Liver Disease in the era of HIV

and HAART
Dr Farida Amod
August 5 2014

HIV and the liver
Aetiology of Liver disease

Mechanisms of liver injury

TB/HIV coinfection and the liver

Drugs and the liver

Definition of Hepatic Injury

Hepatotoxcity:3-5 fold increase from baseline
in serum ALT and AST levels (>120 IU/L).

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.
If ultra-sound reveals normal ducts, a liver
biopsy is recommended

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


Common aetiologies for liver disease of
HIV infected patients

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

Mixed Pattern
Steatosis
Gallstones
alcohol use,
drugs


Common aetiologies for liver disease
of HIV-infected patients

Cholestatic Pattern
Bacteria (Mycobacteria)
Fungal
Lymphoma
Kaposis sarcoma
Drugs - co- trimoxazole, erythromycin, co- amoxicillin
clavulanate, ARVs, TB drugs
Steatosis


Indications for liver biopsy

Persistent abnormal liver enzymes

Hepatomegaly

And/or fever

Focal liver mass

TB and the liver
HIV and TB
SA 3
rd
highest TB burden in the world
SA- 4
th
highest MDR TB rate
60 -80% of new cases of TB are coinfected
2 fold higher risk of adverse events in HIV-
infected persons
DILI complicates TB treatment in 5-30% of
patients
TB Liver
Extra-pulmonary TB commonly involves the liver
and abdomen
AIDS defining
Fever, weight loss, hepatosplenomegaly
Liver biopsy : culture and histology
Histology : hepatic granulomas, may or may not be
AFB +
Drug induced liver injury more common
Anti-tuberculous drugs and HAART


TB and HIV therapy should not be initiated
simultaneously due to
overlapping toxicities
drug interactions
adherence requirements
possible paradoxical reactions


TB Therapy and HAART

The current recommendation are:
- CD4 < 50 cells/ul ART should be initiated as
soon as TB drugs are tolerated.(2 weeks)
- CD4 50-200 cell//ul ART therapy after 2-8
weeks TB therapy
- Efavirenz based ART preferred to nevirapine
- Nevirapine : increased risk of hepatotoxicity
and alteration of drug levels

Drugs and the Liver
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

Risk factors for DILI
In patients receiving TB treatment or ART
Age >35 years
Female
Hep B sAg positivity, Hep C
Alcohol use
Slow acetylator status
Extensive TB
Increase in baseline ALT
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


Drug Induced Hepatitis

Implicated drugs
Cotrimoxazole

ART

TB drugs

antifungals

macrolides

First line Tb drugs ass with
hepatotoxicity
INH

Rifampicin

PZA
Management of TB-DILI patients
Re-introduction of first line drugs preferred (mild to
moderate DILI)

Rechallenge NOT recommended for those with
fulminant hepatitis, treat as MDR TB. Avoid RIF, INH,
PZA
If intensive phase interrupted, restart full treatment
course from day that alternate treatment is
successfully re-introduced

ART is indicated in all TB/HIV patients independent of
CD4
DILI whilst on TB drugs and ARVs
If on NVP based regimen, change to efavirenz
If on efavirenz, start on PI (lopinavir/r) with
dose adjustment
If DILI develops on PI based regimen (double
dose Lop/r), replace with 150mg rifabutin 3
times a week and atazanavir/r (or std dose
aluvia)
After ART rechallenge, check ALT 2 weekly for
2 months

HIV/HBV co-infection

Chronic Hep B - persistence of serum HBsAg for
longer than 6 months,

Chronic HBV liver disease : cause of morbidity and
mortality in HIV + patients

Liver disease is accelerated in HBV/HIV- coinfected
patients

toxicity of antiretroviral drugs is also increased

Treatment of HIV/Hep B co-infection
antiretrovirals i.e. lamivudine, emtricitabine,
tenofovir show anti-HBV activity in addition to
anti-HIV activity

Their use in co-infected subjects could provide a
benefit in treatment of liver disease, but this still
has not been fully assessed.

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
scr 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
scr >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