Laboratory Diagnosis of Liver Disease


By the end of this session the reader should be able to:

  • To describe the basic functions of the liver
  • To describe how to use the laboratory to determine if liver disease is present
  • To describe how to use the laboratory to determine what type of liver damage is present (cellular vs. biliary tract)
  • To list the various tests used to diagnose hepatitis
  • Describe the use of the serum transaminases and bilirubin in evaluating hepatic parenchymal damage and function
  • Describe the use of the serum alkaline phosphatase, gamma glutamyl transferase, and bilirubin in evaluating biliary tract disease
  • Describe conditions in which the serum unconjugated bilirubin is elevated without significant elevations of the conjugated bilirubin
  • Describe conditions in which the serum conjugated bilirubin is elevated without significant elevations of the unconjugated biliruin
  • Describe conditions in which both serum conjugated and unconjugated bilirubin are elevated
  • Discuss "delta bilirubin" and its significance
  • Discuss the formation of urobilinogen and its diagnostic use
  • Discuss the alteration of serum proteins in liver diseases
  • Discuss aminoaciduria in liver failure
  • Discuss abnormalities in blood coagulation in liver disease
  • Discuss causes of hyperammonemia
  • Discuss the causes of DeRitis ratio > 1 and < 1
  • Discuss alkaline phosphatase isoenzymes and their diagnostic use


Alkaline phosphatase - enzyme found in a variety of tissues; commonly used to diagnose hepatic and bone diseases

Ascites - Serous fluid that accumulates in the abdominal cavity

AST - aspartate aminotransferas commonly used to detect cellular hepatic damage; sometimes referred to as SGOT

ALT - alanine aminotransferase; commonly used to detect cellular hepatic damage; sometimes referred to as SGPT

Bile - A fluid synthesized by the liver and secreted into the duodenum via the bile ducts, the important constituents of which are conjugated bile salts, cholesterol, phospholipids, bilirubin diglucuronide, and electrolytes

Bilirubin - end product of heme metabolism produced in liver, spleen and bone marrow

Cholangitis - Inflammation of the bile ducts

Cholestasis - Decreased bile flow resulting from either intrahepatic or extrahepatic obstruction

Cirrhosis - Liver disease characterized by regenerative nodules and diffuse interlacing bands of fibrous tissue dividing the hepatic parenchyma into micronodular or macronodular patterns

Direct (conjugated) bilirubin - bilirubin that has been taken up by the liver cells and conjugated to form the water-soluble bilirubin diglucuronide

GGT - gamma glutamyl transferase; useful to help determine if elevations of alkaline phosphatase are due to bone or liver; this enzyme is very sensitive to alcohol consumption

Hepatic Encephalopathy - a neuropsychiatric syndrome occurring secondary to advanced liver disease with hyperammonemia; manifested by aberrant behavior and even coma

Hepatitis - inflammation of the liver

Indirect (unconjugated) bilirubin - free bilirubin that has not been conjugated with glucuronic acid

Jaundice - a syndrome characterized by hyperbilirubinemia and deposition of bile pigment in the skin, mucous membranes, and sclera, with resulting yellow appearance of the patient; called also icterus

Kernicterus - a clinical syndrome of the neonate, resulting from high levels of unconjugated bilirubin, which pass the immature blood-brain barrier of the newborn and cause degeneration of cells of the basal ganglia and hippocampus

Portal hypertension - any increase in portal vein pressure due to anatomical or functional obstruction (for example, alcoholic cirrhosis) to blood flow in the portal venous system

Varices - enlarged and tortuous veins, arteries, or lymphatic vessels, usually seen in the esophagus or stomach, commonly caused by cirrhosis and leading to portal hypertension


In the liver, important synthetic, catabolic, and detoxifying functions take place. Complete loss of the liver or its functions results in death within hours or days. The hepatic parenchymal cells are involved in carbohydrate metabolism (glycogen synthesis, glycogenolysis, gluconeogenesis), protein synthesis (most plasma proteins including the coagulation factors, except factor VIII and immunoglobulins), lipid metabolism, (lipoproteins, phospholipids, fats, cholesterol), storage functions (probably all vitamins except vitamin C, iron, copper, trace metals), excretion (bilirubin, bile salts, copper), and detoxification (ammonia, steroid hormones, drugs, poisons).

Liver disease may be a process confined to the organ itself (e.g., infection, cirrhosis, cholestasis, neoplasms) or be a consequence of systemic disease (e.g., cardiac insufficiency, hemochromatosis, hemolytic disease, metastatic disease).

Many drugs are cleared by hepatic mechanisms, and many drug interactions occur at the hepatic level. In addition, several drugs cause hepatic damage, consequently it is essential for pharmacists to understand how to use the laboratory to:

  1. Assess the state of biochemical functions of the liver
  2. Differentiate pathologic processes from drug-induced effects
  3. Diagnose etiology

Some tests may belong to more than one category, e.g. bilirubin.

Tests of Hepatic Parenchymal Damage

Tests of hepatocellular damage (reference range)

  • AST (10-45 U/L)
  • ALT (10-45 U/L)
  • Bilirubin (conjugated and total) (<0.2 and <1.2 mg/dL, respectively)

Tests of biliary tract disease

  • Alkaline phosphatase (ALP) (30-130 U/L)
  • Gamma glutamyl transferase (GGT)
    • female <24 U/L
    • male <38 U/L
  • Bilirubin (conjugated and total) (< 0.2 and < 1.2 mg/dL, respectively)

Tests of Etiology

  • Hepatitis virus antigens; HBsAg, HCV by PCR
  • Hepatitis virus antibodies (e.g., HAV-IgG, HAV-IgM, HBcAb, HBeAb, HBsAb, HCAb)
  • α-fetoprotein
  • Immunoglobulins
  • Autoantibodies (antimitochondrial, smooth muscle, antinuclear)
  • Iron, transferrin, ferritin (hemochromatosis)
  • Copper, ceruloplasmin (Wilson’s disease)


Disease Tests
Acute hepatitis AST, ALT, GGT, LDH, serum bilirubin conjugated & total, viral antigens
Chronic hepatitis ALT, AST, viral antigens, viral antibodies, serum protein electrophoresis, bilirubin conjugated & total
Cirrhosis Serum protein electrophoresis, ALT, AST, alkaline phosphatase, bilirubin conjugated and total, GGT, folic acid, B12, ammonia
Cholestasis Alkaline phosphatase, GGT, bilirubin total and conjugated
Focal lesions or infiltration Alkaline phosphatase, GGT
Primary hepatocellular carcinoma α-Fetoprotein, alkaline phosphatase, GGT, AST
The first three are genetic metabolic disorders:
Gilbert's disease Bilirubin, total and conjugated (varies with eating and fasting)
Dubin-Johnson and Rotor syndromes Bilirubin, conjugated and total
Crigler-Najjar syndrome Bilirubin, total and conjugated
Workup of jaundice Bilirubin, total and conjugated, bilirubin in urine, AST, ALT, alkaline phosphatase, GGT, haptoglobin, plasma hemoglobin, hematologic parameters (for hemolysis)
Hemochromatosis Serum iron and total iron-binding capacity, % saturation of TIBC or transferrin, ferritin, tests for cirrhosis, α-fetoprotein
Wilson's disease Serum copper, ceruloplasmin, tests for cirrhosis



Reference Range: Conjugated bilirubin <0.2 mg/dL
Total <1.2 mg/dL

Bilirubin, the end product of heme catabolism, is transported to the liver to be conjugated and excreted via the bile. Most of the bilirubin in blood is in transit from the tissues to the liver, in the unconjugated form, bound to albumin. Only small amounts of conjugated bilirubin are normally found in blood, and it is believed that the usual analytical methods tend to overestimate it in the low reference range. Bilirubin determinations are reported in two fractions, the “conjugated” and the “total.” These names derive from Van den Bergh's observation in l916 that there are two types of reactions of serum bilirubin with Ehrlich's reagent (diazotized sulfanilic acid):
  1. A direct reaction occurs within one minute of the addition of the aqueous Ehrlich's reagent to water-soluble or conjugated bilirubin (both mono- and diglucuronides).
  2. An indirect reaction occurs after incubation with caffeine for 30 minutes to remove water-insoluble or unconjugated bilirubin from albumin

The laboratory now reports bilirubin results as the conjugated (direct) fraction and the total, i.e., the sum of the conjugated and unconjugated bilirubin. Unconjugated bilirubin is no longer measured or reported as such, but in practice is inferred by the clinician from the difference (total bilirubin minus the conjugated fraction). However, this theoretical scheme does not hold completely true in practice in that the chemical reactions do not allow for perfect separation between the conjugated and unconjugated bilirubin. This is of no clinical significance.

Hemolysis interferes with the test, causing an erroneous lowering of results (depending on methodology). Bilirubin is very light sensitive and samples must be analyzed within one to two hours or kept in the dark. Bilirubin is stable for months when serum is frozen, and protected from light.

Fasting increases bilirubin in blood slightly in the normal person and more markedly in Gilbert’s disease (see section below). It decreases with sunbathing and is slightly lower in women than in men.

Low bilirubin values have no demonstrated clinical significance.

Elevations of the unconjugated bilirubin without significant elevations of the conjugated are seen in:

  • Hemolytic disorders
  • Gilbert’s syndrome (transport and conjugation defect, bilirubin 2-3 mg/dL)
  • Arias syndrome (partial conjugation defect, bilirubin more than 6 mg/dL)
  • Crigler-Najjar syndrome (glucuronyl transferase deficiency; 2 types)
  • Immaturity of the liver in the newborn (this is very common)
  • Cirrhosis (often no elevations)

Elevations of the conjugated bilirubin with lesser increase of the unconjugated form are seen mostly in the early phases of cholestasis and are transient, with day to day fluctuation of the two fractions. Textbook descriptions of conditions typically characterized by an elevation of the conjugated bilirubin often neglect to mention that these conditions are also accompanied by an elevation of the unconjugated bilirubin (e.g., Dubin-Johnson, Rotor).

Elevations of the conjugated plus unconjugated bilirubin are seen in:

  • Hepatitis (the liver still functions but swelling interferes with bile flow)
  • Cirrhosis (only in presence of other active liver disease)
  • Posthepatic obstruction (stones in the common bile duct, cancer)
  • Dubin-Johnson syndrome - young women on contraceptives or pregnant, usually related to estrogen-induced inability to excrete bilirubin (liver pigmentation; gallbladder not visualized; excretory defect)
  • Rotor’s syndrome (no liver pigmentation; gallbladder visualized; excretory defect)
  • Some forms of drug-induced cholestasis

A third form of bilirubin “tightly” bound to plasma albumin has been characterized by high performance liquid chromatography (HPLC). This form of bilirubin (“delta-bilirubin”) is not detected to any significant extent in sera from normal adults, or in sera from patients with unconjugated hyperbilirubinemia. However, increased levels of delta-bilirubin are observed in sera from patients with prolonged conjugated hyperbilirubinemia (e.g., patients with cholestasis, cirrhosis, hepatitis, Dubin-Johnson syndrome, biliary atresia of the newborn). It has been suggested that a spontaneous reaction between bilirubin glucuronides and albumin results in a covalent linkage, presumably an amide bond, of pigment to the serum albumin. The concentration of delta-bilirubin varies over a wide range, but it may account for 30-50%, and in some instances as much as 90%, of the total serum bilirubin. Delta-bilirubin is believed to be responsible for persistence of conjugated hyperbilirubinemia following clinical disappearance of bilirubinuria. Delta-bilirubin per se is not cleared into the urine since it is bound to albumin.


Only the conjugated, water-soluble form of bilirubin (the direct) is excreted into the urine. Since the conjugated bilirubin concentration in serum normally is very low, the urine normally also contains less than 0.2 mg/dL of bilirubin, an amount not detectable by conventional tests. Thus, detectable bilirubinuria is abnormal and for its demonstration qualitative or semi-quantitative tests suffice.

Urine containing bilirubin is yellowish-green and, when shaken, the resulting foam also turns yellowish-green. If bilirubin is absent, this foam usually is white. Bilirubin in urine is detected by:

  1. The Fouchet's test,
  2. A tablet test (Ictotest),
  3. A paper strip test (Bilistix)

Bilirubinuria is seen in:

  • Biliary obstruction
  • Hepatocellular damage
  • Dubin-Johnson syndrome
  • Rotor’s syndrome

In conditions with an elevation of only unconjugated bilirubin, bilirubinuria is not present.


The water-soluble conjugated bilirubin excreted into the bile is converted by bacterial action in the gut into a number of products called urobilinoids, consisting of colorless chromogens (urobilinogens in urine, stercobilinogens in stool) and their pigmented oxidation products (urobilin, stercobilin). The color of the stool, previously believed to be due to stercobilin, now is known to be due to another class of compounds which are dipyrroles called pentdyopents.

The urobilinogens are partially reabsorbed by the gut and through the portal circulation are re-excreted through the liver and the bile. However, a small proportion of these recirculating urobilinogens escape the liver and are excreted into the urine where they are normally detectable.

Reference Range: up to 4 mg/d

Urinary urobilinogens are absent in complete biliary obstruction, when no bilirubin glucuronides reach the gut and no chromophores are found (stools are chalky-white).

Urinary urobilinogens are increased in hemolytic anemia, when greater amounts of bilirubin are excreted by the liver and in early liver damage, when re-excretion of urobilinogen into the bile is impaired. Values >5 mg/d are abnormal; occasionally values in excess of 300 mg/d are seen.

A semi-quantitative test for urobilinogen is performed on a two-hour (timed) urine specimen.

Reference Range: 0.1-0.8 Ehrlich units/2 h

A screening test based on the use of "Uro-bilistix" (Ames Company) is available and now more often performed than the semi-quantitative two-hour Ehrlich urine test.

Fecal Urobilinogens

This test is not often performed.

Reference Range: 75-400 mg/d, or 125 to 400 Ehrlich units per day
Decreased in: biliary obstruction
Increased in: hemolytic anemia

Fecal urobilinogens are absent in newborns and begin to appear as the infants acquire normal intestinal bacterial flora, usually within a few weeks.

Plasma Proteins

Plasma total protein concentrations in liver disease often are near normal because a decrease of albumin is offset by an increase of globulins and the concept of the ratio of albumin:globulin (A/G ratio), as used in the past, reflects this. Reference Range: 1.5:1 to 3.0:1.

Most useful are albumin measurements in the assessment of the severity of impairment of the synthetic functions of the liver. Chronic proliferative disease of the liver (cirrhosis, chronic hepatitis) leads to polyclonal hypergammaglobulinemia as demonstrated by the “beta-gamma bridging” on serum protein electrophoresis. . IgA is affected more than other immunoglobulins because most is manufactured in lymphoid tissue of the gut. It drains first into the portal system and is catabolized in the liver. When portal circulation is compromised, IgA survives and is reflected in the serum protein electrophoresis pattern.

Albumin is also important in the evaluation of renal disease.

Reference Range: Total proteins, 6.0 - 8.0 g/dL
Albumin, 3.3 - 5.0 g/dL

Blood Coagulation

A prolongation of the prothrombin time (PT) is an indicator of hepatic dysfunction as the synthesis of the coagulation factors is impaired in hepatocellular disease. Furthermore, impaired absorption in the gut, particularly of fat soluble substances, often accompanies liver disease which may result in decreased absorption of vitamin K, needed for the production of factors II, VII, IX and X. In more severe conditions, the PTT (partial thromboplastin time) also becomes prolonged.

Dysfibrinogenemias, an interferent with fibrin-polymerization, have also been reported in severe liver disease.

Fibrinolysis is increased in some patients with hepatic disease, presumably because of reduced synthesis of plasmin inhibitors by the diseased liver.

Amino Acids

In severe cirrhosis or hepatitis, the handling of amino acids by the liver cell is impaired, resulting in higher blood levels and increased aminoaciduria. There is little clinical value in their determination.

In severe liver necrosis, aminoaciduria reaches such proportions that the solubility of certain amino acids is exceeded and crystals are formed, such as the characteristic leucine “spheres” and tyrosine “rosettes” (see under Urinalysis) which are encountered in the urine in “acute yellow liver atrophy.”

Blood Ammonia

Elevated blood ammonia is seen in severe liver disease and in actual or impending hepatic coma. The elevations are due to reduced removal of ammonia from the portal blood, and "shunting" of portal blood, bypassing the liver. Proteins absorbed in the gut first pass through the liver in the portal circulation. Blood ammonia levels show some, but not close, correlation with the presence and deepness of the coma.

Elevated blood ammonia levels are seen in:

  • Severe liver disease
  • Hepatic coma and Reye's syndrome
  • Severe heart failure
  • Azotemia
  • Cor pulmonale
  • Erythroblastosis fetalis
  • Intestinal fistulas and blind loops
  • Prolonged shock
  • Intestinal bleeding
  • Transient hyperammonemia of the neonate

Congenital hyperammonemia is seen in:

  1. Inherited defects in urea cycle
  2. Defects in propionic, methyl malonic and isovaleric acid metabolism

Reference Range: 10 - 35 µmol/L

AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase)

These transaminases are the most sensitive indicators of hepatic cell injury. They may be elevated without elevation of bilirubin or other detectable impairment of liver function. Their highest levels are seen in acute hepatic necrosis. Their elevations usually parallel each other with the following exceptions:

AST is generally higher than ALT in:
myocardial infarction
metastatic carcinoma
progressive muscular dystrophy
DeRitis ratio$\left(\frac{ALT}{AST} \right ) < 1$
ALT is generally higher than AST in:
acute hepatic necrosis (viral hepatitis)
intrahepatic cholestasis
infectious mononucleosis
DeRitis ratio$\left(\frac{ALT}{AST} \right ) > 1$

ALT elevations without those of AST are occasionally seen in mild hepatic disease and in the recovery phase of hepatitis, as the ALT elevations persist longer than those of AST. ALT is generally a more sensitive indicator of acute liver cell damage than AST.

Reference Range: AST, 10 - 45 U/L
ALT, 10 - 45 U/L

Alkaline Phosphatase (ALP)

This enzyme is present in high concentration in the lining of the biliary system (bile canaliculi) and escapes into the bloodstream when the lining cells are affected by inflammation, necrosis, or obstruction. In obstruction, marked increase in serum concentrations are probably due to release of the enzyme into the circulation as a result of cell fragmentation by the increase of bile acids.

Elevations of this enzyme in the blood are a sensitive indicator of a biliary process but they are also seen in liver cell damage. The general rule applies that the higher the alkaline phosphatase, the greater the chances for post-hepatic obstruction. If the elevation is less than three times normal, consider hepatocellular disease; if greater than three times the upper reference limit, consider post-hepatic obstruction.

Focal lesions in the liver may lead to significant elevations of the alkaline phosphatase without a raised bilirubin. The liver has a large functional reserve and in this situation the unaffected liver tissue has sufficient capacity to excrete the bilirubin, while the alkaline phosphatase remains circulating in the blood.

It must be kept in mind that there are other important sources of alkaline phosphatase such as the bones and the gastrointestinal mucosa, the placenta, and certain tumors (Regan and Nagao isoenzymes).

There are at least twenty isoenzymes of alkaline phosphatase that can be separated using capillary electrophoresis, but the procedure is technically complex and interpretation of results is difficult. The alkaline phosphatases also show differential heat stability when exposed to 56 or 60°C in the following order: bone < intestine < liver < placenta, Regan isoenzyme (most heat stable) and the heat stability test of alkaline phosphatase takes advantage of this. Remember this by “bone burns and liver lives” and “BILP.”

In 1994, Hybritech introduced a specific test, Ostase®, for the bone isoenzyme. The only limiting factor is a ~12% cross-reactivity with the liver isoenzyme.

Reference Range: 30 - 130 U/L

GGT (Gamma Glutamyl Transferase)

This enzyme is found in liver and pancreas, but in even larger amounts in the kidney. Elevations of the hepatic alkaline phosphatase can be due to a bone disease or due to cholestasis. Therefore, GGT determinations are helpful in differentiating bone and liver sources of alkaline phosphatase, since there are no significant amounts of GGT in bone. GGT is also a sensitive indicator of alcohol-induced liver disease and of recent alcohol ingestion.

It is used in alcohol treatment programs to detect a return to drinking. Even changes within the reference range may be significant if one knows the patient’s baseline results.

Up to seven isoenzyme fractions of GGT have been demonstrated with starch gel electrophoresis but no clinical application has as yet been defined.

Reference Range: male, <38 U/L; female, <24 U/L


Case 1

(Ann. Pharmacother. 36(12):1887-1889, 2002)

A 41-year-old white man had received a prescription for celecoxib 200 mg/d for 3 days for pain associated with right-knee trauma. Shortly after taking the second dose of the drug, he began to experience epigastric pain, nausea, anorexia, malaise, pruritus, cutaneous and scleral jaundice with dark urine, and pale stools. In spite of the symptoms, the man took the final dose (total dose: 600 mg). The symptoms persisted and, 48 hours after the third dose of celecoxib, he was seen by his family physician, who found: a total bilirubin 8.4 mg/dL, direct bilirubin 7.6 mg/dL, AST 97 IU/L, ALT 234 IU/L, and GGT 134 IU/L.

  1. How do you interpret these lab values?
  2. What is the significance of the pale stools?
  3. What other tests should be ordered?
  4. Is this a common adverse drug reaction for this class of drugs?
  5. What percent of patients that present with cholestasis are drug-induced?
  6. How should this patient be treated?

Case 2

(Am. J. Med. Sci. 325(5):292-295, 2003)

A previously healthy 65-year-old man developed scleral jaundice. Simultaneously, he experienced severe fatigue, and reported light-colored stools, dark urine, and generalized pruritus. The patient denied abdominal pain, fever, abnormal bleeding, or skin rashes. One month before the onset of symptoms, he was prescribed terbinafine (Lamisil; Novartis Pharmaceuticals Corp., New Jersey) for onychomycosis (fungal infection of the nails).

Initial laboratory tests showed bilirubin 21 mg/dL, (conjugated bilirubin, 18.8 mg/dL), aspartate aminotransferase 313 IU/L (reference range: 8-58 IU/L), alanine aminotransferase 179 IU/L (reference range: 8-52 IU/L), and alkaline phosphatase 1040 IU/L (reference range: 34-124 IU/L).

  1. How do you interpret these lab values?
  2. What other lab tests should be ordered?
  3. Is this a common ADR for this drug?
  4. How should this patient be treated?

Case 3

(Am. J. Med. Sci. 325(1):31-33, 2003)

An 80-year-old man had been diagnosed with hypopharyngeal cancer and received radiation therapy. He had an episode of acute bronchitis, for which he was given 500 mg of oral amoxicillin/clavulanic acid (Augmentin). Because of persistent upper respiratory symptoms and fever over the subsequent 2 days, 500 mg of oral ciprofloxacin twice a day was added. Within 48 hours, the patient’s fevers began to subside, with an improvement in respiratory symptoms. Six days later, the patient developed a generalized maculopapular, intensely pruritic rash. Pertinent laboratory studies showed total bilirubin of 0.8 mg/dL, aspartate aminotransferase (AST) of 150 U/L, alanine aminotransferase (ALT) of 154 U/L, alkaline phosphatase of 120 U/L, serum albumin of 2.1 g/dL, and prothrombin time of 13.9 seconds. Four days later the liver profile showed an AST of 577 U/L, ALT of 972 U/L, ALP of 358 U/L, total bilirubin of 1.9 mg/dL, direct bilirubin of 1.1 mg/dL, and GGT of 638 U/L.

  1. What is the interpretation of these lab values?
  2. Propose a mechanism for these observations.
  3. What is the mechanism of action of Augmentin?
  4. Is this a common ADR for these compounds?
  5. How should this patient be treated?

Case 4

A 30-year-old woman presents with fever (104 °F) and chills 11 days after returning from central Africa. She had spent three weeks visiting the homeland of her boyfriend and lived in relatively squalid conditions while there. The first two days she drank tap and local water, after which (on advice of other tourists) she drank only bottled water. She ate all food offered to her and after two weeks developed diarrhea with two episodes of high fever. She had no nausea or vomiting. She was treated with an unidentified local medication, and her symptoms resolved spontaneously. At her clinic visit now, her laboratory data are: AST 525 U/L, ALT 615 U/L, total bilirubin 0.4 mg/dL, conjugated bilirubin 0.1 mg/dL, and ALP 111 U/L. Both a "mono-spot" test and a malaria smear were negative. She has no history of drug abuse. Her physical examination was unremarkable.

  1. What is the likely diagnosis for this patient?
  2. What further tests should be performed to confirm the diagnosis?

Case 5

A 45-year-old unemployed man presents with a chief complaint of painful joints. Approximately 10 months ago, while in jail, he experienced the onset of acute stiffness and contractures of the right fingers. The joints of both upper and lower extremities were painful (upper more so than lower). The patient was unable to get out of bed for 3 weeks. He noted that his stools had become lighter in color. He experienced no abdominal pain, anorexia, jaundice, weight loss, fever, chills, nausea, vomiting, or lethargy and he denied any history of ethanol or other drug abuse. He remembered being "exposed" to one of the inmates who was jaundiced. Over the past 10 months, the patient's joint symptoms have lessened but he still experiences joint stiffness in the right upper extremity especially his elbow and shoulder. His physical exam was unremarkable except for pain and decreased range of motion of the right arm. His laboratory data were: AST 201 U/L, ALT 223 U/L, total bilirubin 1.0 mg/dL, conjugated bilirubin 0.1 mg/dL, and ALP 95 U/L.

  1. What is your diagnosis?
  2. What additional tests should be requested?

Case 6

A 65-year-old woman with a long history of alcohol abuse now presents with confusion. She has had a 20 year drinking history during which she consumed 1 gallon of wine per day. Over the last two years, she has begun to experience decreased coordination as well as a loss of balance, dysarthria, and ataxia. Three months ago, she lost the ability to leave the house alone. Over the past three days, her mental status has declined until she demonstrated child-like speech and became very lethargic.

Laboratory results 2 years earlier were: ALP 171 U/L, AST 89 U/L, bilirubin (conjugated/total: 1.3/1.9 mg/dL), and HBsAg negative. Recently a CT scan of her head showed increased ventricular size with an atrophic vermis.

On physical exam today, the patient lies on a stretcher with rolling eyes, protruding tongue, and dysarthric speech. She has a slightly enlarged liver (span of 10 cm). Her lab data are: AST 67 U/L, ammonia 62 µmol/L, conjugated bilirubin 0.1 mg/dL, total bilirubin 2.7 mg/dL, amylase 60, CK 251 U/L, PT 15 sec (control 11 sec), PTT 48 sec (control 32 sec). Both the toxicology screens and cultures were negative.

What is the most likely explanation for these findings?

Case 7

A 32-year-old nonpregnant woman, G2P2, was seen in the Emergency Department because of recurrent epigastric pain and colicky pain in the right upper quadrant. The current episode began four hours after a “heavy” dinner and was characteristic of previous episodes that had occurred several times a year for the past three years. The pain had become more severe during the more recent episodes, and the patient developed an intolerance for fatty foods.

Vitals: T37.2°C, P82, BP 124/74, R16

Labs: WBC 8.6x103 cells/µl, Hb 13.1 g/dl, Hct 40%, Na 138 mEq/L, K 4.5 mEq/L, SUN 11 mg/dl, serum creatinine 0.4 mg/dl, total protein 6.1 g/dl, albumin 3.6 g/dl, total bilirubin 2.4 mg/dl, conjugated bilirubin 1.4 mg/dl, AST 80 U/L, ALT 28 U/L, ALP 400 U/L, GGT 120 U/L
Physical exam revealed tenderness without rebound in the right upper quadrant. Bowel sounds were normal. The urine was slightly dark.

1. Based on her clinical presentation, what is your differential diagnosis?

2. What is the concentration of unconjugated bilirubin? What is the significance of the elevated total bilirubin and conjugated bilirubin?

3. Why are the AST and ALT relatively normal? What do the elevation of ALP and GGT suggest?

4. Why is the urine dark?

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