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- 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 levels

- SAAG > 1.1: high portal pressure; portal HTN or CHF


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

- most effective within 8 hours of ingestion


Herbal liver injury

- just because its natural doesn't mean it won't cause damage



- 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