Alcoholic Liver Disease Flashcards
Leading cause of liver transplantation in US
Alcoholic liver disease (replaced HCV)
Patterns of injury in alcoholic liver disease
Fatty liver (Simple steatosis)- present in almost all with chronic alcohol abuse
Alcoholic hepatitis
Chronic hepatitis with fibrosis or cirrhosis
Progression of liver with ALD
Normal liver Steatosis Steatohepatitis Fibrosis Cirrhosis Hepatocellular carcinoma
When is there an increased risk of developing cirrhosis?
Men >3 drinks per day > 5 yrs
Women > 2 drinks per day> 5 yrs
Risk factors of ALD
Women are more sensitive to alcohol (develop more severe at lower doses with shorter duration)
African American>Hispanic>Caucasian males
Obesity
Genetic factors
Hep C leads to more rapid progression of liver disease
Smoking (risk of hepatocellular cancer)
Recommendation for alcohol for HCV obese pt
No more than 1 drink per day
Risk factors for ALD based on alcohol
Amt ingested (most important) Type maybe (beer or spirits more) Pattern (drinking outside of meal time is worse)
Pathophysiology of fatty liver (hepatic steatosis)
Increased mobilization of free fatty acid from peripheral fat stores
Increased TAG formation
Decreased fatty acid oxidation
Reduced lipoprotein release by liver
Simple uncomplicated fatty liver
Usually asymptomatic and self limited (may be completely reversible with abstinence for 4-6 wks)
What is alcoholic hepatitis?
Inflammation of liver characterized by necrosis and fibrotic scarring (with history of chronic or current heavy alcoholic consumption
Presentation of alcoholic hepatitis
Can be asymptomatic, mild or severe
Severe with marked impairment of liver function:
Low fever, leukocytosis
Hepatic encephalopathy
Spider angiomas
Jaundice, hepatosplenomegaly with liver tenderness, edema, ascites, variceal bleeding!!!
Oliguria
What is hepatic encephalopathy?
When liver can’t get rid of toxins like ammonia (due to hepatocellular dysfunction and portosystemic shunting) and they develop neuro sxs
Labs seen in alcoholic hepatitis
Leukocytosis with left shift Macrocytosis (MCV>100) Thrombocytopena AST/ALT ratio 2:1 (AST is 2-6x ULN) but both <300 ALP mildy elevated Elevated bilirubin (more direct) PT/INR elevated Low albumin Hyponatremia, hypokalemia GTP elevated Low folate
What is seen on histology for alcoholic hepatitis?
Fatty infiltration
Neutrophil infiltration around clusters of necrotic hepatocytes
Clumps of intracellular material (Mallory bodies)
Fibrosis around hepatic venules (precursor to cirrhosis)
How to diagnose ALD
Liver biopsy required when unclear history of alcohol use and elevated liver tests and it is confounded by other risk factors for liver disease and we’re considering tx with steroids
Tx of hepatic encephalopathy
Treat precipitating factors (GI bleeding, infection, sedating meds, lyte abnormalities, constipation and renal failure)
Lactulose for overt HE and secondary prophylaxis (also can use rifaximin)
Signs of hepatic encephalopathy
EEG changes and flapping tremor (asterxisis-put hands out and back and they tremor)
Grades of hepatic encephalopathy
I- changes in behaviors, mild confusion, slurred speech, disordered sleep (sublinical or covert encephalopath)
II- lethargy, moderate confusion (asterixsis)
III-marked confusion (Stupor), incoherent speech, sleeping but can arouse
IV-coma, unresponsive to pain
Stroop test
For HE
Brief cognitive screening tool to evaluate psychomotor speed and cognitive flexibility (can diagnose minimal HE well)
Management of alcoholic hepatitis
Hospitalize if high mortality rate (based on risk assessment calculators)
Discontinue all alcohol and complete abstinence is essential
If fluid overloaded, use diuretics (ascites etc)
Sodium restricted diet
Discontinue nonselective BBs b/c increased risk of AKI
Risk calculators for alcoholic hepatitis
Model of End Stage Liver Disease (MELD)> 20 is severe with poor prognosis Maddery discriminant factor (MDF) >32 is severe AH Lillie score (labs over time) is used to determine if steroids should be continued!!!
Tx for severe alcoholic hepatitis
MDF>32 or MELD>20
Consider the steroid tx and discontinue if no effective on day 7 using Lillie score
Liver transplant in select population
What is cirrhosis?
Widespread destruction and regeneration of liver tissue with marked increase in fibrotic connective tissue
Regenerated liver tissue forms nodules and permanently alters structure
Impaired liver function when increased connective tissue
Necrosis and fibrosis leads to deteriorration
Can have inflammatory cell infiltration
What is compensated cirrhosis?
Portal pressure <10
Median survival about 12 yrs
May have splenomegaly (thrombocytopenia, leukopenia, anemia, AST elevation)
What is decompensated cirrhosis?
Increased portal pressure with decreased liver function
Median survival <2 yrs
Hepatic BF is bypassing vascular scars
Have portal HTN, porto-systemic shunting and impaired liver function
Clinical manifestations of cirrhosis with increased portal HTN
Ascites Esophageal and rectal varices Splenomegaly Dilated abd veins Encephalopathy Jaundice
Extra manifestations of decompensated cirrhosis
Fatigue, anorexia, weakness, palmar erythema, parotid enlargement, Dupuytrens contracture, jaundice, gynecomastia, testicular atrophy, spider nevi, muscle wasting, anemia
Signs of HE
Similar labs to alcoholic hepatitis
Sites of obstruction in portal HTN
Prehepatic (portal vein thrombosis)
Intrahepatic (cirrhosis)
Posthepatic (CHF, constrictive pericarditis)
What is the problem with portal HTN?
Promotes collateral circulation: Esophageal varices and rectal varices that can bleed Splenomegaly Ascites (caput medusa) HE
Labs in cirrhosis
Similar to alcoholic hepatitis
AST elevation (Can be normal in compensated)
Anemia
Thrombocytopenia
Coag abnormalities (not synthesize clotting factors)
Tx of cirrhosis
Prevent complications of portal HTN and cirrhosis: Variceal surveillance (EGD) and banding HCC surveillance (US q6mos and maybe AFP) Non selective BB prophylaxis to prevent variceal bleeding (HR 55-60 and SBP<90) and wouldn't need to keep doing EGDs if so
Tx of ascites
Adhere to less than 2g soidum
Diuretics
Fluid restriction ONLY if sodium <125
If refractory, stop BB, therapeutic paracentesis (with albumin if >5-6L drained)
Transjugular intrahepatic portosystemic shunt (TIPS)
Complications of Transjugular intrahepatic portosystemic shunt (TIPS)
Stenosis or thrombosis
HE (b/c not filtering toxins)
Liver transplant and cirrhosis
Refer for this with decompensated cirrhosis and MELD> or equal to 15
Must do 6 mos abstinence before considering (begin AA etc immediately)
Prognosis of alcoholic fatty liver
Complete resolution may occur is STOP alcohol
Prognosis of alcoholic hepatitis
Prognosis depends on severity
Mild is often reversible but need to d/b EtOH
If recurrent episodes, irreversible progressive liver disease and decompensated cirrhosis
Prognosis of alcoholic cirrhosis
Worse
If continue to drink, 4 yr survival if have major complication is <20%
Complications of cirrhosis
Portal HTN (dilated abd veins, ascites, congestive splenomegaly, esophageal varices and rectal varices)
Spontaneous bacterial peritonitis (infected ascetic fluid)
Hepatic encephalopathy
Hepatorenal syndrome
What is hepatorenal syndrome?
Functional renal failure in setting of decompensated cirrhosis
Types of hepatorenal syndrome
Type 1-rapidly and progressive renal failure with severe multi-organ failure (survival usually <4 wks)
Type 2: usually associated with refractory ascites (survival about 6 mos)
Criteria to diagnose hepatorenal syndrome
Cirrhosis with ascites
Absence of shock
Renal impairment (rise in Cr of .3 mg/dL within 48 hr+ or 50% increase in baseline in 7 days)
No improvement with correction of volume status and albumin x 2 days (withdraw diuretics)
Absence of other causes of AKI (shock, infection, bleeding, sepsis, fluid losses etc)
Presentation of hepatorenal syndrome
Ascites Serum Cr level >1.5 mg/dL Azotemia (increased BUN) Oliguria (urine vol <500 ml/d) Hyponatremia (<130 mEq/L) Hypotension
How to prevent hepatorenal syndrome
Use albumin IV with large vol paracentesis (5L)
Protect GI bleeding with EGDs and BB use
Don’u use NSAIDs or supplements
Use SBP prophylaxis for pts that had previous dx of SBP, had variceal bleed for 3-7 days, pts with ascetic protein <1.5 g/dl
What’s good to remember with alcoholics
Some will have a secondary or co-existing etiology of liver disease so must exclude other diseases with serological testing and maybe liver biopsy
3 kinds of liver masses
Benign lesions that need no further intervention
Benign lesions that need investigation and therapy
Malignant lesions
What benign liver lesions require no intervention?
If IDed on imaging: Cavernous hemangioma <4 cm Focal nodular hyperplasia Simple cyst < 4 cm and asymptomatic Focal fatty change/sparing
What benign liver lesions need management?
Adenoma (malignant potential and risk of bleeding-use of OCPs)
Liver abscess (pyogenic, amebic)
Inflammatory pseudotumor
Atypical/complex cysts and large symptomatic simple cysts
*refer to confirm and do management
Malignant lesions of the liver
Metastases
Lymphoma (Great Masquerader)
Primary liver neoplasm (hepatocellular carcinoma, cholangiocarcinoma, other tumors like cystadenocarcinoma or angiosarcoma)
What are hepatocellular carcinomas?
Neoplasms arising from parenchymal cells
When should you be suspicious for hepatocellular carcinoma?
Cirrhotic pts or pts with non-cirrhotic hep B with liver lesion on imaging
When do you see hepatocellular carcinoma more?
Male
Pts with chronic liver disease (hep C, autoimmune hep)
What pts should have surveillance done for hepatocellular carcinoma?
All suspected cirrhotic pts from any liver disease (platelet <150,000 or US elastography with kPA>20)
Chronic Hep B non cirrhotic (asian females >50, asian males >40, any age with FH and person dx of hep B, Africans and African American black >20)
What is the screening for hepatocellular carcinoma?
US q 6 mos and maybe AFP too
Sxs of hepatocellular carcinoma
Cachexia, weakness, weight loss
Sudden appearance of ascites
Labs in hepatocellular carcinoma
Elevated alk phos
Elevated AFP (not sensitive)
Tri-phasic CT first and if non-diagnostic due tri-phasic MRI (with gadolinium contrast)
Liver bx is not diagnositc (not needed if imaging is typical and AFP is elevated
Why can you usually not resect a hepatocellular carcinoma?
Due to background cirrhosis
Non-cirrhotic HBV is usually resectable tho
Can do with cirrhotic HCC if bilirubin is normal and no portal HTN
When can you do liver transplant with hepatocellular carcinoma?
1 lesion up to 5 cm or 3 lesions up to 3 cm AND no vascular invasion or distant spread
What to do for hepatocellular carcinoma with small tumors in non-operative pts?
Radiofrequency ablation
Another option for large tumors in hepatocellular carcinoma
Transarterial radioembolization or radiation if sufficient hepatic reserve
End stage tx for hepatocellular carcinoma
Symptomatic (if just advance disease then systemic therapy for distant spread)
