Simple FactSheet: Lactic Acidosis and Hepatic Steatosis

Lactic Acidosis
and Hepatic Steatosis
a Simple FactSheet from the AIDS Treatment Data Network

||||| Lactic Acidosis and Hepatic Steatosis:

This rare but very serious side effect is caused by damage to the mitochondria in liver cells. Lactic acid is a waste product made by cells that aren't getting enough energy from their mitochondria. Build up of lactic acid in the body can be life-threatening. Secondary to lactic acidosis, droplets of fat can build up inside liver cells, a problem called hepatic steatosis. The liver can also become enlarged, a condition which doctors call hepatomegaly.

||||| Symptoms:

Symptoms are severe nausea, vomiting and abdominal pain that doesn't go away. Shortness of breath and/or rapid breathing may also occur. If you experience nausea, vomiting and abdominal pain it's very important to contact your healthcare provider immediately. If you have lactic acidosis the NRTIs must be stopped to avoid further complications, which can be fatal.

||||| Drugs responsible:

This problem has been reported with zidovudine (AZT, Retrovir), didanosine (ddI, Videx) and stavudine (d4T, Zerit) but can potentially be caused by all available NRTIs.

||||| Risk of experiencing this side effect:

Reports so far indicate this side effect is very rare. A report based on 10,000 people that had taken Retrovir found six cases of lactic acidosis and hepatic steatosis. When doctors at the large Johns Hopkins Clinic in Baltimore searched their records for the period July 1989 to July 1994, they found two cases out of 1,836 people. The US Food and Drug Administration (FDA) recently looked all the reports they'd received of life-threatening lactic acidosis. Since NRTI drugs have been available, there have been 60 cases reported to the FDA. The majority of the cases were women, and the FDA reported that obesity seemed to increase the risk of developing lactic acidosis.

More recent studies have found that while life-threatening cases of lactic acidosis are rare, changes in the levels of lactic acid in the blood (see below) with mild or no symptoms are more common. A report by Swiss doctors found that lactic acid was above normal levels in 107 out of 1598 (about 10% or 1 in 10) people studied. Only 14 of these people (about 1% or 1 out of 100) had levels that were more than twice the normal levels.

||||| Diagnosis:

Blood tests can help diagnose lactic acidosis. Measurements of lactic acid in the blood (called serum lactate levels) are taken. Lactate levels above 5 mmol/L are considered dangerous, but it's important to note that lactic acidosis can sometimes develop even though lactate levels are below this level.

Doctors can also measure the acidity of the blood by testing what's called the blood pH. Normal blood pH is generally between 7.35 and 7.45. In cases of lactic acidosis, the pH may drop to less than 7.35. Levels of something called serum bicarbonate may also fall below normal levels. The normal range for serum bicarbonate is generally 21-28 mEq/L. A procedure called a liver biopsy may sometimes be done to help diagnose lactic acidosis. This usually involves taking a small piece of tissue from the liver to look for evidence of fat droplets in the cells (hepatic steatosis).

||||| Treatment:

There is no proven treatment for lactic acidosis other than stopping the NRTI drugs as quickly as possible. In serious cases, hospitalization and supportive care may also be needed. One or two reports have suggested that the vitamin supplements riboflavin (vitamin B2) or co-enzyme Q-10 may help speed recovery from lactic acidosis, but this is not yet proven.

||||| Lactic Acid and Lipodystrophy:

Some researchers think that mild increases in lactate levels may contribute in some way to the body shape changes known as lipodystrophy. In particular, the loss of fat tissue in the face (causing a shrunken or wasted look) may be linked to damage to mitochondria. A study presented at the recent International AIDS Conference in Durban, South Africa looked at fat tissue from people with lipodystrophy under a special microscope. The researchers saw evidence of damage to mitochondria along with a build up of fat droplets (steatosis). More research is needed to confirm these findings and work out how best to treat the problem.

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Last modified: 8/15/2006
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\|\|\|\|\| Lactic Acidosis and Hepatic Steatosis:
This rare but very serious side effect is caused by damage to the mitochondria in liver cells. Lactic acid is a waste product made by cells that aren't getting enough energy from their mitochondria. Build up of lactic acid in the body can be life-threatening. Secondary to lactic acidosis, droplets of fat can build up inside liver cells, a problem called hepatic steatosis. The liver can also become enlarged, a condition which doctors call hepatomegaly.
\|\|\|\|\| Symptoms:
Symptoms are severe nausea, vomiting and abdominal pain that doesn't go away. Shortness of breath and/or rapid breathing may also occur. If you experience nausea, vomiting and abdominal pain it's very important to contact your healthcare provider immediately. If you have lactic acidosis the NRTIs must be stopped to avoid further complications, which can be fatal.
\|\|\|\|\| Drugs responsible:
This problem has been reported with zidovudine (AZT, Retrovir), didanosine (ddI, Videx) and stavudine (d4T, Zerit) but can potentially be caused by all available NRTIs.
\|\|\|\|\| Risk of experiencing this side effect:
Reports so far indicate this side effect is very rare. A report based on 10,000 people that had taken Retrovir found six cases of lactic acidosis and hepatic steatosis. When doctors at the large Johns Hopkins Clinic in Baltimore searched their records for the period July 1989 to July 1994, they found two cases out of 1,836 people. The US Food and Drug Administration (FDA) recently looked all the reports they'd received of life-threatening lactic acidosis. Since NRTI drugs have been available, there have been 60 cases reported to the FDA. The majority of the cases were women, and the FDA reported that obesity seemed to increase the risk of developing lactic acidosis. More recent studies have found that while life-threatening cases of lactic acidosis are rare, changes in the levels of lactic acid in the blood (see below) with mild or no symptoms are more common. A report by Swiss doctors found that lactic acid was above normal levels in 107 out of 1598 (about 10% or 1 in 10) people studied. Only 14 of these people (about 1% or 1 out of 100) had levels that were more than twice the normal levels.
\|\|\|\|\| Diagnosis:
Blood tests can help diagnose lactic acidosis. Measurements of lactic acid in the blood (called serum lactate levels) are taken. Lactate levels above 5 mmol/L are considered dangerous, but it's important to note that lactic acidosis can sometimes develop even though lactate levels are below this level. Doctors can also measure the acidity of the blood by testing what's called the blood pH. Normal blood pH is generally between 7.35 and 7.45. In cases of lactic acidosis, the pH may drop to less than 7.35. Levels of something called serum bicarbonate may also fall below normal levels. The normal range for serum bicarbonate is generally 21-28 mEq/L. A procedure called a liver biopsy may sometimes be done to help diagnose lactic acidosis. This usually involves taking a small piece of tissue from the liver to look for evidence of fat droplets in the cells (hepatic steatosis).
\|\|\|\|\| Treatment:
There is no proven treatment for lactic acidosis other than stopping the NRTI drugs as quickly as possible. In serious cases, hospitalization and supportive care may also be needed. One or two reports have suggested that the vitamin supplements riboflavin (vitamin B2) or co-enzyme Q-10 may help speed recovery from lactic acidosis, but this is not yet proven.
\|\|\|\|\| Lactic Acid and Lipodystrophy:
Some researchers think that mild increases in lactate levels may contribute in some way to the body shape changes known as lipodystrophy. In particular, the loss of fat tissue in the face (causing a shrunken or wasted look) may be linked to damage to mitochondria. A study presented at the recent International AIDS Conference in Durban, South Africa looked at fat tissue from people with lipodystrophy under a special microscope. The researchers saw evidence of damage to mitochondria along with a build up of fat droplets (steatosis). More research is needed to confirm these findings and work out how best to treat the problem.