AJR 2004; 183:1605-1607
© American Roentgen Ray Society
Hepatic Steatosis and Pancreatitis Associated with the Use of Stavudine in a Patient with HIV Infection
Hsin-Yi Lai1,
Jeon-Hor Chen1,
Po-Pang Tsai1,
Mao-Wang Ho2 and
Wu-Chung Shen1
1 Department of Radiology, China Medical University Hospital, No. 2, Yuh-Der
Rd., Taichung 404, Taiwan.
2 Department of Internal Medicine, China Medical University Hospital, Taichung
404, Taiwan.
Received November 3, 2003;
accepted after revision February 2, 2004.
Address correspondence to J.–H. Chen
(chenjh{at}www.cmuh.org.tw).
Introduction
Lactic acidosis with hepatic steatosis and pancreatitis are rare
complications in patients receiving nucleoside reverse transcriptase
inhibitors (NRTIs) therapy for HIV infection or AIDS
[1–3].
In this article, we report on a patient with HIV infection who developed these
life-threatening complications after receiving stavudine treatment for 6
months. The literature has few, if any, reports regarding the sequential
change in imaging findings in such cases
[4]. Physicians must be
familiar with the clinical conditions and imaging features of these entities
so that the therapeutic agents can be immediately suspended, and death can be
averted.
Case Report
A 27-year-old woman in whom HIV infection had been diagnosed 3 years
earlier presented in the emergency department of our hospital because of a
1-week history of nausea and vomiting. Her most recent antiretroviral regimens
included stavudine, lamivudine, and nelfinavir mesylate, which she had been
taking for 6 months. The patient denied excessive alcohol intake, and test
results for the hepatitis B surface antigen and hepatitis C viral antibody
were negative. A sonogram of the abdomen obtained 6 months earlier revealed
normal and homogeneous echogenicity of the liver. No focal lesion or fatty
liver was noted (Fig. 1A).
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Fig. 1A. —27-year-old woman with HIV infection receiving nucleoside
reverse transcriptase inhibitors therapy. Sonogram obtained 6 months before
admission reveals normal homogeneous echogenicity of liver. No focal lesion or
definite fatty liver is seen.
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|
Physical examination revealed an alert overweight woman. Marked
hepatomegaly was found, but the abdomen was soft and without tenderness. The
bowel sounds were normally active. Laboratory data showed elevated hepatic
aminotransferase levels (aspartate aminotransferase, 94 U/L; alanine
aminotransferase, 49 U/L). The blood gas data revealed acidosis (pH, 7.219;
PCO2, 21.7 mm Hg; PO2, 101 mm Hg; bicarbonate, 9 mmol/L;
oxygen saturation, 96.6%; and anion gap, 23 mmol/L). Increased lactate level
(86.9 mg/dL) was also noted. Lactic acidosis was suggested.
Sonography showed hepatomegaly with increased echogenicity and decreased
definition of the portal and hepatic veins, indicating fat infiltration of
liver. CT performed 10 days later revealed hepatomegaly and decreasing density
of the hepatic parenchyma (Fig.
1B). The pancreas, however, appeared normal and without evidence
of acute pancreatitis on sonography and CT. HIV infection with lactic acidosis
and hepatic steatosis due to NTRIs (stavudine) therapy was diagnosed, and the
patient was admitted to our hospital for further evaluation and treatment.
After suspension of the anti-HIV medication and prescription of sodium
bicarbonate, the severity of lactate acidosis subsided (lactate level
decreased from 86.9 to 59 mg/dL and bicarbonate level increased from 9 to 25.7
mmol/L).
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Fig. 1B. —27-year-old woman with HIV infection receiving nucleoside
reverse transcriptase inhibitors therapy. Unenhanced abdominal CT scan
obtained 10 days after admission shows hepatomegaly and decreased overall
attenuation of hepatic parenchyma. Pancreas appeared normal and without
evidence of acute pancreatitis at this time.
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The patient's nausea, vomiting, and abdominal pain persisted for
approximately 1 month. Another abdominal CT examination was performed, the
findings of which revealed, when compared with those of CT examination
performed 1 month earlier, rapid deterioration of the fatty liver
(Fig. 1C). Enlargement and
swelling of the pancreatic tail with indistinct organ contour, parenchymal
inhomogeneity, and fluid collection in left anterior pararenal space led to
diagnosis of acute pancreatitis. The laboratory data showed increasing hepatic
aminotransferase levels (aspartate aminotransferase, 126 U/L; alanine
aminotransferase, 68 U/L) and pancreatic enzyme levels (lipase, 729 U/L;
amylase, 224 U/L).
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Fig. 1C. —27-year-old woman with HIV infection receiving nucleoside
reverse transcriptase inhibitors therapy. Contrast-enhanced abdominal CT scan
obtained 1 month after B reveals rapid deterioration of fatty liver
when compared with liver seen on earlier scan; liver was prominently enlarged.
Histogram (superimposed on right) shows severity of fatty liver by displaying
number of pixels (vertical axis) of specific attenuation values (transverse
axis). Circle indicates area measured on histogram.
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After continuously supportive treatment for 1 month, the patient's symptoms
and condition improved (aspartate aminotransferase, 74 U/L; alanine
aminotransferase, 65 U/L; lipase, 85 U/L; amylase, 78 U/L; lactate, 19.6
mg/dL). The patient was discharged uneventfully, and follow-up CT showed that
the size of the liver had significantly decreased and that hepatic steatosis
and pancreatitis had improved (Fig.
1D).
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Fig. 1D. —27-year-old woman with HIV infection receiving nucleoside
reverse transcriptase inhibitors therapy. Follow-up CT scan obtained 1 month
after C showed significantly decreased liver size and improved
pancreatitis. Histogram (superimposed on right) revealed markedly improved
hepatic steatosis. Circle indicates area measured on histogram.
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Discussion
Global spread of the HIV epidemic has led to unprecedented advances in
antiviral chemotherapy [1].
During the past 5 years, options for antiretroviral therapy have rapidly
increased [2]. Highly active
antiretroviral therapy involves the use of multiple concurrent antiretroviral
medications, combining agents from different classes
[2]. Although this therapy
allows the patients to survive much longer, it also increases their exposure
to medications. The side effects of antiretroviral therapy include lactic
acidosis, hepatic steatosis, pancreatitis, peripheral neuropathy, and myopathy
[3,
4]. Articles concerning the
sequential changes of complications detectable on diagnostic imaging are quite
scarce [4].
Severe hepatic steatosis and lactic acidosis among patients infected with
HIV-1 were first described in the early 1990s
[4]. The incidence of
nucleoside analogue–induced macrovesicular steatosis with hepatomegaly
and lactic acidosis among patients with HIV is estimated at only 1.3 per 1,000
patients [5]. The risk factors
of hepatic steatosis and lactic acidosis include obesity for females and
prolonged use of NRTIs [3].
Complications might occur 5–13 months after therapy is initiated
[2]. Symptoms include
gastrointestinal complaints such as abdominal distention, anorexia, nausea,
vomiting, abdominal pain and diarrhea, weight loss, and hepatomegaly
[3]. Significant laboratory
features include an increased anion gap, and elevated levels of
aminotransferases, creatine phosphokinase, lactate dehydrogenase, lipase, and
amylase [3,
6].
Hepatic steatosis is a rare but potentially life-threatening toxicity seen
with the use of NRTIs [3,
4]. The mechanisms of
NRTI-induced fat accumulation in the liver are not well known. Current
research suggests that nucleoside analogue toxicity results in mitochondrial
injury [4], including impaired
oxidation of fatty acids that leads to accumulation of fat droplets within the
liver cells [3,
4,
6,
7]. CT or sonography can
reliably reveal a fatty liver. Sonography shows increased echogenicity and
decreased definition of the portal and hepatic veins, and CT shows decreased
density of the hepatic parenchyma and relatively significant increase in the
attenuation of blood vessels within the liver parenchyma.
Failure to suspend NRTIs therapy in the presence of lactic acidosis and
hepatic steatosis may result in progressive lactic acidosis, dyspnea,
tachypnea, and ultimately respiratory failure
[3]. Therefore, early
recognition of liver toxicity is important, and thus HIV patients at risk of
liver disease should be monitored regularly
[5]. In addition, if a fatty
liver rapidly deteriorates in a patient with HIV-1 infection, the possibility
of drug-induced hepatic steatosis should always be considered. After
discontinuation of antiretroviral drugs, the hepatomegaly and hepatic
steatosis reverse.
Another relatively infrequent but serious toxicity due to NRTIs is acute
pancreatitis. The incidence of pancreatitis is higher in patients with the
more advanced disease of AIDS or with higher doses of the drugs
[8]. An incidence of 1–7%
has been reported in patients treated with 400 mg of stavudine per day.
Pancreatitis usually develops 3–5 months after therapy is initiated.
Typical symptoms include abdominal pain, nausea, vomiting, and fever
[2]. The mechanism of
NRTIs-induced pancreatic inflammation is unknown
[2]. Imaging findings on
sonography and CT may reveal inflammation in and around the pancreas that
resembles the alcoholism-induced pancreatitis. Because a significant number of
patients may have increased amylase and lipase levels but display no
definitive pancreatic inflammation on imaging and clinical findings, the
abnormal laboratory features should be carefully correlated with clinical
signs and symptoms and results of imaging studies before making a definitive
diagnosis of drug-induced pancreatitis
[2,
8].
The rapid development of acute pancreatitis and severe fatty liver in our
reported patient after suspension of stavudine is interesting and deserves
attention. The mechanism involved is, however, not fully understood. The
duration needed for repair of the injured mitochondria and reproduction of
cytochrome-c oxides after suspension of therapeutic drugs might
account for the further progression of these complications. This case serves
as a reminder for the clinician to continuously monitor the condition of
patients with HIV or AIDS even after suspension of stavudine.
In conclusion, although rarely encountered, drug-induced hepatic steatosis
and pancreatitis should be listed in the differential diagnosis when an
HIV-positive patient undergoing NRTI treatment shows rapid deterioration of
fatty liver and acute pancreatitis. Immediate suspension of the antiviral
drugs is important to prevent death.
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Introduction
Case Report
