Dr Upali Weragama MBBS(Pera), MD(Col), MRCP(UK), MAGA(USA) Consultant Physician, Sri Lanka Police Hospital, Colombo

1. Dr Upali Weragama MBBS(Pera),
MD(Col), MRCP(UK), MAGA(USA)
Consultant Physician
Sri Lanka Police Hospital
Colombo

2. •Although substantial reduction in AIDS deaths
•Liver disease emerging as an important non-AIDS
related cause of death among HIV infected patients
•Accounting for 14-18% of all deaths in this
population
•Almost half of deaths among hospitalized HIV
infected patients

4. Clinician
Deranged LFT
Decompensation
ART
Including
Immune
Reconstitution
Biliary
Complications Alcohol and substance
abuse

9. HIV-HCV coinfected individuals treated for HCV
who achieve SVR have lower rates of HIV
progression and non-liver mortality

11. Treatment of HIV/HCV coinfection
PEG-IFN/ribavirin (low efficacy adverse events
associated with IFN-based therapy)
availability of HCV direct-acting antivirals (DAAs)
( specially NS5A & NS5B classes)
Daclatasvir plus sofosbuvir , with or without
ribavirin
 safe/appropriate antiretroviral drugs – ritonavir,
darunavir, atazanavir, lopinavir, efavirenz, rilpivirine,
raltegravir, and dolutegravir.

12. Although HCV-infected patients have a higher incidence of
ART-related liver toxicity
may leads to inappropriate ART discontinuation
the benefits of ART for HIV treatment are profound
will have beneficial effects on the progression of liver
disease in coinfection as improvement in CD4 count may
decrease fibrosis progression
therefore, ART should not be withheld inappropriately
in the coinfected population

16. •HIV-infected patients have a lower rate of
spontaneous clearance of HBeAg
•increased HBV replication
• higher rate of loss of anti-HBs Ab and reactivation
of HBV
•increased progression to cirrhosis, decompensation
& HCC
• higher liver-related mortality compared to HBV
monoinfected individuals

18. The decision to initiate HBV treatment depends
on whether the patient meets indications to treat
either HIV or HBV

19. Treatment decisions of Chronic Hepatitis B
HBe status
Age of the patient & comrbidities
Presence of significant fibrosis / cirrhosis
ALT level
HBV DNA level

20. In patients with HIV and HBV coinfection, HBV
infection should be treated only in conjunction with
HIV infection.
 Treatment of HBV infection alone without
addressing the HIV infection will lead to emergence
of resistant HIV strains

21. •If there is no indication to treat either infection, the
patient should be monitored closely.
• If treatment is indicated for either HIV or HBV, ART
should be initiated and should include the
combination of tenofovir , emtricitabine and
lamivudine (anti-viral agents with dual activity).
•Avoid entecavir mono-therapy.

24. Classes of Antiretroviral agents
•Nucleoside reverse transcriptase inhibitors (NRTIs)
•Protease inhibitors (PIs)
•Nonnucleoside reverse transcriptase inhibitors
(NNRTIs)
•Fusion inhibitors
•CCR5 co-receptor antagonists (entry inhibitors)
•HIV integrase strand transfer inhibitors

25. Direct drug toxicity and/or drug metabolism
Hypersensitivity reactions
Mitochondrial toxicity
IRIS (Immune reconstitution inflammatory
syndrome)

26. IRIS describes a collection of inflammatory disorders
associated with
paradoxical worsening of preexisting infectious
processes following initiation of antiretroviral
therapy
in the setting of successful HIV RNA suppression
previous subclinical and later unmasked by the host's
regained capacity to mount an inflammatory response.

27. The syndrome generally manifests within the first two
months of ART initiation and is accompanied by a
precipitous decline in HIV RNA and rise in CD4 count.
In patients with HBV & HCV, immune restoration can
lead to clinical flares of hepatitis due to the immune
response to the virus.

32. Main adverse effect of the NRTI class - mitochondrial
toxicity
The spectrum ranges from nonspecific symptoms to
lactic acidosis syndrome with fulminant hepatic
failure.

33. Lactic acidosis syndrome
Is manifested by nausea, vomiting and abdominal
pain, rapidly progressing to tachypnoea with severe
acidosis.
Liver function tests may be modestly elevated in this
setting, often with AST greater than ALT.
Late recognition of this syndrome usually is
associated with death of the patient.

34. All NNRTIs except etravirine have the ability to
cause some degree of hepatotoxicity.
Delavirdine and efavirenz can increase transaminase
levels
nevirapine can cause severe toxicity (the NNRTI most
associated with hepatotoxicity)

35. Protease inhibitors-
asymptomatic hyperbilirubinemia is common with
atazanavir and indinavir
does not require discontinuation of therapy in the
absence of concomitant elevation in levels of liver
transaminases

36. Chemokine Receptor Antagonists
severe hepatotoxicity has been reported with maraviroc
be cautioned when maraviroc is administered to any
patient predisposed to hepatic impairment

37. Given the large benefit of ART, which clearly
outweighs its potential risks for liver toxicity, it is
unjustifiable to inappropriately defer antiretroviral
therapy.
Clinicians need to educate the patient regarding
symptoms and signs of hepatotoxicity, assess risk
factors for drug injury, address those factors that can
be modified, and be vigilant for the earliest signs of
drug injury.

40. Non-alcoholic fatty liver disease (NAFLD) in HIV-
positive patients is associated with HIV specific
factors, such as lipodystrophy and the use of
antiretroviral therapy (ART), as well as higher risk of
insulin resistance.
Traditional risk factors (including obesity, insulin
resistance and the metabolic syndrome).
As a consequence, and given the ageing HIV
population, NAFLD has been reported in up to 40–
60% of HIV-infected individuals.

41. Causes of non-cirrhotic PHT in HIV
Nodular regenerative hyperplasia
strong association with- Didanosine &
Stavudine
Hepatoportal scerosis

46. A significant proportion of patients with features
suggestive of biliary tract disease will be found to have
common conditions such as
cholelithiasis
benign bile duct strictures
periampullary neoplasms
Such readily treatable conditions must be excluded
prior to searching for an AIDS-associated diagnosis

51. Hepatic safety profile of antiretroviral drugs. RTV, ritonavir (*at full doses, not when used as
booster); ddI, didanosine; d4T, stavudine; AZT, zidovudine; ABV, abacavir; TDF, tenofovir; 3TC,
lamivudine; FTC, emtricitabine; NVP, nevirapine; EFV, efavirenz; TPV, tipranavir; APV, amprenavir;
DRV, darunavir; ATV, atazanavir; LPV, lopinavir; SQV, saquinavir; NFV, nelfinavir; T20, enfuvirtide;
NRTI, nucleoside reverse transcriptase inhibitors; NNRTI, nonnucleoside reverse transcriptase

53. In addition to drug injury, flares in serum
transaminase concentrations in a patient with chronic
HBV can be related to several different factors,
including viral rebound after withdrawal of effective
anti-HBV therapy, breakthrough of drug-resistant
HBV strains or spontaneous flares of HBV viraemia.
[21,27-29]
The clinician must bear this in mind before
misinterpreting hepatic flares as drug injury.

55. Estimated numbers of Co-infected
persons (worldwide)

56. by the presence of HIV p24 within Kupffer cells
and hepatic endothelial cells
HIV messenger RNA within hepatocytes
however, whether HIV itself directly damages the
liver?