Hepatitis C, Chronic

Liver tests are needed if not previously done; they include serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase.

Other tests should be done to evaluate liver function; they include serum albumin, bilirubin, platelet count, and prothrombin time/international normalized ratio (PT/INR).

Patients should be tested for HIV Diagnosis Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more and hepatitis B infection Diagnosis Hepatitis B is caused by a DNA virus that is often parenterally transmitted. It causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Fulminant hepatitis and... read more because transmission of these infections is similar.

If symptoms or signs of cryoglobulinemia develop during chronic hepatitis C, cryoglobulin levels and rheumatoid factor should be measured; high levels of rheumatoid factor and low levels of complement suggest cryoglobulinemia.

Patients with chronic HCV infection and advanced fibrosis or cirrhosis should be screened every 6 months for hepatocellular cancer Diagnosis Hepatocellular carcinoma usually occurs in patients with cirrhosis and is common in areas where infection with hepatitis B and C viruses is prevalent. Symptoms and signs are usually nonspecific... read more with ultrasonography and serum alpha-fetoprotein measurement, although the cost-effectiveness of this practice, particularly serum alpha-fetoprotein measurement, is debated.

(See also the American Association for the Study of Liver Disease’s [AASLD] practice guidelines Recommendations for testing, managing, and treating hepatitis C and the AASLD/Infectious Disease Society of America's [IDSA] When and in whom to initiate HCV therapy.)

For chronic hepatitis C, treatment is recommended for all patients, except those with a short life expectancy due to comorbid conditions that cannot be remediated by HCV therapy, liver transplantation, or another directed therapy.

The goal of treatment is permanent elimination of HCV RNA (ie, SVR), which is associated with permanent normalization of aminotransferase levels and cessation of histologic progression. Treatment results are more favorable in patients with less fibrosis than in patients with cirrhosis.

Until late 2013, all genotypes were treated with pegylated interferon alfa plus ribavirin. Now, interferon-based treatment regimens are no longer used, and ribavirin is no longer considered first-line and is used only in certain alternative regimens. Currently, all patients are treated with direct-acting antivirals (DAAs) that affect specific HCV targets, such as proteases or polymerases (see also HCV genotype 1 HCV genotype 1 Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Diagnosis is confirmed by finding positive anti-HCV and positive... read more and HCV genotypes 2,3, 4, 5, and 6 HCV genotypes 2, 3, 4, 5, and 6 Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Diagnosis is confirmed by finding positive anti-HCV and positive... read more ).

DAAs currently used to treat HCV include

DAAs are not used as single drugs but are used in specific combinations to maximize efficacy.

Sofosbuvir is given in combination with other drugs. The preferred combinations include

Sofosbuvir can also be given with ribavirin (for genotypes 1 through 6), simeprevir (for genotype 1), or daclatasvir (for genotypes 1 through 3) in all-oral regimens, but these regimens are not preferred.

The single pill containing sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg orally once a day for 12 weeks is used for re-treatment of chronic HCV infection in adults who have genotype 1, 2, 3, 4, 5, or 6 and were previously treated with a regimen containing an NS5A inhibitor or who have genotype 1a or 3 and were previously treated with a regimen containing sofosbuvir without an NS5A inhibitor ( 1 Treatment references Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Diagnosis is confirmed by finding positive anti-HCV and positive... read more ). This combination pill (sofosbuvir, velpatasvir, and voxilaprevir) is not recommended for patients with moderate or severe hepatic impairment, and no dosage can be recommended for patients with severe renal impairment.

Elbasvir/grazoprevir in a single pill is used to treat HCV genotypes 1 and 4.

Glecapravir and pibrentasvir are available in a single pill to treat HCV genotypes 1 through 6.

The following 5-drug regimen, although not preferred, is effective against genotypes 1 and 4:

Paritaprevir/ritonavir/ombitasvir plus dasabuvir, although not preferred, is available in a single package for genotypes 1 and 4.

Ritonavir increases levels of paritaprevir but has no direct antiviral activity.

Current recommendations for HCV treatment are evolving rapidly. Hepatitis C Guidance 2019 Update: AASLD-IDSA (Infectious Diseases Society of America) recommendations for testing, managing, and treating hepatitis C virus infection from the American Association for the Study of Liver Disease (AASLD) and the Infectious Diseases Society of America (IDSA), available online, are updated frequently.

Decompensated cirrhosis due to hepatitis C is the most common indication for liver transplantation Liver Transplantation Liver transplantation is the 2nd most common type of solid organ transplantation. (See also Overview of Transplantation.) Indications for liver transplantation include Cirrhosis (70% of transplantations... read more in the US. HCV recurs almost universally in the graft. Before the use of DAAs, patient and graft survival was less favorable than when transplantation is done for other indications. However, when DAAs are used, the SVR rate in patients who have had a liver transplant exceeds 95% whether they have cirrhosis or not. Because SVR rates are so high, transplantation of hepatitis C–positive organs is being done increasingly, particularly among recipients who are also hepatitis C–positive, thus expanding the pool of potential donors. If the recipient and donor are hepatitis C–positive, treatment can be postponed until after transplantation. As a result, an unnecessary pretransplantation course of treatment can be avoided.

Regimens of elbasvir/grazoprevir or glecaprevir/pibrentasvir are now considered to have a good safety profile and are effective in patients with end-stage kidney disease, including dialysis patients.

Treatment of hepatitis C in patients with decompensated cirrhosis should be done in consultation with hepatologists, ideally in a liver transplant center. HCV regimens that include protease inhibitors should not be used in patients with decompensated cirrhosis because levels of protease inhibitors are increased in patients with hepatic dysfunction.

Hepatitis B reactivation resulting in liver failure and death has been reported during or after HCV treatment with DAAs. Therefore, all patients with hepatitis C being treated with DAAs should be checked for evidence of chronic or prior hepatitis B; tests should include all of the following:

Patients with chronic hepatitis B or evidence of prior hepatitis B should be monitored for reactivation during and after HCV treatment, and HBV antiviral therapy Treatment Hepatitis B is a common cause of chronic hepatitis. Patients may be asymptomatic or have nonspecific manifestations such as fatigue and malaise. Diagnosis is by serologic testing. Without treatment... read more should be considered during the course of HCV treatment.

Genotype 1 is more resistant to traditional treatment with dual therapy with pegylated interferon-alpha plus ribavirin than other genotypes. However, now with the use of interferon-free regimens of direct-acting antivirals (DAAs), the rate of SVR has increased from < 50% to ≥ 95%.

First-line regimens for HCV genotype 1 include

Fixed-dose combination of ledipasvir 90 mg/sofosbuvir 400 mg is given orally once a day for 8 to 12 weeks depending on history of prior treatment, pretreatment viral load, and degree of liver fibrosis.

Fixed-dose combination of elbasvir 50 mg/grazoprevir 100 mg is given orally once a day, with or without ribavirin 500 to 600 mg orally twice a day, for 12 to 16 weeks depending on history of prior treatment, degree of liver fibrosis, and, in patients with genotype 1a, the presence or absence of baseline NS5A resistance–associated variants to elbasvir.

Fixed-dose combination of velpatasvir 100 mg/sofosbuvir 400 mg is given orally once a day for 12 weeks.

Fixed-dose combination of glecaprevir 300 mg/pibrentasvir 120 mg is given orally once a day for 8 to 16 weeks, depending on history of prior treatment and degree of liver fibrosis.

Alternative regimens for HCV genotype 1 include

Simeprevir can cause anemia and photosensitivity. All protease inhibitors have drug-drug interactions.

Ribavirin is usually well-tolerated but commonly causes anemia due to hemolysis; dosage should be decreased if hemoglobin decreases to < 10 g/dL (100 g/L). Ribavirin is teratogenic in both men and women, requiring contraception during treatment and for 6 months after treatment is completed.

For genotype 2, one of the following combinations is recommended:

An alternative regimen for genotype 2 is

For genotype 3, first-line treatments include

An alternative regimen for genotype 3 is

For genotype 4, first-line treatments include

An alternative regimen for genotype 4 is

For genotypes 5 and 6, first-line treatments include