Cirrhosis And Liver Transplant Flashcards
Hepatic fibrosis
1 cause of hepatic fibrosis = alcohol
Is caused by overly exuberant wound healing in which excessive connective tissue builds up
Medical disorders:
- autoimmune hepatitis
- certain storage diseases and inborn errors of metabolism
- congenital hepatic fibrosis
- chronic infections of bacterial/viral/parasitic
- nonalcoholic steatohepatitis (NASH)
- primary biliary cirrhosis
- primary sclerosing cholangitis
Does hepatic fibrosis by itself cause symptoms?
No but the resulting portal HTN and hepatocyte death will
Symptoms include
- fatigue
- anorexia
- muscle cramps
- disturbed sleep
- hematemesis/melena or hematochezia
- spider telangiectasia/palmer erythema/contracture
- vitamin deficiencies
- jaundice
- hepatosplenomegaly
- gastric/rectal varices
- hepatic encephalopathy w/ asterixis
- ascites and peripheral edema
How to diagnose ascites and edema
Paracentesis and send to lab:
- get CBC, gram stain, culture and albumin
- **if albumin gradient of (serum:ascites) is greater than 1.1 = portal HTN
Treatment for liver cirrhosis symptoms
Ascites and edema
- diuretics
- trans jugular intrahepatic portosystemic shunt (TIPS) (usually only if refractory presents)
- large volume paracentesis
Peritonitis = 2nd/3rd gen cephalosporin or fluroquinolone are 1st line
Thrombocytopenia/coagulopathy
- phytonadione 5mg PO/IV daily
- FFP only for severe hemorrhage cases
Esophageal/gastric varices
- 30% of patients with varices will bleed and mortality worsens with only one bleeding incidence
1) goal is to prevent bleed first if possible = endoscopy and BBs/banding if large
2) actual treatment is antibiotics/octerotide/ infusion and band ligation or sclerotherpy (usually use both though) - can also give vitamin K if elevated PT/INR and lactulose if patient is encephalopathic
What are options to use if chronic bleeding occurs and you can’t get to surgery?
Balloon tube tamponade
- usually 1st line and controls acute hemorrhages
Portal decompressive procedures
- transvenous intrahepatic Portosystemic shunt surgery (TIPS)
- emergency portosystemic shunt surgery
Hepatorenal syndrome
Occurs 10% of patients with advanced cirrhosis
- always shows the following 4 things:
1) azotemia (creatinine rises 0.3 points in 48hrs or an increase of 50% or more from baseline
2) macroscopic signs of structural kidney injuries
3) shock
4) failure of kidney function to improve following 2 days of diuretic withdrawal and volume expansion with albumin
Spectrum of Neurocognitive Impairment in cirrhosis (SONIC)
A revised staging system for encephalopathy
1) absent
2) covert
3) drowsiness
4) stupor
5) coma
How to treat hepatic encephalopathy
1) low protein diet
2) give lactulose and rifaximin and zinc supplements
Hepatopulmonary and portopulmonary HTN
Occurs in 5-32% of cirrhosis patients
Have significant SOB with a triad of:
1) liver cirrhosis
2) increased alveolar + arterial gradients while patient is breathing room air
3) AVMs or intrapulmonary vascular dilations
- *there is no good medical treatment**
- after confirmation usually give epoprostenol, bosentan or ambrisentan and sildenafil or tadalafil combination to lower pulmonary HTN
- DONT give BBs or CBBs they worsen it
being female and having autoimmune hepatitis are extreme risk factors
Child-Pugh scoring system
Estimates the severity of liver cirrhosis and the potential mortality rate
Based off the following 5 factors:
1) ascites
- none = 1
- slight = 2
- moderate/severe = 3
2) Encephalopathy
- none = 1
- slight/moderate = 2
- severe = 3
3) bilirubin count
- <2.0 = 1
- 2-3 = 2
- > 3 = 3
4) albumin
- >3.5 = 1
- 2.8-3.5 = 2
- <2.8 = 3
5) prothrombin time (PT)
- 1-3 sec = 1
- 4-6 sec = 2
- > 6 sec = 3
Scores:
1) 5-6 = A (1yr = 100%; 2yr = 85%)
2) 7-9 = B (1yr = 80%; 2yr = 60%)
3) 10-15 = C (1yr = 45%; 35%)
What auto antibodies are present for types 1-3 autoimmune hepatitis/?
Type 1 = ANA/SMA/anti-FLAG/L-PAG
- safest and mild type
- liver cirrhosis chance = 45%
- treatment is usually successful
- **most common
- easy to diagnose
Type 2 = Anti-LKM1/anti-LC1
- worst type
- liver cirrhosis chance = 80%
- treatment is usually not successful and the disease often remits
- easy to diagnose
Type 3= Anti-SLA
- 2nd worst type but usually doesnt fail treatment
- liver cirrhosis chance = 75%
- treatment is usually successful
- hard to diagnose
AUDIT-C score
Determines the likelihood that drinking is negatively affecting the patients health
In men = score > or equal to 4 is positive
In women = score > or equal to 3 is positive
Liver transplantation indications
End stage cirrhosis
- or hep C cirrhosis
Fulminant hepatic necrosis
Hepatocellular carcinoma
Biliary atresia
What are absolute contraindications to liver transplant?
Elevated intracranial pressures (>40mmHg)
Low cerebral perfusion pressure (<60 mmHg)
- common in fulminant liver failure
Severe pulmonary HTN
- Mean pulmonary arterial pressure > 50mmHg
Sepsis is present
Metastatic HCC is present
What are risk factors for graft failure in transplants?
Patients body will reject the transplant
Age > 50 or <13
Hepatic steatosis
Elevated LFTs/bilirubin or both
Prolonged stay in the ICU
Hypotension requiring vasopressors
Hypernatremia
Liver being donated is from older patient
HLA mismatching is high
Autoimmune disorders
possible female -> male donating (low evidence on this though)
How does immunosupression work for liver transplant patients?
1) Anti-IL2 receptor monoclonal antibodies (daclizumab/basiliximab)
- given day of transplant surgery
2) calcineuin inhibitor (cyclosporine or tacrolimus)
- varies time frame but starts after transplant is finished
3) mycophenolate mofetil
4) corticosteroids
- taper off after 3-4 weeks except in autoimmune hepatitis (permanent)
What are the 4 categories of liver rejection?
all show fever except chronic
all show jaundice
1) Hyper acute = presents with VERY high AST/ALT and bilirubin and coagulopathy
2) accelerated = same as #1 but also ascites
3) acute = pain, anorexia, very dark urine and very light stools
4) chronic = presents with ascites and vanishing bile duct syndrome (everything is elevated and DEAK deficiencies are present)
Liver transplant rejection differential diagnosis
1) viral hepatitis
- can be hep B/C, CMV, Epstein Barr
2) calcineurin inhibitor toxicity
3) Cholestasis
Treatment for liver rejection
IV corticosteroids (1st line)
Anti-thymocyte globulin (2nd line)
retransplantation when immunosuprresants do not work
Early complications of liver rejection
all occurs within 2 months usually
Most common = biliary dysfunction
Hepatic artery thrombosis
Hepatic artery mycotic aneurysm
Hepatic artery rupture
Primary nondysfunction
Late complications of liver rejection
Cholestasis or cholangitis caused by intrahepatic or anastomatic bile duct structures
Most late complications end up requiring retransplant
- strictures are pretty common and seen in 25-30% of patients*
- more common in deceased donor grafts
Survival rates are slightly lower in deceased donors and grants are lower than actual tissue across the board
What is the most common virus to recur after transplant?
Hepatitis C
How is acetaminophen metabolized
90% is metabolized in the liver by glucuronidation and sulfation pathways
- produces glucuronide and sulfate moiety respectfully (these are both nontoxic)
8% is oxidized in CYP-P450 system (especially 2E1)
- generates NAPQI which is a TOXIC metabolite unless it is bound to glutathione
- if bound to glutathione = gets degraded into cysteine and mercapturic acid (both non toxic)
What happens to acetaminophen toxicity?
Clearance and metabolism shifts towards CYP450 metabolism
- NAPQI levels increase dramatically
- glutathione stores cant keep up = toxic to liver and causes fulminant liver failure
