Liver & Biliary Disorders Flashcards
Ascites
- most common complication of cirrhosis
- 50% of cirrhotics will die within 2 yrs of onset of ascites
- physical exam worthless, ultrasound is the way to go
- paracentesis part of physical exam
Indications for paracentesis
- new onset ascites
- signs of infection
- any evidence of clinical deterioration
- relief of symptoms due to tense ascites
Lab tests on ascitic fluid
- cirrhotic: serum ascites-albumin gradient, cell count w/ differential, ascitic fluid cultures in addition to the above
- absence of liver disease: cytology, AFB culture, triglycerides, amylase
Serum-ascites albumin gradient (SAAG)
- SAAG > 1.1 = portal hypertension
- SAAG
SAAG levels
- SAAG > 1.1: high portal pressure; portal HTN or CHF
- SAAG
Spontaneous Bacterial Peritonitis (SBP)
- result of bacterial translocation from gut due to impaired barrier
- 2/3 of pts present with abdominal pain, fever, diarrhea NOT peritonitis
- 1/3 asymptomatic
Diagnosis of SBP
- > 250 PMNs/mm3 in ascitic fluid
- cultures negative 50% of the time
- monomicrobial: E coli, klebsiella
- polymicrobial: anaerobic or fungal (secondary peritonitis i.e. perforated viscus)
Treatment of SBP
- antibiotic: Cefotaxime
- IV albumin infusion: 1.5g/kg bw on day 1, 1g/kg bw on day 3
- aminoglycosides should NOT be used
Candidates for prophylaxis of SBP
- hospitalized cirrhotics w/ GI bleeding
- non bleeding cirrhotics w/ ascites and: protein 2.5, SBP
- various antibiotic regimen are effective
Management of Ascites
- sodium restricted diet (2g/d)
- diuretics: spironolactone (K+ sparing) with furosemid (K+ wasting)
- NO IV diuretics: too rapid volume loss = renal hypoperfusion
Causes of poor response to treatment of ascites
- inadequate sodium restriction
- inadequate diuretic dosage
Endpoints of ascites treatment
- weight loss of .5-1 kg/day
- urinary Na:K ratio > 1 indicates good response
- fluid restriction not necessary except for significant hyponatremia (Na 120, creatinine >2, or encephalopathy
Large volume paracentesis
- rapid relief of symptoms but does not treat underlying cause
- if used w/ out sodium restriction ascites reaccumulates
- not first line therapy
- albumin infusions used to blunt changes in volume (8g/L removed)
- smaller volume taps
Variceal bleeding
- 1/3 who have varices will bleed from them
- bleeding associated w/ 30% risk of mortality
- accounts for 80% of GI bleeding in cirrhotics
Management of suspected variceal hemorrhage
- life threatening event: admit to ICU
- hemodynamic resuscitation: large bore IVs, blood products
- consider intubation, call GI
- begin somatostatin or octreotide (decreases portal pressure)
Treatment of variceal bleeding
- endoscopic therapy: ligation
- TIPS when can’t be stopped endoscopically
- antibiotic prophylaxis (quinolone)
Transjugular intrahepatic portosystemic shunt (TIPS)
- shunt to bypass the liver vasculature: portal vein to IVC
Primary prophylaxis of variceal hemorrhage
- screen cirrhotics for varices
- nonselective B-blockers: propranol or nadolol
- Goal: reduction in hepatic venous pressure gradient by 25%/below 12
- Alternate: 25% decrease in HR or HR of 50-60bpm
Hepatic encephalopathy (HE)
- due to impaired hepatic clearance of neurotoxic molecules (ammonia)
- most cases precipitating cause can be identified, treatment of cause usually results in complete resolution
Evolution of hepatic encephalopathy
- first sign: sleep disturbance
- asterixis: flapping hand tremor
- altered reflexes
Diagnosis of HE
- CLINICAL diagnosis: based on signs of liver disease, asterixis, hyperreflexia
- elevated blood ammonia levels NOT required to make diagnosis
Precipitants of hepatic encephalopathy
- GI bleed, infection, constipation, hypoxia, electrolyte imbalance, use of sedatives, or tranquilizers
Treatments of HE
- lactulose: osmotic laxative
- neomycin or rifaximin: if no response to lactulose
- sodium benzoate rarely used
Hepatocellular carcinoma (HCC)
- primary liver cancer: 80% occur in setting of cirrhosis
- incidence in cirrhotics is 3-5%/year
- risk is even higher with cirrhosis due to chronic viral hepatitis
HCC screening and treatment
- cirrhotic patients: ultrasound q 6mos +/- serum alpha fetaprotein
- treatment: liver transplant if limited tumor burden, local Rx, systemic Rx
Liver transplantation in HCC
- can be life saving
- timing of transplant is KEY
- MELD score used to predict 3 month mortality, thus priority for transplant
Model for end stage liver disease: MELD Score
- based on 3 lab scores: objective
- serum creatinine, serum bilirubin, INR
Liver function tests
- not tests of liver function
- estimate metabolic function
- indicate cholestasis
- reflective of hepatocellular injury
Indices of metabolic function
- serum albumin, bilirubin, prothrombin time
- estimate severity of liver disease in pts WITH cirrhosis
Cholestasis lab values
- hallmark is elevation of alkaline phosphatase: bone and placenta can be other sources as well
- bilirubin need not be elevated for pattern to be cholestatic
Alkaline phosphatase
- heat fractionation: antiquated approach to identifying source of elevated alk phos that can yield equivocal results
- isolated alkaline phosphatase: order GGT or 5’ nucleotidase, canalicular enzymes, so if elevated alk phos is coming from live
Causes of cholestasis
- extrahepatic biliary obstruction
- drug induced
- cholestatic liver diseases
- infiltrative diseases
- sepsis
Gilbert’s syndrome
- genetic condition effecting 5% of population
- causes isolated unconjugated hyperbilirubinemia
- not a disease; needs no treatment
Indices of hepatocellular injury
- alanine aminotransferase
- aspartate aminotransferase
- highest levels of ALT in liver so specific
- AST found in other places
Elevated aminotransferases
- correlation b/w height of elevation and degree of necrosis is poor
- normal values don’t preclude significant liver injury
AST:ALT ratio
- AST:ALT usually 2 suggestive of alcoholic liver disease
Differential diagnosis of AST/ALT > 1000
- acute viral hepatitis
- toxin (mushroom poisoning)
- drug (acetaminophen)
- ischemia (“shock liver”)
Major complications of cirrhosis
- ascites
- variceal bleeding
- hepatic encephalopathy
- hepatocellular carcinoma
Morphology of alcohol related liver disease
- fatty change: steatosis
- steatohepatitis
- cirrhosis
Alcoholic steatohepatitis vs. NAFLD/NASH: clinical
- alcohol: EtOH, AST»ALT, GGT high, elevated MCV
- NAFLD/NASH: metabolic syndrome, obesity, or diabetes, ALT>AST, low titre positive ANA
Alcoholic steatohepatitis vs. NAFLD/NASH: histology
- alcohol: more ballooned hepatocytes, more mallory hyaline, more neutrophilic inflammation
- NAFLD/NASH: more fat, numerous glycogenated nuclei, less active
Autoimmune hepatitis
- 4:1 female predominance
- can be associated with other autoimmune conditions
- treatment: immunosuppression-prednisone
Autoimmune hepatitis: aspects in favor
- female
- high protein (globulin)
- HLA DR3 or DR4
- other autoimmune disease
Drug induced liver injury: types
- type A: predictable, dose dependent toxicity, characteristic histology-EX: acetaminophen
- type B: unpredictable, occur at therapeutic doses, may be accompanied by systemic features (fever, rash, eosinophilia, autoantibodies)-EX: nitrofurantoin
Clinical features and diagnosis of DILI
- hepatitis or cholestasis
- diagnosis: exclusion of other causes, known effect of drug, chronology (onset within 90 days of beginning drug, may become evident after stopping drug)
Treatment of DILI
- stop the drug
- only specific antidote is N-acetyl-cysteine (acetaminophen)
- liver transplant for fulminant hepatic failure
DILI histology
- mimics of all patterns of liver disease
- recognition based on temporal relationship: when was drug started, when was jaundice or abnormal test noted
Antidote to acetaminophen
N-acetyl-cysteine
- most effective within 8 hours of ingestion
Herbal liver injury
- just because its natural doesn’t mean it won’t cause damage
Hemochromatosis
- autosomal recessive disorder
- leads to iron overload
- multiple organs effected: bronze diabetes
Hemochromatosis mutations
- mutations affect transmembrane protein HFE (C282Y, H63D)
- HFE mutations appear to disrupt sensing of iron status in hepatocytes
- pts homozygous for C282Y defect or compound heterozygous C282Y/H63D
Hemochromatosis: diagnosis, caveat, biopsy, treatment
- diagnosis: transferrin saturation > 45% prompts HFE genotyping
- caveat: iron studies frequently abnormal in patients liver disease
- biopsy: pts with HFE mutations, or abnormal transferrin saturation
- treatment: phlebotomy to mobilize iron stores
Primary biliary cirrhosis (PBC)
- damage to small bile ducts
- most pts not cirrhotic at presentation: “primary biliary cholangitis”
- autoimmune etiology
PBC presentation, serology, consequences, treatment
- presentation: WOMEN, most asymptomatic at dx
- serology: anti mitochondrial Ab 90%
- consequences: pruritis, hyperlipidemia, bone density, cirrhosis
- treatment: ursodiol may slow progression of liver disease
Primary sclerosing cholangitis (PSC)
- chronic disease characterized by inflammation and fibrosis of intra AND extra hepatic bile ducts leading to STRICTURES
- diagnosis: cholestatic chemistries plus multiple bile duct strictures and segmental dialtions (RADIOLOGIC diagnosis)
- autoantibodies present (ANCA, ANA) but no required for diagnosis
PSC: presentation, risks, treatment
- up to 80% of cases occur in setting of IBD
- symptoms: RUQ discomfort, fatigue, pruritis; look for stricture
- risk: colon cancer, cholangio cancer
- treatment: no medical treatment, transplant/surgical resection of obstruction
Diseases affecting intrahepatic biliary tree
- PBC: intrahepatic only
- PSC: intra/extrahepatic
Features common to PBC and PSC
- elevated alkaline phosphatase and GGT
- patchy involvement of triads
- destruction of interlobular bile ducts
Features differentiating PBC and PSC
- PBC: antibody-antimitochondrial, IBD-uncommon, cholangiogram-pruned biliary tree, extrahepatic ducts-not involved, distinctive lesion-florid duct, cholangiocarcinoma-no
- PSC: antibody-UC ANCA, IBD-common, cholangiogram-beaded bile ducts, extrahepatic ducts-involved, distinctive lesion-fibro obliterative
Autoimmune liver disease
- autoimmune hepatitis + PBC (more likely) or PSC
