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Clinical Cases highlighting Liver

Disease in HIV Infection


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.

Used to exclude obstructive jaundice

Cholestasis
Frequently seen, multifactorial
TB liver, TB IRIS
Drugs
Opportunistic infections
malignancies
Fatty liver
Biliary tract disease


Common Aetiologies for liver disease in
HIV-infected patients

Cholestatic Pattern
Mycobacteria (M.tb, MAC)
Fungal

Malignancies/ lymphoma/ Kaposis sarcoma

Drugs: co- trimoxazole, erythromycin, Augmentin, ARVs, TB
drugs
Steatosis / fatty liver

Biliary tract disease



Common Aetiologies for liver disease in
HIV infected patients

Hepatocellular Pattern
Viral hepatitis (A,B,C)
CMV
EBV
Auto immune
Drugs

Mixed Pattern
Steatosis
Gallstones
alcohol use,
drugs


Drug Induced Hepatitis

Implicated drugs
Cotrimoxazole

ART

TB drugs

antifungals

macrolides

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

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