GI and Liver
October 26th, 2012
Don C. Rockey
A 48‐year‐old man with chronic alcoholism is evaluated because of progressive abdominal distention.
 He complains of anorexia, weakness, and a 9‐kg (20‐lb) weight loss over the past six months.  Physical examination is unremarkable except for a temperature of 37.6 C (99.6 F), ascites, and signs of weight loss.

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Laboratory studies:
Hemoglobin
Hematocrit
Leukocyte count Serum aminotransferases:
AST
ALT
Serum alkaline phosphatase Serum bilirubin:
Total
Direct
Serum albumin
13.9 g/dL
41%
7200/cu mm;
(normal differential)
184 U/L
90 U/L
116 U/L
1.1 mg/dL
0.3 mg/dL
3.1 g/dL
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Radiograph of the chest is normal. Ultrasound examination of the abdomen demonstrates ascites. Paracentesis yields clear, nonbloody fluid. Ascitic fluid leukocyte count is 760/cu mm (70% mononuclear cells), protein is 4.4 g/dL, and albumin is 2.6 g/dL. Rockey 2012
Which of the following is the most likely diagnosis?
(A) Cirrhosis with spontaneous bacterial peritonitis
(B) Tuberculous peritonitis
(C) Liver metastasis
(D) Portal vein thrombosis
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Serum‐Ascites Albumin Gradient (SAAG)
Serum albumin 3.1 – Ascitic fluid albumin 2.6 =
0.5
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Serum‐Ascites Albumin Gradient (SAAG)
 Easily the most useful test in the evaluation of ascites.
 A high gradient - difference of greater than 1.1 g/dl - identifies
portal hypertensive causes of ascites
 A low gradient - difference of less than 1.1 g/dl - identifies non
portal hypertensive causes of ascites
 In a study by Runyon et al (AIM ‘92), 1275 patients were
prospectively evaluated with paired serum and ascitic fluid
samples.
 The ascitic fluid total protein (AFTP) classified only 56% of
cases correctly, compared to the SA gradient, which classified
97% correctly. Of interest, the AFTP did appear to separate
most sterile cirrhotic ascites (AFTP < 2.5 g/dl) samples from
cardiac ascites (AFTP > 2.5 g/dl)
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Serum‐Ascites Albumin Gradient (SAAG)
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Serum‐Ascites Albumin Gradient (SAAG)
High Gradient
(>1.1g/dl)
Low Gradient
(< 1.1 g/dl)
Cirrhosis
Cardiac ascites
Liver mets (massive)
PV thrombosis
Veno‐occlusive disease
Budd‐Chiari
Myxedema
Mixed causes
TB (without cirrhosis)
Peritoneal carcinomatosis
Pancreatic ascites (no cirrhosis)
Biliary ascites (no cirrhosis)
Bowel obstruction or infarction
Nephrotic syndrome
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Which of the following is the most likely diagnosis?
(A) Cirrhosis with spontaneous bacterial peritonitis
(B) Tuberculous peritonitis
(C) Liver metastasis
(D) Portal vein thrombosis
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 71y/o man admitted for GI bleeding
 Past history of heavy beer consumption, also a history of pancreatitis, presumed ETOH  No past hx of liver disease
 No medications  On admission, NAD, BP 120/72, HR 98, melena
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 Laboratory data – Hgb 9.1, plts 135, AST 48, ALT 33, T bili 1.1, Alk phos 155, PT‐INR 1.0, BUN 33, Cr 1.2
 EGD – negative, no ulcer disease, no portal hypertension
 RUQ doppler ultrasound revealed normal appearing liver, normal ducts
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 Received 2 units of PRBCs
 Was about to be discharged, developed another episode of melena, HR 110
 Repeat endoscopy
 No EVs, normal stomach, normal duodenum, blood in the second portion of the duodenum
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Which of the following is most likely to yield the correct diagnosis?
(A) Endoscopic ultrasound
(B) Doppler ultrasound
(C) MRI of the abdomen
(D) Angiography
(E) Enteroscopy
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Take Home Points
 History of pancreatitis is key
 Ill defined bleeding source
 Must move rapidly and definitively to make a diagnosis
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Which of the following is most likely to yield the correct diagnosis?
(A) Endoscopic ultrasound
(B) Doppler ultrasound
(C) MRI of the abdomen
(D) Angiography
(E) Enteroscopy
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
A 67‐year‐old man with chronic atrial fibrillation comes to the emergency department because of severe periumbilical pain and nausea that started suddenly two hours ago. He describes the pain as “severe.”

On physical examination the patient appears acutely ill. He is unable to find a comfortable position. Temperature is 37.2 C (99.0 F). Pulse rate is 110 per minute; rhythm is irregular. Blood pressure is 150/90 mm Hg. The abdomen is soft, flat, and nontender to palpation. Bowel sounds are active. No enlarged organs or masses are noted.
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Laboratory studies:
Hemoglobin
Leukocyte count
Serum electrolytes
Serum amylase
Serum bilirubin (total)
Serum alkaline phosphatase
14.0 g/dL
12,000/cu mm
Normal
120 U/L
1.0 mg/dL
130 U/L
Upright and supine plain films of the abdomen show a nonspecific bowel gas pattern.
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Which of the following diagnostic studies should you recommend now? (A) Laparotomy
(B) Upper endoscopy
(C) Computed tomography of the abdomen
(D) Doppler ultrasound examination of the abdomen
(E) Mesenteric angiography
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Acute Mesenteric Ischemia
• A high index of suspicion in the setting of a compatible history and physical examination serves as the cornerstone to Dx
• Immediate diagnostic evaluation
• Patients older than 60  history of atrial fibrillation
 recent myocardial infarction
 congestive heart failure
 arterial emboli
 postprandial abdominal pain and weight loss
 *Abdominal pain that is out of proportion to physical Rockey 2012
examination
Acute Mesenteric Ischemia
• Laboratory data:  Hemoconcentration, leukocytosis, and metabolic acidosis, with •
•
•
•
high anion gap and lactate concentrations.  High levels of serum amylase, aspartate aminotransferase, lactate dehydrogenase
High levels of serum amylase, aspartate aminotransferase, lactate dehydrogenase
Diagnosis:
• MR or CR angio evolving; test of choice angiography
Therapy:
• difficult, related to revascularization
Prognosis:
• Guarded
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Which of the following diagnostic studies should you recommend now? (A) Laparotomy
(B) Upper endoscopy
(C) Computed tomography of the abdomen
(D) Doppler ultrasound examination of the abdomen
(E) Mesenteric angiography
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 41 yo female with a past history of UC
 Treated intermittently with mesalamine and prednisone  1 week of progressively more frequent diarrhea, occasional blood stools, up to 8 per day
 + some abd pain, tenesmus, no F
 Was begun on a course of prednisone by her primary GI (now on 20 mg/day), perhaps a little better
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 On exam, slightly uncomfortable, AF. Abd soft, but diffusely tender
 Laboratory data – Hgb 10.4, MCV 81, WBC 9.8
 C diff toxin negative
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Which of the following diagnostic studies should you recommend now? (A) Repeat C dificile toxin assay
(B) Upper endoscopy
(C) Computed tomography of the abdomen
(D) Colonoscopy
(E) MRI of the abdomen
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 Difficult to 

differentiate clinically
High index of suspicion required
Different clinical patterns Rockey 2012
Which of the following diagnostic studies should you recommend now? (A) Repeat C dificile toxin assay
(B) Upper endoscopy
(C) Computed tomography of the abdomen
(D) Colonoscopy
(E) MRI of the abdomen
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 38 yo housewife with a history of HTN, presents with nausea, dark urine, and slight eye discoloration 2 weeks PTA.  Drinking wine with dinner (no more than one or two per evening). Sexually active.
 Taking ES Excedrin, ibuprofen, spironolactone, and nitrofurantoin. Also, taking herbal supplements for weight loss about 1 month previously for about 3 weeks, stopped after began to get tired.  On examination, slightly obese (BMI 31), jaundiced, and tired appearing. Liver span was 14 cm, and slightly tender, without mass. No ascites.
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Laboratory studies:
Serum bilirubin (total)
Serum alkaline phosphatase
Serum aminotransferases:
AST
ALT
Serum albumin
INR
13.5 mg/dL
350 U/L
2,556 U/L
1,592 U/L
3.2 g/dL
1.9
 RUQ doppler ultrasound – normal ducts, normal flow
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Which of the following is the most likely cause of the abnormalities in liver function?
(A) Autoimmune hepatitis
(B) Acute viral hepatitis A
(C) Acute viral hepatitis B
(D) Drug induced liver injury
(E) Acute fatty liver disease of pregnancy
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Laboratory studies:
Acetaminophen
HAV IgM
HCV Ab
HBV sAg
ANA
AMA
9
Negative
Negative Negative
1:20
1:20
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Which of the following is the most likely cause of the abnormalities in liver function?
(A) Autoimmune hepatitis
(B) Acute viral hepatitis A
(C) Acute viral hepatitis B
(D) Drug induced liver injury
(E) Acute fatty liver disease of pregnancy
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Which of the following medications is the most likely cause of the abnormalities in liver function?
(A) Spironolactone
(B) Acetaminophen
(C) Herbal medication(s)
(D) Ibuprofen
(E) Nitrofurantoin
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Liver biopsy
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• Any drug can cause DILI
• Assessment of causality is extremely difficult; usually a diagnosis of exclusion
• The most critical component is typically timing: most episodes of DILI happen within 5‐90 days of exposure.
• DILI caused by certain drugs is often associated with a classic signature (hepatocellular, cholestatic, immunoallergic patterns)
• The most classic drugs associated with DILI are augmentin, dilantin, valproic acid, and isoniazid
(This case is tricky because nitrofurantoin causes DILI)
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Liver tests rapidly declined
Herbalife® Hepatotoxicity
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Which of the following medications is the most likely cause of the abnormalities in liver function?
(A) Spironolactone
(B) Acetaminophen
(C) Herbal medication(s)
(D) Ibuprofen
(E) Nitrofurantoin
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 Acetaminophen
 DILI
 Viral hepatitis
 Shock liver (ischemic hepatitis)
 Passed gallstone (choledocholithiasis)
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 48 y/o male with history of ETOH pancreatitis  Progressive abdominal pain last 2 weeks
 Active drinking vodka until 2 d PTA
 On exam, T 99.6, HR 92, Bp 110/67, + shifting dullness, with diffuse tenderness Rockey 2012
 Laboratory data – amylase 459, AST 85, ALT 22, T bili 2.1, Alk phos 121, PT‐INR 1.4, Alb 3.1, Cr 1.4
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Which of the following is most likely to yield the correct diagnosis?
(A) Esophagogastroduodenoscopy
(B) Doppler ultrasound of the abdomen
(C) MRI of the abdomen
(D) Paracentesis
(E) Angiography
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 Paracentesis – WBC 1,345, 22% PMNs, Alb 2.1, SAAG (1.0); gram stain – no organisms
 CT – pancreatic calcification, ascites, no liver lesions, splenomegaly
 Differential diagnosis, next test?
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 Paracentesis – WBC 1,345, 22% PMNs, Alb 2.1, SAAG (1.0); gram stain – no organisms
 CT – pancreatic calcification, ascites, no liver lesions, splenomegaly
 Differential diagnosis, next test?
Ascitic fluid amylase 12,053
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Which of the following is most likely to yield the correct diagnosis?
(A) Esophagogastroduodenoscopy
(B) Doppler ultrasound of the abdomen
(C) MRI of the abdomen
(D) Paracentesis
(E) Angiography
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 Setting of chronic pancreatitis  Pancreatic ductal disruption
 Ascites fluid – inflammatory (amylase)  Very difficult to differentiate from SBP
 Treatment is ERCP with PD stenting, or drainage of pseudocyst if present, or surgical correction of the defect
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 35 y/o male history of mid‐epigastric and right upper quadrant pain for the last month  10 pound weight loss and some SOB
 No past hx of liver disease and no medications  On exam, confortable, VS normal, Temp 99.4. Abd soft, slight mid‐epi tenderness; stool G +
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Laboratory studies:
Hemoglobin
Leukocyte count 4% Serum aminotransferases:
AST
ALT
Serum alkaline phosphatase Serum bilirubin:
Total
Direct
Serum albumin
INR
11.9 g/dL
14,200/cu mm;
(differential: 34% segs, 8% band forms, 40% lymphs, eos, 16% monos)
18 U/L
14 U/L
216 U/L
1.3 mg/dL
0.4 mg/dL
3.2 g/dL
1.2
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Blood culture specimens obtained during a febrile period show no growth. Which of the following should you do now? (A) Order serologic test for Echinococcus granulosus; begin mebendazole
(B) Order serologic test for Entamoeba histolytica; begin metronidazole
(C) Begin intravenous piperacillin/sulbactam and gentamicin
(D) Arrange for laparotomy
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Liver Abscess
• Two varieties
• Different epidemiology • Pyogenic ‐‐ elderly male, risk factors
• Amebic ‐‐ young male, risk factors
• Etiology of PLA has shifted dramatically; historically pylephlebitis, has shifted now to either biliary in etiology or cryptogenic
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Liver Abscess
• Often is a subacute illness.
• The most common symptoms are RUQ pain and fever,
but these are present together in only ≈ 40% of cases.
• Right sided lung findings are common.
• Laboratory tests are abnormal, but often nonspecific,
except in the case of associated biliary tract disease in
which case the bili and alk phos are elevated.
Abnormalities in these tests should direct one to the
biliary tract and an early ERCP, particularly if cholangitis
is in the differential diagnosis.
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Liver Abscess
• Distinguishing pyogenic liver abscesses from amebic
liver abscesses may be very difficult on clinical grounds
as the presentation is very similar.
• The best clinical clue to differentiate between PLA and
ALA is the epidemiologic setting. A history of diarrhea
is usually not helpful, but recent travel to endemic areas
of amebiasis is often present in patients with ALA.
• Amebic antibodies are very sensitive in the setting of
ALA.
• Lesion aspiration may also be very helpful.
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Liver Abscess
• The patient had traveled to Mexico
City to visit his relatives 3 months PTA.
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Blood culture specimens obtained during a febrile period show no growth. Which of the following should you do now? (A) Order serologic test for Echinococcus granulosus; begin mebendazole
(B) Order serologic test for Entamoeba histolytica; begin metronidazole
(C) Begin intravenous piperacillin/sulbactam and gentamicin
(D) Arrange for laparotomy
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 67 y/o man admitted for jaundice; first noted yellow eyes 8 weeks previously
 Drank beer daily (2 six packs), but stopped when noticed jaundice
 Family noted that he was confused and jaundiced
 No past hx of liver disease
 No medications Rockey 2012
 PE ‐ Jaundice, NAD, 122/72 HR 76, RR 10, AF, shifting dullness, liver 16 cm in span, no splenomegaly
 Laboratory data ‐ AST 98, ALT 43, T bili 8.1, Alk phos 1,790, PT‐INR 1.0, Cr 1.7, UA + protein
 Ascites tapped – straw colored, SAAG 1.4
 RUQ doppler ultrasound revealed normal ducts, hepatomegaly
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 Developed progressive renal failure, thought to be secondary to hepatorenal syndrome due to alcoholic liver disease. Died 12 days after admission.
 Differential diagnosis?
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•
•
Autopsy revealed a liver weighing 2,800 g, heart and kidneys also enlarged. Liver ‐
Rockey DC. Southern
Medical Journal, 92:236241
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 Urine protein – 2,800 mg/24 hours
 + light chains
Take Home Points
 Not all ascites is due to primary liver disease, even with a portal hypertensive SAAG
 Clue here was unusual liver tests and renal disease, atypical (protein)
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 Malignancy
 Tuberculosis
 Granulomas
 Amyloid
 Microabscesses
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A 74‐year‐old man is admitted to the hospital because of painless massive hematochezia. Eighteen months ago, a similar episode required hospitalization and transfusion of three units of packed red blood cells. At that time, colonoscopy documented pancolonic diverticulosis. Medical history is otherwise unremarkable. On physical examination the patient is in no distress. Blood pressure and pulse rate show orthostatic changes. The abdomen is nontender. Rectal examination discloses maroon‐colored stool. Hemoglobin is 8.2 g/dL, and hematocrit is 24%. Rockey 2012
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

The patient is given two units of packed red blood cells. There is no blood on nasogastric lavage. Colonoscopy documents diverticula; fine details are not well visualized because of old blood and blood clots. No other colonoscopic abnormalities are seen. Seven more units of packed red blood cells are transfused because of persistent bleeding. Nasogastric aspirate is negative for blood. Radiolabeled red blood cell scan is negative, and abdominal angiography reveals no obvious site of active bleeding. Upper endoscopy is normal. Three additional transfusions are required because of subsequent intermittent bleeding.
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Which of the following is the most appropriate next step?
(A) Observation and continued blood transfusions
(B) Repeat abdominal angiography
(C) Right hemicolectomy
(D) Subtotal colectomy and ileoproctostomy
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 Diverticula common in elderly patients  Disease of western society
 Bleeding  occurs only in a small # of those with tics
 may be the first manifestation of disease
 is NOT associated with diverticulitis
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 Bleeding is brisk and painless
 20% continue, 20% stop & rebleed, 60% never bleed again
 Colonoscopy cannot localize
 Radionuclide scanning/angio may localize
 Therapy may be difficult
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A 25‐year‐old white woman is admitted to you because she has weight loss, diarrhea and iron deficiency anemia. Her INR is 1.4.
 Her referring physician considered a diagnosis of celiac sprue; however, an assay for anti‐endomysial antibodies was negative.  Upper endoscopy shows notched duodenal folds. Biopsy specimens reveal total villous atrophy – suggestive of celiac sprue. 
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The negative antibody assay results are most consistent with which of the following diagnoses?
(A) IgA deficiency
(B) IgG deficiency
(C) Concomitant vasculitis
(D) Dermatitis herpetiformis
(E) T‐cell lymphoma
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 Very common
 Protean manifestations
 Diarrhea, bloating, pain
 Malabsorption
 Complications – malignancy
 Therapy typically effective
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• Pathology
– Typical – Marsh classification
• Antibodies
– Rule out IgA deficiency (15%)
Sensitivity
Gliadin
80%
Reticulin
80-90%
Endomysial
80-90%
t Transglutaminase 89%
Specificity
70%
80%
80%
95%
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The negative antibody assay results are most consistent with which of the following diagnoses?
(A) IgA deficiency
(B) IgG deficiency
(C) Concomitant vasculitis
(D) Dermatitis herpetiformis
(E) T‐cell lymphoma
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You are asked to evaluate a 45‐year‐old man, who has just been hospitalized because of new‐
onset ascites, hematemesis, and melena. He has a history of chronic alcoholism but has not consumed alcoholic beverages for one year.  Physical examination reveals scleral icterus, proximal muscle wasting, multiple spider angiomas, and marked abdominal distention due to ascites. The patient is lucid with no evidence of asterixis.

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Laboratory studies: Hematocrit
Leukocyte count
Platelet count
Serum aminotransferases:
AST
ALT
Serum alkaline phosphatase
23%
4500/cu mm
72,000/cu mm
187 U/L
90 U/L
154 U/L Rockey 2012
Laboratory studies: (continued)
Serum bilirubin (total)
Serum albumin Serum ceruloplasmin
Serum ferritin Serum iron Serum total iron‐binding capacity HBsAg
Anti‐HCV (ELISA) 4.5 mg/dL
2.7 g/dL
Normal
Normal
Normal
Normal
Negative
Positive
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The patient is given six units of packed red blood cells. Emergency upper endoscopy documents grade 3 esophageal varices, which are treated with band ligation. His condition stabilizes, and you recommend sodium restriction, diuretic therapy, and octreotide infusion.  Two days later, another episode of massive hematemesis occurs. Balloon tamponade is required after repeat band ligation fails to stop the bleeding. 
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Which of the following statements is correct regarding the use of a transjugular intrahepatic portosystemic shunt (TIPS) in this patient?
(A) It should be used because endoscopic band ligation has failed
(B) It should not be used until endoscopic sclerotherapy has been tried
(C) It should not be used because it will complicate management of the patient's ascites
(D) It should not be used because of the high risk of hepatic encephalopathy
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Transjugular Intrahepatic Portal‐
Systemic Shunt (TIPS)
Pre‐TIPS (portal vein)
Post‐TIPS (hepatic‐portal vein)
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Transjugular Intrahepatic Portal‐
Systemic Shunt (TIPS)
Contraindications
• Portal vein occlusion
• Polycystic liver disease
• Liver abscess
• Cholangitis
• Anomalous vena caval anatomy
• Severe hepatic encephalopathy
• Severe hepatic dysfunction
• ? Renal insufficiency
• Cardiac insufficiency
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Hemoperitoneum
Capsular hematoma
Hemobilia
< 5%
Portal vein thrombosis
Bacteremia
Fever
5 ‐ 10 %
Hepatic encephalopathy
15 ‐ 25%
Variable
Shunt occlusion
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Which of the following statements is correct regarding the use of a transjugular intrahepatic portosystemic shunt (TIPS) in this patient?
(A) It should be used because endoscopic band ligation has failed
(B) It should not be used until endoscopic sclerotherapy has been tried
(C) It should not be used because it will complicate management of the patient's ascites
(D) It should not be used because of the high risk of hepatic encephalopathy
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 A 52 y.o. man with HCV is referred for evaluation after he is found to have HCV by his PCP  Abnormal liver tests for several years
 Genotype 1a, viral load 1.1 x 106 (IU/mL)
 He claims he is tired, but has no other symptoms
 PMH – unremarkable, no other disease, denies risk factors for transmission
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 PE: VS normal, normal liver size  Lab data: AST 51, ALT 59, Alb 4.1, PT INR 1.0
 Hgb 14.1, plts 139,000
 What do you recommend?
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How do you stage his disease non‐invasively?
 Can’t
 APRI
 Fibrotest
 Fibrosure
 Ultrasound
 MR‐Elastography
 Other
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APRI = AST to Platelet Ratio Index
AST (U/L)
x 100
AST ULN (U/L)
Platelet count (109/L)
= APRI Value
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Illustrative Case
52 y.o. man with HCV ‐ AST 51 (ULN, 40 U/L), plts 139
51
= 1.3
40
x 100 = 130
= 0.94 or 0.9
139
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APRI and Fibrosis
(“Significant fibrosis” - M2-4)
Test
Threshold
No. of
Studies
(patients)
Sensitivity
Specificity
0.5
0.7
1.0
1.5
16 (3,277)
3 (438)
2 (473)
15 (3,146)
86%
81%
59%
35%
54%
50%
86%
91%
(From Shaheen and Meyers, Hepatology 2007)
APRI and Fibrosis
(“Significant fibrosis” - M2-4)
Test
Threshold
No. of
Studies
(patients)
Sensitivity
Specificity
0.5
0.7
1.0
1.5
16 (3,277)
3 (438)
2 (473)
15 (3,146)
86%
81%
59%
35%
54%
50%
86%
91%
(From Shaheen and Meyers, Hepatology 2007)
 Liver biopsy ‐ Grade 2 inflammation, Stage 1‐2 fibrosis
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 New case
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 New case
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