Cirrhosis & Hepatic Disorders

_______ is the end stage of chronic liver disease, and acute illness does not lead to it because the liver repairs itself.

Cirrhosis

What are the four structural stages of liver disease leading up to cancer?

• Healthy Liver

• Fatty Liver

• Hepatic Fibrosis

• Cirrhosis

_______ cirrhosis presents only with abnormal laboratory findings and features no obvious signs or symptoms.

Compensated

_________ cirrhosis features abnormal laboratory findings combined with dangerous clinical manifestations.

Decompensated

What are the specific toxin accumulation signs and symptoms seen in cirrhosis?

• Altered mental status

• Asterixis (liver "flap")

What is the characteristic physical exam finding for the liver "flap"?

When the patient's wrists and fingers "flap" due to a brief, rapid relaxation of wrist dorsiflexion.

Which hormone dysregulation symptoms occur in cirrhosis due to the liver's role in processing excess estrogen?

• Amenorrhea

• Erectile dysfunction

• Gynecomastia

• Sterility

• Hypogonadism

Excessive ______ in cirrhosis causes clinical signs such as jaundice, pruritus, dark urine, and pale stools.

bilirubin

Why do cirrhosis patients experience easy bruising and GI bleeding (such as hematemesis and melena)?

Low clotting factors and low platelets

What physical signs are driven specifically by portal hypertension resulting from pressure build-up in the portal system?

• Ascites

• Splenomegaly

• Umbilical hernias

• Caput medusae

What clinical exam maneuvers are utilized to assess a patient for ascites?

• Percussing for "shifting dullness"

• Tapping to feel a "fluid wave

What skin and nail manifestations are driven by excess estrogen in a cirrhotic patient?

• Spider angiomata

• Palmar erythema

• Terry nails

________ is an effect of liver cell failure characterized by breath that smells like a freshly opened corpse.

Fetor hepaticus

What specific laboratory abnormalities are typically expected on a CMP, CBC, and Coagulation panel for a patient with cirrhosis?

• Low albumin

• Elevated bilirubin

• Elevated/normal AST/ALT

• Low platelets and anemia

• Elevated PT, PTT, and bleeding time

What non-invasive blood-based scoring systems are used to estimate the degree of liver fibrosis to help rule down advanced disease?

• FIB-4

• NAFLD Fibrosis Score

What diagnostic tool is considered the gold standard for diagnosing cirrhosis?

Liver biopsy

What non-invasive ultrasound-based alternative measures liver stiffness?

Liver elastography (Fibroscan™)

Why is an endoscopy (EGD) indicated as part of the diagnostic and screening workup for a patient with cirrhosis?

To evaluate and screen for esophageal varices.

Name the six major clinical complications associated with cirrhosis.

• Portal hypertension

• Hepatic encephalopathy

• Bleeding esophageal varices

• Hepato-renal syndrome

• Spontaneous bacterial peritonitis

• Hepatocellular carcinoma

________ encephalopathy entails normal consciousness, personality, neurological examination, electrencephalogram.

Grade 0

________ encephalopathy entails restlessness, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cps waves.

Grade 1

________ encephalopathy entails lethargy, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves.

Grade 2

________ encephalopathy entails somnolent (drowsy), stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves.

Grade 3

________ encephalopathy entails unrousable coma, no presonality/behavior, decerebrate (arms and legs straight out), slow 2-3 cps delta activity.

Grade 4

A 54-year-old patient with a history of decompensated cirrhosis is brought to the clinic by family. The patient is lethargic, time-disoriented, displaying an inappropriate affect, and exhibits a noticeable asterixis during exam. EEG shows slow triphasic waves. What grade of hepatic encephalopathy is this patient experiencing?

Grade 2

How is cirrhosis managed?

• Multidisciplinary team (PCP, gastroenterologist, dietician, social worker)

• Palliative care & slow progression to decompensated state

• Liver transplant (Curative) if qualifying

What two prognosis calculators are used in clinical practice to understand mortality risk and plan for liver transplants?

• Child-Pugh Score

• MELD score

What are the key dietary and lifestyle recommendations given to a patient with cirrhosis to prevent bleeding risks and manage fluid overload?

• Avoid EtOH/hepatotoxins

• Avoid NSAIDs/ASA

• Consume a low-sodium/low-carb diet

• Eat frequent high-protein snacks

What are the health maintenance screening guidelines for a patient with cirrhosis to check for Hepatocellular Carcinoma (HCC)?

Screening every 6 months via a liver ultrasound combined with a serum alpha-fetoprotein test

________ works as an osmotic laxative to draw water out and lower ammonia levels to treat encephalopathy.

Lactulose

________ is used to improve portal hypertension.

Carvedilol

_______ (spironolactone and furosemide) are prescribed to manage fluid overload like ascites and edema.

Diuretics

_________ is a procedure that surgically connects a branch of the portal vein (which flows into the liver) directly to a branch of the hepatic vein (which flows out of the liver) to decompress portal pressures.

Trans-jugular Intra-hepatic Porto-systemic Shunt (TIPS)

_________ is defined as inflammation of the liver that lasts less than 6 months.

Acute hepatitis

What are the two main ways that acute hepatitis present? (though may be asymptomatic)

• Elevated transaminases

• Acute liver failure

 Rank the general etiologies of acute hepatitis from most common to least common.

1. Drugs/toxins

2. Infection

3. Autoimmune

4. Genetic

In the United States, ________ are the most common cause of acute hepatitis.

drugs/toxins

Globally, the most common cause of acute hepatitis is ________.

Hepatitis A

List at least four examples of drugs or toxins that can cause acute hepatitis.

• Alcohol (EtOH)

• Acetaminophen (APAP)

• NSAIDs, anticonvulsants

• Herbal supplements

Acute hepatitis symptoms can range from none to acute liver failure, and may include __________ pain.

right upper quadrant (RUQ)

Which two physical exam findings indicate physical enlargement of the abdominal organs during acute hepatitis?

• Hepatomegaly

• Splenomegaly

What clinical sign signifies that acute hepatitis has progressed to acute liver failure?

Encephalopathy

What is the primary laboratory hallmark of hepatitis, and what causes it?

Transaminase elevation; caused by hepatocellular injury

Aside from AST and ALT, what other laboratory values are commonly elevated on a typical liver panel for acute hepatitis?

• GGT

• Bilirubin

• Alkaline Phosphatase (AlkPhos)

What two specific laboratory changes indicate that a patient with hepatitis has entered acute liver failure?

• Elevated PT/INR

• Low albumin

What AST to ALT ratio and associated lab finding are highly characteristic of alcohol-associated hepatitis?

AST to ALT ratio is >2 + elevated GGT

________ is strictly defined as hepatitis that is complicated by coagulopathy and any degree of encephalopathy.

Acute liver failure

In acute infectious hepatitis, the ALT level is typically higher than the AST level.

True

What is the expected clinical duration of a Hepatitis A infection, and how is it managed?

2-6 weeks; managed with supportive care as it is self-limiting

What first-line medication must be given intravenously to ALL patients with acute liver failure?

IV N-acetylcysteine, whether  or not an acetaminophen (APAP) overdose is suspected

A 23-year-old woman presents with a 7-day history of fever, fatigue, nausea, anorexia, and RUQ tenderness. She recently returned from surfing in Peru, where she ate street vendor food. Labs reveal AST 456, ALT 349, AlkPhos 529, GGT 245, and elevated atypical lymphocytes. Her HepA IgM is negative (HepA IgG positive from prior vaccine). A specialized viral panel returns positive for Hepatitis E IgM. What is her prognosis and management?

Good prognosis

• managed with supportive care and avoidance of EtOH/APAP for 6 months

A 22-year-old male presents with worsening RUQ pain/fullness, finger joint stiffness, and mild fatigue. He never drinks alcohol, has no travel history, and has normal lifestyle markers. Labs show AST 82, ALT 114, and an elevated serum ferritin of 364. A right upper quadrant ultrasound shows a liver measuring 19 cm with diffuse fatty replacement. What is the most likely diagnosis and its inheritance pattern?

Hereditary Hemochromatosis; autosomal recessive

What is the gold standard diagnostic test to confirm hereditary hemochromatosis?

HFE gene testing

What is its primary first-line management of hereditary hemochromatosis?

Scheduled therapeutic phlebotomy (often once or twice weekly) and avoiding iron supplements and alcohol

The underlying pathophysiology of hereditary hemochromatosis involves dysregulation of iron absorption caused by a genetic malfunction in the __________ , resulting in low hepcidin production.

HFE protein

________ is defined as liver inflammation, destruction, and regeneration lasting greater than 6 months.

Chronic Liver Disease

List the three most common general etiologies of chronic liver disease.

•  Metabolic syndrome (MASLD)

• Alcohol

• Chronic viral hepatitis

What does the medical acronym MASLD stand for, and what was its former name?

Metabolic-Associated Steatotic Liver Disease; formerly known as NAFLD (Non-Alcoholic Fatty Liver Disease)

______ affects 36% of the U.S. population and is closely tied to metabolic syndrome, particularly insulin resistance and diabetes mellitus.

MASLD

Approximately 20% of patients with MASLD progress to __________, which introduces severe inflammation, drives liver fibrosis, and eventually leads to cirrhosis.

MASH (Metabolic Steato-hepatitis)

What are the clinical components that define Metabolic Syndrome (Syndrome X)?

• Central obesity

• High blood pressure

• High triglycerides

• Low HDL-cholesterol

• Insulin resistance

 What is the typical clinical presentation of a patient with MASLD, and what lab finding must be present?

Generally asymptomatic (possible hepatomegaly); must have elevated AST/ALT (ALT > AST).

What is the preferred first-line imaging modality to screen for a fatty liver, and what are its limitations?

Right Upper Quadrant (RUQ) ultrasound

• cannot detect fibrosis or rule out cirrhosis