Alcoholic Hepatitis, Cirrhosis, DILI & Drug Dosing in Liver Disease

These question-and-answer flashcards review key points on alcoholic hepatitis management, cirrhosis complications and treatments, drug-induced liver injury patterns and antidotes, and principles of drug dosing in liver disease, mirroring the lecture content.

What is the defining cause of alcoholic hepatitis?

Excessive and prolonged consumption of alcohol, causing direct liver toxicity.

Which symptom of alcoholic hepatitis must develop within three months of presentation?

New-onset jaundice, characterized by yellowing of the skin or eyes, indicating recent liver dysfunction.

Name four common symptoms of alcoholic hepatitis besides jaundice.

Anorexia, fever, right upper-quadrant or epigastric pain, and abdominal distension from ascites.

Which two liver enzymes are moderately elevated in alcoholic hepatitis?

AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase), reflecting damage to the liver cells.

What characteristic AST:ALT ratio suggests alcoholic hepatitis?

An AST:ALT ratio greater than 1, frequently exceeding 2.

List three laboratory abnormalities besides AST/ALT commonly seen in alcoholic hepatitis.

Elevated bilirubin, elevated GGT, elevated INR, or neutrophilic leukocytosis.

Write the Maddrey Discriminant Function (DF) formula for bilirubin in mg/dL.

DF = 4.6 × (Patient PT – Control PT) + Total bilirubin.

At what Maddrey DF value is short-term mortality considered high?

DF ≥ 32, signifying severe alcoholic hepatitis and a high risk of short-term mortality.

Which medication class is first-line for severe alcoholic hepatitis (DF ≥32)?

Glucocorticoids, such as prednisolone, to suppress the inflammatory response that drives liver injury.

Why is prednisolone preferred over prednisone in alcoholic hepatitis?

Prednisone is the active form and requires hepatic conversion to prednisolone, which may be impaired.

State the standard prednisolone dose and duration for severe alcoholic hepatitis.

40 mg orally daily for 28 days, followed by a taper if responding.

Give two absolute contraindications to glucocorticoid therapy in alcoholic hepatitis.

Active infection/sepsis or gastrointestinal bleeding.

Which drug is an alternative to steroids when they are contraindicated in alcoholic hepatitis?

Pentoxifylline, which works by inhibiting TNF- α synthesis.

Explain pentoxifylline’s mechanism of action in alcoholic hepatitis.

By inhibiting the synthesis of tumor necrosis factor- α (TNF- α), a pro-inflammatory cytokine.

What is the usual dose of pentoxifylline for severe alcoholic hepatitis?

400 mg orally three times daily for 28 days (adjust once daily if CrCl <30 mL/min).

Name three supportive measures in the overall management of alcoholic hepatitis.

Alcohol withdrawal management, hemodynamic and nutritional support, and referral to an alcohol-use disorder program.

What hepatic structural change defines cirrhosis?

Replacement of normal liver tissue with regenerative nodules surrounded by dense, diffuse fibrosis.

How does cirrhosis lead to portal hypertension?

Distorted architecture increases intrahepatic vascular resistance, impeding portal blood flow.

What is the most common cause of ascites in cirrhosis?

Portal hypertension causes fluid accumulation in the peritoneal cavity.

List four common laboratory abnormalities in cirrhosis.

Hypoalbuminemia, elevated PT/INR, thrombocytopenia, and elevated alkaline phosphatase.

State two classic physical findings of cirrhosis related to hormone imbalance.

Gynecomastia and spider angiomata (spider-like blood vessels on the skin).

What is first-line pharmacotherapy for uncomplicated ascites?

Spironolactone 100 mg + furosemide 40 mg orally daily.

When is albumin infusion recommended after large-volume paracentesis?

When more than 5 liters of ascitic fluid is removed, and administer 5-10 grams of albumin per liter.

Define spontaneous bacterial peritonitis (SBP) using PMN count.

Ascitic fluid polymorphonuclear leukocytes ≥ 250 cells/mm³.

Give the empiric antibiotic of choice for SBP.

Cefotaxime 2 g intravenously every 8 hours for 5 days.

Which three alternative antibiotics may be used for SBP if cefotaxime isn’t available?

Ceftriaxone, ciprofloxacin, or ofloxacin.

What adjunct infusion reduces renal failure risk in SBP and when is it given?

Intravenous albumin with 1.5 g/kg within 6 h of diagnosis and 1 g/kg on day 3.

Name the two main drugs for treating hepatic encephalopathy (HE).

Lactulose and rifaximin.

Describe lactulose’s mechanism for lowering serum ammonia.

It exerts a cathartic effect that shortens gastrointestinal transit time, acidifies the colon, promoting bacterial uptake of ammonia, and reduces glutamine absorption from the gut.

What is the target stool frequency when titrating lactulose for chronic HE?

Two to three soft stools per day.

State the standard rifaximin dose used with lactulose for refractory HE.

550 mg orally twice daily.

Which somatostatin analogue is used during acute variceal bleeding?

Octreotide to reduce splanchnic blood flow.

Why are prophylactic antibiotics given during acute variceal bleeding?

To prevent SBP and other infections to improve survival rates.

List two first-line prophylactic antibiotics during acute variceal bleed.

Ceftriaxone (IV) or ciprofloxacin/trimethoprim-sulfamethoxazole (oral).

What is the target resting heart rate when titrating non-selective beta blockers for primary variceal prophylaxis?

A reduction to 55−60 beats per minute or a significant decrease from baseline.

Give two situations in which non-selective beta blockers should be avoided in cirrhosis.

Systolic BP <90 mm Hg or acute kidney injury.

Explain how non-selective beta blockers lower portal pressure.

They achieve β1 blockade, which decreases cardiac output, and β2 blockade, which causes unopposed α1-mediated splanchnic vasoconstriction, thereby reducing portal inflow.

What is the appropriate management approach if the serum ammonia level is elevated in a cirrhotic patient alone?

No specific treatment is warranted based on an elevated ammonia level alone.

Which two types of benzodiazepine metabolism are less affected in cirrhosis?

Phase II (glucuronidation) agents like lorazepam, oxazepam, and temazepam.

Which benzodiazepine is preferred for acute anxiety in a cirrhotic patient?

Temazepam (or lorazepam/oxazepam) because it undergoes phase II metabolism.

Differentiate phase I and phase II hepatic metabolism effect in cirrhosis.

Phase I is markedly reduced, while phase II is relatively preserved.

State the Child-Pugh score ranges for classes A, B, and C.

A: 5-6, B: 7-9, C: 10-15.

Give the two-year survival percentage for Child-Pugh class C.

Approximately 35 %

Provide the formula to correct total phenytoin level for hypoalbuminemia.

Corrected concentration = Measured level / [(0.275 × albumin) + 0.1].

What corrected phenytoin level is obtained for a measured 16 µg/mL with albumin 2.1 g/dL?

Approximately 30 µg/mL (supratherapeutic).

How does cirrhosis alter drug protein binding?

Decreased albumin and α1-acid glycoprotein increase free (unbound) drug fraction.

What other acronym describes DILI (drug-induced liver injury)?

DILD (Drug-Induced Liver Disease)

List the three patterns of DILI.

Hepatocellular, cholestatic, and mixed injury.

In DILI, what R value suggests hepatocellular injury?

R > 5, indicating predominant ALT elevation.

Which laboratory profile best indicates cholestatic injury: high ALT or high alkaline phosphatase?

High alkaline phosphatase with elevated bilirubin and less prominent ALT elevation.

Name the toxic metabolite responsible for acetaminophen hepatotoxicity.

N-acetyl-p-benzoquinone imine

How does N-acetylcysteine treat acetaminophen overdose?

It replenishes hepatic glutathione and acts as a sulfhydryl substitute to detoxify NAPQI.

State the total IV N-acetylcysteine dose in the 21-hour regimen.

300 mg/kg; 150 mg/kg over 1 hour + 50 mg/kg over 4 hours + 100 mg/kg over 16 hours.

Which antidote is used for valproate-induced hyperammonemia and fatty liver?

Intravenous L-carnitine.

Explain why slow NAT2 acetylators are at greater risk for isoniazid hepatotoxicity.

They accumulate toxic acetylhydrazine metabolites more slowly detoxified to non-toxic forms.

Which imaging or procedure is mandatory to diagnose portal hypertension-related varices?

Esophagogastroduodenoscopy to directly visualize and assess esophageal and gastric varices.

Define the serum-ascites albumin gradient (SAAG) value indicating portal hypertension.

SAAG greater than 1.1 g/dL.

What drug class should be discontinued in severe alcoholic hepatitis because of AKI risk?

Non-selective beta blockers for renal perfusion.

List three common adverse effects of chronic glucocorticoid therapy.

Emotional lability, increased risk of infection, and osteoporosis.

Which diuretic alone is inferior for ascites and generally not recommended as monotherapy?

Furosemide.

What serious renal complication occurs in 30-40 % of SBP cases?

Hepatorenal syndrome / acute kidney injury.

Which two laboratory values in cirrhosis suggest reduced synthetic liver function?

Low albumin and prolonged PT/INR.

What common antibiotic combination (brand name) can cause both hepatocellular and cholestatic DILI?

Amoxicillin-clavulanate.

Name a psychiatric drug notorious for cholestatic DILI that often presents in the first 2–3 weeks.

Chlorpromazine.

Which antiarrhythmic accumulates in tissues and may cause phospholipidosis after long-term use?

Amiodarone.

Describe the relationship between early aminotransferase elevations on statins and true hepatotoxicity risk.

Mild asymptomatic ALT rises are common and usually not clinically significant.

What type of hepatic lesion with blood-filled cavities is associated with androgens and azathioprine?

Peliosis hepatis.

What is the first management step when DILI is suspected?

Discontinue the suspected offending drug.

When is therapeutic drug rechallenge considered in DILI?

Only when the causative role is uncertain and the benefits outweigh the risks.

Which phase of drug metabolism (I or II) is more impaired by hepatic portasystemic shunting?

Phase I (oxidative, CYP-mediated).

How does decreased hepatic blood flow in cirrhosis affect high-extraction-ratio drugs?

It reduces first-pass metabolism, increasing systemic bioavailability.

Give an example of a high-protein-binding drug requiring dose adjustment or monitoring in low albumin.

Phenytoin.