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Title: The investigation and diagnosis of 2 cases of liver disease.

Introduction:
Liver is the largest internal organ in the body, performing more than 5,000 separate bodily functions, from cleansing the blood of toxins to converting food into nutrients to controlling hormone levels. Usually Liver disease is reflected by biochemical abnormalities of 1 of 2 different hepatic systems or of liver function. Even though tests that measure the level of serum liver enzymes are commonly referred to as liver function tests (LFTs), they generally reflect hepatocyte integrity or cholestasis rather than liver function. Biochemical markers of liver include:

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Alanine Aminotransferase (ALT) and Aspartate aminotransferase (AST) are enzymes found in the heart, liver and muscle. They are sensitive biomarker of hepatocellular damage. However, ALT is considered more specific to liver damage as it has less activity in extra-hepatic tissue than AST.

Alkaline Phosphatase (ALP) is an enzyme found in the bone, bile duct, placenta and liver. In liver, It is a canicular enzyme that plays a role in bile production. Therefore, increased levels of ALP may indicate liver inflammation and/or blockage of the bile duct (cholestasis).

Gamma glutamyl transferase (GGT) is an enzyme found in the cell membranes of liver, pancreas, intestine and kidneys. Its function is to catalyze transfer of glutamyl group from peptides to other amino acids. Its correlated levels with ALP indicate hepatobiliary origin problems (Cholestasis).

Bilirubin is a breakdown product of heamolysis taken up by liver cells and conjugated to water-soluble product excreted in bile. Elevations may indicate hepatic or extra-hepatic disorders. It also helps in diagnosing Jaundice and its fractionation aid in distinguishing conjugated from unconjugated hyperbilirubinaemia.

Clinical Details:
• Patient A:
A 26 years old female presented to Tallaght University Hospital (TUH) with symptoms of abdominal pain, itch, arthralgia (x2/52), new facial rash and a sore throat in July 2018. After admission, liver function tests (LFTs) were performed over the course of several months and results showed consistent increase in liver enzymes. She had no past medical history. She was not on regular medication but received penicillin following the onset of sore throat, after other symptoms.
• Patient B:
A 59 years old female was presented to oncology unit in TUH with symptoms of intra-hepatic infection. The patient was already attending TUH.

Laboratory Investigation
• Patient A:
Over the course of several months, Liver function tests (LFTs) were performed in the clinical chemistry lab in Tallaght Hospital. After registration, samples were centrifuged. The aim of centrifugation is to separate blood contents (cells & platelets) from plasma. Then, LFTs were performed on these samples using automated system Roche C8000.
The LFTs in TUH include:
-Total protein
-Albumin
-Bilirubin
-Alkaline Phosphatase (ALP)
-Alanine Aminotransferase (ALT)
– Gamma glutamyl transferase (GGT)

The LFTs showed extremely elevated liver enzymes levels (with ALT level exceeding 1000 IU/L), which is an indication of acute liver damage.

Differential diagnosis of Hepatitis
Acute or chronic hepatitis refers to an inflammatory condition of the liver. Hepatitis’s most common cause is viral infection. However, there are other possible causes of hepatitis such as autoimmune hepatitis which occurs when the body makes antibodies against liver tissue. Hepatitis can also be caused as a secondary result of medications, drugs, toxins and alcohol (3).
With hepatitis being caused by the virus A, B, C, and E diagnosis is a lot more complicated as all the isoforms show similar symptoms. Thus, laboratory testing is important to identify the exact causative virus so that the appropriate treatment can be initiated appropriately (4).

Approach for Differential diagnosis of Hepatitis
Diagnosis is a critical decision point at which sufficient evidence has to be collected to get a clear clinical picture about the patient before beginning of the treatment. Laboratory tests for hepatitis are critical for the clinician to confirm ?ndings about the clinical condition of the patient because of various causative agents of the disease (3).

Detection of the specific virus that causes viral hepatitis is only possible by detection of serological markers of respective viruses through
immunological tests. The speci?c causative virus can be detected using these diagnostic tests which can help aid in initiating the right treatment (4).

The ideal approach for detection of specific causative agent is demonstrated below.
Immunological Tests Panel:
• Hepatitis A IgM Antibody (Anti HAV – lgM)
• Hepatitis E IgM Antibody (Anti HEV- lgM)
• surface antigen of the hepatitis B virus (HBsAg)
• Anti-Hepatitis B core total antibodies (Anti HBc)
• Anti-Hepatitis C virus (Anti HCV)
• Human immunodeficiency virus (HIV)
• Autoimmune Hepatitis diagnostic panels (4)

Following initial findings, differential diagnosis of hepatitis was made. However, the serology results were negative for hepatitis.

The patient didn’t show any signs of suspicious lesions upon Magnetic resonance imaging (MRI) test results either. MRI is a noninvasive spectroscopic imaging technique used in medical settings to produce detailed pictures of the inside of the human body. The MRI test is based on the principles of nuclear magnetic resonance (NMR), which is a spectroscopic technique used to obtain microscopic chemical and physical data about molecules. this magnetic resonance imaging is accomplished through the absorption and emission of energy of the radio frequency (RF) range of the electromagnetic spectrum. It can be used to help diagnose or monitor treatment for several of conditions within the chest, abdomen and pelvis (5).

Patient B:
A blood sample was received into the clinical chemistry main lab in TUH. It was registered and centrifuged. Then, LFTs were performed on this sample using automated system Roche C8000. LFTs results showed elevated liver enzymes levels (with GGT & ALP levels exceeding 800 IU/L) which is indication of obstructive pattern liver damage (Cholestasis).
Ultrasound (US) of the liver was performed but no obvious biliary duct dilation was detected. However, upon magnetic resonance cholepancreatography (MRCP) test the results showed moderate intrahepatic biliary ductal dilatation secondary to large central necrotic nodal mass at the porta hepatis.