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Successful Treatment of Hepatitis B and C: Don't Forget the Liver!!!

Published:September 18, 2014DOI:https://doi.org/10.1016/j.amjmed.2014.09.008
      SEE RELATED ARTICLE p. 90
      We have been aware of hepatitis B and C for decades. Both viruses are associated with a chronic carrier state and risk of developing cirrhosis and hepatocellular carcinoma. Successful control but not cure of hepatitis B was achieved several years ago after the development of direct-acting antiviral drugs. Treatment of hepatitis C began with the use of interferon alpha, which led to viral clearance in less than 20% of cases. After decades of slowly improving therapies based on the use of interferon alpha, we are now entering a new era of noninterferon-based therapies that depend solely on direct-acting antiviral drugs. Most patients with hepatitis C virus currently receive their treatment from gastroenterologists and hepatologists. Other physicians are less likely to treat these patients because of the toxicity of the therapy with interferon alpha. With the development of direct-acting antiviral drugs, more physicians will be willing to treat patients with hepatitis C virus because of the limited number of side effects and high rate of success with a short period of treatment (12 weeks).
      • Kowdley K.V.
      • Lawitz E.
      • Poordad F.
      • et al.
      Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1.
      • Afdhal N.
      • Reddy K.R.
      • Nelson D.R.
      • et al.
      Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.
      The concern is that the focus will be only on the infection and not on the potentially life-threatening liver injury that may not be apparent clinically.
      In contrast to many malignancies, the incidence of hepatocellular carcinoma in the United States is increasing and is a major indication for liver transplantation and a significant cause of mortality in this patient population.
      • Bruix J.
      • Sherman M.
      Management of hepatocellular carcinoma.
      In one series, 530 patients with hepatitis C virus with advanced fibrosis were treated with interferon-based therapies and followed for a median of 8.4 years.
      • Van der Meer A.
      • Veldt B.J.
      • Feid J.J.
      • et al.
      Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.
      The rate of hepatocellular carcinoma per 100 person years in those without viral clearance was 2.6, and this rate decreased to 0.55 in those who were successfully treated. All-cause mortality was reduced by approximately 50% in those who cleared the virus compared with those not clearing the virus. However, it is important to note that even those with viral clearance were still at risk for developing hepatocellular carcinoma up to 7 years after treatment.
      • Van der Meer A.
      • Veldt B.J.
      • Feid J.J.
      • et al.
      Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.
      Similar studies in patients infected with hepatitis B virus again show a reduction but not elimination of the risk for development of hepatocellular carcinoma in patients who responded to treatment.
      • Arends P.
      • Sonneveld M.J.
      • Zoutendijk R.
      • et al.
      Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians.
      Because the risk for development of hepatocellular carcinoma is significant in those with advanced liver fibrosis, societies have recommended that these individuals undergo screening for hepatocellular carcinoma every 6 to 12 months.
      • Bruix J.
      • Sherman M.
      Management of hepatocellular carcinoma.
      In this issue of The American Journal of Medicine, Singal et al
      • Singal A.G.
      • Li X.
      • Tiro J.
      • et al.
      Racial, social, and clinical determinants of hepatocellular carcinoma surveillance.
      examined how well these guidelines were being followed in a group of 904 patients with cirrhosis due to a variety of causes. Only 13% had annual surveillance and 2% had biannual surveillance, mostly performed in hepatology clinics. Inconsistent surveillance was more likely in those who were uninsured, who visited their primary care physician or hepatologist less frequently, who were black, and who had nonalcoholic steatohepatitis. Failure to know a patient had cirrhosis also reduced surveillance rates. Last, longer periods of follow-up reduced the rate of surveillance, suggesting a belief among some physicians that a negative screen indicates a reduced likelihood of subsequently developing hepatocellular carcinoma. These suboptimal rates of screening have been seen in other populations.
      • El-Serag H.B.
      • Alsarraj A.
      • Richardson P.
      • et al.
      Hepatocellular carcinoma screening practices in the Department of Veterans Affairs: findings from a national facility survey.
      • Park J.H.
      • Kim T.O.
      • Yang S.Y.
      • et al.
      Hepatocellular carcinoma screening in a hepatitis B virus-infected Korean population.
      Despite clearance of hepatitis C virus in almost all patients treated with the new direct-acting antiviral drugs, we must not lose interest in continued screening of those with advanced fibrosis. When evaluating a patient for treatment, an assessment for the presence of significant fibrosis is required by using tests such as the FibroSURE™, elastography, imaging, or a liver biopsy. If stage 3 or 4 fibrosis is found, then screening for hepatocellular carcinoma for the foreseeable future is required. Telling a patient who has significant fibrosis that successful treatment of the infection is the end of the story is a mistake and will lead to patients presenting with advanced hepatocellular carcinoma that cannot be treated successfully, resulting in poor patient survival.

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      Linked Article

      • Racial, Social, and Clinical Determinants of Hepatocellular Carcinoma Surveillance
        The American Journal of MedicineVol. 128Issue 1
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          Less than 1 in 5 patients receive hepatocellular carcinoma surveillance; however, most studies were performed in racially and socioeconomically homogenous populations, and few used guideline-based definitions for surveillance. The study objective was to characterize guideline-consistent hepatocellular carcinoma surveillance rates and identify determinants of hepatocellular carcinoma surveillance among a racially and socioeconomically diverse cohort of cirrhotic patients.
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