Overview of the management of chronic hepatitis C virus infection
Author
Sanjiv Chopra, MD
Section Editor
Adrian M Di Bisceglie, MD
Deputy Editor
Anne C Travis, MD, MSc, FACG
Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2012. | This topic last updated: 11 9, 2011.
INTRODUCTION — Hepatitis C virus (HCV) can cause both acute and chronic hepatitis. The acute process is self-limited, rarely causes hepatic failure, and usually leads to chronic infection. Chronic HCV infection often follows a progressive course over many years and can ultimately result in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. (See "Clinical manifestations and natural history of hepatitis C virus infection".)

This topic will provide a general overview of the issues involved with the treatment of chronic HCV. Patient selection for treatment, specific treatment regimens, predictors of treatment success, and the management of treatment induced side effects are discussed in detail elsewhere. (See "Patient selection for antiviral therapy for chronic hepatitis C virus infection" and "Treatment regimens for chronic hepatitis C virus genotype 1" and "Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4" and "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection" and "Management of the side effects of peginterferon and ribavirin being used for treatment of chronic hepatitis C virus infection".)

GUIDELINES — Treatment guidelines for chronic hepatitis C virus (HCV) infection were published in 2009 by the American Association for the Study of Liver Diseases (AASLD) [1]. The discussion that follows is consistent with those guidelines, which can be accessed at: www.aasld.org/practiceguidelines/Pages/default.aspx.

GENERAL MANAGEMENT — Antiviral therapy is the cornerstone of treatment of chronic hepatitis C virus (HCV) infection. Other general measures in the management of patients with chronic HCV include psychologic counseling, symptom management, dose adjustment of medications, and screening for complications of cirrhosis.

Additional testing — Patients diagnosed with HCV should also be tested for HIV and hepatitis B due to the common modes of transmission. (See "Serologic screening for HIV infection" and "Serologic diagnosis of hepatitis B virus infection".)

Counseling — Although most patients with chronic HCV infection are asymptomatic at the time of diagnosis, they are faced with a significant threat to their health, which can have important emotional and physical consequences. Counseling and screening for depression should be a major consideration, both at diagnosis and during subsequent follow-up. Many patients benefit from participation in a support group. (See "Patient information: Hepatitis C (Beyond the Basics)".)

Counseling should include discussions about the routes of HCV transmission, as most patients are concerned about sexual transmission and the risk of infecting household contacts (table 1). (See "Epidemiology and transmission of hepatitis C virus infection".)

Diet — Many patients are concerned about dietary factors that could favorably or adversely affect the disease. Although no particular diet has been shown to be beneficial in patients with chronic HCV infection, alcohol promotes the progression of chronic hepatitis C. As a result, we recommend abstinence. (See "Hepatitis C and alcohol", section on 'How much alcohol is too much?'.)

Coffee consumption (more than two cups per day) has been associated with a reduced risk of hospitalization and mortality from chronic liver disease [2,3]. However, this observation does not justify recommending increased consumption of coffee.

Fatigue — Many patients with HCV complain of fatigue. The cause of the fatigue is uncertain and may be difficult to ascribe to liver disease alone rather than another illness such as depression. Fatigue improves in some patients who have a sustained virologic response following interferon-based therapy. One of the largest series addressing this issue included 431 patients who underwent treatment for HCV. Fatigue improved significantly more often in responders than in nonresponders (35 versus 22 percent) [4].

Ondansetron (a 5-HT3 receptor antagonist, 4 mg twice daily) significantly improved fatigue in a placebo-controlled trial involving 36 patients [5]. The rationale for its use was based upon the observation that serotonin is associated with fatigue in animal and human models [6]. However, long-term efficacy is unclear, and treatment may be associated with constipation and cardiac arrhythmias.

Dose adjustments of medications — Prescription and over-the-counter medications usually do not require a dose adjustment in patients who have normal hepatic function. However, nonsteroidal anti-inflammatory drugs can be hepatotoxic and should be avoided in patients with advanced liver disease. (See "Drugs and the liver: Metabolism and mechanisms of injury".)

Many patients voice concern about taking acetaminophen due to its association with liver injury when taken in high doses. Patients do not need to avoid acetaminophen, but we suggest that the dose of acetaminophen not exceed 2 g per 24 hours. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis".)

While statins are frequently withheld from patients with chronic liver disease, available data fail to show an increased risk of adverse effects in patients with compensated chronic liver disease, suggesting that statin use is safe in patients with stable HCV infection [7,8]. In addition, there are some data that suggest statin use is associated with increased sustained virologic response rates following treatment with peginterferon and ribavirin [9].

Screening for esophageal varices and hepatocellular carcinoma — Patients with cirrhosis should be screened for the presence of esophageal varices by upper endoscopy. Patients with cirrhosis should undergo surveillance for hepatocellular carcinoma (HCC) because HCC occurs at a rate of 1 to 4 percent per year. (See "Clinical features and diagnosis of primary hepatocellular carcinoma", section on 'Screening and surveillance' and "Overview of the complications, prognosis, and management of cirrhosis", section on 'Preventing complications'.)

Vaccination — Recommendations for the vaccination of patients with chronic HCV are presented separately. (See "Immunizations for patients with chronic liver disease".)

GOAL OF ANTIVIRAL THERAPY — The goal of antiviral therapy in patients with chronic HCV is to eradicate HCV RNA, which is predicted by attainment of a sustained virologic response (SVR). An SVR is associated with a 98 to 100 percent chance of being HCV RNA negative during long-term follow-up [10,11], and attaining an SVR has been associated with decreases in all-cause mortality, liver-related death, need for liver transplantation, hepatocellular carcinoma rates, and liver-related complications [11-16]. (See 'Predictors of a treatment response' below.)

PATIENT SELECTION FOR ANTIVIRAL THERAPY — The decision to treat a patient with chronic HCV infection is based upon several factors, including the natural history of the disease, the stage of fibrosis, and the efficacy and adverse effects related to therapy. Therapy is generally considered appropriate for patients who:

Are 18 years of age or older
Have HCV RNA detectable in the serum
Have a liver biopsy with chronic hepatitis and significant fibrosis
Have compensated liver disease
Have acceptable hematologic and biochemical indices
Are willing to be treated and conform to treatment requirements
Have no contraindications to treatment
Additional factors such as alcohol use, drug use, chronic kidney disease, or prior liver transplantation are also taken into account when deciding whether to start a patient on antiviral therapy. The selection of patients for antiviral therapy is discussed in detail elsewhere. (See "Patient selection for antiviral therapy for chronic hepatitis C virus infection".)

TREATMENT OPTIONS — Patients with genotype 1 should be treated with peginterferon, ribavirin, and a protease inhibitor. Patients with other genotypes are treated with peginterferon and ribavirin. Detailed discussions of the various treatments for HCV can be found elsewhere.

(See "Treatment regimens for chronic hepatitis C virus genotype 1".)
(See "Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4".)
(See "Mechanism of action and efficacy of peginterferon for the treatment of chronic hepatitis C virus infection".)
(See "Mechanism of action and efficacy of ribavirin for the treatment of chronic hepatitis C virus infection".)
(See "Studies of telaprevir and boceprevir in the treatment of chronic hepatitis C virus genotype 1".)
(See "Mechanism of action and efficacy of standard interferon alfa for the treatment of chronic hepatitis C virus infection".)
(See "Investigational therapies for hepatitis C virus infection", section on 'NS3/4A protease inhibitors'.)
PREDICTORS OF A TREATMENT RESPONSE — As noted above, the goal of therapy is to eradicate the hepatitis C virus. Several viral-, patient-, and treatment-related factors influence a patient's chance of eradicating the virus. (See 'Goal of antiviral therapy' above and "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection".)

Important predictors of a treatment response include:

HCV genotype (genotypes 2 and 3 are more responsive to treatment than genotypes 1 and 4)
Baseline viral load (≤600,000 to 800,000 IU/mL)
Race (whites have higher response rates than African Americans and Latino whites)
Host genetic factors (eg, IL28B polymorphisms)
Use of combination therapy with peginterferon and ribavirin
Treatment adherence
ASSESSING A TREATMENT RESPONSE — Changes in viral load during therapy are used to determine if a patient is responding to treatment and to predict whether the patient is likely to eradicate the virus. In general, the earlier the HCV RNA becomes undetectable during treatment, the more likely a patient is to eradicate the virus. (See "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection", section on 'Changes in viral load during treatment'.)

Several terms are used to describe the response to antiviral therapy in patients with chronic HCV infection:

Rapid virologic response (RVR): HCV RNA negativity after four weeks of treatment; if the HCV RNA remains negative at 12 weeks it is known as an extended rapid virologic response (eRVR)
Early virologic response (EVR): at least a 2 log10 reduction in HCV RNA (a partial EVR) or HCV RNA negativity (a complete EVR) by week 12 of treatment
Delayed virologic response: HCV RNA negativity at week 24 in patients who fail to achieve a complete EVR (such patients are also known as "slow responders")
End of treatment response (EOT): HCV RNA negativity at the end of treatment
Relapse: reappearance of HCV RNA in patients who were HCV RNA negative at the end of treatment
Sustained virologic response (SVR): absence of HCV RNA by polymerase chain reaction six months after stopping treatment
In addition to assisting with prognostication, changes in viral load during therapy may have a role in determining the appropriate length of therapy. (See "Response-guided therapy for chronic hepatitis C virus infection".)

SIDE EFFECTS OF TREATMENT — Side effects are observed in almost 80 percent of patients receiving peginterferon and ribavirin combination therapy for chronic HCV (figure 1). Treatment-induced side effects include:

Flu-like symptoms
Anemia
Neutropenia
Thrombocytopenia
Rashes
Hair loss
Thyroid dysfunction
Depression
Fatigue
Irritability and mania
Nonproductive cough
Dyspnea
Ophthalmologic disorders such as retinal hemorrhages
Teratogenicity
Exacerbations of autoimmune diseases
Patients receiving telaprevir or boceprevir are at increased risk for developing anemia. In addition, telaprevir is frequently associated with rashes. (See "Studies of telaprevir and boceprevir in the treatment of chronic hepatitis C virus genotype 1" and "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Side effects of treatment'.)

Care of patients with chronic hepatitis C depends upon recognition of those at increased risk for side effects, anticipation (and prevention) of side effects, and appropriate response when they occur. Furthermore, the ability to achieve a sustained virologic response to therapy depends in part upon the degree of compliance with therapy. Reduction of the dose of antiviral medications (or their discontinuation) due to side effects can potentially compromise the outcome, depending upon when dose reduction occurs. (See "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection", section on 'Treatment-related factors' and "Management of the side effects of peginterferon and ribavirin being used for treatment of chronic hepatitis C virus infection".)

TREATMENT OF EXTRAHEPATIC MANIFESTATIONS — Chronic HCV is associated with extrahepatic manifestations such as cryoglobulinemia, porphyria cutanea tarda, and autoimmune disorders. (See "Extrahepatic manifestations of hepatitis C virus infection".)

Some of the manifestations that may respond to treatment for HCV include:

Cryoglobulinemia
Porphyria cutanea tarda
Leukocytoclastic vasculitis
Necrolytic acral erythema
Glomerulonephritis
NOVEL/INVESTIGATIONAL TREATMENTS — The search for new therapies for chronic HCV is ongoing. Major research efforts are underway to identify new therapies that can increase the SVR rate and/or lower the incidence of side effects. The main targets of most new therapies are the HCV-encoded proteins that are vital to the replication and life cycle of the virus. These targets include the HCV-encoded:

NS2/3 autoprotease
NS3 RNA helicase
NS5A protein
NS5B RNA dependent RNA polymerase
Another line of investigation has focused on host-encoded proteins that are essential for viral replication, such as cyclophilins. Investigational therapies for chronic HCV infection are discussed in detail elsewhere. (See "Investigational therapies for hepatitis C virus infection".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient information: Hepatitis C (The Basics)" and "Patient information: Latest medicines for hepatitis C (The Basics)")
Beyond the Basics topics (see "Patient information: Hepatitis C (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS

In addition to antiviral therapy, considerations in the treatment of patients with chronic hepatitis C virus (HCV) include psychologic counseling, alcohol avoidance, symptom control, dose adjustment of medications, and screening for complications of cirrhosis. (See 'General management' above.)
The goal of treatment in patients with chronic HCV is to eradicate HCV RNA, which is associated with decreases in all-cause mortality, liver-related death, need for liver transplantation, hepatocellular carcinoma rates, and liver-related complications. (See 'Goal of antiviral therapy' above.)
Peginterferon combined with ribavirin (plus boceprevir or telaprevir in patients with genotype 1) is the standard treatment for patients with chronic HCV infection. (See "Treatment regimens for chronic hepatitis C virus genotype 1" and "Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4".)
Important predictors of a treatment response include the HCV genotype, baseline viral load, race, host genetic factors (eg, IL28B polymorphisms), and treatment related factors, such as the choice and dose of medications. (See "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection".)
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