General considerations -
See American Gastroenterology Association technical review on liver function tests in Gastroenterology 2002;123:1367.
-
If asymptomatic, repeat to confirm; if still abnormal, decide which pattern LFT abnormalities fit into:
-
Hepatocellular, elevated transaminases with normal-mildly elevated alk phos and normal to elevated bilirubin
-
Cholestatic, elevated alk phos and bilirubin with normal to mild elevations in aminotransferases
-
Mixed picture and infiltrative
H
Causes of chronically elevated transaminases
Hepatic causes
Alcohol abuse
Medication
Chronic hepatitis B and C
Steatosis and nonalcoholic steatohepatitis
Autoimmune hepatitis
Wilson’s disease (in patients <40)
Alpha1-antitrypsin deficiency
Non hepatic causes
Celiac sprue
Inherited disorders of muscle metabolism
Acquired muscle diseases
Strenuous exercise
From N Engl J Med 2000;342:1266
epatocellular pattern, etiologies -
AST (SGOT) can be found in, in decreasing order: liver, cardiac muscle, skeletal muscle, kidney, brain, pancreas, lungs, leukocytes, and erythrocytes
-
ALT (SGPT) much more specific to liver
-
Causes of acute transaminitis
-
Acute viral hepatitis (A, B, C, D, E)
-
Toxin or drug (e.g. acetaminophen)
-
Ischemic (e.g. shock liver)
-
In critical illness, transaminitis usually multifactorial from intrahepatic cholestasis secondary to sepsis, hepatic congestion from CHF, and/or medications
-
Degree of aminotransferase elevation does not correlate with hepatocyte necrosis
-
Alcoholic liver disease:
-
A
Drugs associated with liver injury
Hepatitis-like injury
Acetaminophen
Alpha-methyldopa
Diclofenac and other NSAIDs
Glyburide
Isoniazid
Methorexate
Niacin
Nitrofurantoin
Statin drugs
Cholestasis
Amoxicillin/clavulanate
Androgens
Captopril
Chlorpromazine
Erythromycin
Estrogens (oral contraceptives)
Parenteral nutrition
Tolazamide
Tolbutamide
Trimethoprim-sulfamethoxazole
ST:ALT > 2 because of relative deficiency of ALT given alcohol-related deficiency of pyridoxal-6-phosphate, required for ALT activity
-
AST can be elevated up to 8x normal
-
ALT could be normal to 5x normal
-
Hepatic steatosis and NASH
-
Associated with increased body mass index, diabetes, and hypercholesterolemia
-
Can progress to cirrhosis
-
AST and ALT < 4x normal and AST:ALT < 1; alk phos normal or up to 2x normal; usually asymptomatic; can be evaluated by RUQ ultrasound and then liver biopsy
-
Hereditary hemochromatosis
-
Initial test Fe and TIBC
-
Ff Fe/TIBC > 45%, check ferritin
-
Ferritin > 400 ng/ml in men and > 300 ng/ml in women suggestive; then send for HFE genotype
-
Hepatic iron index (ratio of liver concentration of iron to age of patient) > 2.0 is diagnostic
-
Screen with SPEP; 80% patients will have hypergammaglobulinemia (2x upper limit of normal is specific)
-
Check ANA (>1:160, especially in homogeneous pattern) and anti-smooth muscle antibody
-
Liver biopsy for definitive diagnosis
-
Most patients <40
-
Screening test is serum ceruloplasmin; suggestive if low (<200mg/L) or presence of Kayser-Fleischer rings or 24-hr urine copper >100 mcg/d
-
Definitive diagnosis by liver biopsy showing >250 mcg Cu/g liver
-
Suspect if weight loss, malabsorptive diarrhea, arthritis, vague abdominal pain
-
Screen with antiendomysial IgA (most sensitive and specific) and/or antigliadin IgA and IgG
-
I
ALT and AST >15X upper limit of normal
-
Acute viral hepatitis (A-E, herpes)
-
Medications/toxins
-
Ischemic hepatitis
-
Autoimmune hepatitis
-
Wilson’s disease
-
Acute bile duct obstruction
-
Acute Budd-Chiari syndrome
-
Hepatic artery ligation
f SPEP shows low alpha globulin levels, send for serum AT levels (<80 mg/dL suggestive) and PiZZ phenotyping
-
Rapid rise in AST and ALT in 24 hrs but rapid resolution in 2-6 days
-
Mild bilirubin elevation (<4x normal); alk phos < 2x normal
Transaminitis, evaluation -
Degree of AST and ALT elevation and AST:ALT ratio
-
AST:ALT > 2 and AST < 300 IU/L suggest alcoholic hepatitis
-
AST:ALT ratio 1 in fatty liver disease or acute or chronic viral hepatitis
-
AST:ALT >1 can be seen in cirrhosis from any cause
-
AST:ALT >4 is highly suggestive of fulminant Wilson’s hepatitis
-
AST and ALT levels of >15X upper limit normal, see table
-
If not clearly medication- or alcohol-induced liver disease, initial tests include hep B sAg, hep B sAb, hep B cAb, hep C Ab, hep A IgM and IgG (if clinically indicated), Fe/TIBC, ceruloplasmin (if age < 40), SPEP (assess for autoimmune hepatitis and alpha1-antitrypsin deficiency), TSH
-
If hypergammaglobulinemia on SPEP, check ANA and anti-smooth muscle Ab to assess for autoimmune hepatitis; will need liver biopsy for definitive diagnosis
-
If alpha-globulin band low on SPEP, check alpha1-antitrypsin level
-
If Fe/TIBC > 45%, high suspicion of hemochromatosis, send for ferritin.
-
If ferritin high, check genotype of HFE and liver biopsy; hepatic iron index of >1.9 on liver biopsy c/w homozygous HFE
-
If suspicion of Wilson’s high (e.g. neurologic symptoms, age <40), and ceruloplasmin level not decreased, check for Kayser-Fleischer rings; if still negative, check 24-hr urine for copper excretion (>100 mcg/d is suggestive)
-
If all the above negative, check abdominal ultrasound to assess for fatty infiltration into the liver to suggest hepatic steatosis or NASH; definitive diagnosis requires liver biopsy
-
Additional tests if initial ones are negative to evaluate for nonhepatic source of transaminases
-
Antiendomysial and antigliadin Abs to look for celiac sprue, CK to look for muscle disease
-
Consider liver biopsy if no clear diagnosis
Cholestatic pattern -
Causes include biliary obstruction (stones, cancer, stricture), PBC, PSC, intrahepatic cholestasis of sepsis, medications, infiltrative disease
-
Alkaline phosphatase present in liver, bone, intestine, kidney, placenta, leukocytes, small intestine, and neoplasms
-
Rise of alk phos up to 3x normal nonspecific; striking elevation seen in infiltrative processes (primary or metastatic tumor) or biliary obstruction (intra- or extrahepatic)
-
5
Infiltrating diseases of the liver that can cause elevated serum alk phos
-
Sarcoidosis
-
Tuberculosis
-
Fungal infection (e.g. coccidiodomycosis, histoplasmosis)
-
Other granulomatous diseases
-
Amyloidosis
-
Lymphoma
-
Metastatic malignancy
-
Hepatocellular carcinoma
nucleotidase found in liver, cardiac muscle, brain, blood vessels, and pancreas but significant elevation of serum levels almost exclusively seen in liver disease; may take several days for elevated levels to be detected; sensitivity comparable to that of AP in detecting biliary obstruction, hepatic infiltration, and cholestasis
-
Primary biliary cirrhosis
-
Seen in women in their 50-60s, especially those with hypercholesterolemia
-
Bilirubin normal initially
-
AMA IgM highly suggestive of PBC
-
Definitive diagnosis by liver biopsy
-
Primary sclerosing cholangitis
-
Affects men in their 30-40s
-
H Isolated hyperbilirubinemia -
Indirect hyperbilirubinemia, >85% of total bilirubin is unconjugated
-
Total bilirubin usually never >6 mg/dL in hemolysis
-
Check reticulocyte count and hemolysis labs
-
Direct hyperbilibinemia, >50% of total bilirubin is conjugated
Causes of indirect hyperbilirubinemia
Hemolysis
Ineffective erythropoiesis
Resorption of large hematoma
Crigler-Najjar syndrome
Gilbert’s syndrome (bilirubin usually <3)
Shunt hyperbilirubinemia
Hepatic causes of direct hyperbilirubinemia
Bile duct obstruction
Hepatitis
Cirrhosis
Medications/toxins
Primary biliary cirrhosis
Primary sclerosing cholangitis
Sepsis
Total parenteral nutrition
Vanishing bile duct syndromes
Dubin-Johnson Syndrome
Rotor’s Syndrome
istory of inflammatory bowel disease (especially UC) suggestive
-
Diagnosis by ERCP and/or liver biopsy
-
Infiltrative diseases (see box)
Cholestatic pattern, evaluation -
Confirm hepatic origin of elevated alkaline phosphatase with 5 nucleotidase (more commonly performed at MGH than GGT)
-
Right upper quadrant ultrasound to assess for cholestasis or infiltrative disease
-
If U/S negative, check anti-mitochondrial Ab (good sensitivity and specificity) to evaluate for primary biliary cirrhosis
-
If positive, consider liver biopsy
-
If both RUQ U/S and anti-mitochondrial Ab negative
-
Consider liver biopsy and/or ERCP if alk phos > 50% above normal (ERCP can assess for PSC; liver biopsy may miss it)
Deanna Nguyen, M.D.
B Etiologies -
Alcohol and gallstones are the most common two causes comprising 75% of cases
-
Ampullary obstruction (diverticula, tumor, worms, foreign body)
-
Hypertryglyceridemia (>1000 mg/dL and accounts for <4% of cases)
-
Hypercalcemia (<2% pts with hyperparathyroidism)
-
Drugs (ddI, tetracyclines, sulfa agents, furosemide, valproic acid, tamoxifen, pentamidine, azathioprine, metronidazole, mercaptopurine)
-
Infections (mumps, EBV, HIV, CMV, HSV, ascariasis, coxsackie, viral hepatitis)
-
Vascular causes (vasculitis, ischemia, atherosclerotic emboli)
-
Trauma (blunt)
-
Iatrogenic (post-ERCP, post-abdominal surgery)
-
Toxins (scorpion venom, organophosphorous insectisides, methyl alcohol)
-
Pregnancy (multifactorial)
-
Idiopathic (10%)
ackground (Do Not Edit This Line This is Hidden Text) -
Pancreatitis is a common reason for admission for management of pain and emesis/dehydration and for management of complications.
-
Complications include (see below):
-
Pseudocyst formation
-
Pancreatic necrosis
-
Abscess formation
-
Chronic pancreatitis (and possible pancreatic cancer) with chronic pain and exocrine insufficiency.
Points to consider in the history -
Time frame of symptoms (nausea and vomiting, abdominal pain radiating to back, pain may be relieved while sitting up/forward and may worsen with food)
-
Travel history
-
History of and risk factors for dyslipidemia (DM, hypothyroidism) or hypercalcemia (e.g., hyperparathyroidism)
-
Good medication and alcohol history
-
History of biliary colic or known risk factors of cholelithiasis
Helpful studies and laboratory information (Do Not Edit) -
Serum amylase: increases 2-3 hrs after attack and stays high for 3-4 days
-
No correlation between peak level and severity
-
Non-pancreatic causes of elevation are renal failure, viscus perforation/infarct, ectopic pregnancy, cancer, macroamylassemia
-
Serum lipase: more sensitive and specific and remains elevated longer than amylase
-
Serum calcium, lipids, LDH, CBC, albumin, glucose, liver chemistries
-
RUQ ultrasound to evaluate biliary tree for obstruction/cholelithiasis
-
CXR may show pleural effusion or ARDS
-
CT scan with contrast to evaluate for necrosis or presence of pseudocyst or abscess (evaluate for necrosis after 1 week). Consider CT scan in patients who are deteriorating or who have severe pancreatitis, i.e. not all patients require CT scan.
-
Note that controversy exists whether or not ionic contrast may worsen pancreatitis.
-
ERCP ± sphincterotomy in setting of biliary obstruction
Complications -
Pseudocyst. Non-epithelial lined cavity often presenting with persistent pain and hyperamylasemia. 50-80% resolve within 6 weeks
-
Pancreatic abscess. Develops within 2-4 weeks, often presenting with fever, pain, and persistent hyperamylasemia
-
100% mortality if not drained; affects 30% pts with severe acute pancreatitis.
-
E. coli, Pseudomonas, Klebsiella, and Enterococcus spp are most common; 75% are monomicrobial
-
Systemic inflammatory response syndrome
-
Pancreatic ascites and pleural effusion (left>right)
-
Metastatic fat necrosis/panniculitis(Do Not Edit)
-
Chronic pancreatitis
Main goals and mainstays of treatment (Do Not Edit) -
Early ERCP in patients with gallstone pancreatitis who have obstructive jaundice (bilirubin >5) or biliary sepsis
-
Treatment of hypercalcemia
-
Cessation of possible causative drugs
-
Mild pancreatitis is treated for several days with supportive care consisting of analgesia, IVF, and NPO.
-
Consider nasogastric tube for ileus or vomiting.
-
Role of antibiotic prophylaxis (in absence of necrosis) is controversial. Studies have shown decreased frequency of sepsis but no different in mortality rate with imipenem.
-
Surgery is indicated only when necrotizing pancreatitis is infected.
-
Acute necrotizing pancreatitis (involving more than 30% of pancreas) generally warrants broad spectrum antibiotics (e.g. imipenem or meropenem).
-
Enteral feeding via nasojejunostomy tube should be attempted with high protein/low fat preparations if pts are NPO for more than 7-10 days. Consider TPN in patients who do not tolerate enteral feeding.
-
Oral refeeding when abdominal pain and tenderness resolve and there is no complication. Begin with liquids.
Deanna Nguyen, M.D.
Background -
Severe acute hepatitis = jaundice and coagulopathy without hepatic encephalopathy
-
Fulminant hepatic failure, as defined by Trey and Davidson initially = severe acute hepatitis + hepatic encephalopathy within 8 weeks of onset of jaundice without previous existing liver disease
-
More recently, ALF defined as fulminant hepatic failure if hepatic encephalopathy develops within 2 weeks after onset of jaundice and as subfulminant hepatitis if encephalopathy develops in 2-12 weeks.
Etiologies (Do Not Edit This Line) -
Multiple etiologies have been demonstrated to cause acute liver failure.
-
Data from NIH ALF Study of 206 patients identified these as etiologies:
-
Acetaminophen 38%
-
Indeterminate 18%
-
Drug reaction (INH, rifampin, PTU, amiodarone) 14%
-
Viral hepatitis (0.2-0.4% of hep A, 1.0-1.2% of hep B) 12%
-
Autoimmune
-
Ischemic (Budd-Chiari, shock, veno-occlusive disease)
-
Wilson’s
-
Pregnancy (acute fatty liver of pregnancy, HELLP)
-
Malignancy (lymphoma most common)
-
Other etiologies have been described: carbon tetrachloride, Amanita phalloides mushrooms, NSAIDs, halothane, Ecstasy, HDV, HEV in pregnant women in their third trimesters, valproic acid, tetracycline, Reye’s syndrome
Complications -
Cerebral edema (develops in 80% of pts with grade 3-4 encephalopathy, due to increased permeability of BBB), most common cause of death.
-
R King’s College Criteria Acetaminophen -
Arterial pH <7.3 (irrespective of grade of encephalopathy) OR
-
Grade III/IV encephalopathy AND PT >100 s AND creatinine >3.4
All other causes -
PT >100 s (irrespective of grade of encephalopathy) OR
Any three of the following -
Age <10 or >40
-
Etiology: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic
-
Duration of jaundice before onset of encephalopathy >7 days
-
PT >50 s
-
Bilirubin >18 mg/dL
enal failure
-
Bacterial infection
-
Additional complications include:
-
Hemodynamic instability (high cardiac output but low peripheral resistance), hemorrhage, hypoglycemia, pulmonary edema, respiratory alkalosis, hyponatremia, hypophosphatemia, pancreatitis
Prognostic tools -
King’s College Criteria for need for liver transplantation (most often used); see box
-
APACHE II score (worse if >15 in acetaminophen group, >13 in non-acetaminophen)
-
Serum AFP (increase in AFP from day 1 to day 3 had a 83% sensitivity and 68% specificity for predicting outcome)
-
Clichy criteria
-
Hepatic encephalopathy (grade III-IV) and factor V level <20% in pts <30 y.o. or <30% in pts >30 y.o. are associated with low likelihood of spontaneous recovery
-
Admission encephalopathy grade and bilirubin level have been noted to be independent predictors of spontaneous survival.
-
Specifically, a mean total bilirubin of 6 among survivors and 17 among non-survivors. Also 65-70% survival in patients with grade I-II encephalopathy compared to <20% survival in patients with grade IV encephalopathy.
-
Liver pathology: >70% necrosis associated with 90% mortality rate without transplantation
-
MELD scale. Model End Stage Liver Disease. New model for scoring severity (calculator also available on Palm software MedCalc).
-
Score = 9.57 ln (creatinine) + 3.78 ln (total bilirubin) + 11.2 ln (INR) + 6.43
where creatinine, bilirubin, and INR > 1, creatinine <4, maximum MELD score is 40
-
In acute liver failure from acetaminophen toxicity, arterial lactate >3.5 mmol/L had good predictive value
-
Early after admission (median 4 h), 67% sens, 95% specific for death; after fluid resuscitation (median 12 h), arterial lactate >3.5 mmol/L 76% sens, 97% spec (Lancet 2002;359:558).
Main goals and mainstays of treatment (Do Not Edit) -
Airway and hemodynamic stabilization of patient
-
Refer (to GI liver fellow) for possible transplantation evaluation
-
Look for potentially reversible cause.
-
Acetaminophen (N-acetylcysteine), Amanita poisoning (consider high dose penicillin and parenteral silibinin), Budd-Chiari (surgery), acute fatty liver of pregnancy (delivery), autoimmune (steroids +/- cytotoxic agents).
-
N-acetylcysteine most helpful when given within 12 hours of acetaminophen ingestion but should be given to all patients with acetaminophen toxicity; consider it even for non-acetaminophen ALF since there is some evidence to suggest efficacy
-
For hepatic encephalopathy, consider lactulose; avoid benzodiazepenes due to upregulation of GABA receptors
-
Supportive therapy for cerebral edema (often the mode of death):
-
ICP monitoring to maintain cerebral perfusion pressure >50 mm Hg, mannitol for elevated ICP in pts without renal failure (elevation of head of bed, hyperventilation, steroids probably not useful)
-
Frequent monitoring of glucose given possible impaired hepatic gluconeogenesis and glycogenolysis, dextrose drips for hypoglycemia
-
FFP, platelets only if evidence of bleeding
-
Vasopressors to support organ perfusion
-
Serial blood cultures q48 hrs and low threshold for broad spectrum antibiotics since ALF pts may not mount elevated WBC or fever due to impaired immune system
-
If dialysis necessary, CVVH better than HD to avoid rapid fluid shifts
-
Transplantation remains best therapy with survival of about 50-90% but organ supply and high acute mortality from sepsis and cerebral herniation remain as obstacles. Most recent data show that only 29% are transplanted.
-
On the horizon:
-
Molecular Adsorbent Recycling System (MARS), hemodiafiltration against albumin able to remove low molecular weight toxins
-
Extracorporeal liver assist devices as a bridge to transplantation and to possibly, spontaneous recovery (uses pig or human hepatocytes)
Survival data -
Overall survival = 60%; outcomes are best for acetaminophen (65% overall survival) and worst if idiosyncratic drug reaction or indeterminate cause (14% and 11% survival, respectively)
-
H
Deanna Nguyen, M.D.
igh mortality rate from cerebral edema, renal failure, sepsis, multisystem organ failure
Toxic dose -
Minimal toxic single dose, 7.5 to 10 g for an adult.
-
Toxicity likely to occur with single ingestions greater than 250 mg/kg or those greater than 12 g over a 24-hour period.
-
Virtually all patients who ingest doses in excess of 350 mg/kg develop severe liver toxicity.
Pathophysiology (Do Not Edit This Line) -
Route. Oral ingestion, peak serum levels can occur within 30-60 minutes but can take up to 4 hours depending on the rate of gastric emptying. The serum half-life is 2-3 hours and is not affected by renal clearance.
-
Mechanism. Acetaminophen is primarily cleared by the liver metabolism. The majority (95%) of acetaminophen is converted to glucuronidated or sulfonated metabolites that are inactive and non-toxic.
-
5% of acetaminophen is converted by hepatic P450 enzymes to N-acetyl-p-benzoquinoneimine (NAPQI), a highly reactive species. NAPQI is further conjugated to glutathione to produce an inactive metabolite.
-
In overdose, the sulfonation and glucuronidation pathways are saturated and more drug is shunted to P450 pathways to produce NAPQI. Increased levels of NAPQI rapidly deplete glutathione stores.
-
Once glutathione stores are exhausted, NAPQI reacts with cellular components resulting in hepatocyte necrosis.
-
Modifying factors. Alcoholism, pre-existing liver disease, and medications that induce microsomal P450 enzymes may all augment hepatotoxicity in acetaminophen use.
Clinical manifestations
Stage I. Initial 24 hours post ingestion
|
Anorexia, nausea, vomiting, diaphoresis, and malaise
|
Stage II. 24-48 hours post ingestion
|
Improved symptoms, right upper quadrant pain, elevation of liver enzymes (transaminases), LDH, bilirubins and increased PT.
|
Stage III. 72-96 hours post ingestion
|
Hepatic enzymes peak. Develop sequelae of hepatic failure including jaundice, coagulopathy, and encephalopathy.
Renal failure and myocarditis may occur. Death can result
|
Stage IV. >4-14 days
|
Complete resolution and recovery
|
Emerg Med Clin North Am 1984; 2:103-119
| Diagnosis -
History of ingestion, stage I symptoms (see above), evidence of unexplained hepatic failure
-
Key information includes amount of drug ingested and time elapsed from ingestion
-
Serum acetaminophen levels—draw at 4 hours post ingestion (level of drug peaks at 4 hours), refer to nomogram—use serum level and time elapsed since ingestion to determine toxicity risk
Management -
Gastric decontamination. Gastric lavage if ingestion <4 hours to presentation
-
Activated charcoal. 50-100 g, adsorbs drug, most effective if given <4 hrs, but may help >4hrs
-
N-acetylcysteine. Replenishes glutathione stores. Can be given with charcoal without loss of efficacy.
-
Initial dose of N-acetylcysteine. 140 mg/kg po or nasogastric tube, draw serum acetaminophen level at 4 hrs post ingestion
-
Subsequent therapy. If the serum level is toxic per nomogram, then admit patient and administer 17 doses of 70 mg/kg N-acetylcysteine po or nasogastric tube q4h over the next 72 hours.
-
Draw LFTs (AST, ALT, bilirubin), LDH, and PT for a baseline, follow daily for 72 hours. Also consider checking lactic acid (see acute liver failure section).
-
See acute liver failure section for prognostic indicators.
Hours after acetaminophen ingestion
nomogram adapted from Harrison’s Principles in Internal Medicine
Ravi Joshi, M.D.
G Modified Child-Turcotte-Pugh score |
Parameter
|
1 point
|
2 points
|
3 points
|
1. Ascites
|
none
|
slight
|
moderate or worse
|
2. Total bilirubin
|
<2
|
2-3
|
>3
|
3. Prothrombin time
|
|
|
|
Sec over control
|
1-3
|
4-6
|
>6
|
INR
|
<1.7
|
1.8-2.3
|
>2.3
|
4. Albumin
|
>3.5
|
2.8-3.4
|
<2.7
|
5. Encephalopathy
|
none
|
1-2
|
3-4
|
CTP score
|
CTP class
|
1 yr survival
|
2 yr survival
|
5-6
|
A
|
100%
|
85%
|
7-9
|
B
|
80%
|
60%
|
10-15
|
C
|
45%
|
35%
|
eneral considerations -
Liver biopsy is gold standard for diagnosis of cirrhosis
-
RUQ ultrasound to look for ascites, vascular patency, echogenicity/morphology of liver, biliary tree, hepatocellular carcinoma
-
Serum AFP (for HCC)
-
Hyponatremia (volume overloaded), anemia (multifactorial), thrombocytopenia (hypersplenism and thrombopoieten deficiency)
Ascites -
Most common complication of cirrhosis
-
50% develop ascites within 10 years
-
Multifactorial etiologies leading to avid Na retention by the kidney and transudation across the peritoneum, as well as hypoalbuminemia, and increased hepatic lymph production
-
Differential diagnosis includes portal hypertension (cirrhosis, cardiac, hepatic vein obstruction, portal vein/splenic vein obstruction, schistosomiasis) vs. non-portal hypertension (malignancy, pancreatitis, nephrogenic, infectious (TB), chylous, biliary
-
Diagnostic tap: cell count with differential, albumin, total protein, amylase, triglycerides, gram stain, culture (in blood culture bottles at bedside), cytology
-
SAAG = serum albumin ascites albumin gradient.
-
SAAG >1.1, 97% accurate for portal HTN
-
Sodium restriction is paramount (<90 mEq/day)
-
Fluid restriction to <1500 mL/day (<1000 mL/day if serum Na <120 mEq/L)
-
Diuretics
-
UNa>30 mEq/L: spironolactone 100 mg po qd alone
-
UNa 10-30 mEq/L: furosemide 40 mg po qd and spironolactone 100 mg po qd
-
UNa < 10 mEq/L: furosemide and spironolactone (40:100 ratio), sodium/fluid restriction, and large volume paracentesis
-
Paracentesis, indicated in tense ascites and/or refractory ascites with low UNa
-
TIPS as a bridge to transplantation if ascites refractory
Spontaneous bacterial peritonitis (SBP) -
Risk factors: low ascites total protein (<1.0)
-
Must be ruled out in all cirrhotics who are admitted since its presentation ranges from asymptomatic state to sepsis; 10-30% hospitalized cirrhotics have SBP
-
Diagnose with paracentesis; three categories:
-
Culture positive/neutrocytic (>250 PMN/cc), most common
-
Culture negative/neutrocytic >250 PMN/cc,
-
Culture positive/non-neutrocytic (<250 PMN/cc)
-
Bacteriology: E. coli > Klebsiella > Strep pneumoniae > other gram negative rods. Anaerobes are rare (<5%)
-
Treat with cefotaxime (or equivalent) 2 gm IV q8h x 5 days
-
Some repeat paracentesis at day 3 to show cell count decline
-
Albumin infusions (1.5 gm/kg on day 1 and 1.0 gm/kg on day 3) have been shown to improve mortality when given with antibiotics potentially by preserving renal function through volume expansion (N Engl J Med 1999;341:403)
-
Consider prophylaxis with quinolone since 60% will recur within 1 yr
Secondary peritonitis -
If ascitic fluid is neutrocytic, and has 2 out of 3 of following: total protein > 1g/dL, glucose <50 mg/dL, LDH >nl for serum.
-
Must exclude bowel perforation or intra abdominal abscess.
-
Treat with metronidazole and cefotaxime; consider emergency surgery.
Esophageal variceal bleeding -
Requires hepatic venous-wedge gradient of >12 mm Hg to occur.
-
Average lifetime risk is 30% in cirrhotics without previous variceal bleed.
-
Predictors: Child class C, large varices, red wale markings, alcohol.
-
Volume resuscitate, pRBCs, and FFP transfusion.
-
Octreotide drip 50 mcg IV bolus then 50 mcg/hr.
-
Endoscopic band ligation slightly more effective than injection sclerotherapy
-
Rarely, urgent TIPS.
-
Prophylaxis with surveillance banding, non-selective beta blockers (nadolol or propranolol).
-
Goal HR<25% of baseline ± nitrates
Non-variceal upper GI bleeding -
Gastric varices accounts for 10% of all UGI bleeding in cirrhotics.
-
Portal hypertensive gastropathy accounts for up to 40% of all UGI bleeding in cirrhotics.
-
Average lifetime risk is 30% in cirrhotics without previous variceal bleed.
-
Treatment same as for esophageal variceal bleeding, although tend to be more difficult to treat.
-
Propranolol is treatment of choice for portal hypertensive gastropathy.
Hepatic encephalopathy -
Manifestation of porto-systemic shunting with ammonia, and benzodiazepene-like false neurotransmitters accounting for encephalopathy
-
Often precipitated by infection (SBP), azotemia, GI bleeding, dietary indiscretion, sedatives, hypoxia, hypotension, development of HCC
-
L Grading hepatic encephalopathy -
Grade 1, restless, inverted sleep pattern, mild confusion, irritable with tremor and apraxia
-
Grade 2, lethargy, slow responses, inappropriate behaviors, disoriented to time, asterixis, hypoactive DTRs
-
Grade 3, omnolence but rousability, disoriented to place and time, + asterixis, hyperactive DTRs
-
Grade 4, coma.
actulose titrated to 2-4 bowel movements/day (usually requires 30-60 g/day)
-
Neomycin (4-6 g/day) but caution because of potential nephrototoxicity
-
Metronidazole (800 mg/day) x 1 week as effective as neomycin
Hepatorenal syndrome -
Probability of occurrence 18% at 1 yr, 39% at 5 yr
-
Poor prognostic event marked by azotemia and oliguria refractory to volume challenges.
-
Urine sediment is bland and low urine sodium
-
Rule out other causes (hypovolemia, ATN, obstruction, drug effects, abdominal compartment syndrome (check “bladder” pressure, abdominal compartment syndrome not likely <10 mm Hg and usually present when >25 mm Hg)
-
Precipitants: infection, over-diuresis, large volume paracentesis, aminoglycosides, NSAIDs
-
Fluid challenges, remove all diuretics, nephrotoxins, and precipitants, consider large volume paracentesis
-
Midodrine (7.5-12.5 mg po tid) and octreotide (100-200 mcg sc tid) (Hepatology 1999;29:1690)
-
Norepinephrine and albumin (Hepatology 2002;36:374).
-
Transjugular intrahepatic portosystemic shunt (TIPS)
-
Transplant evaluation
Hepatopulmonary syndrome -
Rare complication of unknown etiology characterized by dyspnea, pulmonary vascular dilatation, and hypoxemia (PaO2 <70 mm Hg); associated with orthodeoxia (upright hypoxia)
-
Pathologically marked by diffuse (type I) large (type II) arterio-venous shunts in the pulmonary circulation (possibly related to increased circulating NO)
-
Diagnose by trans thoracic echo with bubble and macroaggregated radioactive albumin lung scan
-
Improves with transplantation
-
IR-guided embolization of AV communications if PaO2 <150 mm Hg on 100% O2
-
Methylene blue (Ann Intern Med 2000;133:701)
Portopulmonary hypertension -
Rare cause of secondary pulmonary hypertension (all pts have signs of portal HTN)
-
Present with DOE, syncope.
-
Diagnosis of pulmonary hypertension by TTE and/or cath and demonstration of reversal of flow in portal vein on Doppler ultrasound
-
High mortality with liver transplant if mean PA pressures >35 mm Hg
-
Responds to IV prostacyclin in some patients
Hepatic hydrothorax -
Right (66%) > bilateral (17%) = left (17%) pleural effusion which is transudative and often in association with large ascites; caused by migration of fluid across diaphragm
Endocrinopathies -
Hypogonadism
-
Thyroid dysfunction: high TSH, low T4, low T3, high rT3 akin to euthyroid sick syndrome
Vasculitis (hepatitis B, hepatitis C) -
Polyarteritis nodosa with hepatitis B
-
Essential mixed cryoglobulinemia (type II cryoglobulinemia) and type III cryoglobulinemia with hepatitis C
Hepatocellular carcinoma -
Associated with cirrhosis (from any cause)
-
A
Deanna Nguyen, M.D.
ssociated with hepatitis B carrier state
Deanna Nguyen, M.D.
B Some literature regarding bowel regimens -
Psyllium superior to docusate sodium in patients with chronic constipation in randomized double blind study (Aliment Pharmacol Ther 1998;12:491-7)
-
Comparison of Miralax with lactulose in chronic constipation showed higher stool frequency with Miralax (Gut 1999;44:226)
-
“Although these [docusates, e.g. Colace] remain very popular agents, clinical studies suggest that docusates are of little use in the prophylaxis of constipation in elderly bed-ridden patients” (Aliment Pharmacol Ther 2001;15:749)
ulking Osmotic agents -
Poorly absorbed disaccharides
-
Lactulose. Metabolized in colon by bacteria to short chain fatty acids.
-
Sorbitol
-
GoLYTELY (polyethylene glycol 3350, sodium sulfate)
-
NuLYTELY (polyethylene glycol 3350, NaHCO3, KCl)
-
Miralax (polyethylene glycol 3350)
Stimulant laxatives -
Ionic detergents leading to stool softening; perfusion studies suggest that docusates inhibit fluid absorption or stimulate secretion in jejunum.
-
Diphenylmethane derivatives
-
Phenolphthalein (withdrawn from U.S. market because of rodent data suggesting carcinogenesis).
-
Bisacodyl (Dulcolax)
-
Alters net fluid and electrolyte transport, direct effects on colonic motility (e.g. as suppository).
-
Stimulates intestinal formation of prostaglandins, serotonin, and histamine to increase colonic secretions.
Other agents -
Enemas, disimpaction in selected circumstances (may need to individualize treatment)
-
Neostigmine
-
Acetylcholinesterase inhibitor, given 2 mg iv, useful for colonic decompression in Ogilvie’s syndrome (N Engl J Med 1999;341:137).
-
Side effects include symptomatic bradycardia requiring atropine, crampy abdominal pain, excessive salivation and vomiting.
-
Dopamine antagonist, useful in diabetic gastroparesis; has rarely been associated with tardive dyskinesia and extrapyramidal side effects.
-
Given 200 mg iv q8h (not po); acts on motilin receptors.
-
Improves gastric emptying in critically ill patients, delayed gastric emptying in diabetic gastropathy (Crit Care Med 2000;28:2657); effects comparable to metoclopramide.
-
Naloxone (Narcan) enterally
-
In critically ill patients on fentanyl sedation, naloxone 8 mg po q6h decreased gastric tube reflux and frequency of pneumonia, no effect on inducing bowel movements (Crit Care Med 2003;31:776).
-
V
Evan Dellon, M.D.
Andrew Yee, M.D.
arious studies suggest reversal of opioid-associated constipation.
MGH Medical Housestaff Manual
150>70>10>50>250>120>1000>1500>90>2>4>4>30>10>4x>80>40>
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