Diagnosis of and Monitoring of Hepatitis B

1
Diagnosis of and Monitoring of Hepatitis B C
co-infection

• Dr. Juan A. Pineda
• Unit of Infectious Diseases
• Hospital Universitario de Valme
• Seville, Spain.

2
Diagnosis of HCV Infection in HIV Carriers
Test
When and to whom
Serum HCV antibodies (EIA)

• All HIV patients at first visit
• Periodically in Anti-HCV-negative

• All Anti-HCV positive
• Anti-HCV negative with unexplained
• liver disease.
• Acute hepatitis C suspicion

Plasma HCV-RNA (RT-PCR)
HCV genotype (LiPA)
At least, when HCV treatment is planned
3
Measuring liver fibrosis in HIV/HCV-coinfection
Reasons to measure liver fibrosis in all
HIV/HCV-coinfected patients

• Prognostic value.
• Impact on management decisions.
• Diagnosis of silent cirrhosis screening for
  complications.
• Decision to start Hep C Rx hard-to-treat
  patients.

4
Procedures to assess liver fibrosis in
HIV/HCV-coinfection
5
Simple biomarkers of liver fibrosis in
HIV/Hepatitis C coinfection

• Applicable in low-resource settings.
• Useful to identify a number of patients with
  significant (Metavir F2) fibrosis1, and,
  depending on the biomarker, to rule out advanced
  fibrosis2.
• Suitable to monitor changes in fibrosis3.
• Most commonly used APRI1 Forns Index1 FIB-44.

1Macías J et al. Gut 200655409414 2Tural C et
al. Clin Gastroenterol Hepatol 2009 7
339-345 3Halfon P et al. Anivir Ther 2009 14
211-219 4Sterling RK et al. Hepatology
2006431317-1325
6
Performance of transient elastography
(FibroScan) in in HIV/Hepatitis C coinfection
ROC Curves of Transient Elastography (n169)2

• High accuracy in advanced fibrosis and cirrhosis.
  Cutoff for cirrhosis14.6 KPa1,2.
• Accuracy for Metavir F2 increases with two
  cutoffs3
• 6 kPa lack of F2
• 9 kPa presence of F2

1De Lendinghen V, et al. J Acquir Immune Defic
Syndr 200641175-179. 2Vergara S, et al. Clin
Infect Dis 200745969-974. 3Macías J, et al. J
Hepatol 2008 49916-922.
7
Transient elastography in monitoring changes in
liver damage
Liver stiffness at baseline and at the SVR
evaluation time point2

• LS declines in patients treated for HCV1.
• A significant fall has been reported in
  HIV/HCV-coinfected patients with SVR2.
• TE may be useful to monitor changes in liver
  fibrosis in HIV/HCV-coinfected patients.

p0.005
1Vergniol J, et al. J Viral Hepat 2009 16
132-140 2Del Valle, et al. CROI 2009 Abstract
826.
8
Monitoring of the response to therapy against HCV
The road map and types of response
10 IU/mL
Rapid virological response
Virological breaktrough
Complete early virological response
Sustained virological response
Slow virological response
Relapse
Non-response
9
Diagnosis of HBV infection in HIV carriers
Test
When and to whom
HBsAg, Anti-HBs, Anti-HBc (EIA)
All HIV patients at first visit
HBeAg, Anti-HBe (EIA)
All HBsAg-positive
HBV-DNA (TaqMan RT-PCR)

• All chronic HBV infections
• Patients with isolated Anti-HBc?

HBV genotype (LiPA)
Not routinely used
HBV genotypic resistance (PCR, Sequentiation)

• At virological breakthrough
• Role in adapting Rx to be defined

10
Assessment of liver injury in HIV/HBV-coinfection

• Aminotransferases
• Liver biopsy
• High ALT or HBV DNAgt2000 IU/mL, unless anti-HBV
  Rx is indicated irrespective of liver injury.
• Most HIV/HBV patients would not require biopsy.
• Noninvasive methods
• Biomarkers
• Transient elastography

EASL guidelines on the management of chronic
hepatitis B. J Hepatol 2009 50 227-242.
11
Performance of transient elastography in chronic
hepatitis B
Yield of TE in the assessment of fibrosis in
chronic hepatitis B monoinfection
The role of FibroScan in monitoring changes in
hepatitis B- associated liver injury needs to be
defined.
Marcellin P, et al. Liver Int 2009 29 242-247
12
Monitoring of the response to Anti-HBV Rx
The road map and types of response
7 6 5 4 3 2 1
DNA HBV logs IU/ml
Weeks
12 24

48
Virological breaktrough
Primary non-response
Serological response
Virological response
Complete remission
Partial virological response
From EASL guidelines on the management of chronic
hepatitis B. J Hepatol 2009 50 227-242.
13
Diagnosis of and monitoring of HIV/HCV
co-infection. Remarks.

• Liver fibrosis should be measured in all
  HIV/HCV-co-infected patients. Non-invasive
  methods enable us to do it.
• The response to therapy is assessed using plasma
  HCV-RNA. Elastography and biomarkers are useful
  to monitor changes in liver damage.

14
Diagnosis of and monitoring of HBV co-infection.
Remarks.

• The use of highly sensitive procedures to detect
  HBV-DNA is critical to prevent resistance.
• Transient elastography seems to be useful to
  assess liver fibrosis in HIV/HBV-coinfected
  patients.

15
Acknowledgements

• All the members of the Hepavir Group of the
  Andalusian Society for Infectious Diseases
  (SAEI).
• Dr J. Macías.