Hepatology

Ascites
Adapted in part from Jaffe DL, Chung RT, Friedman LS. Management of portal hypertension and its complications. Med Clin North Am. 1996;80:1021-1034.
Pathophysiology
Stimulation of renin-angiotensin-aldosterone system®renal Na and water retention
inc Pressure in hepatic sinusoids and splanchnic vessels
Clinical Signs and Symptoms
Medium/large volume ascites can be detected on physical exam generally by a distended abdomen, shifting dullness or a fluid wave
Workup

New onset: needs diagnostic paracentesis to determine cause (even if admitted for other reason)
If you suspect ascites but none is apparent on physical exam, get an abdominal ultrasound to detect fluid and mark ascites for paracentesis
Looking for infected ascites is part of the workup in a patient with cirrhosis and fever/leukocytosis/altered mental status.

Send ascitic fluid for:
Cell count and differential
Albumin (also send serum albumin)
Protein <1g/dL increases risk of SBP
Bacterial culture
Others: LDH, glucose, amylase, cytology, AFB
Etiologies
Classification by serum ascites albumin gradient
>95% accuracy

SAAG = Serum Albumin - Ascites Albumin

Etiology of Ascites Based On SAAG
High Gradient >= 1.1 g/dl	Low Gradient < 1.1 g/dl
Cirrhosis	Nephrotic syndrome
Alcoholic hepatitis	Peritoneal carcinomatosis
Cardiac ascites	Pancreatic ascites
Fulminant hepatic failure	Tuberculous peritonitis
Budd-Chiari syndrome	Biliary ascites
Massive hepatic metastases	Collagen vascular disease serositis
Veno-occlusive disease
Portal vein thrombosis
Myxedema
Fatty liver of pregnancy

Treatment

Initial:
Dietary salt restriction
Spironolactone 100 mg daily + furosemide 40mg daily
In this proportion as long as renal function is preserved
Fluid restriction only if hyponatremic (Na < 120-125 mEq/L)

Refractory ascites:
Serial large-volume paracentesis or transjugular intrahepatic portosystemic shunt (TIPS)

Paracentesis
Indications for Diagnostic Paracentesis
New onset ascites
Patients with ascites and fever, leukocytosis or other signs/symptoms of infection
Patients with cirrhosis who have ascites at the time of hospitalization
Patients with cirrhosis and ascites who have worsening of their clinical condition or deterioration in laboratory parameters (i.e. acidosis, azotemia)
Indications for Therapeutic Paracentesis
Tense ascites
Respiratory distress
Procedure
Paracentesis can be performed via the RLQ, LLQ or the midline approach.
Make sure the bladder is empty if doing the midline approach.
Make sure to percuss the area before doing the procedure. If minimal ascites present, have radiology do an ultrasound and mark the fluid or do an ultrasound guided paracentesis.

Alternative to thoracentesis tray (we do not have paracentesis trays):
1% lidocaine
18 gauge needle ×2, 25 gauge needle ×1, 5 cc syringe ×1, 30 cc syringe ×2
Chlorhexidine prep sponges ×3 (or Betadine swabs)
4x4 gauze
Culture bottles
Lavender and red top tubes
Vacuum bottles
Male-male tubing for therapeutic tap (some people prefer using an Angiocath instead of a regular needle when doing a large volume tap)
Get help from your resident if you are not comfortable with the procedure (This rule applies to ALL procedures!)
Explain the procedure including risks to the patient and get informed consent.
Make sure the unit secretary makes the correct lab requisition for the tests.
Don't leave the patient unattended while doing a large volume tap (i.e. while the needle or Angiocath is still in the peritoneal cavity)
Make sure to follow-up on the ascitic fluid lab results, especially the cell count as you may need to start antibiotics (see SBP section)
Spontaneous Bacterial Peritonitis (SBP)
Adapted in part from Guarner C, Soriano G. Spontaneous Bacterial Peritonitis. Seminars in Liver Disease. 1997;17:203-217.
Definition

Bacterial infection of ascitic fluid:
PMN count >= 250 cells/mm³ OR ascitic fluid WBC >= 500 cells/mm³ with a positive fluid culture

Culture-negative neutrocytic ascites:
PMN count >= 250 cells/mm³ with a negative fluid culture (subtract 1 PMH for every 250 RBCs)
One should rule out previous treatment with antibiotics, TB, pancreatitis, etc.
Pathogens
Common organisms are E. coli , Klebsiella pneumoniae, Enterobacteriaceae, Streptococcus pneumoniae, and Enterococcus.
Cirrhotic patients can also get secondary bacterial peritonitis, which usually requires surgical intervention.
One should suspect secondary peritonitis with perforation if the ascitic fluid meets 2 or more of the following:
Total WBC >10,000
Total protein > 1 g/dl
Glucose < 50 mg/dl
LDH > 225 milliunits/ml (or higher than upper normal for serum)
Multiple organisms cultured
Failure to improve after 48 hours of standard therapy
Risk Factors
Severe liver disease
GI hemorrhage
Prior SBP
Ascitic fluid protein <= 1 g/dl
Clinical Signs and Symptoms
Fever, abdominal pain, hepatic encephalopathy, vomiting, diarrhea
Diagnosis
Abdominal paracentesis
Send fluid for cell count and differential and send fluid directly in the culture bottles
Treatment
Start antibiotic therapy as soon as the diagnosis of SBP is made based on fluid PMN count OR earlier if clinically indicated
Third generation cephalosporin (ceftriaxone OR cefotaxime) HIGH dose 2gm/day.
IV albumin 1.5 g/kg on admission and 1 g/kg 48 hours later has been shown in one study to improve the probability of survival by preventing hepatorenal syndrome (which occurs in up to 30% of patients with SBP). This study was open-labeled trial with a total of 126 patients, and the dose of albumin used is empirical, and a lower dose may be just as efficacious. (NEJM 1999;341:403-409 and NEJM 2004;350:1646-1654)
Consider IV albumin in patients with a serum creatinine > 1 mg/dl OR a total bilirubin > 4 mg/dl. (Diagnosis, prevention, and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;preprint)
Prevention
Long term prophylaxis indicated for patient with prior SBP episode with 1^st line Cipro 750mg PO weekly or 2^nd line TMP/SMX DS 5x week.
In patients with cirrhosis who are hospitalized with GI bleeding, initiate IV antibiotics with transition to norfloxacin 400 mg qday or TMP/SMX DS for 7 days once patients are stable and tolerating orals.
In patients with cirrhosis hospitalized for other reasons and whose ascitic total protein is <1, start norfloxacin or TMP/SMX just during hospitalization
Hepatic Encephalopathy
Adapted in part from Jaffe DL, Chung RT, Friedman LS. Management of portal hypertension and its complications. Med Clin North Am. 1996;80:1021-1034.
Consider the diagnosis in any patient with clinical or laboratory evidence of liver disease and altered mental status.
Can present as insomnia, seizures, delirium and coma and occurs in patients with cirrhosis, portal hypertension, and portosystemic collaterals.
Usually patients have asterixis on physical exam (also seen in other conditions) and have an elevated serum ammonia level.
Precipitating factors
GI bleeding, infection, increased dietary protein intake, azotemia, constipation, sedative/analgesics/tranquilizers, volume depletion, hypoglycemia.
Treatment
Correcting the precipitating cause
Lactulose (start with 30 cc t.i.d. and titrate to 3-4 soft bowel movements per day)

Can be used as second-line agents: rifaximin (a nonabsorbable derivative of rifampin) to decrease the colonic concentration of ammoniagenic bacteria
Of note, rifaximin may be as effective and better tolerated than lactulose, though it is not FDA-approved for hepatic encephalopathy
Dietary protein restriction (0.8g/kg/day) but no definitive data.
Abnormal Liver Function Tests
Adapted in part from MKSAP 14 and The Washington Manual
Liver Tests

Aminotransferases (AST, ALT):
ALT (SGPT) is more specific for the liver
AST (SGOT) can be derived from the liver, heart or skeletal muscle
High levels of AST and ALT (about 10× normal) usually indicate acute hepatocellular injury
In alcoholic liver disease, AST and ALT are generally modestly elevated (about 5-6× normal) and the AST/ALT ratio is around 2

Alkaline phosphatase: derived from liver, intestine, bone, kidney, and placenta.

GGPT, 5'-nucleotidase are more "liver specific" enzymes
Alkaline phosphatase is increased in biliary obstruction, cholestasis, and space occupying lesions

Albumin and prothrombin time: markers of synthetic function

Bilirubin: marker of clearance
Patterns of Liver Injury

Hepatocellular: incinc aminotransferases + inc alkaline phosphatase +/- inc bilirubin
Viral, autoimmune, or drug-induced hepatitis, ischemic, toxic, hereditary, nonalcoholic steatohepatitis (NASH)

Cholestasis: incincalkaline phosphatase + inc bilirubin +/- inc aminotransferases
Hepatocellular dysfunction:
Biliary epithelial damage from hepatitis, cirrhosis
Intrahepatic cholestasis from medications, sepsis, primary biliary cirrhosis, CHF
Biliary obstruction

Isolated Hyperbilirubinemia:
Conjugated: impaired excretion (hepatocellular injury, Dubin-Johnson)
Unconjugated: overproduction (hemolysis) or impaired conjugation (Gilbert's, Crigler-Najjar)

Infiltrative: inc alkaline phosphatase +/- inc bilirubin or aminotransferases
Malignancy, granulomas, abscess
Mnemonic for Differential Diagnosis for Abnormal LFTs

Autoimmune hepatitis/Hepatitis A
Hepatitis B
Hepatitis C

Drugs/Medications: acetaminophen, NSAIDs, antibiotics, statins, anti-epileptics, anti-TB.

EtOH

Fatty Liver/Nonalcoholic steatohepatitis

Granulomatous

Hemochromatosis/Wilson's/a1-antitrypsin deficiency

Hepatitis Serologies
	Hepatitis A	Hepatitis B	Hepatitis C	Hepatitis D*	Hepatitis E
Transmission	Fecal/oral Blood	Blood Sexual Perinatal	Blood Sexual (rare) Perinatal (rare)	Blood Sexual Perinatal	Fecal/oral
Incubation	2-6 weeks	1-6 months	2 weeks-6 months	3 weeks-3 months	3-6 weeks
Acute Infection	Anti-HAV IgM	HBsAg Anti-HBc IgM	Tests may be negative Anti-HCV Ab HCV RNA	Anti-HDV IgM HDAg Hep B markers	Anti-HepE IgM
Chronic Infection	N/A	HBsAg Anti-HBc total	Anti-HCV Ab HCV RNA RIBA II	HDAg anti-HDV total Hep B markers	N/A
Recovered	Anti-HAV Ab	Anti-HBs Ab Anti-HBc total	Anti-HCV Ab RIBA II	Anti-HDV total	Anti-HepE Ab
Vaccinated	Anti-HAV Ab	Anti-HBsAb	N/A	N/A	N/A
*Hepatitis B infection needed for Hepatitis D Adapted from MKSAP 14 and The Washington Manual