Patient selection for antiviral therapy for 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: 2 28, 2012.
INTRODUCTION — The decision to treat a patient with chronic hepatitis C virus (HCV) infection is based upon several factors, including the natural history and stage of the disease, the efficacy of therapy, and potential side effects. In general, patients being considered for treatment should have histologic and virologic evidence of chronic HCV infection. When identifying patients who are candidates for treatment, factors that are associated with a favorable response (eg, HCV genotype 2) should be weighed against factors associated with a lower likelihood of response (eg, older age). (See "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection".)

This topic will review patient selection for antiviral therapy with peginterferon and ribavirin. Patients with HCV genotype 1 may also be candidates for treatment with a protease inhibitor (eg, telaprevir or boceprevir). The treatment of acute HCV, as well as detailed information on the use of peginterferon, ribavirin, and protease inhibitors for the treatment of chronic HCV are discussed separately. (See "Diagnosis and treatment of acute hepatitis C in adults" and "Treatment regimens for chronic hepatitis C virus genotype 1" and "Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4" and "Treatment of hepatitis C virus infection in the HIV-infected patient".)

GUIDELINES — The 2009 guidelines from the American Association for the Study of Liver Diseases (AASLD) are commonly used in making decisions about which patients to treat [1]. The guidelines can be accessed at www.aasld.org/practiceguidelines/Pages/default.aspx. It should be noted that these guidelines were issued prior to the availability of protease inhibitors for the treatment of HCV.

In 2012, UK consensus guidelines were released regarding the treatment of genotype 1 patients with protease inhibitor based-triple therapy [2]. The discussion that follows is consistent with both the AASLD and UK consensus guidelines.

PATIENTS FOR WHOM THERAPY IS WIDELY ACCEPTED — Therapy is generally accepted for patients with all of the following characteristics:

At least 18 years of age
HCV RNA detectable in the serum
Liver biopsy with chronic hepatitis and significant fibrosis (bridging fibrosis or higher)
Compensated liver disease
Total serum bilirubin <1.5 g/dL (25.7 micromol/L)
INR <1.5
Albumin >3.4 g/dL (34 g/L)
Platelet count >75,000 cells/mm3 (75,000 x 10(6)/L)
No evidence of hepatic encephalopathy or ascites
Acceptable hematological and biochemical indices
Hemoglobin >13 g/dL for men and >12 g/dL for women
Neutrophil count >1500 cells/mm3 (1500 x 10(6)/L)
Creatinine <1.5 mg/dL (133 micromol/L)
Willing to be treated and to conform to treatment requirements
No contraindications to treatment
In addition, the 2012 UK consensus guidelines recommend treatment with peginterferon, ribavirin, and a protease inhibitor (telaprevir or boceprevir) for most patients with genotype 1, including patients who are treatment naïve or who have failed prior therapy with peginterferon and ribavirin [2]. The guidelines note that because of drug interactions, treatment of patients with HIV needs to be considered on a case-by-case basis. In addition, the guidelines do not currently recommend treatment in patients with decompensated liver disease, hepatitis B co-infection, or active cancer, or in patients who have undergone organ transplantation due to limited data. (See "Treatment of hepatitis C virus infection in the HIV-infected patient".)

PATIENTS WHO MAY BE CANDIDATES FOR THERAPY — Therapy can be considered in the following settings:

Patients who failed prior treatment (nonresponders and relapsers) with standard interferon (with or without ribavirin) or peginterferon monotherapy. As noted above, the 2012 UK consensus guidelines recommend protease inhibitor-based triple therapy for patients with genotype 1, regardless of prior treatment response. (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4", section on 'Relapsers and nonresponders'.)
Current users of illicit drugs or alcohol who are willing to participate in a substance abuse program (such as a methadone program) or alcohol support program. (See 'Active illicit drug use' below and 'Ongoing alcohol use' below.)
Liver biopsy without fibrosis or with only mild fibrosis. (See 'Persistently normal serum ALT' below and 'Mild liver disease' below.)
Acute hepatitis C. (See "Diagnosis and treatment of acute hepatitis C in adults".)
Coinfection with HIV. (See "Evaluation of the HIV-infected patient with chronic hepatitis C virus infection" and "Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4", section on 'Coinfection with HIV'.)
Less than 18 years of age. (See "Hepatitis C virus infection in children", section on 'Treatment'.)
Chronic kidney disease either requiring or not requiring hemodialysis. (See "Renal disease associated with hepatitis C virus infection" and "Hepatitis C virus infection in patients on maintenance dialysis".)
Decompensated cirrhosis. (See 'Decompensated cirrhosis' below.)
Recipient of a liver transplant. (See 'Recurrence after liver transplantation' below.)
For patients with genotype 1 being considered for protease inhibitor based-triple therapy, caution should be exercised in patients with significant neutropenia, thrombocytopenia, or anemia, or who are taking medications that may interact with protease inhibitors (table 1 and table 2).
PATIENTS IN WHOM THERAPY IS CONTRAINDICATED — Antiviral therapy with peginterferon and ribavirin for chronic HCV infection is contraindicated in patients who have one or more of the following:

Major, uncontrolled depressive illness
A kidney, heart, or lung transplant
Autoimmune hepatitis or other conditions known to be exacerbated by interferon or ribavirin
Untreated thyroid disease
Severe concurrent disease such as severe hypertension, heart failure, significant coronary artery disease, poorly controlled diabetes, obstructive pulmonary disease
Known hypersensitivity to drugs used to treat HCV
Therapy is also contraindicated in patients who are:

Less than two years of age
Pregnant, contemplating pregnancy (including men), or unwilling to assure contraception; ribavirin is pregnancy category X due to significant teratogenic and embryocidal effects, and interferon is pregnancy category C (see "Mechanism of action and efficacy of ribavirin for the treatment of chronic hepatitis C virus infection", section on 'Adverse effects of ribavirin')
INFLUENCE OF SIDE EFFECTS AND DRUG INTERACTION ON PATIENT SELECTION — Interferon monotherapy and combination therapy with ribavirin and telaprevir or boceprevir (for patients with genotype 1) are associated with several adverse effects. In some patients, treatment is contraindicated due to the risk of side effects, whereas in others, treatment should be undertaken with extreme caution. Conditions that may be complicated or worsened by side effects of treatment include significant anemia or leukopenia, pregnancy, severe depression or other psychiatric conditions, cardiac disease, poorly controlled diabetes, seizure disorders, and autoimmune or potentially immune-mediated diseases. In addition, treatment efficacy may be reduced with advancing age (particularly in those older than 60 years) because of an increased frequency of side effects requiring dose reduction [3]. (See "Management of the side effects of peginterferon and ribavirin being used for treatment of chronic hepatitis C virus infection" and "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection", section on 'Dose reduction and adherence' and "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Side effects of treatment'.)

Drug interactions are also an important consideration in patients with genotype 1 who are being considered for treatment with a telaprevir or boceprevir and should be taken into account prior to starting therapy (table 1 and table 2). (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Drug interactions with protease inhibitors' and "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Potential drug interactions'.)

PATIENT EVALUATION PRIOR TO TREATMENT

Liver biopsy — Most patients undergo liver biopsy prior to treatment of chronic hepatitis C virus (HCV) infection, although the utility of a routine biopsy continues to be debated. A liver biopsy has many practical advantages in the care of patients with HCV in whom treatment is being considered, especially patients with genotype 1 infection [4]. (See "Histologic scoring systems for chronic liver disease" and "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection".)

Advantages of a pretreatment liver biopsy include:

Liver histology is useful for predicting the stage and prognosis of the disease. Once identified, patients with cirrhosis should undergo periodic screening for hepatocellular carcinoma and esophageal varices. (See "Prevention of hepatocellular carcinoma and recommendations for surveillance in adults with chronic liver disease" and "Overview of the complications, prognosis, and management of cirrhosis", section on 'Variceal bleeding'.)
A liver biopsy can establish the presence of concomitant diseases (such as hemochromatosis, alcoholic hepatitis, nonalcoholic steatohepatitis/nonalcoholic fatty liver disease, and hepatic sarcoidosis) and the degree to which these conditions contribute to the patient's liver disease.
Once treatment has started, baseline liver histology can assist in decisions regarding medication adjustments in patients who experience adverse effects (eg, the threshold to discontinue therapy may be relatively high in patients who have advanced histologic features).
In the past, a liver biopsy was recommended in all patients with chronic hepatitis C prior to treatment [5]. However, current guidelines recognize that a liver biopsy may not be necessary in all patients [1]. In particular, a biopsy may not be required prior to treatment of patients with genotype 2 or 3 (in whom the virologic response rate is as high as 80 percent), provided that other causes of liver disease have been excluded.

We generally perform a liver biopsy prior to treatment in patients with genotypes 1 and 4. For patients with genotypes 2 and 3 we do not routinely perform a pretreatment liver biopsy, but we do perform a liver biopsy in those who do not respond to therapy. Following treatment, we do not perform a repeat liver biopsy in patients who have had a sustained virologic response. By contrast, a repeat liver biopsy may be performed in two years (some authorities use longer intervals) to evaluate disease progression in patients who do not respond to treatment or who decline treatment. There is little information on the appropriate interval for subsequent evaluations.

Noninvasive measures of hepatic fibrosis may be an alternative to liver biopsy in selected patients. (See "Noninvasive assessment of hepatic fibrosis".)

Evaluation for conditions that might affect therapy — Prior to initiating antiviral therapy, a thorough evaluation for other types of liver disease should be obtained, and other medical conditions should be investigated since they may have a bearing on the treatment plan. As examples:

Interferon is contraindicated in patients with active major depression because such patients are at risk for committing suicide during treatment. (See "Neuropsychiatric side effects associated with interferon-alfa plus ribavirin therapy: Recognition and risk factors" and "Neuropsychiatric side effects associated with interferon-alfa plus ribavirin therapy: Treatment and prevention".)
Patients with underlying autoimmune disorders may be at increased risk from therapy with interferon. (See "Principles of interferon therapy in liver disease and the induction of autoimmunity".)
Ribavirin is contraindicated in patients who are pregnant, contemplating pregnancy (including men), or are unwilling to assure contraception (ribavirin is pregnancy category X due to significant teratogenic and embryocidal effects). (See "Mechanism of action and efficacy of ribavirin for the treatment of chronic hepatitis C virus infection", section on 'Adverse effects of ribavirin'.)
Other liver diseases can interact adversely with chronic hepatitis C. As an example, alcohol abuse reduces the responsiveness to interferon, accelerates disease progression, and increases the risk of hepatocellular carcinoma [6,7]. As a result, patients with chronic hepatitis C should be counseled not to drink alcohol. In addition, steatosis is associated with lower treatment response rates. (See "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection", section on 'Other predictors'.)
Certain underlying diseases can modify the treatment plan. Patients with concurrent hereditary hemochromatosis or porphyria cutanea tarda, for example, should first be treated with phlebotomy to reduce iron accumulation.
Patients with concurrent human immunodeficiency virus (HIV) infection have an accelerated rate of progression of HCV. The responsiveness to interferon is determined in part by the immune status and is lower overall than in patients infected with HCV alone. (See "Evaluation of the HIV-infected patient with chronic hepatitis C virus infection" and "Treatment of hepatitis C virus infection in the HIV-infected patient".)
Patients being treated for HCV with peginterferon and ribavirin who have insulin resistance have lower sustained virologic response rates. (See "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection", section on 'Insulin resistance'.)
Multiple drug interactions exist with telaprevir and boceprevir and need to be taken into account prior to starting one of these agents. (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Drug interactions with protease inhibitors'.)
SPECIAL SITUATIONS — While the decision to offer therapy to a treatment-naïve patient with a detectable viral load, significant chronic hepatitis and fibrosis on liver biopsy, and without any contraindications to treatment is usually straight-forward, the decision is more complicated in patients who do not meet these criteria.

Relapsers and nonresponders — The decision to retreat patients who fail to respond to treatment or who relapse after treatment should take into account the following [1,8]:

The previous type of response
The previous therapy and the difference in the potency of the new therapy
The severity of the underlying liver disease (see "Histologic scoring systems for chronic liver disease")
Viral genotype and other predictive factors of response (see "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection")
Tolerance and compliance with previous therapy
HCV genotype since protease inhibitor based-triple therapy is an option in patients with genotype 1
In addition, IL28B genotype (CC, CT, or TT) may be a factor to take into consideration [9,10]. In one study of patients who had failed prior therapy for HCV genotype 1, IL28B genotype CC was associated with an increased chance of attaining an SVR [10]. (See "Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection", section on 'IL28B polymorphisms'.)

Persistently normal serum ALT — Up to 30 percent of patients with chronic hepatitis C virus (HCV) infection have a persistently normal serum alanine aminotransferase (ALT) level. The optimal management of such patients remains controversial. As a group, they may have a better prognosis than those who have elevated serum ALT levels [11]. (See "Approach to patients with chronic hepatitis C virus infection and normal serum aminotransferases", section on 'Course and management'.)

A role for treatment is supported by the observation that some of these patients have substantial inflammation on liver biopsy [12]. In addition, the response to combination therapy with peginterferon plus ribavirin in patients with normal serum aminotransferases is similar to the response in those with elevated aminotransferase levels.

It is reasonable to withhold treatment in patients with persistently normal serum ALT levels who have characteristics associated with slower rates of progression of hepatic fibrosis, such as HCV acquisition before the age of 35 years, female sex, alcohol abstinence, and no or minimal fibrosis on liver biopsy [13]. By contrast, we offer treatment to patients who do not fit this profile and whose initial biopsies show moderate activity or some degree of fibrosis because the risk of disease progression is increased in such patients. We usually treat these patients using combination therapy with peginterferon plus ribavirin (plus a protease inhibitor for patients with genotype 1). (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4".)

Mild liver disease — Patients who have a persistent elevation in serum ALT levels but do not have fibrosis and have minimal necroinflammatory changes are likely to have slow disease progression [14]. Such patients can be monitored periodically. However, the decision to treat should be individualized. We treat these patients in the same way as patients with a persistently normal ALT.

Extrahepatic manifestations of HCV infection — Interferon alfa has been used with reasonable success for the treatment of some extrahepatic manifestations of HCV infection, such as essential mixed cryoglobulinemia and glomerulonephritis. (See "Treatment of essential mixed cryoglobulinemia" and "Extrahepatic manifestations of hepatitis C virus infection".)

Advanced hepatic fibrosis and compensated cirrhosis — The efficacy of treatment in patients with advanced hepatic fibrosis or compensated cirrhosis has been derived mostly from subgroup analyses of large clinical trials. The analyses have suggested that the response rate is lower in these patients than in those without cirrhosis. The use of growth factors (such as erythropoietin, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor) may be helpful during treatment by limiting the need for reductions in the dose of antiviral therapy. (See "Management of the side effects of peginterferon and ribavirin being used for treatment of chronic hepatitis C virus infection".)

A 2010 meta-analysis of 26 studies examined the association between achieving a sustained virologic response (SVR, defined as a negative HCV RNA six months after the completion of therapy) and adverse outcomes in patients with advanced fibrosis or cirrhosis [15]. Patients with advanced fibrosis or cirrhosis who underwent treatment but did not attain an SVR had a liver-related mortality rate of 2.7 percent per year. Patients with chronic HCV and advanced fibrosis who did achieve an SVR had a much lower risk of liver-related mortality (relative risk [RR] 0.19; 95% confidence interval 0.10-0.37). Patients who attained an SVR were also significantly less likely to develop hepatocellular carcinoma (RR 0.32) or hepatic decompensation (RR 0.13).

In a study of patients with advanced hepatitis C (Ishak fibrosis score of at least 3), 140 patients who attained an SVR were compared with 309 patients who had no response to therapy and 77 patients who experienced viral breakthrough or relapse [16]. Patients were followed for a median of 86, 85, and 79 months, respectively. Compared with patients who had no response to treatment, the patients who attained an SVR had significantly lower morbidity rates (21 versus 2 percent) and lower mortality rates (27 versus 3 percent). There were no significant differences in the morbidity and mortality rates when the patients who had attained an SVR were compared with the patients who experienced viral breakthrough or relapse.

Based upon the improved prognosis in patients with advanced fibrosis or compensated cirrhosis who receive treatment with peginterferon and ribavirin, we suggest that these patients receive treatment if they are otherwise candidates. Patients with genotype 1 should also receive telaprevir or boceprevir, provided there are no contraindications.

Decompensated cirrhosis — The primary treatment for patients with decompensated cirrhosis is liver transplantation. However, experienced hepatologists may consider antiviral therapy in patients with mild degrees of decompensation [1,17]. Decompensated cirrhosis refers to a history of or the presence of, ascites, hepatic encephalopathy or jaundice (table 3). In addition, marked abnormalities in serum albumin, bilirubin, and prothrombin times are features of decompensation. (See "Liver transplantation for hepatitis C virus infection" and "Overview of the complications, prognosis, and management of cirrhosis".)

A few reports have described treatment of patients with decompensated cirrhosis with peginterferon and ribavirin therapy [18]. Treatment has been associated with substantial side effects and dropouts, but some patients have achieved an SVR, which has been associated with improved survival [18,19]. At present, such treatment should only be attempted at centers with experience and systems to care for such patients, preferably in the context of a clinical trial.

Recurrence after liver transplantation — Recurrence of HCV occurs in more than 95 percent of patients after liver transplantation. Disease progression in this setting is more rapid, and complications are more frequent than in immunocompetent patients with HCV infection [14]. Disease progression correlates with HCV RNA levels at the time of transplantation, the age of the organ donor, and the degree of immunosuppression in the post-transplant period.

There are few high-quality studies to guide treatment of HCV after liver transplantation. Antiviral therapy is generally initiated only if there is significant histologic liver injury. However, the therapeutic options are limited in this population, and rigorous clinical trials are difficult to conduct. (See "Liver transplantation for hepatitis C virus infection", section on 'Treatment of recurrence'.)

Kidney disease — The renal diseases associated with HCV and issues related to HCV infection in patients on maintenance dialysis are discussed separately. (See "Renal disease associated with hepatitis C virus infection".)

Active illicit drug use — Whether treatment with interferon-based regimens should be offered to patients who are actively using illicit drugs is controversial [20,21]. Treatment of such patients should be individualized. The 2009 guideline issued by the AASLD recommends that treatment should not be withheld from those who currently use illicit drugs or those who are in a methadone maintenance program, provided that they wish to be treated and are willing and able to maintain close monitoring and practice contraception [1].

An important adjunct to treatment is continued support from drug abuse and psychiatric counseling services. HCV therapy can be successful even when patients have not been abstinent from continued drug use or are receiving pharmacologic treatments for drug dependency (eg, methadone or subcutaneous naltrexone) [20,22,23]. (See "Treatment of opioid use and dependence" and "Overview of the recognition and management of the drug abuser".)

Ongoing alcohol use — Alcohol is an important cofactor in HCV disease progression, and the amount of alcohol that is safe during treatment is unknown. While a history of alcohol abuse is not an absolute contraindication to treatment, continued alcohol use decreases the response to therapy, and patients should be encouraged to abstain from alcohol. In patients who continue to drink alcohol, treatment should be performed along with efforts to treat the alcohol abuse. (See "Hepatitis C and alcohol" and "Psychosocial treatment of alcohol abuse and dependence".)

One study demonstrated that patients with ongoing alcohol use or less than six months of sobriety prior to treatment can be successfully treated using a multi-disciplinary approach that included addiction care [24]. An SVR was achieved in 35 of 73 patients (48 percent), which was similar to the rate seen in matched controls who did not drink (49 percent SVR rate). Factors associated with an increased SVR rate included a low viral load and length of abstinence during treatment.

Children — The management of children with hepatitis C virus infection is discussed elsewhere. (See "Hepatitis C virus infection in children", section on 'Treatment'.)

PROPORTION OF PATIENTS WHO RECEIVE TREATMENT — The proportion of patients with chronic HCV infection who are treated has not been accurately determined, but the reported rate has ranged from 12 to 28 percent [25-27].

Of 327 patients referred to a liver clinic in a metropolitan area, 83 (28 percent) were ultimately treated [25]. The most common reasons for a lack of treatment were failure to adhere to evaluation procedures (37 percent), medical or psychiatric contraindications (34 percent), patient preferences (11 percent), absence of HCV RNA (10 percent), and normal liver enzymes (5 percent).
Among 134,934 HCV-infected United States veterans, only 12 percent were treated [26]. Furthermore, of those on treatment who were followed for more than one year, only 23 percent completed a full 48-week course of treatment. Noncompletion was significantly associated with baseline anemia and depression.
Other risk factors for nontreatment include relatively inexperienced providers, older age, single patients, hepatic dysfunction, genotype 1, African American race with genotype 1, and anemia [27].

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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)")
Beyond the Basics topics (see "Patient information: Hepatitis C (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS

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. In general, patients being considered for treatment should have histologic and virologic evidence of chronic HCV infection. (See 'Introduction' above and "Overview of the management of chronic hepatitis C virus infection", section on 'Guidelines' and 'Liver biopsy' above.)
Treatment is generally indicated in treatment-naïve patients with a detectable viral load, significant chronic hepatitis and fibrosis on liver biopsy, and without any contraindications to treatment. (See 'Patients for whom therapy is widely accepted' above.)
Treatment decisions in other populations can be more difficult. (See 'Special situations' above.)
The decision to retreat patients who fail to respond to treatment or who relapse after treatment should take into account multiple factors, including the previous type of therapy, the severity of the underlying liver disease, and factors that predict a response to treatment, such as viral genotype. (See 'Relapsers and nonresponders' above.)
We suggest monitoring without specific treatment for women with a persistently normal ALT or mild liver disease who acquired the disease under the age of 35 years, do not drink alcohol, and have no or minimal fibrosis on liver biopsy (Grade 2B). (See 'Persistently normal serum ALT' above and 'Mild liver disease' above.)
We suggest treatment with peginterferon plus ribavirin for patients with a persistently normal ALT or mild liver disease who do not fit the above profile and whose initial biopsies show moderate activity or some degree of fibrosis (Grade 2B). Patients with genotype 1 should also receive a protease inhibitor (telaprevir or boceprevir) (Grade 1A). (See 'Persistently normal serum ALT' above and "Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4" and "Treatment regimens for chronic hepatitis C virus genotype 1".)
We suggest treatment with peginterferon and ribavirin for patients with advanced fibrosis or compensated cirrhosis who are otherwise candidates for antiviral therapy (Grade 2B). As above, patients with genotype 1 should also receive a protease inhibitor. While the response rate to treatment in these patients is lower than the response rate in patients without cirrhosis, achievement of a sustained virologic response in such patients is associated with decreased rates of mortality, hepatocellular carcinoma, and hepatic decompensation. (See 'Advanced hepatic fibrosis and compensated cirrhosis' above.)
Patients with active substance abuse should receive ongoing support from drug/alcohol abuse and psychiatric counseling services during antiviral treatment. (See 'Active illicit drug use' above and 'Ongoing alcohol use' above.)
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REFERENCES
Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.
Ramachandran P, Fraser A, Agarwal K, et al. UK consensus guidelines for the use of the protease inhibitors boceprevir and telaprevir in genotype 1 chronic hepatitis C infected patients. Aliment Pharmacol Ther 2012; 35:647.
Iwasaki Y, Ikeda H, Araki Y, et al. Limitation of combination therapy of interferon and ribavirin for older patients with chronic hepatitis C. Hepatology 2006; 43:54.
Perrillo RP. The role of liver biopsy in hepatitis C. Hepatology 1997; 26:57S.
The National Institutes of Health Consensus Development Conference. Management of hepatitis C. Hepatology 1997; 26 Suppl 1:1S.
Okazaki T, Yoshihara H, Suzuki K, et al. Efficacy of interferon therapy in patients with chronic hepatitis C. Comparison between non-drinkers and drinkers. Scand J Gastroenterol 1994; 29:1039.
Nalpas B, Driss F, Pol S, et al. Association between HCV and HBV infection in hepatocellular carcinoma and alcoholic liver disease. J Hepatol 1991; 12:70.
Seeff LB, Hoofnagle JH. National Institutes of Health Consensus Development Conference: management of hepatitis C: 2002. Hepatology 2002; 36:S1.
Chevaliez S, Soulier,A, Hezode C, et, al. The IL28B genotype is a major determinant in the induction of a virological response by high-dose peginterferon and ribavirin in null-resonders to standard-of-care therapy. Hepatology 2010; 52:383A.
O'Brien TR, Everhart JE, Chung RT, et, al. An IL28B genotype-based model for personalized prediction of response to pegylated-interferon-alfa and ribavirin in the treatment of chronic hepatitis C. Hepatology 2010; 52:382A.
Mathurin P, Moussalli J, Cadranel JF, et al. Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity. Hepatology 1998; 27:868.
Puoti C, Magrini A, Stati T, et al. Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels. Hepatology 1997; 26:1393.
Missale G, Cariani E, Lamonaca V, et al. Effects of interferon treatment on the antiviral T-cell response in hepatitis C virus genotype 1b- and genotype 2c-infected patients. Hepatology 1997; 26:792.
National Institutes of Health Consensus Development Conference Panel statement: management of hepatitis C. Hepatology 1997; 26:2S.
Singal AG, Volk ML, Jensen D, et al. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol 2010; 8:280.
Morgan TR, Ghany MG, Kim HY, et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology 2010; 52:833.
Everson GT, Trotter J, Forman L, et al. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology 2005; 42:255.
Iacobellis A, Siciliano M, Perri F, et al. Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study. J Hepatol 2007; 46:206.
Iacobellis A, Perri F, Valvano MR, et al. Long-term outcome after antiviral therapy of patients with hepatitis C virus infection and decompensated cirrhosis. Clin Gastroenterol Hepatol 2011; 9:249.
Jeffrey GP, MacQuillan G, Chua F, et al. Hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implants. Hepatology 2007; 45:111.
Edlin BR, Seal KH, Lorvick J, et al. Is it justifiable to withhold treatment for hepatitis C from illicit-drug users? N Engl J Med 2001; 345:211.
Mauss S, Berger F, Goelz J, et al. A prospective controlled study of interferon-based therapy of chronic hepatitis C in patients on methadone maintenance. Hepatology 2004; 40:120.
Bonkovsky HL, Tice AD, Yapp RG, et al. Efficacy and safety of peginterferon alfa-2a/ribavirin in methadone maintenance patients: randomized comparison of direct observed therapy and self-administration. Am J Gastroenterol 2008; 103:2757.
Le Lan C, Guillygomarc'h A, Danielou H, et al. A multi-disciplinary approach to treating hepatitis C with interferon and ribavirin in alcohol-dependent patients with ongoing abuse. J Hepatol 2012; 56:334.
Falck-Ytter Y, Kale H, Mullen KD, et al. Surprisingly small effect of antiviral treatment in patients with hepatitis C. Ann Intern Med 2002; 136:288.
Butt AA, McGinnis KA, Skanderson M, Justice AC. Hepatitis C treatment completion rates in routine clinical care. Liver Int 2010; 30:240.
Kanwal F, Hoang T, Spiegel BM, et al. Predictors of treatment in patients with chronic hepatitis C infection - role of patient versus nonpatient factors. Hepatology 2007; 46:1741.
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