1. Causes of end-stage liver failure:
-Most common: Viral Hepatitis (B/C), alcohol (15-20% of heavy drinkers will develop cirrhosis)
-Increased back-pressure (ischemic and pressure damage)
---CHF: R heart failure, constrictive pericarditis
---Budd-chiari (hepatic vein thrombosis): lupus, polycythemia vera
---Veno-occlusive disease: injury to hepatic venous sinus endothelium (usu zone 3) leads to accumulation of clotting factors/fibrinogen -> veno-occlusion -> ischemia. Causes: high-dose cytotoxic therapy (bone marrow transplant), high-dose radiation to the liver (>30 gy), toxins like pyrrolizidine from herbal remedies (coltsfoot: flowers look like dandelions, leaves shaped like colts foot, used for respiratory symptoms, comfrey: fast-growing leafy green, called knit-bone in times past, used as topical and oral treatment for bone/skin concerns
-Direct damage to hepatocytes
---Ischemia (zone 3): shock (although if your shock is bad enough to lead to hepatic ischemia, you probably have bigger problems), hepatic artery thrombosis (i.e. sickle cell)
---Toxins (usu zone 1): amanita (zone 2), tylenol, methotrexate
---Viral: yellow fever (zone 2)
---Autoimmune hepatitis (+ANA, +a-smooth muscle antibody)
---Accumulation of toxic metabolites: hemochromatosis, wilson's, A1AT deficiency
---Accumulation of bile: PBC (a-mitochondrial ab), PSC, biliary atresia, choledochal duct cyst. In latter 2, need to diagnose and get Kasai by 2 mos.
---NASH
2. Complications of end-stage liver failure: Varices
-Pathophys: portal hypertension leads to back pressure into portosystemic anastamoses.
-Why you should screen for Esophageal varices: they're present in an estimated 30% of people with compensated cirrhosis and 60% of those with decompensated cirrhosis; annual first hemorrhage rate among those with varices is 12%, mortality from a variceal hemorrhage is 15-20%. Screen with endoscopy.
-if someone doesn't yet have a varix, timolol does not prevent them from getting varices or affect mortality/dev ascites/transplant need, and is associated with more b-blocker related serious complications {NEJM 2005, placebo-controlled RCT, n=213}
-If someone is found to have an esophageal varix, you can control it endoscopically (banding), or medically (prophylactic beta-blockers: they block b2 mediated vasodilation and allow unopposed alpha-1 constriction of splanchnic vessels). Nonselective b-blockers are effective in decreasing bleeding events (12 vs 23%), deaths due to bleeding (5 vs 10%), and are nearly significant in reducing overall mortality (21 vs 27%) {Lancet 1990, meta-analysis of RCTs, overall n=797). Recognize however that b-blockers are not benign, and suppress cardiac function, cause bronchoconstriction, impotence, fatigue.
-If someone is actively bleeding from an esophageal varix, you can band it endoscopically, or give octreotide (causes splanchnic vessel vasoconstriction somehow, possibly via suppression of vasodilatory hormones like glucagon) or vasopressin although that has more side effects.
3. Complications of ESLD: Ascites
-Pathophys: backpressure of fluid into vessels leading to liver combined with low albumin.
-Evaluate: abd u/s which can detect as little as 30mL of fluid. Make sure its not due to some other cause, like SBP, by taking a diagnostic tap: look at the cell counts, culture it/gram stain, albumin gradient<1.1 g/dL implies that it's not caused by portal HTN, look for another cause.
-Treatment: Diurese (lasix spironolactone) low-sodium diet to keep fluids off, paracentesis if the belly looks tense or it's causing symptoms (SOB, early satiety).
4. Complications of ESLD: Hepatic encephalopathy
-Accumulation of toxic metabolites, notably ammonia. Occurs in 50% of cirrhotics.
-Precipitants: alkalosis, hypokalemia (too much lasix), sedating drugs
-Treatment: lactulose, prevents absorption of ammonia,
5. Complications of ESLD: Hepatorenal syndrome
-Accumulation of blood in splanchnic vessels leads to steal phenomenon as blood is shunted away from kidneys, leading to prerenal syndrome.
-Additionally, it is thought that some toxin that accumulates in the face of decreased hepatic function acts as a renal vasoconstrictor. Direct NO injections into the renal arteries are not effective at reversing this condition, so it is either operating at a level deeper than NO, through an alternate and more potent pathway, or the NO injections were unsuccessful at reaching the full vasculature of the kidneys.
-Treat with ornipressin, vasopressin analogue which preferentially constricts splanchnic vessels. 2012 Cochrane review of multiple RCTs found terlipressin, another vasopressin analogue, decreased mortality (RR 0.76) and increased reversal of hepatorenal syndrome, but at the cost of increased cardiac complications (11% vs 0%)
6. Complications of ESLD: Spontaenous Bacterial Peritonitis (SBP)
-Pathophys: The ascitic fluid can become secondarily infected.
-Look for: fever, mental status changes, abd pain, vomiting, rebound tenderness.
-Diagnosis: paracentesis WBC>500, PMN>250, +gram stain or culture (although culture negative does not rule out
-Bugs: e.coli, klebsiella, s.pneumo
-Treat with antibiotics, repeat paracentesis in 2-3 days. symptoms should improve in 24-48 hours.
-Prognosis: 20-30% mortality rate, worse outcome if diagnosed late, can lead to sepsis.
7. Complications of ESLD: Coagulopathy: 
-Liver stops making coagulation factors; unresponsive to vitamin K.
-Treat with FFP (if its really bad, may need to run continuous infusion)
8. When doing a liver transplant, you want your patient to be volume-down, and you want to make sure their mean pulmonary artery pressure <35. The reason is that livers are very sensitive to back pressure, and the less volume there is the less there will be to back up from the heart into the liver. Once you put in the new liver and unclamp, reperfusion injury will wash inflammatory/pro-oxidant mediators from new liver (which just spent a long time in cold ischemia) into the lungs, causing some pulmonary vessel spasm. This will lead to a temporary increase in pulm aa pressure; if the baseline pulm aa pressure was already high, then it might go so high that the R heart can't push through it, blood will back up into the liver and damage it. And then you'll be left with choosing between pushing volume and significantly damaging the new liver, or not pushing volume and risking losing cardiac output.
9. MELD score was developed to predict survival of patients getting TIPS (Original study in Hepatology, n=231) now used to determine transplant list order for patients with chronic liver disease. MELD score: 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Ln serum creatinine (mg/dL)] + 6.43. If the pt has had dialysis at least 2x in the last week, Cr score is automatically increased to 4. Any value <1 is automatically assigned a 1, to prevent negative numbers coming out of the ln. Acute liver failure patients get priority over even the sickest chronic liver failure patients.
10.Blood type in solid-organ transplants: Rh factor is unimportant, only need to match blood type. In USA, blood types from most to least common: O, A, B, AB. As in blood, O's are universal donors and AB's are universal receivers.