HCV Flashcards
What family of viruses does Hepatitis C Virus (HCV) belong to?
Flavivirus
What type of genetic material does HCV have?
Single-stranded RNA (ssRNA)
Is Hepatitis C Virus (HCV) enveloped or non-enveloped?
Enveloped
Can HCV be prevented with a vaccine?
No, there is no vaccine for HCV
Why is there no vaccine effective against HCV?
The tremendous antigenic variety of HCV has significantly slowed efforts to develop an effective vaccine. Hepatitis C virus (HCV) has 6 or more genotypes and multiple subtypes that differ in genomic composition by as much as 30%-35%. This is largely due to the fact that the virion-encoded RNA-dependent RNA polymerase has no proofreading 3’ → 5’ exonuclease activity, which results in many errors during replication. Although most patients are infected with a single genotype, the high mutation rate leads to the development of distinct quasispecies within infected individuals over time. These variant strains differ primarily at hypervariable genomic regions, such as those found in the sequences coding for its envelope glycoproteins. The continuous generation of novel envelope glycoproteins prevents infected individuals from mounting an effective immune response. As production of host antibodies against a quasispecies commences, that strain dies off and new ones take its place. Genetic variations created during hepatitis C virus (HCV) replication result in marked variety in the antigenic structure of HCV envelope proteins. The production of host antibodies lags behind that of new mutant HCV strains, preventing infected individuals from mounting an effective immune response.
How is HCV primarily transmitted?
Bloodborne transmission (IV drug use, transfusions before 1992)
A 53-year-old woman presents to the primary care clinic to discuss symptoms of lethargy and unintentional weight loss of 11 lbs (22.2 kg) due to poor appetite over the past few months. The patient has also noticed significant yellowing and itchiness of the skin. The patient used IV drugs for many years but has not used drugs in the past four years.
There is no history of liver disease in the patient’s family. The patient does not consume alcohol or use tobacco products. Vital signs are unremarkable. On physical examination, the patient is jaundiced. Ophthalmologic and neurologic examinations show no abnormalities. The abdomen is minimally distended without tenderness to palpation.
Blood work shows hemoglobin 10.1 g/dL and platelets 120/mm^3.Which of the following tests would most likely establish the underlying diagnosis?
A) Serum ceruloplasmin
B) Serum hepatitis C antibody
C) Serum transferrin saturation
D) Serum transaminases
E) Serum protein electrophoresis
Chronic HCV infections often present with an indolent course of symptoms or with signs and symptoms of cirrhosis. History should focus on assessing high-risk behaviors or exposures (e.g., tattooing with non-sterile equipment, IV drug use, and sexual contact with a known HCV carrier). This patient presenting with lethargy, anorexia, weight loss, jaundice, and history of IV drug use likely has hepatitis C viral (HCV) infection, which may have led to cirrhosis in this case. Testing for serum hepatitis C antibodies would be the first step toward making the diagnosis. HCV is a bloodborne infection transmitted via contaminated blood or sexual contact which can cause an asymptomatic acute infection. If the infection is not cleared, it can lead to chronic infection, which predisposes patients to cirrhosis and hepatocellular carcinoma. Hepatitis C should be suspected in patients with known high-risk behaviors or exposures (e.g., tattooing with non-sterile equipment, IV drug use, sexual contact with a known HCV carrier). It should also be part of the differential diagnosis for patients presenting with jaundice, abdominal pain, anorexia, and similar symptoms suggestive of liver disease. Patients with an acute HCV infection will usually have abdominal pain and nausea. Severe pruritus may be present as well. In contrast, patients with chronic HCV are more likely to present with an indolent course of slowly progressive symptoms, but can also present with new-onset cirrhosis. Workup should include HCV antibody testing, INR, complete metabolic panel, and a liver ultrasound.
What is the most common method of transmission of HCV in the developed world?
Hepatitis C virus (HCV) is transmitted most efficiently through percutaneous exposure to blood. As such, most cases in the Western world arise in those with a history of intravenous drug use.
Is HCV commonly transmitted sexually?
Rarely, but possible
What percentage of HCV infections become chronic?
Approximately 50% in adults, 90% in neonates
What is the most common presentation of HCV?
Initial infections are usually asymptomatic, but most lead to chronic hepatic infection, putting patients at risk for cirrhosis and hepatocellular carcinoma.
What are the common symptoms of acute HCV infection when it is symptomatic?
Although HCV is often asymptomatic, HCV can present with mild flu-like symptoms, fatigue, myalgia, arthralgia, nausea, and jaundice.
What is the most severe complication of chronic HCV infection?
Cirrhosis and hepatocellular carcinoma
What test is used for screening HCV infection?
Anti-HCV antibodies (ELISA).
HCV antibody testing is used for screening, as it identifies those exposed to the virus. To determine which patients have ongoing, active disease, further testing is required to document HCV RNA in the blood. This is accomplished with HCV nucleic acid testing (NAT). Patients with positive HCV NAT are candidates for treatment with antiviral therapy.
Why does HCV screen require further workup?
A positive serologic test for hepatitis C virus (HCV) requires further investigation to evaluate for chronic infection. In asymptomatic patients, 3 potential explanations should be considered: persistent infection, cleared infection, or false-positive antibody test. Diagnosis of chronic CV requires both a positive serologic test and a confirmatory nucleic acid test to confirm HCV RNA in the blood.
What test is used to confirm active HCV infection?
HCV RNA PCR
HCV antibody testing is used for screening, as it identifies those exposed to the virus. To determine which patients have ongoing, active disease, further testing is required to document HCV RNA in the blood. This is accomplished with HCV nucleic acid testing (NAT). Patients with positive HCV NAT are candidates for treatment with antiviral therapy.
Which serologic marker indicates active HCV replication?
HCV RNA
Which test determines HCV genotype for treatment selection?
HCV genotype testing.
Patients with positive HCV NAT should undergo further evaluation to identify the HCV genotype and the extent of liver fibrosis (eg, liver biopsy); aminotransferases do not provide a clear picture of disease progression. Confirmation with HCV NAT is required.
What is the most common genotype of HCV?
Genotype 1
What is the primary treatment for chronic HCV infection?
Direct-acting antiviral (DAA) therapy using a NS3/4A protease inhibitor plus NS5A inhibitor
What are examples of NS3/4A protease inhibitors used in HCV treatment?
Glecaprevir, Paritaprevir, Simeprevir, Telaprevir
What are examples of NS5A inhibitors used in HCV treatment?
Ledipasvir, Pibrentasvir, Velpatasvir
What is an example of an NS5B inhibitor used in HCV treatment?
Sofosbuvir
What is the recommended regimen for Genotype 1 HCV?
- Glecaprevir-pibrentasvir
- Ledipasvir-sofosbuvir
- Sofosbuvir-velpatasvir
What is the recommended regimen for Genotype 2 HCV?
Sofosbuvir-velpatasvir
A 62-year-old man presents to the gastroenterology clinic for follow-up of chronic hepatitis C. Four weeks ago, the patient was diagnosed with chronic hepatitis C infection and was started on sofosbuvir-velpatasvir. The patient has no significant past medical history and takes no medications. He drinks a few beers during the week and 5-6 beers on the weekends. AST, ALT, and total bilirubin were mildly elevated at that time. On today’s visit, the patient is feeling well and has more energy since starting treatment. Temperature is 37.0 °C (98.6 °F), pulse is 78/min, blood pressure is 110/71 mmg, respiratory rate is 12/min, and SpOz is 100% on room air. Repeat AST, ALT, and total bilirubin levels have significantly improved. Which of the following is the best next step in management?
A) Check serum GGT
B) Check serum HCV RNA
C) Provide alcohol cessation counseling
D) Perform CT scan of the abdomen and pelvis
E) Vaccinate against hepatitis D virus
Patients with active HCV infection should be treated with antivirals (e.g., sofosbuvir-velpatasvir, glecaprevir-pibrentasvir), counseled about lifestyle modifications (e.g. alcohol cessation), and vaccinated against hepatitis A and B virus. AST, ALT, bilirubin, and INR should be monitored, and HCV RNA should be repeated after 12 weeks of therapy. This patient with chronic hepatitis C infection is responding well to recently started antiviral treatment based on improving symptoms and laboratory studies. Hepatitis C virus (HCV) is transmitted via contaminated blood or sexual contact and can cause an asymptomatic acute infection. If the infection is not cleared, it can lead to chronic infection, which predisposes the patient to cirrhosis and hepatocellular carcinoma. Hepatitis C should be suspected in patients with known high-risk behaviors or exposures (e.g., tattooing with non-sterile equipment, IV drug use, sexual contact with a known HCV carrier). When HCV is suspected, serum HCV antibody testing should be performed. If positive, serum HCV RNA should then be tested to determine if the patient has an active infection with a positive viral load. Patients with active infection (positive HCV RNA) should be treated with antivirals, such as sofosbuvir-velpatasvir or glecaprevir-pibrentasvir. Patients should also be counseled about lifestyle modifications (e.g. alcohol cessation) and vaccinated against hepatitis A and B virus. AST, ALT, bilirubin, and INR should be monitored serially to ensure improvement. Serial ultrasounds can be performed as well, and alpha-fetoprotein testing is sometimes performed if cirrhosis is present. After 12 weeks of therapy, HCV RNA testing should be repeated to assess the virologic response to treatment.
What is the role of interferon and ribavirin in HCV treatment today?
No longer first-line; replaced by direct-acting antivirals (DAAs)
Why is HCV-associated liver disease dangerous?
Chronic inflammation leads to fibrosis, cirrhosis, and hepatocellular carcinoma
What is the major reason HCV lacks a vaccine?
High genetic variability and rapid mutation rate
How long should patients with HCV be monitored after treatment?
Sustained virologic response (SVR) at 12 weeks post-treatment indicates cure
