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Management of Hepatitis C Infection

Stefan Zeuzem, MD
Program Director
Jordan J. Feld, MD, MPH
Hemant Shah, MD, MScCH HPTE
Released: June 17, 2019

Management of Acute HCV Infection

Identifying Acute HCV and the Need for Treatment

The identification of acute HCV infection is complicated by the lack of symptoms during the acute phase in approximately 85% of cases.[193] Nonetheless, the importance of identifying acute hepatitis C early is underscored by the high likelihood of developing chronic infection (approximately 50% to 85%) if untreated and the high success rate of antiviral therapy in patients with acute infection. Factors that have been shown to be associated with spontaneous viral clearance in patients with acute infection include female sex,[194] younger age,[195] symptomatic disease,[196] and HCV RNA clearance during the initial 4-5 weeks following the onset of symptoms.[197] A polymorphism near the IL28B gene has also been shown to be associated with spontaneous resolution of acute HCV infection. In an analysis of the IL28B rs12979860 single nucleotide polymorphism in 190 women with acute genotype 1b HCV infection acquired from a single source, spontaneous viral clearance occurred in 64% of patients with the CC genotype vs 24% of patients with the CT genotype, and 6% of patients with the TT genotype (P < .001 for CC vs CT or TT).[198] A separate study of 632 individuals with acute HCV infection found spontaneous HCV clearance was independently associated with female sex, IL28B CC genotype, and HCV genotype 1 infection.[199] The effect of CC genotype and genotype 1 infection on spontaneous clearance was greater in women than in men. Among HIV-infected men, spontaneous clearance was predicted by a high CD4+ cell count, elevated ALT and bilirubin, and a rapid reduction in HCV RNA level.[200]

For more information from inPractice on the diagnosis of acute HCV infection, click here.

Interferon-based antiviral treatment of patients with acute hepatitis C significantly reduces the risk of developing chronic infection, with a 49% (95% CI: 33% to 65%) absolute risk reduction observed in a meta-analysis of 12 studies compared with no treatment.[201] Although there are minimal data on interferon-free regimens for acute HCV infection, they are likely to be very effective. Studies with standard interferon alfa monotherapy have revealed SVR rates of 83% to 100%.[202-204] Treatment with peginterferon monotherapy is associated with similarly high rates of SVR among acutely infected patients who are adherent to therapy and who receive an adequate dose.[205-207] Although these studies have demonstrated the efficacy of antiviral therapy in clearing acute HCV infection, there is no consensus on the optimal regimen or on the timing and duration of therapy in this setting.

Although treatment of acute HCV infection is likely to be effective, a strategy of watchful waiting with a plan for treatment if chronicity develops may also be appropriate. In regions of the world where interferon will remain an important component of HCV therapy in the future, there is greater rationale to treat acute infection given the much higher response rates in the acute stage of infection. Decisions about treatment of acute HCV infection require a case-by-case evaluation based on the specific characteristics of the individual and on current and expected access to therapies.

Even before the development of new effective therapies, several studies have supported a delay in initiating therapy for the first 12 weeks following infection to allow patients who would spontaneously clear the virus the opportunity to avoid unnecessary treatment. For example, in a study evaluating the initiation of antiviral therapy after 3 months following the onset of acute HCV infection, 52% of 46 symptomatic patients experienced spontaneous viral clearance, generally within 12 weeks after the onset of symptoms.[196] Of note, all asymptomatic patients in this study failed to spontaneously clear virus, making the case for considering early therapy in patients with asymptomatic acute hepatitis C. Data suggest that the IL28B polymorphism genotype may factor into optimal treatment timing for acute hepatitis C. A multiple-source cohort of patients with acute HCV infection were treated with interferon or peginterferon with or without ribavirin beginning at least 24 weeks after the initial diagnosis.[208] In addition to finding that IL28B CC genotype was the only statistically significant predictor of spontaneous disease resolution (odds radio: 3.87; 95% CI: 1.71-8.51), this study showed that 100% of adherent CC genotype patients who initiated therapy within 48 weeks of diagnosis achieved SVR compared with 28% of those with CT/TT genotypes. Among patients who initiated therapy after 48 weeks, there was no significant difference in response rate by IL28B genotype. According to the investigators, the results suggest that patients with IL28B CC or CT genotype do not experience a reduction in efficacy if therapy is initiated within 48 weeks or later following the onset of symptoms.

Guidance on Acute HCV Management

Guidance on the management of acute HCV infection has been provided in the AASLD and the IDSA guidelines. Although there are currently limited data on the use of DAAs to treat acute HCV, trials are ongoing. Given the efficacy of DAAs in chronic infection and the possibility of spontaneous viral clearance, the guidance recommends monitoring for spontaneous viral clearance for a minimum of 6 months with a plan to treat those who progress to chronicity. Current recommendations from the AASLD/IDSA regarding patients with acute hepatitis C include[54]:

  • Laboratory monitoring of HCV RNA (eg, every 4-8 weeks) for 6-12 months recommended to determine spontaneous clearance or persistent infection
  • Counseling on avoidance of hepatotoxic drugs (eg, acetaminophen), alcohol consumption, and HCV transmission to others recommended; patients with HCV related to injection drug use should be referred to an addiction specialist
  • Delaying treatment may be acceptable to monitor for spontaneous clearance for at least 6 months
  • If the decision is made to initiate treatment, recommended therapies include the same regimens as for chronic HCV infection
  • If planning to initiate therapy during acute infection period, patients should be monitored for HCV RNA for at least 12-16 weeks to allow for spontaneous clearance before starting treatment

Recommendations from the EASL differ somewhat in that they recommend treatment of acute HCV infection and include guidance on the use of specific DAA-based regimens in this setting according to HCV genotype (Table 42).[88] The guidelines state that treatment may need to be increased to 12 weeks for patients with HIV coinfection or high HCV RNA viral load. SVR should be assessed at 12 and 24 weeks after completion of therapy because late relapses have been reported.

The guidelines for acute HCV management from AASLD[54] and EASL[88] are summarized in Table 42.

Table 42. Guidelines for the Management of Acute HCV Infection


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