Hepatic Disease

What characteristics does fulminant (acute) liver failure have?

• (+) encephalopathy

• (+) coagulopathy (INR > 1.5)

When do the characteristics of fulminant (acute) liver failure (encephalopathy and coauglopathy) start to show?

within 8 weeks of onset of acute liver disease

When do the characteristics of subfulminant (acute) liver failure (encephalopathy and coauglopathy) start to show?

between 8 weeks and 6 months after onset of acute liver injury

What is acute-on-chronic liver failure?

acute deterioration in liver function (“decompensation”) and other organ failure (“multi-organ failure”) in a person with pre-existing chronic liver disease

What is the #1 cause/RF of acute liver failure?

acetaminophen; approx. half of these are from suicide attempts

What is the #2 cause/RF of acute liver failure?

idiosyncratic drug reactions (IDR)

What is the main type of idiosyncratic drug reaction that leads to acute liver failure?

reaction to abx

What is Reye syndrome?

rare case of hepatic encephalopathy associated with ASA use during acute viral infections (especially influenza or VZV) or w/ underlying metabolic disorders

What are the 3 biggest diagnostic methods for acute liver failure

1. PT/INR > 1.5

2. Serum NH3 level

3. ABG

What does elevated serum NH3 support in acute liver failure?

hepatic encephalopathy diagnosis

How will the CMP appear in a patient with acute liver failure?

INCREASED AST, ALT, DeRitis ratio (AST/ALT)

What is the initial step in acute liver failure management?

immediate hospitalization

What management is given when treating acute liver failure due to acetaminophen overuse?

N-acetylcysteine (NAC) administration

When is N-acetylcysteine (NAC) administration used?

Both to treat underlying acetaminophen use leading to acute liver failure and just to treat liver failure of any cause

When should N-acetylcysteine (NAC) administration be given?

ASAP

What is used to determine the use of liver transplantation?

MELD score

What is the #1 cause of mortality in acute liver failure?

cerebral edema and sepsis/SIRS

What are the 2 cirrhosis categories?

1. compensated (pt has cirrhosis, but really hasn’t had sxs yet)

2. decompensated

What are the inflammatory causes of cirrhosis?

• chronic hep C

• chronic hep B

What are the toxic causes of cirrhosis?

alcohol

What is a metabolic-associated cause of cirrhosis?

MALFD/MASH

What are possible complications of cirrhosis?

• portal HTN

• coagulopathy

• neurological dysfunction, specifically encephalopathy (HE)

• hepatocellular cancer (HCC)

What are the general signs of cirrhosis?

fetor hepaticus (breath odor - musty, sweet, sulfurous)

What are the skin signs of cirrhosis?

jaundice, spider telangiectasia, palmar erythema

What are the chest signs of cirrhosis?

pleural effusion

What are the breast/axillae signs of cirrhosis?

gynecomastia

What are the abdominal signs of cirrhosis?

ascites, caput medusa, hepatomegaly, splenomegaly

What are the PV signs of cirrhosis?

peripheral edema

What are the neuro/psych signs of cirrhosis?

AMS, asterixis

What is found on the CBC w/differential ± peripehral smear in cirrhosis patients?

thrombocytopenia- most common cytopenia associated with cirrhosis

What is found on the CMP in cirrhosis patients?

• AST, ALT, alk phos will be variable (transaminases can be lower in late-stage disease)

• DeRitis ratio (AST/ALT) > 1 (1.4-2)

• bilirubin - progressive increase

• albumin decrease

  • hyponatremia common

What is found on other labs in cirrhosis patients?

• PT/INR - prolonged

• serum NH3 level likely elevated

What imaging is done for cirrhosis?

• US, specifically elastography (FibroScan)

• magnetic resonance elastography (MRE)

What is the definitive dx of cirrhosis?

liver biopsy

What is the METAVIR scoring system based off of?

liver biopsy-based system

What is the METAVIR scoring system grade based off of?

inflammatory activity

What is the METAVIR scoring system stage based off of?

degree of scarring/fibrosis

What should be avoided in cirrhosis management?

avoid hepatotoxic agents

What should be done for cirrhosis management in order to prtoect the liver?

vaccines - HAV, HBV (if not the etiology)

Which cirrhosis treatment is used to manage volume shifting/third-spacing?

loop diuretics (furosemide) + aldosterone antagonist (sprionolactone or eplerenone)

Which cirrhosis treatment is used to manage portal HTN and variceal bleeding?

• non-selective beta-blockers

• for acute bleeding: vasopressin analogues (terlipressin) and somatostatin analogues (octreotide)

• EGD tx - endoscopic variceal ligation

Which cirrhosis treatment is used to manage encephalopathy?

lactulose, rifaximin

What is the 5-year survival rate of liver transplantations?

>80%

What is checked for the child-pugh score and classification?

bilirubin, albumin, PT/INR, ascites, encephalopathy grade

What Child-Pugh class and score can be listed for transplant?

class B - 7-9

What score is required for transplant listing in MELD scoring?

17+

What are the types of viral hepatitis?

A, B, C, D, E

What type of virus is HAV?

RNA virus

What type of virus is HBV?

DNA virus

What type of virus is HCV?

RNA virus

What type of virus is HDV?

defective RNA virus

When is the only time HDV can occur?

only in the presence of HBsAg

What type of virus is HEV?

RNA virus

How is HAV transmitted?

fecal-oral

How is HBV transmitted?

via infected body fluids

How is HCV transmitted, and what are 60% trasmitted through?

blood (blood-borned), 60% trasnmitted through injection drug use

How is HDV transmitted?

infected body fluids, mostly blood

What is the most common cause of acute viral hepatitis worldwide?

HEV, so ask about travel

What are the ways HEV can be transmitted?

• fecal-oral

• zoonotic (swine, cow, etc)

• blood, perinatal trasnmission rare but possible

What is the clinical presentation of viral hepatitis?

onset - abrupt or insidious; may be asymptomatic

Which viral hepatitis form has no chronic carrier state?

HAV

What can viral hepatitis lead to?

cirrhosis, hepatocellular carcinoma (HCC)

What form of PV (vasculitis) complication is seen in HBV?

polyarteritis nodosa (PAN)

What are the neurocomplications seen in viral hepatitis?

• guillian-barre syndrome in hep B

• transverse myeltitis, peripheral neuropathy in others

What is a skin complication of viral hepatitis, and which type causes it the most?

serum sickness-like reaction (SSLR), usually caused by HBV

What are the common findings of the CMP in viral hepatitis diagnosis?

INCREASED AST, ALT, deritiis ratio (AST/ALT) <1

What will IgM be in acute hepatitis A?

positive

What will IgM be in someone with a previous HAV infection OR prior vaccination?

negative

What is the initial screening test for Hep C?

anti-HCV antibody

What is the confirmatory test required for diagnosis in Hep C?

HCV RNA

What screening confirms hep D?

HDV RNA

In Hep E, if an anti-HEV Ab is positive, what do we confirm with?

anti-HEV IgM OR HEV RNA OR rising IgG titers (5x in 2 weeks)

What confirms active Hep E infection (acute or chronic)

HEV RNA

What is HEV RNA used for?

used to diagnose chronic disease; Abs simply show exposure (either recent or remote)

What is the general management of viral hepatitis?

patient education and supportive care

What is the mainstay of therapy in Hep C, and the cure rate?

antivirals, cures 95%

True or False: No routine screening recommendations currently exist for Hep A?

true

How is HBV prevented?

vaccination

What does the triple panel test for HBV screening that all adults get at least once contain?

1. HBsAg

2. anti-HBs

3. total anti-HBc

What are all pregnant women screened for during each pregnancy in HBV screening?

HBsAg

Is there a vaccine for HCV?

NO

What is done if a patient is screened and has positive HCV Ab?

anti-HCV w/ reflex to NAT from HCV RNA

What is the prognosis of acute viral hepatitis in many cases?

self-limited

What is alcohol-associated steatosis?

steatosis without fibrosis

What is alcohol-associated steatohepatitis?

evidence of inflammation and hepatocellular injury

What is alcohol-associated cirrhosis?

cirrhotic change on imaging, evidence of portal HTN

What is considered excessive ETOH intake?

> 30 kg/day

What is the most common precursor to cirrhosis in the US?

excessive ETOH intake

What are the pathophysiolgies associated with alcohol-associated liver disease?

• alcohol dehydrogenase (ADH)

• acetaldehyde

• increased lipogenesis

• increased fatty acid mobilization from adipose tissue and intestine

• oxidized FFAs build up, can be directly toxic to hepatocytes and provoke an immune response

What does oxidized FFAs build up, being directly toxic to hepatocytes and provoking an immune response, lead to in alcohol-associated liver disease pathophysiology?

leads to steatosis, inflammation (cell death/fibrosis/cirrhosis), impaired function

How do symptoms usually present in alcohol-associated liver disease?

do not present as severe until severe disease is present (as in decompensated disease or alcohol-associated hepatitis)

What are the findings of alcohol-associated hepatitis?

• rapid onset jaundice, fever, malaise, hepatomegaly

• elevated bilirubin, AST/ALT >1.5

What is wernicke-korsakoff syndrome (WKS)?

neuropsychiatric disorder due to severe deficiency of Wthiamine (vitamin B1) commonly associated with chronic alcohol abuse?

What is the acute phase of WKS?

wernicke encephalopathy

What is the triad seen in Wernicke encephalopathy?

1. confusion/delirium

2. oculomotor dysfunction (nystagmus)

3. ataxia

What does the acute phase of WKS require?

emergency treatment of IV thiamine (BEFORE any glucose)

What is the chronic phase of WKS known as?

korsakoff syndrome

What deRitits ratio is highly suggestive of ALD?

ratio >2.1

What is GGT?

marker for heavy or chronic alcohol use

What type of workup is done for ALD?

noninvasive fibrosis/cirrhosis w/u with FIB-4 and elastopgraphy