Hepatitis C: A Comprehensive Overview of Effective Treatment Options

Approximately 71 million people worldwide have chronic hepatitis C virus (HCV) infection. HCV causes liver inflammation, which leads to serious liver damage.

HCV is a blood borne virus and the most common route of infection is contact with contaminated blood, for example through intravenous drug use or transfusion of unscreened blood and blood products. HCV has 6 genotypes, which genotype 1 the most common in the United States.

Acute hepatitis is a short-term viral infection, but does not always lead to chronic hepatitis because some patients might clear the virus from their body before it progresses to chronic HCV. Ten percent to 15% of patients who have acute HCV are able to resolve the virus without any complications.

Most patients with acute HCV do not experience symptoms, and even if they experience symptoms, they are mild. Chronic HCV is known as a “silent” infection because most patients do not experience any symptoms when they are infected.

Fifty percent of the population infected with HCV are unaware that they are infected because they might not experience any symptoms. Chronic HCV typically begins with an acute phase, but most patients are not diagnosed during the acute phase because they do not experience any symptoms.

Antiviral medications can cure most of patients with infected with HCV.

Presentation

The acute phase of HCV lasts less than 6 months and patients rarely experience any symptoms, but some symptoms that can occur are fatigue, nausea, fever, and muscle aches. Patients will experience an elevation in alanine aminotransferase (ALT) levels and positive HCV RNA after 4 weeks of infection. Anti-HCV antibodies become detectable after 8 weeks of infection.

The chronic phase of HCV lasts more than 6 months but less than 2 years. Some of the symptoms patients may experience are easy bleeding/bruising, fatigue, poor appetite, dark-colored urine, itchy skin, fluid buildup in the abdomen (ascites), confusion (hepatic encephalopathy), weight loss, and jaundice.

Risk Factors

• Born between 1945 and 1965
• Sharing needles or receiving a blood transfusion or any blood product
• Receiving tattoos and body piercings in an unclean environment
• Health care providers
• Born to a mother with active HCV
• Multiple sexual partners
• Co-infection with HIV or other sexually-transmitted diseases

Treatment

Medication

Advantages

Disadvantages

Interferon

First drug to treat HCV.

Adverse reactions: flu-like symptoms, depression, irritability.

No longer used due to side effects.

Ribavirin

Combination product with Harvoni for compensated cirrhosis. Combination product with Epclusa for decompensated cirrhosis.

Pregnancy Category X: men and women need to use 2 forms of contraception during and 6 months after therapy.

Dose adjustment in renal impairment.

Sovaldi

(sofosbuvir)

Genotypes 1-4.

No dose adjustment in renal and hepatic impairment.

Treatment duration: 12-24 weeks.

Monotherapy is contraindicated.

Use with amiodarone and anticonvulsants (carbamazepine, oxcarbazepine, phenytoin, and phenobarbital) is contraindicated.

Olysio

(simeprevir)

Genotype 1.

Decreased risk of rash compared with older HCV regimens.

No dose adjustment in renal impairment.

Treatment duration: 12-24 weeks.

Monotherapy is contraindicated.

Contraindicated with amiodarone, diltiazem, anticonvulsants (carbamazepine, oxcarbazepine, phenytoin, and phenobarbital) and verapamil.

Max dose of atorvastatin is 40 mg and rosuvastatin 10 mg while on therapy.

Do not use in case of sulfa allergy.

Harvoni

(ledipasvir/sofosbuvir)

Genotype 1.

First combination product.

Cure rate: 90%

No dose adjustment needed in hepatic impairment.

Treatment duration: 12-24 weeks.

Contraindicated with rosuvastatin, amiodarone, and anticonvulsants (carbamazepine, oxcarbazepine, phenytoin, and phenobarbital).

Max dose of omeprazole is 20 mg/day and it should be taken at the same time as Harvoni on empty stomach.

Separate antacids by 4 hours.

Max dose of famotidine is 40 mg BID with or 12 hours after Harvoni.

Viekira Pak/XR

(ombitasvir/paritaprevir/ ritonavir/dasabuvir)

Genotype 1.

Interferon-free drug.

Cure rate: 95%

Less expensive than Harvoni.

No dose adjustment needed in renal impairment.

Treatment duration: 12-24 weeks.

Contraindicated with simvastatin, lovastatin, and anticonvulsants (carbamazepine, phenytoin, phenobarbital).

Do not use ethinyl estradiol contraceptives during and 2 weeks after therapy.

Do not use in hepatic impairment.

Daklinza

(daclatasvir)

Genotype 3.

No dose adjustment is necessary in patients with hepatic or renal impairment.

Treatment duration: 12-24 weeks.

Used with sofosbuvir.

Contraindicated with amiodarone, anticonvulsants (carbamazepine, oxcarbazepine, phenytoin, phenobarbital).

Zepatier

(elbasvir/grazoprevir)

Genotype 1 and 4.

Fewer side effects than Harvoni and Sovaldi.

Less expensive than Harvoni and Viekira.

No dose adjustment in renal impairment.

Treatment duration: 12-16 weeks.

Contraindicated with carbamazepine, phenytoin, phenobarbital.

Max dose for atorvastatin is 20 mg and rosuvastain is 10 mg.

Do not use in hepatic impairment.

Epclusa

(sofosbuvir/velpatasvir)

All HCV genotypes.

Less expensive than Sovaldi and Harvoni.

No dose adjustment is necessary in renal and hepatic impairment.

Treatment duration: 12-24 weeks.

Max dose for Omeprazole is 20 mg/day. Take Epclusa with food 4 hours before PPI. Separate antacids by 4 hours. Max dose of famotidine is 40 mg BID.

Max dose of Rosuvastatin is 10 mg/day.

Contraindicated with amiodarone, carbamazepine, oxcarbazepine, phenytoin, and phenobarbital.

Vosevi

(sofosbuvir, velpatasvir, and voxilaprevir)

All HCV genotypes.

Less expensive than Harvoni and Sovaldi.

Cure rate: 96%

Treatment duration: 12 weeks.

Max dose for Omeprazole is 20 mg/day. Take Vosevi with food 4 hours before PPI. Separate antacids by 4 hours. Max dose famotidine 40 mg BID.

Contraindicated with amiodarone, rosuvastatin, carbamazepine, oxcarbazepine, phenytoin, and phenobarbital.

Max pravastatin dose is 40 mg/day.

Do not use in hepatic impairment.

Mavyret

(glecaprevir and pibrentasvir)

All HCV genotypes

Less expensive than other HCV therapies.

No dose adjustment needed in renal impairment.

Treatment duration: 8 weeks.

Do not use in severe hepatic impairment.

Contraindicated with carbamazepine, phenytoin, phenobarbital, oxcarbezapine, simvastatin, atorvastatin, and lovastatin.

Conclusion

HCV is a curable disease and there are a multitude of new medical advances in this disease state. The medications discussed in the table above have their own advantages and disadvantages, but are similar in efficacy.

Insurance companies are usually the main determinants of which therapy the patient will receive. There are different treatment options available for HCV, therefore patients should get tested for HCV and start their treatment before the disease progresses into its later stages.

About the Author

Krutika Patel is a last year KU School of Pharmacy student. Originally, she is from India, but currently resides in Columbia, MO. She has an interest in the HCV disease state.

References

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Wasserman, Emily. “UPDATED: Zepatier Beats Harvoni, Sovaldi in Hep C Clinical-Data Safety Showdown: Advera Health Analytics.” FiercePharma, Questex, 24 Feb. 2016, www.fiercepharma.com/regulatory/updated-zepatier-beats-harvoni-sovaldi-hep-c-clinical-data-safety-showdown-advera-health.

WHO. “Hepatitis C.” World Health Organization, World Health Organization, July 2017, www.who.int/mediacentre/factsheets/fs164/en/.