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Health Protocols

Hepatitis C

Conventional Treatment

HCV infection is now curable in most cases. “Cure” is defined as absence of HCV from the bloodstream after treatment. This is called sustained virologic response, or SVR.46 This remarkable advancement is the result of the effectiveness of direct-acting antivirals (DAAs). Viral clearance makes possible a range of benefits, both to the liver and other body systems, and can prevent ongoing destruction of cells, tissues, and organs by active HCV.47 As a result of these medical advances, the goals of HCV treatment are now eradication of the virus and preventing progression to negative outcomes like liver cancer or death.

An encouraging example of how these benefits extend beyond just the liver is the improvement in glucose metabolism seen after viral clearance. Although this phenomenon occurred before the advent of DAAs, the high cure rates and short treatment courses with current treatments mean the risk of a common and serious non-hepatic consequence of HCV infection is now far lower in the majority of patients. Several studies found DAA-induced SVR resulted in lower serum glucose and hemoglobin A1C levels, improved insulin sensitivity, a reversal of prediabetes, and a markedly decreased risk of diabetes.48-50 Improvement in conditions related to disturbed glucose and insulin metabolism, including elevated serum triglycerides, low HDL-cholesterol, high blood pressure, and even atherosclerosis has also been observed.50

It is very important to note that achieving a cure with medications does not make you immune to another HCV infection in the future. Re-infection with HCV after an initial cure (often with a different genotype than the original infection) is a concern for some people who engage in high-risk behavior.16

Direct-acting Antivirals (DAAs)

The development and approval of DAA therapy, which first became available in 2011, has rapidly transformed the hepatitis C treatment landscape. In the recent past, standard HCV treatment typically consisted of 24 to 48 weeks of treatment with injected pegylated interferon alpha plus oral ribavirin, which produced SVR rates of 40‒50%. These treatment regimens often caused adverse side effects such as hemolytic anemia, psychiatric disturbances, and flu-like symptoms.51 Pegylated interferon has a poor safety profile and is now rarely used for treating hepatitis C. Ribavirin, also associated with significant adverse effects, is sometimes used as an add-on to DAA treatment in certain cases of hepatitis C.52,53

In contrast, DAA regimens can result in SVR rates of over 95% after 8‒16 weeks of treatment, are taken as convenient oral pills, and have a far better side effect profile. In cases with more intractable virus types and more extensive disease, SVR rates of 78‒87% have been reported. Although DAAs remain cost-prohibitive in some cases, the approval of less expensive combination drugs, notably glecaprevir-pibrentasvir (Mavyret), has begun to make treatment more affordable for some.54

There are a variety of DAA medications available. The best approach for any patient is determined by his or her physician, who will take into consideration viral genotype and medical history factors such as liver health, previous treatments, and presence of concomitant infections (eg, HIV or HBV). Table 1 provides a general outline of some of the main variables affecting the choice of medication.47

Table 1: Direct-Acting Antivirals for Hepatitis C Treatment

Drug

HCV genotypes treated

Dosage Regimen

Cirrhosis

Details

Sofosbuvir (Sovaldi)

Suitable for all 6 genotypes

Now primarily used in combination medications, including with daclatasvir

With daclatasvir in advanced cirrhosis

Sofosbuvir in combination with ribavirin was the first FDA-approved all oral therapy for hepatitis C

Daclatasvir (Daklinza)

Genotypes 1‒4

Combined with sofosbuvir and sometimes ribavirin

With sofosbuvir in advanced cirrhosis

Ledipasvir-Sofosbuvir (Harvoni)

Genotypes 1, 4, 5, and 6; including 1A*

(*not including those with 1A and with cirrhosis or who have failed prior treatment)

One pill per day

Yes

For many patients, an eight-week course of treatment is as effective as 12 weeks

The first FDA-approved interferon- and ribavirin-free regimen to treat hepatitis C

Glecaprevir-Pibrentasvir (Mavyret)

Suitable for most patients. SVR rates in the range of 98‒100% for 8 or 12 weeks in genotypes 1, 2, 5, or 6

3 tablets, once daily, with food

Early cirrhosis (class A) only, 12-week treatment

Eight-week treatment of genotypes 3 and 4 resulted in SVR of 95% and 93%

A slightly lower cost option, but availability may be somewhat limited

Sofosbuvir-Velpatasvir (Epclusa)

Genotypes 1–4. Regimens and durations differ depending on genotype

One pill per day

Yes

Elbasvir-Grazoprevir (Zepatier)

Genotypes 1 and 4; genotype 1A requires resistance testing

One pill per day

Yes; not for advanced cirrhosis

Ombitasvir-Paritaprevir-Ritonavir (Technivie)

Genotype 4, including those who have received prior treatment

Oral, two tablets once daily with a meal

No

Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir (Viekira Pak)

Genotype 1a (without cirrhosis or with compensated cirrhosis when given with ribavirin); Genotype 1b (without cirrhosis or with compensated cirrhosis)

Oral, two ombitasvir/ paritaprevir/ritonavir 12.5/75/50 mg tablets once daily in the morning, and one dasabuvir 250 mg tablet twice daily, morning and evening, with a meal

In some cases

Ritonavir boosts efficacy of other medications; it does not have anti-HCV activity

Sofosbuvir-Velpatasvir-Voxilaprevir (Vosevi)

Important option for multiple genotypes when previous DAA treatment has failed

One pill per day, with food

Not suitable for moderate-to-severe (class B or C) cirrhosis or post liver transplant with cirrhosis

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