Applied Evidence

Liver disease: Early signs you may be missing

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Maximizing your care starts with zeroing in on lab values you may be overlooking and taking advantage of algorithms that can help detect fibrosis.




Suspect compensated liver cirrhosis in a patient with abnormal liver function tests, a low platelet count, and prolonged prothrombin time. C
Use ultrasonography as a first-line diagnostic tool for liver cirrhosis. C
Prescribe beta-blockers as prophylaxis for patients at risk for variceal bleeding. A
Work collaboratively with hepatic specialists to manage the care of patients with cirrhosis. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

CASE 1: A patient with mildly elevated ALT and AST

John M., a 63-year-old truck driver with a family history of diabetes and arterial hypertension, is complaining of persistent fatigue—again. He has type 2 diabetes and takes metformin and repaglinide, but his blood pressure is normal. Lab tests reveal a recurrent mild elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of unknown origin; Mr. M. has no history of virus or hepatotoxic drugs, and reports only modest alcohol intake. He is obese, however, with a BMI of 34.5 and a waist circumference of 41 inches.

CASE 2: A patient with abdominal swelling

Anna B., a slim 68-year-old, comes in with 2 acute conditions: About a week ago, she noticed abdominal swelling and low back pain that began suddenly, after she carried a heavy load. She’s taken nonsteroidal anti-inflammatory drugs for 6 days, but the pain has not improved. The patient’s only significant clinical history is a hysterectomy, with oophorectomy, at age 38, and a recurrent elevation of serum transaminase levels that has never been investigated. Examination reveals an important kyphosis, and finger pressure on the vertebral spine or a position change exacerbates the pain. Her abdomen is swollen and tense, with a tympanic sound on the upper abdomen and a dull sound on the lower portion.

If John M. and Anna B. were your patients, would you suspect that they both have advanced liver disease? What diagnostic tests would you order, and how would you manage their care?

Cirrhosis has always been associated with high rates of morbidity and mortality. It is the 12th most common cause of death in the United States;1 in some parts of the world, its ranking as a cause of death is considerably higher.2,3 In recent years, however, cirrhosis has become the focus of greater attention both here and abroad, for 2 reasons: The first is the increasing prevalence of viral hepatitis and steatohepatitis, both of which are prominent causes of cirrhosis. The second is the improvement we’ve made in treatment: Not only can we slow the progression of cirrhosis, but in some cases, we can even restore hepatic function.4

The key to successful management of cirrhosis lies in spotting subtle signs and symptoms well in advance of the serious complications that can arise down the road. Here’s what to look for.

Early warnings you can’t afford to overlook

While the clinical presentation of a patient with liver cirrhosis is often asymptomatic, serum transminases—included in many standard laboratory tests as part of a routine examination—often provide the first sign of a problem.

Mildly elevated ALT in an asymptomatic patient may be transient and benign, or an indication of chronic liver disease.5 In fact, signs suggestive of significant liver disease have been reported in more than 20% of patients with ALT elevation.2 But because abnormal ALT values are common and frequently resolve, many primary care physicians pay little attention to this potentially important finding—and miss a key opportunity for early identification and treatment.6

Look at other lab values, risk factors, as well

Additional lab values that suggest the possibility of cirrhosis include an elevated AST/ALT ratio, a low platelet count (<150,000/L), elevated alkaline phosphatase, elevated bilirubin (>1.1 mg/dL), low serum albumin (<2.5 g/dL), and decreased prothrombin time (<100%). Potential causes include viral hepatitis, heavy alcohol use, hepatotoxic drugs, steatosis, and steatohepatitis.

The next step for a patient with any of these abnormal values is a thorough medication review and medical history. Identify all prescription and nonprescription drugs the patient is taking, as well as any herbal products and supplements, in search of hepatotoxic agents. Amiodarone and valproic acid, among other drugs, may cause steatosis, and some herbal products—particularly kava kava extract, used to treat anxiety and insomnia—have been linked to hepatitis and even liver failure.7 Question the patient about alcohol consumption and a history of conditions associated with liver disease, such as diabetes, hyperlipidemia, and thyroid disorders, as well.


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