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Current Hepatology Reports

Erschienen in:

01.11.2010

Hepatitis B Biomarkers: Clinical Significance of the Old and the New

verfasst von: Andrés Duarte-Rojo, Jordan J. Feld

Erschienen in: Current Hepatology Reports | Ausgabe 4/2010

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Abstract

Chronic hepatitis B is a dynamic disease with a very variable outcome ranging from mild, asymptomatic, nonprogressive disease to end-stage liver disease and/or hepatocellular carcinoma. Clinically significant endpoints take years or decades to develop and thus various biomarkers—ranging from clinical data to sophisticated virologic diagnostics—are used as surrogates for disease progression. Liver biopsy remains a robust indicator of disease severity; however, noninvasive markers may offer a useful alternative with some advantages. Clinical decisions are often made using alanine transaminase; however, it lacks adequate specificity to be used in isolation. Serologic markers (hepatitis B early antigen and hepatitis B surface antigen) provide information about the degree of immune control of viral replication, and thus remain important therapeutic indices. Sensitive measurement of serum hepatitis B virus DNA level is an indispensable biomarker. Its suppression is important, but only because it represents a bridge to more permanent stages of disease resolution. Newer assays, including hepatitis B surface antigen titers and hepatitis B genotyping, have therapeutic implications and are becoming more widely available. Clinicians caring for patients with chronic hepatitis B must be aware of the utility and limitations of available surrogate biomarkers.

Chen CJ, Yang HI, Su J, et al.: Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006, 295:65–73.CrossRefPubMed

Cholongitas E, Senzolo M, Standish R, et al.: A systematic review of the quality of liver biopsy specimens. Am J Clin Pathol 2006, 125:710–721.CrossRefPubMed

Wanless IR, Nakashima E, Sherman M: Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis. Arch Pathol Lab Med 2000, 124:1599–1607.PubMed

Mallet V, Dhalluin-Venier V, Roussin C, et al.: The accuracy of the FIB-4 index for the diagnosis of mild fibrosis in chronic hepatitis B. Aliment Pharmacol Ther 2009, 29:409–415.CrossRefPubMed

Halfon P, Munteanu M, Poynard T: Fibrotest-Actitest as a noninvasive marker of liver fibrosis. Gastroenterol Clin Biol 2008, 32(Suppl 1):22–39.CrossRefPubMed

Ngo Y, Benhamou Y, Thibault V, et al.: An accurate definition of the status of inactive hepatitis B virus carrier by a combination of biomarkers (fibrotest-actitest) and viral load. Plos One 2008, 3:e2573.CrossRefPubMed

Kim BK, Kim DY, Park JY, et al.: Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver Int 2010, 30:546–553.CrossRefPubMed

Castera L, Forns X, Alberti A: Noninvasive evaluation of liver fibrosis using transient elastography. J Hepatol 2008, 48:835–847.CrossRefPubMed

• Stebbing J, Farouk L, Panos G, et al.: A meta-analysis of transient elastography for the detection of hepatic fibrosis. J Clin Gastroenterol 2010, 44:214–219. This study provides a comprehensive analysis of studies to date using transient elastography to assess liver fibrosis.CrossRefPubMed

10.

Coco B, Oliveri F, Maina AM, et al.: Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat 2007, 14:360–369.CrossRefPubMed

11.

Arena U, Vizzutti F, Corti G, et al.: Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology 2008, 47:380–384.CrossRefPubMed

12.

• Kim SU, Kim do Y, Park JY, et al.: How can we enhance the performance of liver stiffness measurement using fibroscan in diagnosing liver cirrhosis in patients with chronic hepatitis B? J Clin Gastroenterol 2010, 44:66–71. This study highlights issues related to using transient elastography in chronic HBV infection, specifically the importance of ALT. ALT may falsely raise fibroscan results, leading to overdiagnoses of cirrhosis.CrossRefPubMed

13.

Chan HL, Wong GL, Choi PC, et al.: Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat 2009, 16:36–44.CrossRefPubMed

14.

Castéra L, Le Bail B, Roudot-Thoraval F, et al.: Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison of transient elastography (Fibroscan) with standard laboratory tests and non-invasive scores. J Hepatol 2009, 50:59–68.CrossRefPubMed

15.

Wong GL, Wong VW, Choi PC, et al.: Development of a noninvasive algorithm with transient elastography (Fibroscan) and serum test formula for advanced liver fibrosis in chronic hepatitis B. Aliment Pharmacol Ther 2010, 31:1095–1103.PubMed

16.

Prati D, Taioli E, Zanella A, et al.: Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002, 137:1–10.PubMed

17.

Kim HC, Nam CM, Jee SH, et al.: Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ 2004, 328:983.CrossRefPubMed

18.

• Ruhl CE, Everhart JE: Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology 2009, 136:477–485.e11. The study confirms that lower thresholds for the upper limit of normal of ALT apply in North America and influence mortality.

19.

Lok AS, McMahon BJ: Chronic hepatitis B: update 2009. Hepatology 2009, 50:661–662.CrossRefPubMed

20.

Iloeje UH, Yang HI, Su J, et al.; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group: Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006, 130:678–686.CrossRefPubMed

21.

• Marcellin P, Bonino F, Lau GK, et al.: Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology 2009, 136:2169–2179.e1–4. This study reports the treatment results for peginterferon in HBeAg ^- CHB, reinforcing that this agent has utility in this disease setting.

22.

•• Buster EH, Hansen BE, Lau GK, et al.: Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa. Gastroenterology 2009, 137:2002–2009. This important paper documents the factors predictive of response in HBeAg ⁺ patients treated with peginterferon.CrossRefPubMed

23.

Yuen MF, Yuan HJ, Wong DK, et al.: Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut 2005, 54:1610–1614.CrossRefPubMed

24.

Chen EQ, Huang FJ, He LL, et al.: Histological changes in Chinese chronic hepatitis B patients with ALT lower than two times upper limits of normal. Dig Dis Sci 2010, 55:432–437.CrossRefPubMed

25.

Yang HI, Lu SN, Liaw YF, et al.: Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002, 347:168–174.CrossRefPubMed

26.

McMahon BJ, Holck P, Bulkow L, Snowball M: Serologic and clinical outcomes of 1536 Alaska natives chronically infected with hepatitis B virus. Ann Intern Med 2001, 135:759–768.PubMed

27.

Liaw YF, Tai DI, Chu CM, Chen TJ: The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 1988, 8:493–496.CrossRefPubMed

28.

Hsu YS, Chien RN, Yeh CT, et al.: Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology 2002, 35:1522–1527.CrossRefPubMed

29.

Chu CM, Liaw YF: Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion. J Viral Hepat 2007, 14:147–152.CrossRefPubMed

30.

Wai CT, Fontana RJ: Clinical significance of hepatitis B virus genotypes, variants, and mutants. Clin Liver Dis 2004, 8:321–352.CrossRefPubMed

31.

•• Fattovich G, Olivari N, Pasino M, et al.: Long-term outcome of chronic hepatitis B in caucAsian patients: mortality after 25 years. Gut 2008, 57:84–90. This is one of the first studies to show the long-term significance of HBeAg clearance and persistent activity of liver disease. Patients with persistent HBeAg or HBeAg ^- CHB had worse survival than inactive carriers or those who cleared HBsAg.CrossRefPubMed

32.

•• Chen YC, Chu CM, Liaw YF: Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology 2010, 51:435–444. This study showed that patient age at HBeAg seroconversion has important prognostic significance. Patients with seroconversion before age 40 years had a very low rate of adverse outcomes.PubMed

33.

Yang YF, Zhao W, Zhong YD, et al.: Interferon therapy in chronic hepatitis B reduces progression to cirrhosis and hepatocellular carcinoma: a meta-analysis. J Viral Hepat 2009, 16:265–271.CrossRefPubMed

34.

Ahn SH, Park YN, Park JY, et al.: Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance. J Hepatol 2005, 42:188–194.CrossRefPubMed

35.

•• Simonetti J, Bulkow L, McMahon BJ, et al.: Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus. Hepatology 2010, 51:1531–1537. This prospective cohort study documented the rate of HBsAg loss and its importance for decreasing the risk of hepatocellular carcinoma.PubMed

36.

Yuen MF, Tanaka Y, Shinkai N, et al.: Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels. Gut 2008, 57:98–102.CrossRefPubMed

37.

• Chen JD, Yang HI, Iloeje UH, et al.: Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010, 138:1747–1754. This study reinforces the point that even patients who clear HBsAg are still at increased risk of developing HCC; however, the risk is significantly lower than for those who remain HBsAg ⁺.CrossRefPubMed

38.

• Yuen MF, Wong DK, Fung J, et al.: HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology 2008, 135:1192–1199. This paper showed that HBsAg clearance before age 50 is associated with a lower risk of hepatoma.CrossRefPubMed

39.

Moucari R, Korevaar A, Lada O, et al.: High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol 2009, 50:1084–1092.CrossRefPubMed

40.

• Brunetto MR, Moriconi F, Bonino F, et al.: Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology 2009, 49:1141–1150. This study documents the utility of HBsAg titers in predicting treatment outcome in patients treated with peginterferon.CrossRefPubMed

41.

Liang TJ: Hepatitis B: the virus and disease. Hepatology 2009, 49(Suppl):S13–S21.CrossRefPubMed

42.

Chevaliez S, Bouvier-Alias M, Laperche S, Pawlotsky JM: Performance of the cobas ampliprep/cobas taqman real-time PCR assay for hepatitis B virus DNA quantification. J Clin Microbiol 2008, 46:1716–1723.CrossRefPubMed

43.

Yuan HJ, Yuen MF, Ka-Ho Wong D, et al.: The relationship between HBV-DNA levels and cirrhosis-related complications in Chinese with chronic hepatitis B. J Viral Hepat 2005, 12:373–379.CrossRefPubMed

44.

Chen YC, Chu CM, Yeh CT, Liaw YF: Natural course following the onset of cirrhosis in patients with chronic hepatitis B: a long-term follow-up study. Hepatol Int 2007,1:267–273.CrossRefPubMed

45.

Feld JJ, Ayers M, El-Ashry D, et al.: Hepatitis B virus DNA prediction rules for hepatitis B e antigen-negative chronic hepatitis B. Hepatology 2007, 46:1057–1070.CrossRefPubMed

46.

Chu CJ, Hussain M, Lok AS: Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology 2002, 36:1408–1415.PubMed

47.

European Association for the Study of the Liver: EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009, 50:227–242.CrossRef

48.

Liaw YF, Leung N, Kao JH, et al.: Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int 2008, 2:263–283.CrossRefPubMed

49.

Perquin M, Reijnders JG, Zhang NP, et al.: HBeAg seroconversion during nucleos(t)ide analogue treatment does not lead to durable remission of chronic hepatitis B. Hepatology 2009, 5:S407A.

50.

van Nunen AB, Hansen BE, Suh DJ, et al.: Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase. Gut 2003, 52:420–424.CrossRefPubMed

51.

Chan HL, Hui AY, Wong ML, et al.: Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut 2004, 53:1494–1498.CrossRefPubMed

52.

• Livingston SE, Simonetti JP, Bulkow LR, et al.: Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. Gastroenterology 2007, 133:1452–1457. This study shows that HBeAg seroconversion occurs much later with genotype C HBV infection.CrossRefPubMed

53.

Livingston SE, Simonetti JP, McMahon BJ, et al.: Hepatitis B virus genotypes in Alaska native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis 2007, 195:5–11.CrossRefPubMed

54.

• Buster EH, Flink HJ, Cakaloglu Y, et al.: Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology 2008, 135:459–467. This study reports long-term results of both HBeAg ⁺ and HBeAg ^- patients treated with peginterferon.CrossRefPubMed

55.

• Liu S, Zhang H, Gu C, et al.: Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst 2009, 101:1066–1082. This study combines data showing an association between mutations in the pre-S region and the development of HCC.CrossRefPubMed

Titel: Hepatitis B Biomarkers: Clinical Significance of the Old and the New
verfasst von: Andrés Duarte-Rojo
Jordan J. Feld
Publikationsdatum: 01.11.2010
Verlag: Current Science Inc.
Erschienen in: Current Hepatology Reports / Ausgabe 4/2010
Elektronische ISSN: 2195-9595
DOI: https://doi.org/10.1007/s11901-010-0053-3

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