Liver diseases are very common in HIV infected patients. This presentation summarized common conditions related to HIV, Hepatitis virus coinfections, hepatotoxicities and other related causes.

1. Liver diseases in patients
with HIV infection
Aung Zayar Paing

2. Introduction
— Abnormal liver function tests can be seen frequently
in HIV patients. (prevalence as high as 30%)
— Liver disease is the second commonest cause of
mortality in HIV patients.
— Hepatitis virus coinfections represent the most
significant cause of liver disease in HIV patients.
— Some other conditions also play their role to cause
liver injury in HIV patients.

3. Lancet 2011; 377: 1198–1209

4. AIDS Rev. 2013; 15:25-31

5. Lancet 2011; 377: 1198–1209

6. Different causes of hepatitis in
HIV infected patients

7. HAIVN M2-08-Hepatic Toxicity in Patients Taking ARVs-EN

8. HAIVN M2-08-Hepatic Toxicity in Patients Taking ARVs-EN

9. Hepatitis Coinfections

10. AIDS Rev. 2013; 15:25-31

11. HBV coinfection
— ARVs like Tenofovir (TDF), Lamivudine (3TC) and
Emtricitabine (FTC) are active against HIV as well
as HBV.
— WHO guideline 2013 recommends to start ART for
HIV-HBV coinfected patients with evidence of
severe chronic liver disease.
— US DHHS guideline advises to start ART for all
patients who need anti-HBV treatment.

12. Hepatic flare up after HAART in
HBV coinfected patients
— Some patients with HIV-HBV coinfection experience
hepatic flare up having high ALT levels.
— Like IRIS associated with OIs, high antigen burden
(high HBV DNA level) (ID 2009:199, Crane et al.
http://jid.oxfordjournals.org/)

13. ALT and HBV DNA values in HF and non-HF subjects over 1st 12 weeks
after HAART initiation.
x-axis: Weeks after HAART initiation. y-axis 1: HBV DNA log 10 c/ml. y-
axis 2: ALT IU/L.
Avihingsanon et al. AIDS Research and Therapy 2012 9:6 doi:10.1186/1742-6405-9-6

14. HCV coinfection
— Nearly 1/3 of HCV patients progress to cirrhosis at
a median time of less than 20 years.
— Compared to HCV monoinfected patients, HIV-
HCV coinfected patients have 3 times greater risk of
progression to cirrhosis or decompensated liver
disease.
— Peginterferon + Ribavirin is the mainstay treatment.
— Interferon sparing regimens are possible for some
genotypes recently after the introduction of new
directly active antiviral (DAA) Sofosbuvir.

15. AASLDGuideline

16. Drug interaction and toxicities
— AZT + RBV - increased risk of anemia
— ddI + RBV – life threatening ddI-associated
mitochondrial toxicity including hepatomegaly/
steatosis, pancreatitis, and lactic acidosis
— ABC - decreased response to PegIFN/RBV ???
— Other DAAs, Boceprevir and telaprevir interacts
significantly with EFV.

17. Hepatitis E virus infection
in HIV patients
— Some studies showed that HIV infected patients
have increased susceptibility to hepatitis E virus
infection.
— Acute HEV infection can mimic drug induced liver
injury.
— HIV patients have risk of chronic HEV infection.
(HEV RNA in serum or stools for 6 months or more)
— Myanmar is one of the countries with high
prevalence of HEV infection.

18. Source:TheLancet2012;379:2477-2488(DOI:10.1016/
S0140-6736(11)61849-7)
Source and route of HEV1–4 infection
HEV1 and HEV2 are waterborne only, with possible human-to-human
transmission, including vertical transmission.

21. Hepatotoxicity of drugs

22. HAIVN M2-08-Hepatic Toxicity in Patients Taking ARVs-EN

23. HAIVN M2-08-Hepatic Toxicity in Patients Taking ARVs-EN

24. Martin Fisher’s presentation: ICVH 2013

25. JournalofHepatology2011vol.54|773–794

26. Martin Fisher’s presentation: ICVH 2013

27. Hyperbilirubinemia due to
some PIs
Liver metabolism of bilirubin and
potential mechanisms of interference
of atazanavir (ATV) and indinavir
(IDV). Uridine diphosphate
glucuronosyltransferase 1A1 is the
liver enzyme that conjugates the
bilirubin. The insertion of an extra
dinucleotide (TA) on the promoter
gene of the UGT1A1 results in a
decreased enzyme activity. Atazanavir
and IDV inhibit the UGT1A1, which in
turn result in hyperbilirubinemia.
http://www.nature.com/tpj/journal/v6/n4/fig_tab/6500374f6.html

28. ACTG grading system for
hepatotoxicity
Grade 1 Grade 2 Grade 3 Grade 4
ALT* ≤ 2.5 x ULN 2.6 – 5.0 x ULN 5.1-10.0 x ULN 10.0 x ULN
If
Grade
1
or
2
hepatotoxicity
occurs
during
NVP
lead-­‐in
dose,
lead-­‐in
dose
can
extend
next
2
weeks
(maximum).
If
ALT
sFll
raised
and
<
grade
2
stop
NVP
and
start
EFV.

29. Other conditions

30. Alcoholic hepatitis
— Alcoholism is common in HIV patients and
alcoholic hepatitis sometimes complicate HIV
treatment.
— Abrupt stopping of alcohol in chronic drinker is
dangerous and the patient may suffer from alcohol
withdrawal. (mild to sever manifestation like
Delirium Tremens)

31. Signs and symptoms
CCO HIV inPractice

32. — AST/ALT ratio - usually > 1
— GGT - may be increased (low sensitivity/specificity
for alcohol abuse
— Bilirubin may be increased
— INR - raised
— PT - prolonged

33. Nonalcoholic Fatty Liver Disease
(NAFLD)
— NAFLD is the condition caused by accumulation of
Triglycerides in hepatocytes associated with obesity,
diabetes mellitus and hyperlipidemia.
— Non-alcoholic steatohepatitis is the progressive
form of NAFLD.
— 40-70% HIV-HCV coinfected patients are found to
have hepatic steatosis.
— The risk is higher in patients taking ddI or d4T
— AST/ALT ration is usually < 1

34. http://dx.doi.org/10.1155/2013/493413

35. Thank you