Clinical Review

Hepatitis C: How To Fine-Tune Your Approach

Clinician Reviews. 2015 September;25(9):535-540

References

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2. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705-714.

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8. Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol. 2014;61:S58-S68.

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11. Solinas A, Piras MR, Deplano A. Cognitive dysfunction and hepatitis C virus infection. World J Hepatol. 2015;7:922-925.

12. Fletcher NF, Wilson GK, Murray J, et al. Hepatitis C virus infects the endothelial cells of the blood-brain barrier. Gastroenterology. 2012;142:634-643.e6.

13. Smith BD, Morgan RL, Beckett GA, et al; Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61:1-32.

14. US Preventive Services Task Force. Final recommendation statement on hepatitis C screening, June 2013. US Preventive Services Task Force Web site. Available at: http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-c-screening. Accessed on December 28, 2014.

15. Arora S, Thornton K, Murata G, et al. Outcomes of treatment for hepatitis C virus infection by primary care providers. N Engl J Med. 2011;364:2199-2207.

16. Morrill JA, Shrestha M, Grant RW. Barriers to the treatment of hepatitis C. Patient, provider, and system factors. J Gen Intern Med. 2005;20:754-758.

17. Shivkumar S, Peeling R, Jafari Y, et al. Accuracy of rapid and pointof- care screening tests for hepatitis C: a systematic review and meta-analysis. Ann Intern Med. 2012;157:558-566.

18. American Association for the Study of Liver Diseases; Infectious Diseases Society of America; International Antiviral Society—USA. HCV guidance: Recommendations for testing, managing, and treating hepatitis C. HCV guidelines Web site. Available at: http://www.hcvguidelines.org. Accessed May 25, 2015.

19. Zarski JP, Bohn B, Bastie A, et al. Characteristics of patients with dual infection by hepatitis B and C viruses. J Hepatol. 1998;28:27-33.

20. Graham CS, Baden LR, Yu E, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis. 2001;33:562-569.

21. Garcia-Tsao G, Friedman S, Iredale J, et al. Now there are many (stages) where before there was one: In search of a pathophysiological classification of cirrhosis. Hepatology. 2010;51:1445-1449.

22. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289-293.

23. Ngo Y, Munteanu M, Messous D, et al. A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C. Clin Chem. 2006;52:1887-1896.

24. Becker L, Salameh W, Sferruzza A, et al. Validation of hepascore, compared with simple indices of fibrosis, in patients with chronic hepatitis C virus infection in United States. Clin Gastroenterol Hepatol. 2009;7:696-701.

25. Bonder A, Afdhal N. Utilization of FibroScan in clinical practice. Curr Gastroenterol Rep. 2014;16:372.

26. Garcia-Tsao G, Sanyal AJ, Grace ND, et al; Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922-938.

27. Ghany MG, Strader DB, Thomas DL, et al; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335-1374.

28. Pessione F, Degos F, Marcellin P, et al. Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C. Hepatology. 1998;27:1717-1722.

29. Mueller S, Millonig G, Seitz HK. Alcoholic liver disease and hepatitis C: a frequently underestimated combination. World J Gastroenterol. 2009;15:3462-3471.

30. Ortiz V, Berenguer M, Rayón JM, et al. Contribution of obesity to hepatitis C-related fibrosis progression. Am J Gastroenterol. 2002;97:2408-2414.

31. Lewis JH, Mortensen ME, Zweig S, et al; Pravastatin in Chronic Liver Disease Study Investigators. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology. 2007;46:1453-1463.

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36. Thomas AM, Kattakuzhy S, Jones S, et al. SVR durability: HCV patients treated with IFN-free DAA regimens. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February, 2015; Seattle, Washington. Abstract 653.

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Look for the evidence of liver disease

Family physicians should order several additional tests for patients found to have chronic HCV infection before referring such patients to a specialist (ALGORITHM). Work-up should include the complete blood count, HCV genotype (which will help guide treatment), liver function tests, international normalized ratio test, and ultrasound of the liver.¹⁸ In addition, all HCV-positive patients should be tested for HIV and HBV, because these co-infections may accelerate liver fibrosis.^19,20

All patients with chronic HCV infection should also be screened for the presence of fibrosis and cirrhosis, as this will influence treatment choice and duration. Signs of cirrhosis that may be evident on physical exam include jaundice, spider angiomata, palmar erythema, encephalopathy with asterixis, and fluid overload, especially ascites. Cirrhosis can be classified clinically as compensated (stage 1 with no varices present and stage 2 with varices present) and decompensated (stages 3 and 4), which is defined as cirrhosis with signs of severe portal hypertension (bleeding varices, ascites, hepatic encephalopathy) or liver insufficiency (jaundice).²¹ Patients with decompensated cirrhosis should be managed by a liver transplant center. For more on cirrhosis, see “Cirrhosis complications: Keeping them under control” (J Fam Pract. 2015;64:338-342).

Several noninvasive alternatives to liver biopsy

Historically, liver biopsy has been the gold standard for staging liver disease. The Metavir scoring system is a histological assessment of the degree of inflammatory activity and the stage of fibrosis.²² The degree of inflammation activity, which is a precursor of fibrosis, is scored from A0 (no activity) to A3 (severe activity). The staging of fibrosis involves a 5-stage scoring system: F0 (chronic hepatitis without fibrosis); F1 (portal fibrosis without septae); F2 (portal fibrosis with rare septae); F3 (many septae without cirrhosis); or F4 (cirrhosis).

That said, noninvasive tests have largely supplanted liver biopsy for fibrosis screening.

Up to 75% of patients with hepatitis C are unaware of their infection.

For example, the FibroSure test uses the patient’s age, gender, and a combination of 6 serum markers of liver function in a computational algorithm to generate a quantitative indicator of liver fibrosis, with a score of 0.0 to 1.0 that corresponds to the Metavir fibrosis score (F0-F4), and an inflammatory activity score (A0-A3).²³ Similarly, HepaScore uses several noninvasive markers to calculate a score from 0.00 to 1.00. A score ≤0.2 accurately excludes significant fibrosis. However, a score of ≥0.55 or higher corresponds to a Metavir score of at least F2, and in such cases further testing would be needed to evaluate for cirrhosis.²⁴

FDA-approved in 2013, transient elastography (FibroScan) is another noninvasive alternative to liver biopsy for determining the stage of liver disease. This bedside test uses ultrasound technology to measure liver stiffness and provides a score ranging from 0 to 75 kPA that correlates with the Metavir score. Although not yet widely available in the United States, FibroScan is becoming increasingly popular as a rapid and noninvasive screening tool for cirrhosis.²⁵

Identifying cirrhosis in patients who have HCV is crucial because such patients need prompt care from a specialist. In addition to receiving HCV treatment, patients with cirrhosis also need regular liver ultrasound exams to screen for HCC (every 6 months) and esophagogastroduodenoscopy to screen for esophageal and gastric varices.²⁶

Advise patients to avoid alcohol, lose weight

Counsel patients who test positive for HCV infection about making lifestyle changes to avoid further liver damage and transmission of HCV to others. Infectious diseases and hepatology society guidelines recommend vaccination against hepatitis A and B for all HCV-infected patients who are not immune to these viruses because acute co-infection could lead to severe acute liver injury.^18,27 Urge all HCV-infected patients to completely abstain from alcohol and, if necessary, refer them to an addiction specialist, because excess alcohol consumption is strongly associated with the development of cirrhosis and HCC.^28,29

Comorbid conditions such as metabolic syndrome, obesity, and hyperlipidemia can worsen the prognosis for HCV-infected patients; therefore, intense counseling on weight loss is recommended.³⁰ Statins are safe and beneficial for HCV patients with hypercholesterolemia and compensated cirrhosis.³¹

Teach patients that the primary mode of transmission of HCV is through infected blood. Sexual transmission of HCV has been well documented in HIV-positive men who have sex with men.³² Although the risk of transmission of HCV among heterosexual couples is extremely low, it is possible, and patients should be counseled accordingly.³³ Transmission of HCV from mother to the baby occurs in up to 6% of births and most commonly occurs during delivery.³⁴

Newer treatments are highly effective and well tolderated

HCV treatment has changed dramatically over the past few years. Previous treatments for HCV, particularly those containing interferon, were known for their poor tolerability due to adverse effects and low cure rates. Compared to previous therapies, the new interferon-free direct-acting antiviral (DAA) regimens are not only less complex but also shorter in duration, ranging from 8 to 24 weeks depending on the patient’s viral load, stage of liver disease, and previous treatment experience.¹⁸ The specific agents and dosages used in DAA regimens aren’t described here because these regimens are rapidly changing. However, continuously updated treatment recommendations from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America are available at http://www.hcvguidelines.org.