Can Liver Function Tests be Normal with Cirrhosis?
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1. What is liver cirrhosis?
Cirrhosis results from any chronic inflammation or injury to the liver tissues. Any condition or disease that causes chronic destruction of the liver cells can result in cirrhosis.
The ongoing inflammation leads to chronic destruction of the liver cells and disruption of its micro-architecture of the liver.
In a trail to healing, the liver cells and other liver tissue components regenerate.
If the inflammation or destruction is limited, the liver is capable of regeneration without significant arrangements in its tissues.
However, if the inflammation is severe or prolonged enough, the liver heals by fibrosis (fibrous tissue replaces the healthy liver cells with its unique arrangement).
Cirrhosis represents the last stage of liver fibrosis. After that, the liver architecture is largely replaced by fibrous tissues and cannot perform its functions.
The commonest causes of liver cirrhosis include:
- Chornic viral hepatits (such as hepatitis B and C).
- Chronic alcholic hepatitis.
- Non-alcholic steatohepatitis.
- Metabolic liver diseases such as Hemochromatosis and Wilson’s disease.
- Autoimmune hepatitis and primary biliary cholangitis.
- Vascular liver diseases such as Budd-Chiari syndrome and veno-occlusive diseases.
- And others.
Cirrhosis starts as a radiological/laboratory finding without symptoms (compensated cirrhosis).
However, the ongoing inflammation and destruction may cause significant loss of liver function (decompensated cirrhosis). In these patients, the symptoms and complications of cirrhosis start to appear.
Symptoms and complications include:
- Early cirrhosis may be asymptomatic or have non-specific symptoms such as weight loss, anorexia, weakness, and fatigue.
- Swollen lower limbs.
- Swollen belly (ascites).
- Gastrointestinal bleeding: vomiting blood (Hematemesis), black tarry stool (melena) passage, or red blood in the stool (hematochezia).
- Hepatic encephalopathy: starts gradually, in the form of behavioral, memory, or sleep changes. It may progress to agitation or complete loss of consciousness.
- Skin bruising dilated veins.
- Muscle wasting and muscle cramps.
2. How is cirrhosis diagnosed?
The diagnosis of advanced (decompensated) liver cirrhosis is often evident. Patients with decompensated liver cirrhosis often have typical symptoms and signs (explained above), such as:
- Swollen limbs and belly.
- Muscle wasting.
- Complications such as hematemesis (vomiting of blood), melena (passage of tarry black stool), or hepatic encephalopathy
- Other symptoms and signs (mentioned in the previous section).
However, the early stages of liver cirrhosis are often asymptomatic, and the diagnosis is often not easy. Moreover, liver function tests can be normal in the early stages of the disease.
The gold standard for diagnosing liver cirrhosis is taking a biopsy from the liver (via specialized needle).
However, it is an invasive technique, and your doctor often diagnosed the disease with non-invasive tests such as:
- Abdominal ultrasonography.
- Abdominal CT.
- Abdominal MRI.
- Transient elastography.
- Nuclear studies.
- Simple scores (depending on a combination of laboratory and clinical signs): such as the AST/Platelet ratio and Bonacini cirrhosis score.
3. Typical liver function tests in liver cirrhosis.
Typically, patients with liver cirrhosis have multiple laboratory abnormalities. The most common abnormalities in liver function tests include:
- Elevated ALT and AST (often mild to moderate elevations).
- Elevated bilirubin.
- Elevated INR (international normalized ratio) and prolonged prothrombin time.
- Low serum albumin.
- Mild elevations in alkaline phosphatase (ALP).
- Mild elevations in gamma Glutamyl transferase (GGT).
- Low serum sodium (hyponatremia).
- In severe cases, kidney function may become affected (high serum creatinine).
- Low platelet count.
- Anemia (low Hemoglobin Levels.
The degree of lab arrangement correlates with the severity of liver cirrhosis. Mild cases of liver cirrhosis may have normal or slightly elevated. As cirrhosis progresses, the laboratory derangements become more profound.
For example, the famous Child-Pugh score to assess the severity of liver cirrhosis assesses the following lab parameters:
- Serum bilirubin.
- INR (international normalized ratio) or Prothrombin Time).
- Serum albumin.
Look at the below table and note the determination of these lab tests and how it correlates to the severity of cirrhosis.
|Bilirubin||<2 mg/dL (<34.2 micromol/L)||2 to 3 mg/dL (34.2 to 51.3 micromol/L)||>3 mg/dL (>51.3 micromol/L)|
|Albumin||>3.5 g/dL (35 g/L)||2.8 to 3.5 g/dL (28 to 35 g/L)||<2.8 g/dL (<28 g/L)|
|Prothrombin time (seconds over control) or||<4||4 to 6||>6|
|INR||<1.7||1.7 to 2.3||>2.3|
|Encephalopathy||None||Grade 1 to 2||Grade 3 to 4|
Another example is the Bonacini cirrhosis discriminant score. The score is calculated by giving the points to the following laboratory parameters (reference):
- >340 – zero points
- 280 to 339 – one point
- 220 to 279 – two points
- 160 to 219 – three points
- 100 to 159 – four points
- 40 to 99 – five points
- <40 – six points
Alanine aminotransferase to aspartate aminotransferase (ALT/AST) ratio:
- >1.7 – zero points
- 1.2 to 1.7 – one point
- 0.6 to 1.19 – two points
- <0.6 – three points
International normalized ratio (INR):
- <1.1 – zero points
- 1.1 to 1.4 – one point
- >1.4 – two points
5. Can you have cirrhosis with normal liver function tests?
The short answer: YES.
As we explained above, cirrhosis refers to extensive fibrosis of the liver. It is a gradual process that occurs over months or years.
So, people with early stages of liver cirrhosis can have normal liver function tests.
In early-stage (compensated) liver cirrhosis, the liver can perform its function. So, liver function tests such as serum albumin and prothrombin time are often normal.
Also, liver enzymes (ALT and AST) may return to normal in the late stages of liver cirrhosis. This is because ALT and AST are secreted from the damage to liver cells. So, in late-stage cirrhosis, there are insufficient cells to produce liver enzymes (ALT, AST).
In conclusion, normal liver function tests cannot exclude liver cirrhosis.
5. Can blood tests (as liver function tests) rule out cirrhosis?
Negative blood tests cannot exclude liver cirrhosis because liver function tests can be normal in early stage (compensated) liver cirrhosis. However, the liver function tests become abnormal as liver cirrhosis progress.
Your doctor will diagnose liver cirrhosis depending on clinical, laboratory, and imaging studies. Sometimes, a biopsy from the liver is needed to exclude cirrhosis.
A biopsy is still the gold standard if your doctor wants to be 100% sure you don’t have cirrhosis.