ombitasvir (in a single pill) once / day Dasabuvir, twice / day ribavirin, twice / day Paritaprevir / ritonavir / ombitasvir plus Dasabuvir are in a single package. Ritonavir increases levels of Paritaprevir, but has no direct antiviral activity. Ribavirin is often used with DAA. Because more and more DAAs evolve quickly arise current recommendations for HCV treatment. Recommendations for testing, handling and treatment of hepatitis C are often used by the American Association for the Study of Liver Disease (AASLD) and the Infectious Diseases Society of America (IDSA), available online, updated. Decompensated cirrhosis due to hepatitis C is the most common indication for liver transplantation in the United States. HCV versa almost everywhere in the graft back, and the probability of survival of the patient and the graft is less than with the transplantation of other indications. Many DAA and interferon-free regimen used in studies in patients with hepatitis C and after liver transplantation. If DAAs are used, the SVR rate exceeds in patients with liver transplantation 95%, regardless of whether they have cirrhosis or nicht.HCV genotype 1 1 genotype resistant to the dual treatment with pegylated IFN-alpha and ribavirin than other genotypes. If any of the following done, the rate of SVR of <50% can increase (dual therapy) up to 95%: The addition of a protease inhibitor (telaprevir, boceprevir or Simeprevir) or a polymerase inhibitor (sofosbuvir) for pegylated IFN-alpha and ribavirin using an interferon-free therapy (eg Simeprevir or daclatasvir plus sofosbuvir;. Ledipasvir / or sofosbuvir Elbasvir / Grazoprevir, 5-drug therapy of Paritaprevir / ritonavir / Ombitasvir, Dasabuvir and ribavirin) as first-line treatment Pegylated IFN-alpha2b at a dose of 1.5 mcg / kg sc once a week and [B], pegylated IFN-alpha-2a [/ B] s.c. at a dose of 180 mg once a week give comparable results. The side effects of pegylated IFN-alpha are similar to those of IFN-alpha, but may be less severe. The contraindications are also similar (s. Above). Interferons are no more than first-line treatment of hepatitis C is recommended. For Ribavirin the dosage is 500-600 mg po 2 times a day. Ribavirin is generally well tolerated, but frequently causes anemia due to hemolysis. In these cases, the dose should be reduced if the hemoglobin falls below 10 g / dl. Ribavirin is teratogenic in men and women and requires contraception during treatment and 6 months after completed treatment. Patients who can not tolerate ribavirin, yet pegylated IFN-alpha should be given. Ribavirin not to use, but reduces the likelihood of successful treatment. A ribavirin monotherapy is worthless. First-line treatments for HCV genotype 1 include fixed-dose combination of Ledipasvir 90 mg / 400 mg po sofosbuvir once / day for 8 to 24 weeks, depending on the history of the previous treatment, pretreatment of the viral load and the degree of liver fibrosis fixed-dose combination of Elbasvir 50 mg / Grazoprevir 100 mg p.o. once / day with or without ribavirin 500 to 600 mg p. o. twice / day for 12 to 16 weeks, depending on the previous treatment, the degree of hepatic fibrosis and in patients with genotype 1a, the presence or absence of base NS5A resistance associated variants of Elbasvir fixed-dose combination of Paritaprevir 150 mg / ritonavir 100 mg / Ombitasvir 25 mg once / day plus 250 mg po Dasabuvir twice / day and ribavirin 500 to 600 mg p.o. twice / day for 12 to 24 weeks depending on the degree of liver fibrosis sofosbuvir 400 mg p.o. once / day plus 150 mg po Simeprevir once / day p.o. with or without ribavirin 500 to 600 mg 2 times a day for 12 to 24 weeks, depending on the degree of liver fibrosis sofosbuvir 400 mg po once / day plus daclatasvir 60 mg once / day with or without ribavirin 500 to 600 mg po 2 times a day for 12 to 24 weeks, depending on the degree of liver fibrosis and the history of the treatment Simeprevir anemia and sensitivity to light can cause. All protease inhibitors interact with other Medikamenten.HCV genotypes 2, 3, 4, 5 and 6 In genotype 2 is one of the following is recommended: 400 mg sofosbuvir p.o. po once daily plus 500-600 mg ribavirin 2 times daily for 12 to 24 weeks. Sofosbuvir 400 mg p.o. once / day plus 60 mg po Daclatasvir once / day for 12 to 24 weeks, depending on the degree of liver fibrosis for genotype 3, the first-line treatments include sofosbuvir 400 mg po once / day plus 60 mg po Daclatasvir once / day p.o. with or without ribavirin 500 to 600 mg 2 times a day for 12 to 24 weeks, depending on the degree of liver fibrosis sofosbuvir 400 mg p. o. once / day plus ribavirin 500 to 600 mg po 2 times / day plus weekly pegylated IFN-alpha for 12 weeks for genotype 4, the first-line treatments include Ledipasvir 90 mg / 400 mg po sofosbuvir once / day for 12 weeks Paritaprevir 150 mg / ritonavir 100 mg / 25 mg po Ombitasvir plus Rivabirin 500-600 mg po once daily 2 times daily for 12 weeks Elbasvir 50 mg / 100 mg po Grazoprevir once / day for 12 weeks ABeiGenotypen 5 and 6, the first-line treatment Ledipasvir comprises 90 mg / 400 mg po sofosbuvir once / day for 12 weeks sofosbuvir 400 mg p. o. once / day plus ribavirin 500 to 600 mg po 2 times / day plus weekly pegylated IFN-alpha for 12 weeks Key points A chronic hepatitis C infection develops in 75% of patients with acute infection and leads to cirrhosis in 20-30%. In some patients with cirrhosis further development into a hepatocellular carcinoma occurs. The diagnosis is confirmed by finding of positive anti-HCV and positive HCV RNA; then a biopsy should be performed and the genotype to be determined. The treatment varies depending on the genotype, but includes the use of one or more direct-acting antiviral drugs, sometimes with pegylated IFN and / or ribavirin. New applications can eliminate permanently HCV RNA in many patients. More information Recommendations for Testing, managing, and Treating Hepatitis C When and in Whom to Initiate HCV Therapy screening for hepatitis C in adults

Health Life Media Team

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