Lactic acidosis, pancreatitis and fatty liver

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http://www.i-base.org.uk/publications/guides/side802/acidosis.html

 

Lactic acidosis, pancreatitis and fatty liver

 

 

Associated drugs:

All nucleoside analogues. d4T, ddI, 3TC, AZT and hydroxyurea have been

particularly linked in reports of lactic acidosis and pancreatitis. PIs and

efavirenz have also been associated with pancreatitis.

 

Lactic acidosis

 

Levels of lactic acid are normally carefully regulated by the liver. Small

increases in lactic acid (called hyperlactataemia) are relatively frequent,

especially after exercise, usually returning to normal spontaneously.

 

If they reach a higher level, there is a risk of lactic acidosis which is a more

rare but potentially fatal side effect related to nucleoside analogues (AZT,

3TC, d4T, ddI and abacavir).

 

Not only do these drugs form the background treatments for nearly all HIV

combinations, but the symptoms of lactic acidosis are common side effects of

other drugs and indeed symptoms common anyway.

 

Symptoms include:

 

unexplained tiredness, often severe

sickness (vomiting) and nausea

pain in the stomach, abdomen and/or liver

unexplained weight loss

difficulty breathing

poor blood circulation – cold hands or feet or bluish skin colour

sudden onset peripheral neuropathy.

 

Before combination therapy was available, this was only very rarely seen in HIV,

and may well have been under diagnosed. Recently the number of reports of lactic

acidosis have increased and drug packaging now includes a clearer caution about

this risk.

 

Pregnancy may be an additional risk factor for lactic acidosis when using

nucleosides.

 

Lactic acidosis is diagnosed through examination, lab tests, an abdominal CT

scan or liver biopsy diagnosis. Although this toxicity is believed to be a

result of damage to part of the cell called mitochondria, there is no simple

test for determining people at highest risk.

 

Although lactic acid in blood can be measured, it is not clear whether high

levels increase the risk of lactic acidosis. Over 50% of people showing a high

reading on one result, return to normal with the confirmatory test. There

appears to be no pattern between high levels and risk of severe toxicity.

 

Because lactic acid increases even with any physical activity, confirmatory

tests should always be taken after you have completely rested for at least 20

minutes. Even going to the gym the day before may affect the results.

 

Treatment and monitoring

Diagnosis and treatment:• Measure levels of lactic acid and blood pH.

• If lactic levels are >5mmol and if you have symptoms or levels are over 10

mmol discontinue HIV medication immediately.

• Use of IV anti-oxidants: L-carnitine and vitamin B complex including thiamine,

riboflavine, nicotinamide, pyridoxine, dichloracetic acid and dexpanthenol is

recommended.

Early diagnosis is essential – and contacting your doctor if you have any of the

symptoms is important. HIV treatments may need to be stopped immediately

depending on blood levels (see inset box).

 

High doses of vitamin B complex with L-carnitine (both IV) until lactate levels

normalise was reported in a Dutch study to improve the chances of survival.

 

Antioxidants may help to overcome mitochondrial toxicity and use of oral

antioxidant supplements such as vitamin C, vitamin B complex, L-carnitine or

co-enzyme-Q may help and are prescribed by some doctors.

 

There are no clear guidelines for restarting nucleoside therapy after a serious

case of mitochondrial toxicity. Although caution is warranted, lack of other

antiretroviral options has lead to people restarting without further toxicity.

 

This proposed mechanism of mitochondrial toxicity is thought to be responsible

for other serious side effects.

 

Pancreatitis

 

Pancreatitis is an inflammation of the pancreas characterised by abdominal or

back pain and vomiting. It can also be alcohol induced and here is little

specific treatment. Blood tests measuring amylase lipase are usually checked to

confirm a diagnosis of pancreatitis. Pancreatitis can be fatal if not treated

early, and can be prevented by stopping or changing the drug HIV drugs.

 

Fatty liver

 

Hepatic steatosis is a medical term for ‘fatty liver’ which can develop from

alcohol use, hepatitis, obesity and drug toxicity with nucleosides.

 

This build-up of fat in the liver can affect the way it processes fats. Hepatic

steatosis often also leads to lactic acidosis, described above. People who weigh

over 70kgs, especially women, may be more at risk of developing hepatic

steatosis and lactic acidosis.

 

Steatosis is also common in HIV-infected children. It is non-specific and has no

impact on disease, diagnostic evaluation or management. Ultrasonography is a

sensitive, accurate, non-invasive screening tool to detect steotosis as this is

not always shown in liver function tests.

 

 

 

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