Prevalence and Challenges of Liver Diseases in Patients with Chronic Hepatitis C Virus Infection

Ira M. JAcobson; Gary L. Davis; Hashem El–Serag; Francesco Negro; Christian trépo


Clin Gastroenterol Hepatol. 2010;8(11):924-933. 

In This Article

Reducing the Impact of Infection

About 85% of HCV-positive persons in the United States general population can be identified on the basis of 3 characteristics: IDU history, blood transfusion before 1992, or abnormal serum alanine transaminase levels.[17] In selected populations, other characteristics might also be useful for screening. A retrospective study of 5400 US veterans found that the following factors predicted HCV infection: IDU, blood transfusion before 1992, service during the Vietnam war, tattoo, and a history of abnormal liver test results.[123] However, HCV risk factor histories are rarely documented in clinical practice.[124] Infected patients can thus remain undiagnosed until they present with hepatic complications. Recent guidelines issued by the American Association for the Study of Liver Diseases (AASLD) make recommendations for diagnosis and counseling of HCV-infected patients on alcohol, weight loss, and treatment to prevent the development of cirrhosis and other complications.[125]

Diagnosis and Screening

Figure 2 summarizes the clinical management of patients at risk of HCV infection. Asking patients about their transfusion history and high-risk drug/sexual behavior during health care visits should be routine, and high-risk patients (history of IDU, blood transfusion before 1992, or HIV-positive) should be tested, with cognizance of the higher prevalence rates in men, "baby boomers," and African Americans. The AASLD guidelines promote screening in at-risk populations to reduce HCV transmission rates.[125] The recent IOM report on viral hepatitis includes a recommendation that federally funded US health care insurers improve access to HCV screening as part of preventative care for the general population, so people at risk of HCV infection can be identified.[15]

Figure 2.

Summary of the screening, diagnosis, and treatment of patients at risk of HCV infection.

Once diagnosed, patients should be evaluated for HCV RNA, genotype, and serologic exclusion of common liver diseases. Baseline imaging (ultrasound) might also be useful. Assessing fibrosis by liver biopsy can be used to estimate prognosis, treatment urgency, and necessity of HCC screening. Surrogate methods, including serum fibrosis markers, imaging techniques, and indirect methods to measure liver stiffness such as transient elastography,[125] might have a future role.

Because insulin resistance enhances fibrosis progression, monitoring insulin resistance, fasting glucose, or insulin levels is advisable. In addition, lifestyle modifications, including weight loss and dietary changes, might reduce insulin resistance and slow the fibrosis rate. All patients should be assessed for immunity against hepatitis A/B by assessment of disease markers and vaccinated if seronegative.[125] Counseling should be offered regarding alcohol consumption, if appropriate.


Currently, the only drugs available to treat HCV are peginterferon and ribavirin. SVR rates associated with peginterferon/ribavirin are suboptimal, particularly for genotype 1–infected patients.[9,10] The AASLD guidelines recommend an individualized treatment approach based on assessment of comorbidities, likelihood of response, and side-effect potential.[125] Although more effective options are needed, successful treatment can eradicate the virus and thereby minimize complications and possibly improve mortality rates.[126,127] Nearly all patients (99.2%) maintain undetectable HCV loads 5 years after attaining SVR, representing a "virologic cure."[126] Some patients with fibrosis who achieve SVR demonstrate an improvement in necroinflammatory activity and fibrosis regression.[128 –130] Furthermore, the 5-year survival of SVR patients is similar to that of the overall population.[130] The role of interferon in preventing HCC is controversial. A reduced risk of HCC has been noted in patients achieving SVR; however, reports of HCC after SVR was achieved in cirrhotic patients indicate a need for surveillance and reinforce the importance of viral eradication before cirrhosis develops.[131,132] Long-term maintenance therapy with peginterferon does not appear to affect the incidence of HCC.[133]

Davis et al[8] extended their multicohort model to include an assessment of treatment effects, predicting that an increase in the proportion of treated patients (or use of treatment with improved viral clearance rate) would result in reduced rates of cirrhosis, liver failure, HCC, and liver-related death.

Education and Counseling

A lack of knowledge about HCV among health care providers, social service providers, and the public is identified by the IOM as a major challenge to controlling the disease. Education and outreach programs for these audiences feature among the recent IOM recommendations for comprehensive viral hepatitis services aimed at preventing viral transmission, missed diagnosis, and poor health outcomes in HCV.[15]

Increasing access to treatment and providing support to optimize therapeutic adherence might help to improve outcomes. This requires a greater emphasis on early detection along with careful, individualized diagnostic assessment and therapeutic decision-making. Many physicians have adopted a "watch-and-wait" approach, particularly for patients with minimal liver disease. Although this might sometimes be appropriate, patients should be advised of the possibility of unexpectedly rapid disease progression and the need for regular follow-up, including repeat biopsies every 3–5 years. The pros and cons of deferring therapy should be discussed in the context of the patient's clinical and histologic profile.

Many eligible patients decline antiviral treatment. In a study of 280 US patients, 41% declined treatment, citing no symptoms and concerns about side effects.[134] Information provided by health care providers is critical; in 3 US cities, interest in HCV treatment among injection drug users was 7-fold higher among patients who were told that they were at risk for cirrhosis or cancer.[135] Patients under regular review are also more likely to be interested in receiving treatment,[135] emphasizing the importance of communication and continuity of care. Several promising agents, including HCV protease and polymerase inhibitors (eg, telaprevir, boceprevir, and R7128), are in phase 2 or phase 3 trials, with a hope of availability within 2–3 years and beyond.


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