Hepatitis C is a viral infection that yields liver inflammation and, in severe cases, liver damage. It is transmitted through contaminated blood.
The Hepatitis C virus is the most prevalent blood-borne pathogen and a significant contributor to mortality and morbidity. Since the emergence of highly effective direct-acting antivirals in 2011, the treatment landscape has significantly changed.
Epidemiology
More than 185 million individuals are estimated to be infected with the Hepatitis C virus. Its prevalence in developed countries typically ranges from 1% to 2%. With 5.0 deaths per 100,000 people in 2013, HCV had the highest mortality rate and fatalities. The frequency of perinatal transmission ranges from 0-4%.
Most patients in Europe and the United States contract the infection through intravenous substance abuse or medical care in regions with limited resources. HCV genotypes vary significantly across the globe, according to classification. About 60–70% of isolates from the United States alone are of genotype 1, widely distributed worldwide.
West and Central Africa region has the highest prevalence of genotype 2. In Asia, genotype 3 is prevalent and is strongly associated with drug use. In North America and the Middle East, genotype 4 is widely distributed. Southeast Asia and South Africa are home to genotypes 5 and 6, respectively. The Congo region is where genotype 7 is found.
Anatomy
Pathophysiology
Four co-receptor molecules allow the RNA virus to enter the hepatocyte through endocytosis. Its positive-stranded RNA is internalized in the cytoplasm, where it is uncoated and transcribed into ten mature peptides, which are then dissociated by virally encoded NS3-4a serine as host proteases.
These fully developed peptides then move to the endoplasmic reticulum, forming a replication complex with the crucial enzyme NS5B RNA-dependent RNA polymerase. This enzyme converts the positive RNA into an intermediate negative strand, which then acts as a template for synthesizing new, positive strands.
These become mature virions combined with the core, enclose glycoprotein, and exit the cell through exocytosis. HCV cannot ingest into the genome of the host. Usually, the virus can be found in plasma within one to four weeks after exposure. In 50-85% of most cases, viremia continues after peaking in the first 8-12 weeks of infection.
After that, it peeks or declines to undetectable levels, known as viral clearance. Weak CD4+ and CD8+ T-cell responses that cannot stop viral replication are thought to cause persistent infection.
Cirrhosis is associated with rapid fibrosis progression and several external variables, including alcohol use, HIV or HBV coinfections, infection with Genotype 3, insulin resistance, obesity, and non-alcoholic fatty liver disease. Through encouraging genetic anomalies and neoplastic clones, liver fibrosis severity closely correlates with an elevated risk of hepatocellular carcinoma.
Etiology
There are three structural proteins, the nucleocapsid protein, core (C), and two envelope proteins, E1 and E2; two proteins required for virion formation, p7 and NS2; and five non-structural proteins required for viral replication such as NS3, NS4A, NS4B, NS5A, and NS5B.
The NS5B RNA polymerase generates a high virion turnover in the absence of proofreading, leading to the creation of viral variants, also known as quasispecies.
Genetics
Prognostic Factors
Only 10-15% of patients have a self-limited disease; the others have a progressing infection. Cirrhosis will affect approximately 20% of people within two decades, and liver cancer will affect another 1 to 5% within three decades.
The condition progresses more frequently among alcoholics, cirrhotics, and individuals with a concomitant HBV infection. Individuals with an undetectable viral load had a lower risk of acquiring cirrhosis and death.
Indicated for Hepatitis C Virus Animal research studies suggest the dosage for dogs is 0.5 mg/kg of their body weight & for rats, it is 2 mg/kg of body weight twice a day for seven days
1 tablet (100mg/400mg-velpatasvir/sofosbuvir) orally every Day
Treatment duration for liver transplant recipients
decompensated cirrhosis of Child-Pugh B or C: sofosbuvir/velpatasir plus ribavirin for 12 weeks
with compensated cirrhosis or Without cirrhosis (Child-Pugh A): sofosbuvir/velpatasvir for 12 weeks
Weight-based ribavirin dose
Above 75 kg: 1200 mg per day orally divided twice a day
Below 75 kg: 1000 mg per day orally divided twice a day
Dose Adjustments
Dosage Modifications Renal impairment
renal impairment, including patients with dialysis: dosage adjustment is not necessary Hepatic impairment
Child-Pugh A, B, or C (Mild, moderate, or severe): dosage adjustment is not required
<3 years: Safety and efficacy not established
>3 years:
<17kgs: 1 tablet (33.75mg/150mg) of pellets orally every day
17 to <35kg: 1 tablet (45mg/200mg) of pellets orally every day
>35kgs:1 tablet(90mg/400mg) orally everyday or 2 tablet(45mg/200mg) orally everyday
Below 3 years: Safety and efficacy is not established
≥3 years
Oral pellets
Below 17 kg: 150 mg sofosbuvir/37.5 mg velpatasvir orally every Day
Oral tablet(s) or pellets
Between 17 to <30 kg: 200 mg sofosbuvir/50 mg velpatasvir orally every Day
≥30 kg: 400 mg/100 mg-sofobuvi/ velpatasvir orally every Day
Treatment duration for liver transplant recipients
decompensated cirrhosis of Child-Pugh B or C: sofosbuvir/velpatasvir plus ribavirin for 12 weeks
with compensated cirrhosis or Without cirrhosis (Child-Pugh A): sofosbuvir/velpatasvir for 12 weeks
Weight-based ribavirin dose
<47 kg: 15 mg/kg/day orally
47-49 kg: 600 mg/day orally (1 x 200 mg AM, 2 x 200 mg PM)
50-65 kg: 800 mg/day orally (2 x 200 mg AM, 2 x 200 mg PM)
66-80 kg: 1000 mg/day orally (2 x 200 mg AM, 3 x 200 mg PM)
>80 kg: 1200 mg/day orally (3 x 200 mg AM, 3 x 200 mg PM)
Dose Adjustments
Dosage Modifications Renal impairment
renal impairment, including patients with dialysis: dosage adjustment is not required Hepatic impairment
Mild, moderate, or severe (Child-Pugh A, B, or C): dosage adjustment is not required
Hepatitis C is a viral infection that yields liver inflammation and, in severe cases, liver damage. It is transmitted through contaminated blood.
The Hepatitis C virus is the most prevalent blood-borne pathogen and a significant contributor to mortality and morbidity. Since the emergence of highly effective direct-acting antivirals in 2011, the treatment landscape has significantly changed.
More than 185 million individuals are estimated to be infected with the Hepatitis C virus. Its prevalence in developed countries typically ranges from 1% to 2%. With 5.0 deaths per 100,000 people in 2013, HCV had the highest mortality rate and fatalities. The frequency of perinatal transmission ranges from 0-4%.
Most patients in Europe and the United States contract the infection through intravenous substance abuse or medical care in regions with limited resources. HCV genotypes vary significantly across the globe, according to classification. About 60–70% of isolates from the United States alone are of genotype 1, widely distributed worldwide.
West and Central Africa region has the highest prevalence of genotype 2. In Asia, genotype 3 is prevalent and is strongly associated with drug use. In North America and the Middle East, genotype 4 is widely distributed. Southeast Asia and South Africa are home to genotypes 5 and 6, respectively. The Congo region is where genotype 7 is found.
Four co-receptor molecules allow the RNA virus to enter the hepatocyte through endocytosis. Its positive-stranded RNA is internalized in the cytoplasm, where it is uncoated and transcribed into ten mature peptides, which are then dissociated by virally encoded NS3-4a serine as host proteases.
These fully developed peptides then move to the endoplasmic reticulum, forming a replication complex with the crucial enzyme NS5B RNA-dependent RNA polymerase. This enzyme converts the positive RNA into an intermediate negative strand, which then acts as a template for synthesizing new, positive strands.
These become mature virions combined with the core, enclose glycoprotein, and exit the cell through exocytosis. HCV cannot ingest into the genome of the host. Usually, the virus can be found in plasma within one to four weeks after exposure. In 50-85% of most cases, viremia continues after peaking in the first 8-12 weeks of infection.
After that, it peeks or declines to undetectable levels, known as viral clearance. Weak CD4+ and CD8+ T-cell responses that cannot stop viral replication are thought to cause persistent infection.
Cirrhosis is associated with rapid fibrosis progression and several external variables, including alcohol use, HIV or HBV coinfections, infection with Genotype 3, insulin resistance, obesity, and non-alcoholic fatty liver disease. Through encouraging genetic anomalies and neoplastic clones, liver fibrosis severity closely correlates with an elevated risk of hepatocellular carcinoma.
There are three structural proteins, the nucleocapsid protein, core (C), and two envelope proteins, E1 and E2; two proteins required for virion formation, p7 and NS2; and five non-structural proteins required for viral replication such as NS3, NS4A, NS4B, NS5A, and NS5B.
The NS5B RNA polymerase generates a high virion turnover in the absence of proofreading, leading to the creation of viral variants, also known as quasispecies.
Only 10-15% of patients have a self-limited disease; the others have a progressing infection. Cirrhosis will affect approximately 20% of people within two decades, and liver cancer will affect another 1 to 5% within three decades.
The condition progresses more frequently among alcoholics, cirrhotics, and individuals with a concomitant HBV infection. Individuals with an undetectable viral load had a lower risk of acquiring cirrhosis and death.
https://www.ncbi.nlm.nih.gov/books/NBK430897/
medtigo
Hepatitis C
Updated :
February 6, 2024
Hepatitis C is a viral infection that yields liver inflammation and, in severe cases, liver damage. It is transmitted through contaminated blood.
The Hepatitis C virus is the most prevalent blood-borne pathogen and a significant contributor to mortality and morbidity. Since the emergence of highly effective direct-acting antivirals in 2011, the treatment landscape has significantly changed.
More than 185 million individuals are estimated to be infected with the Hepatitis C virus. Its prevalence in developed countries typically ranges from 1% to 2%. With 5.0 deaths per 100,000 people in 2013, HCV had the highest mortality rate and fatalities. The frequency of perinatal transmission ranges from 0-4%.
Most patients in Europe and the United States contract the infection through intravenous substance abuse or medical care in regions with limited resources. HCV genotypes vary significantly across the globe, according to classification. About 60–70% of isolates from the United States alone are of genotype 1, widely distributed worldwide.
West and Central Africa region has the highest prevalence of genotype 2. In Asia, genotype 3 is prevalent and is strongly associated with drug use. In North America and the Middle East, genotype 4 is widely distributed. Southeast Asia and South Africa are home to genotypes 5 and 6, respectively. The Congo region is where genotype 7 is found.
Four co-receptor molecules allow the RNA virus to enter the hepatocyte through endocytosis. Its positive-stranded RNA is internalized in the cytoplasm, where it is uncoated and transcribed into ten mature peptides, which are then dissociated by virally encoded NS3-4a serine as host proteases.
These fully developed peptides then move to the endoplasmic reticulum, forming a replication complex with the crucial enzyme NS5B RNA-dependent RNA polymerase. This enzyme converts the positive RNA into an intermediate negative strand, which then acts as a template for synthesizing new, positive strands.
These become mature virions combined with the core, enclose glycoprotein, and exit the cell through exocytosis. HCV cannot ingest into the genome of the host. Usually, the virus can be found in plasma within one to four weeks after exposure. In 50-85% of most cases, viremia continues after peaking in the first 8-12 weeks of infection.
After that, it peeks or declines to undetectable levels, known as viral clearance. Weak CD4+ and CD8+ T-cell responses that cannot stop viral replication are thought to cause persistent infection.
Cirrhosis is associated with rapid fibrosis progression and several external variables, including alcohol use, HIV or HBV coinfections, infection with Genotype 3, insulin resistance, obesity, and non-alcoholic fatty liver disease. Through encouraging genetic anomalies and neoplastic clones, liver fibrosis severity closely correlates with an elevated risk of hepatocellular carcinoma.
There are three structural proteins, the nucleocapsid protein, core (C), and two envelope proteins, E1 and E2; two proteins required for virion formation, p7 and NS2; and five non-structural proteins required for viral replication such as NS3, NS4A, NS4B, NS5A, and NS5B.
The NS5B RNA polymerase generates a high virion turnover in the absence of proofreading, leading to the creation of viral variants, also known as quasispecies.
Only 10-15% of patients have a self-limited disease; the others have a progressing infection. Cirrhosis will affect approximately 20% of people within two decades, and liver cancer will affect another 1 to 5% within three decades.
The condition progresses more frequently among alcoholics, cirrhotics, and individuals with a concomitant HBV infection. Individuals with an undetectable viral load had a lower risk of acquiring cirrhosis and death.
https://www.ncbi.nlm.nih.gov/books/NBK430897/
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