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Hepatology 101
August 20, 2015
Douglas Koo, MD, MPH, FACP
Department of Medicine, Hospital Medicine Service
Outline
Abnormal LFTs
Biliary tract disease
Ascites
LFTs
Case
HPI: duration of exposure and LFT abnormalities
PMH: DM, high BMI, autoimmune disease, transfusion
or transplant before 1972 (HBV) or 1992 (HCV)
Meds: new meds, vitamins, herbals, OTCs,
acetaminophen
FH: liver disease, autoimmune disease
SH: alcohol consumption, occupational exposure,
travel, from viral hepatitis endemic areas, IVDU,
tattoos
ROS: jaundice, rash, arthralgia, myalgia, anorexia,
weight loss, abdominal pain, fever, chills, pruritus
PE: Encephalopathy (inverted sleep-wake, irritability,
tremor, confusion), asterixis, jaundice, temporal
wasting, scleral or sublingual icterus, fetor hepaticus,
JVD, spider angiomata, gynecomastia, hepatomegaly,
splenomegaly, caput medusae, ascites, testicular
atrophy, thenar atrophy, palmar erythema,
Dupuytren’s contractures, LE edema
LFTs
• Total Protein 8.2
• Albumin 4.6
• TBili 18.9
• AST 1460
• ALT 2645
• Alk Phos 120
• PT 16.4
• INR 1.39
• PTT 35.8
LFTs: the players
LFT Abnormality measured Notes
Albumin Synthetic function Heavy alcohol use, chronic
inflammation, malnutrition
PT/INR Synthetic function Low vitamin K, warfarin
AST Hepatocellular damage High concentrations in cardiac
tissue, skeletal muscle, blood
ALT Hepatocellular damage Low concentrations in non-
hepatic tissue; more specific
Bilirubin Cholestasis, impaired
conjugation, biliary
obstruction
Hemolysis
Alkaline phosphatase Cholestasis, infiltrative
disease, biliary obstruction
Bone disease, leukemia,
lymphoma, CKD, CHF,
sarcoidosis, hyperthyroidism,
hyperparathyroidism,
pregnancy, post-prandial
LFT pattern is important for DDx
HEPATOCELLULAR
ALT, AST > Alk Phos
CHOLESTATIC
Alk Phos > ALT, AST
*Bilirubin can be elevated in both and do not help to distinguish
Hepatocellular pattern: AST, ALT in disease
Quinn PG, Johnston DE. Gastroenterologist 1997.
Hepatocellular pattern
Mild (<5x nl) Severe(>15x nl)
Steatosis/steatohepatitis
Chronic hepatitis B, C
Alcohol hepatitis (2:1 AST/ALT ratio)
Cirrhosis
Acute viral hepatitis (A-E, EBV, CMV)
Medications/toxins
Autoimmune hepatitis
Wilson’s disease
Hemochromatosis
Alpha1 antitrypsin deficiency
Celiac disease
Nonhepatic:
Hemolysis
Myopathy (3:1 ratio)
Thyroid disease
Strenuous exercise
Acute viral hepatitis (A-E, EBV, CMV)
Medications/toxins
Autoimmune hepatitis
Wilson’s disease
Ischemic hepatitis
Acute Budd-Chiari syndrome
Acute bile duct obstruction
Back to the case
Acute viral hepatitis (A-E, EBV, CMV)
Medications/toxins
Autoimmune hepatitis
Wilson’s disease
Ischemic hepatitis
Acute Budd-Chiari syndrome
Acute bile duct obstruction
• Total Protein 8.2
• Albumin 4.6
• TBili 18.9
• AST 1460
• ALT 2645
• Alk Phos 120
Hep A total Ab positive
Hep A IgMAb negative
Hep B surface Ab positive
Hep B surface Ag negative
Hep B core Ab negative
Hep B PCR <5 IU/mL
Hep C antibody negative
Hep C PCR <10 IU/mL
Narrowing our differential dx pays off
Cholestatic pattern
Confirm hepatobiliary source (check GGT)
RUQ sono
Dilated bile ducts Non-dilated bile ducts
Extrahepatic cholestasis Intrahepatic cholestasis
ERCP, MRCP, or CT
Check AMA
PBC ERCP, MRCP or biopsy
Malignant
- Hepatobiliary tumor
- Porta hepatis node
Benign
- Choledocholithiasis
- Chronic pancreatitis
- HIV cholangiopathy
- Parasitic infections
PBC
PSC
TPN
Sepsis
Pregnancy
Hepatic congestion/CHF
Drugs (steroids, Bactrim)
Infiltrative diseases (sarcoid, amyloid,
lymphoma,TB, fungal, HCC, mets)
Isolated hyperbilirubinemia
Unconjugated/Indirect Conjugated/Direct
Increased production
- Hemolysis
- Dyserythropoiesis
-Transfusion
- Large hematoma resorption
Impaired uptake
- CHF
- Portosystemic shunt
- Meds
Impaired conjugation
- Gilbert’s syndrome
- Crigler-Najjar syndrome
- Hyperthyroidism
- hepatitis, cirrhosis,Wilson’s
*see pathway for Cholestatic pattern
Biliary tract disease
Biliary disease
Case
• 52F metastatic colon adenocarcinoma
– diagnosed 2y ago, mets to lung, liver, bone, peritoneum
– p/w fever 101 at home, chills, rigors, mild abdominal pain
• PMH/PSH: biliary stent placed 3wks prior, PE, hypothyroidism, depression,
GERD, colectomy, HAIP, cholecystectomy, liver resection, RFA lung mets
• MEDS: enoxaparin, synthroid, escitalopram, pantoprazole, celecoxib, fentanyl
patch, hydromorphone, laxatives
• SH: current 15pk-yr smoker, social EtOH, married
• ROS: +epigastric abd pain, +nausea, +vomiting, +rhinorrhea, +nasal
congestion, -dyspnea, -chest pain, -cough, -hematuria, -dysuria, +dark urine, -
jaundice
Workup
• PE: 37.6 80/54 112 18 95% RA, mild confusion, mild epigastric tenderness
• Labs
• Lactic acid 3.1
• UA +urobilinogen
• Blood cultures pending
• CXR negative
5
0.4
15
10
32
262
146
3.3
118
24
7
159
5.4
85
307
11.7 33.5
1.1
0.6
3
121
Diagnosis
• Cholangitis; Biliary sepsis
– Ascending bacterial infection from duodenum
– Charcot’s triad (fever, RUQ pain, jaundice) 50-75%
– Reynold’s pentad (above + confusion and hypotension)
– Up to 40% mortality rate from multiorgan failure (liver, kidney)
– Significant endotoxemia
– Risk factors: biliary obstruction and stasis (stone, stricture), stent
– Imaging: US, CT, MRCP, ERCP, HIDA
Management of cholangitis
• Volume resuscitation/restore perfusion, antibiotics for polymicrobial
infection (check out our ID website); 80% will respond
• DRAINAGE!
• Electrolyte management, correct coagulopathy
• Consults: ICU, GI, IR (when percutaneous approach needed)
• Urgent! Persistent pain, fever, hypotension, confusion
Diagnosis
Management
Chole…
• Cholangitis
• Cholecystitis
– 90% gallstones
– 10% acalculous (critically ill, elderly, post-op)
– ERCP vs cholecystectomy vs cholecystostomy
• Chole(docho)lithiasis
– Saturation of bile with cholesterol or bilirubin + stasis
– Biliary “colic”: episodic RUQ or epigastric abdominal pain with quick
onset and slow resolution min to hours, nausea, fatty foods
• Imaging sensitivity:
– Cholelithiasis: U/S>CT
– Cholecystitis HIDA>CT=U/S
Ascites
Paracentesis
Indications
• To evaluate new onset ascites of
unclear etiology
• To evaluate for SBP
(spontaneous bacterial
peritonitis) in pt with known
ascites
• To perform large volume
paracentesis and provide comfort
or relieve respiratory
compromise
Contraindications
• Coagulopathy?
• Thrombocytopenia?
• DIC
• Abdominal wall collateral veins
• Abdominal wall cellulitis
• Surgical scars
• Caution in:
– Renal failure, organomegaly,
bowel obstruction, intrabdominal
adhesions, distended bladder
Sites
2 cm below umbilicus in midline
- linea alba lacks blood vessels
RLQ or LLQ 2 to 4 cm medial and
cephalad to ASIS
- lateral to rectus sheath to avoid
puncture of inferior epigastric artery
An ultrasound study demonstrated that a LLQ tap site is superior to a midline site; the
abdominal wall is relatively thinner in the left lower quadrant while the depth of fluid
is greater
Sakai H et al. Choosing the location for non-image guided abdominal paracentesis. Liver Int. 2005.
Advancing catheter through skin
Angular insertion Z-tract
or
Albumin after LVP in portal HTN & cirrhosis
• “interesting” “unresolved” “controversial”
• No study has shown a survival advantage
• Reasonable to forego albumin if <5L LVP
• I was taught give 50cc of 25% albumin (12.5g) per 2L removed
• NEJM article and video: recommend use of albumin if >5 L of ascites
removed (6 to 8 g per liter of fluid removed)
Appearance of ascites
• Clear/translucent yellow: uncomplicated in the setting of
cirrhosis
• Cloudy: infection
• Milky: “chylous ascites”, high triglyceride concentration,
cirrhosis or malignancy
• Pink/bloody: traumatic tap, leakage from punctured collateral
from previous tap, malignancy
• Brown/molasses: if bilirubin is greater than serum, concern
for ruptured gallbladder or perforated duodenal ulcer
Diagnosis and evaluation of patients with ascites. UpToDate.
2 questions: Infection? Portal HTN?
• Cell count: PMN > 250 cells/mm3
• If bloody or >50K RBCs, subtract 1
PMN for every 250 red cells
• Culture used to confirm diagnosis of
SBP
– Volume affects culture
sensitivity; goal 10cc per bottle
– Fill culture bottles at bedside
• SAAG = Ascites albumin value –
Serum albumin value
SBP treatment: RememberAlbumin
Malignant ascites
• Median survival 1-4 months
• Symptomatic relief
– Diuretics
– Tenckhoff catheter
Thank you!

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Hepatology 101

  • 1. Hepatology 101 August 20, 2015 Douglas Koo, MD, MPH, FACP Department of Medicine, Hospital Medicine Service
  • 4. Case HPI: duration of exposure and LFT abnormalities PMH: DM, high BMI, autoimmune disease, transfusion or transplant before 1972 (HBV) or 1992 (HCV) Meds: new meds, vitamins, herbals, OTCs, acetaminophen FH: liver disease, autoimmune disease SH: alcohol consumption, occupational exposure, travel, from viral hepatitis endemic areas, IVDU, tattoos ROS: jaundice, rash, arthralgia, myalgia, anorexia, weight loss, abdominal pain, fever, chills, pruritus PE: Encephalopathy (inverted sleep-wake, irritability, tremor, confusion), asterixis, jaundice, temporal wasting, scleral or sublingual icterus, fetor hepaticus, JVD, spider angiomata, gynecomastia, hepatomegaly, splenomegaly, caput medusae, ascites, testicular atrophy, thenar atrophy, palmar erythema, Dupuytren’s contractures, LE edema
  • 5. LFTs • Total Protein 8.2 • Albumin 4.6 • TBili 18.9 • AST 1460 • ALT 2645 • Alk Phos 120 • PT 16.4 • INR 1.39 • PTT 35.8
  • 6. LFTs: the players LFT Abnormality measured Notes Albumin Synthetic function Heavy alcohol use, chronic inflammation, malnutrition PT/INR Synthetic function Low vitamin K, warfarin AST Hepatocellular damage High concentrations in cardiac tissue, skeletal muscle, blood ALT Hepatocellular damage Low concentrations in non- hepatic tissue; more specific Bilirubin Cholestasis, impaired conjugation, biliary obstruction Hemolysis Alkaline phosphatase Cholestasis, infiltrative disease, biliary obstruction Bone disease, leukemia, lymphoma, CKD, CHF, sarcoidosis, hyperthyroidism, hyperparathyroidism, pregnancy, post-prandial
  • 7. LFT pattern is important for DDx HEPATOCELLULAR ALT, AST > Alk Phos CHOLESTATIC Alk Phos > ALT, AST *Bilirubin can be elevated in both and do not help to distinguish
  • 8. Hepatocellular pattern: AST, ALT in disease Quinn PG, Johnston DE. Gastroenterologist 1997.
  • 9. Hepatocellular pattern Mild (<5x nl) Severe(>15x nl) Steatosis/steatohepatitis Chronic hepatitis B, C Alcohol hepatitis (2:1 AST/ALT ratio) Cirrhosis Acute viral hepatitis (A-E, EBV, CMV) Medications/toxins Autoimmune hepatitis Wilson’s disease Hemochromatosis Alpha1 antitrypsin deficiency Celiac disease Nonhepatic: Hemolysis Myopathy (3:1 ratio) Thyroid disease Strenuous exercise Acute viral hepatitis (A-E, EBV, CMV) Medications/toxins Autoimmune hepatitis Wilson’s disease Ischemic hepatitis Acute Budd-Chiari syndrome Acute bile duct obstruction
  • 10. Back to the case Acute viral hepatitis (A-E, EBV, CMV) Medications/toxins Autoimmune hepatitis Wilson’s disease Ischemic hepatitis Acute Budd-Chiari syndrome Acute bile duct obstruction • Total Protein 8.2 • Albumin 4.6 • TBili 18.9 • AST 1460 • ALT 2645 • Alk Phos 120 Hep A total Ab positive Hep A IgMAb negative Hep B surface Ab positive Hep B surface Ag negative Hep B core Ab negative Hep B PCR <5 IU/mL Hep C antibody negative Hep C PCR <10 IU/mL
  • 12. Cholestatic pattern Confirm hepatobiliary source (check GGT) RUQ sono Dilated bile ducts Non-dilated bile ducts Extrahepatic cholestasis Intrahepatic cholestasis ERCP, MRCP, or CT Check AMA PBC ERCP, MRCP or biopsy Malignant - Hepatobiliary tumor - Porta hepatis node Benign - Choledocholithiasis - Chronic pancreatitis - HIV cholangiopathy - Parasitic infections PBC PSC TPN Sepsis Pregnancy Hepatic congestion/CHF Drugs (steroids, Bactrim) Infiltrative diseases (sarcoid, amyloid, lymphoma,TB, fungal, HCC, mets)
  • 13. Isolated hyperbilirubinemia Unconjugated/Indirect Conjugated/Direct Increased production - Hemolysis - Dyserythropoiesis -Transfusion - Large hematoma resorption Impaired uptake - CHF - Portosystemic shunt - Meds Impaired conjugation - Gilbert’s syndrome - Crigler-Najjar syndrome - Hyperthyroidism - hepatitis, cirrhosis,Wilson’s *see pathway for Cholestatic pattern
  • 16. Case • 52F metastatic colon adenocarcinoma – diagnosed 2y ago, mets to lung, liver, bone, peritoneum – p/w fever 101 at home, chills, rigors, mild abdominal pain • PMH/PSH: biliary stent placed 3wks prior, PE, hypothyroidism, depression, GERD, colectomy, HAIP, cholecystectomy, liver resection, RFA lung mets • MEDS: enoxaparin, synthroid, escitalopram, pantoprazole, celecoxib, fentanyl patch, hydromorphone, laxatives • SH: current 15pk-yr smoker, social EtOH, married • ROS: +epigastric abd pain, +nausea, +vomiting, +rhinorrhea, +nasal congestion, -dyspnea, -chest pain, -cough, -hematuria, -dysuria, +dark urine, - jaundice
  • 17. Workup • PE: 37.6 80/54 112 18 95% RA, mild confusion, mild epigastric tenderness • Labs • Lactic acid 3.1 • UA +urobilinogen • Blood cultures pending • CXR negative 5 0.4 15 10 32 262 146 3.3 118 24 7 159 5.4 85 307 11.7 33.5 1.1 0.6 3 121
  • 18. Diagnosis • Cholangitis; Biliary sepsis – Ascending bacterial infection from duodenum – Charcot’s triad (fever, RUQ pain, jaundice) 50-75% – Reynold’s pentad (above + confusion and hypotension) – Up to 40% mortality rate from multiorgan failure (liver, kidney) – Significant endotoxemia – Risk factors: biliary obstruction and stasis (stone, stricture), stent – Imaging: US, CT, MRCP, ERCP, HIDA
  • 19. Management of cholangitis • Volume resuscitation/restore perfusion, antibiotics for polymicrobial infection (check out our ID website); 80% will respond • DRAINAGE! • Electrolyte management, correct coagulopathy • Consults: ICU, GI, IR (when percutaneous approach needed) • Urgent! Persistent pain, fever, hypotension, confusion
  • 22. Chole… • Cholangitis • Cholecystitis – 90% gallstones – 10% acalculous (critically ill, elderly, post-op) – ERCP vs cholecystectomy vs cholecystostomy • Chole(docho)lithiasis – Saturation of bile with cholesterol or bilirubin + stasis – Biliary “colic”: episodic RUQ or epigastric abdominal pain with quick onset and slow resolution min to hours, nausea, fatty foods • Imaging sensitivity: – Cholelithiasis: U/S>CT – Cholecystitis HIDA>CT=U/S
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  • 29. Paracentesis Indications • To evaluate new onset ascites of unclear etiology • To evaluate for SBP (spontaneous bacterial peritonitis) in pt with known ascites • To perform large volume paracentesis and provide comfort or relieve respiratory compromise Contraindications • Coagulopathy? • Thrombocytopenia? • DIC • Abdominal wall collateral veins • Abdominal wall cellulitis • Surgical scars • Caution in: – Renal failure, organomegaly, bowel obstruction, intrabdominal adhesions, distended bladder
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  • 31. Sites 2 cm below umbilicus in midline - linea alba lacks blood vessels RLQ or LLQ 2 to 4 cm medial and cephalad to ASIS - lateral to rectus sheath to avoid puncture of inferior epigastric artery An ultrasound study demonstrated that a LLQ tap site is superior to a midline site; the abdominal wall is relatively thinner in the left lower quadrant while the depth of fluid is greater Sakai H et al. Choosing the location for non-image guided abdominal paracentesis. Liver Int. 2005.
  • 32. Advancing catheter through skin Angular insertion Z-tract or
  • 33. Albumin after LVP in portal HTN & cirrhosis • “interesting” “unresolved” “controversial” • No study has shown a survival advantage • Reasonable to forego albumin if <5L LVP • I was taught give 50cc of 25% albumin (12.5g) per 2L removed • NEJM article and video: recommend use of albumin if >5 L of ascites removed (6 to 8 g per liter of fluid removed)
  • 34. Appearance of ascites • Clear/translucent yellow: uncomplicated in the setting of cirrhosis • Cloudy: infection • Milky: “chylous ascites”, high triglyceride concentration, cirrhosis or malignancy • Pink/bloody: traumatic tap, leakage from punctured collateral from previous tap, malignancy • Brown/molasses: if bilirubin is greater than serum, concern for ruptured gallbladder or perforated duodenal ulcer Diagnosis and evaluation of patients with ascites. UpToDate.
  • 35. 2 questions: Infection? Portal HTN? • Cell count: PMN > 250 cells/mm3 • If bloody or >50K RBCs, subtract 1 PMN for every 250 red cells • Culture used to confirm diagnosis of SBP – Volume affects culture sensitivity; goal 10cc per bottle – Fill culture bottles at bedside • SAAG = Ascites albumin value – Serum albumin value
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  • 38. Malignant ascites • Median survival 1-4 months • Symptomatic relief – Diuretics – Tenckhoff catheter