Page 58 - HIVMED_v21_i1.indb

Page 32 of 39 Guideline

In patients with severe hepatitis or jaundice, features of ° Performing routine LFT monitoring in patients on
hepatic encephalopathy (i.e. features of hepatic failure) must ART, in an attempt to detect DILI earlier. There is no
be clinically assessed, and the international normalised ratio evidence to support this approach.
(INR) and serum glucose should be checked.
25. Dyslipidaemia
If the concentration of canalicular enzymes is more
significantly elevated than that of ALT, or if conjugated Key points
bilirubin is elevated, then an ultrasound of the liver should ÿ Protease inhibitors can cause hypertriglyceridaemia and
be conducted to exclude biliary obstruction.
elevated LDL-C.
ÿ Atazanavir/ritonavir and DRV/r are associated with less
Isolated unconjugated hyperbilirubinaemia (drug-induced
Gilbert’s syndrome) is associated with ATV. In this case, all significant lipid abnormalities than LPV/r.
other LFTs are normal and the patient has no other symptoms ÿ Efavirenz can cause elevated total cholesterol and mild
of hepatitis. Although this is a benign condition (it does not hypertriglyceridaemia.
reflect liver injury, but isolated competitive inhibition of the ÿ Dolutegravir does not significantly affect cholesterol.
enzyme in the liver which conjugates bilirubin), it is often ÿ Lipids should be assessed routinely after 3 months on a PI
cosmetically unacceptable to patients, necessitating a switch regimen.
from ATV to an alternative drug.
Protease inhibitors can cause hypertriglyceridaemia and
Although EFV has been recognised as an infrequent cause of elevated LDL-C. Atazanavir/ritonavir and once-daily DRV/r
DILI since it first became available, a novel pattern of DILI (800 mg/100 mg DRV/r) are associated with less severe
associated with the drug has recently been recognised in dyslipidaemia than other boosted PIs; AZT can cause mild
South Africa. Amongst such patients, many had a hypertriglyceridaemia, and EFV can cause elevated total
25
particularly severe pattern of liver injury found on liver cholesterol and mild hypertriglyceridaemia.
biopsy (termed ‘submassive necrosis’, and associated with
severe jaundice and a raised INR). The overall mortality was We suggest that lipids should be assessed routinely after
11%. Whilst severe EFV-related DILI is likely to be uncommon, 3 months on a PI regimen. If normal at this stage, then re-
clinicians should be aware of the features observed:
assessment should be performed only in those with
1. The diagnosis of DILI was generally made after a longer cardiovascular risk factors. Diet and lifestyle modification
duration on EFV (~ 3–6 months) than what is seen with should always be advised. Diet is more effective for controlling
DILI related to NVP or TB medication. hypertriglyceridaemia than hypercholesterolaemia. Other
2. The DILI was not associated with features of cardiovascular risk factors should be addressed. Clinicians
hypersensitivity (e.g. drug rash) and often the first should consider and investigate secondary causes of
symptom was jaundice rather than abdominal symptoms. hypertriglyceridaemia and hypercholesterolaemia (e.g. diabetes,
3. Once EFV was stopped, it typically took several months nephrotic syndrome, alcohol abuse and hypothyroidism).
for LFTs to normalise (median resolution > 6 months).

If patients receiving LPV/r develop significant dyslipidaemia,
We do not advise routine LFT monitoring in patients on ART, as they should be switched to DRV/r or ATV/r, rather than
there is no evidence that this would lead to early detection of
this DILI or improve outcomes. Those managing patients on adding lipid-lowering therapy. However, lipid-lowering
EFV should monitor for symptoms and signs of hepatitis therapy is indicated in patients with persistent elevations
(nausea, vomiting, right-sided abdominal pain or jaundice). If despite switching to DRV/r or ATV/r. Switching the PI to
these occur, then ALT should be assessed, and the patient DTG is another option because DTG has a more favourable
should be examined for jaundice. The patient should be lipid profile than PIs. However, DTG should only be used in
managed appropriately for DILI if there are hepatitis symptoms a regimen in which at least one other ART drug is known to
with ALT > 120 U/L, or if there is jaundice. Efavirenz should be fully active. In patients with hyperlipidaemia on EFV, the
be switched to an alternative drug (e.g. DTG). drug should be switched to DTG or RPV.

Many other drugs can cause hepatotoxicity, notably anti- Marked hypertriglyceridaemia (> 10 mmol/L) can cause
tuberculous agents (including prophylactic isoniazid) and pancreatitis and requires urgent treatment with diet
azoles. Cotrimoxazole is an uncommon cause of hepatitis, modification (restrict total TG intake to < 30 g/day), fibrates
often as part of a systemic hypersensitivity reaction. and switching LPV/r to DRV/r, ATV/r or DTG (fibrates can
be stopped after 1 month, followed by reassessment within
Recommendations for the management of DILI in patients 4–6 weeks).
receiving TB treatment have been published by the Southern
African HIV Clinicians Society in 2013 (see link here). 90 Indications for statin therapy in HIV-positive patients should
° Common pitfalls: be the same as in HIV-negative patients, using the
° Failing to recognise other drugs apart from ART as a Framingham heart disease risk score. As a general rule, in
cause of hepatotoxicity. young patients with isolated elevated cholesterol but no

http://www.sajhivmed.org.za 50 Open Access