Dr Farida Amod HTC-SA Conference August 16-17 2014
HIV and Chronic Hep B infection In the era of HAART declining rates of OIs
Focus shifts to other leading causes of morbidity such as chronic Hep B infection and its complications Liver Disease and HIV Chronic Hepatitis B virus (HBV) infection Complications and monitoring
Drug induced Liver injury (DILI) Mechanisms of Drug induced injury Case 1
40 year old female presented in 2009 with:
jaundice Transaminitis (hepatitis) Hepatomegaly
HBV Serology serology 2009 2010 HB cAb (IgG) positive positive HB sAg positive positive HB sAb negative negative HB eAg positive negative HB eAb negative positive LFT 2009 2010 AST 153 24 ALT 142 17 Natural history of hepatitis B Acute phase Persistent elevation of ALT for >6 months indicates progression to chronic hepatitis. Characterised by persistence of serum HB sAg for longer than 6 months, Rate of progression from acute to chronic hepatitis B is determined by the age at infection: 90% for peri-natally acquired infection, <5% for adult infections
HIV/HBV co-infection
Chronic HBV liver disease : cause of morbidity and mortality in HIV + patients
Liver disease is accelerated in HBV/HIV co-infected patients
Toxicity of antiretroviral drugs is also increased
HBV Serology serology 2009 2010 HB cAb (IgG) positive positive HB sAg positive positive HB sAb negative negative HB eAg positive negative HB eAb negative positive LFT 2009 2010 AST 153 24 ALT 142 17 Chronic Active Hepatitis B
liver biopsy chronic hepatitis with early cirrhosis
HIV co-infected, CD4 400/ul Started on Truvada (TDF/FTC) and efavirenz
After 1 year conversion to HB eAg negativity
2013 - RUQ pain
Case 1 Ultrasound (2013) multiple hyperechoic lesions in both lobes of the liver suggestive of metastases Alphafoetoprotein (AFP) levels very high Biopsy: Hepatocellular Carcinoma (HCC)
Cd4 460, VL undetectable (2013) Irresectable tumour Died shortly thereafter Complications of chronic hep B infection Active inflammation on liver biopsy but may be ansymptomatic or non specific symptoms fatigue
Greater risk of : drug induced liver disease(DILI) Hep B IRIS (in HIV co-infected persons) chronic liver disease and decompensation Cirrhosis HIV and HBV Co-infection with HIV not only associated with more rapidly progressive liver disease
Also greater risk of HCC
Once HCC appears, more aggressive course
No specific guidelines regarding surveillance
Where did we go wrong? Should we have monitored her more closely? Monitoring of chronic HBV infection Serial transaminases and Hep B Viral load (not done in SA)
HB eAg status
Loss of HB sAg
Screening for HCC with Ultrasound and AFP Management Optimum frequency for screening not established ART indicated for all HIV/Hep B co-infected patients Life long treatment for both
Ideally choose 2 of the 3 drugs with dual activity against HIV and Hep B: Tenofovir (TDF) Emtricitabine (FTC) lamivudine Prevention of HCC Vaccination against HBV for all newborns and people at risk to prevent infection. Immune response to vaccine generally lower in HIV- infected people
Antiviral therapy in patients with chronic hep B and HIV infection
Response to treatment associated with lower risk of HCC . Drugs and the Liver
Drug induced Liver injury (DILI) Definition of DILI ALT >200 IU/L and asymptomatic OR
ALT >120 IU/L and symptomatic OR
Total serum bilirubin concentration >40umol/l
Elevated GGT and ALP not included in DILI definition
DILI
Many drugs increase GGT, does not reflect liver injury
Only when increased GGT associated with a proportionate increase in alkaline phosphatase (ALP) should a significant cholestatic injury be contemplated.
Cholestatic liver injury ( ALP & GGT and / or Bilirubin)
Liver ultra-sound: mainstay in the initial evaluation of the investigation of cholestatic liver injury
non invasive, relatively inexpensive and more accessible.
Four main mechanisms of drug- related liver toxicity
direct drug toxicity;
immune reconstitution following initiation of antiretroviral therapy in the presence of HCV/HBV/ or other OIs involving the liver;
hypersensitivity reactions with liver involvement;
mitochondrial toxicity
Hepatotoxicity vs IRIS 30 yr old male (on TDF/ FTC/ boosted atazanavir)
Hep BsAg +/ eAg -/ cIgM -/ cIgG+
All ARVs stopped (week 20)
Hepatitis resolved by week 24
Visit CD4 VL ALT 1 54 >750000 58 20 174 513 1048 24 73 450 000 146 Hepatotoxicity vs IRIS Diff diagnosis Hep B IRIS
drug-induced hepatotoxicity
Visit Hep B Viral load Hep B serology 1 >1000000 sAg +/ eAg- Wk 20 6 400 sAg +/ eAg- cIgM - Conclusion Hepatotoxicity reported increasingly in patients with HIV infection and or TB
Aetiology is often multifactorial and confounded by chronic Hepatitis B or C, alcohol consumption, herbal therapies, and a multitude of drug drug interactions.
Management often requires consultation with an ID physician