# Clinical Cases: Liver Disease

## Case 1: Acute Decompensated Cirrhosis with Ascites

### Patient Presentation
A 58-year-old man with alcohol-related cirrhosis presents with 2 weeks of progressive abdominal distension, ankle swelling, and dyspnea when lying flat. He reports a 15-pound weight gain. He stopped drinking alcohol 6 months ago after being diagnosed with cirrhosis. His medications include spironolactone 100 mg and furosemide 40 mg daily, but he admits to poor compliance and eating salty foods.

### Vital Signs
- Blood Pressure: 105/62 mmHg
- Heart Rate: 88 bpm
- Respiratory Rate: 18/min
- Oxygen Saturation: 95% on room air
- Temperature: 37.1°C

### Physical Examination
- General: Chronically ill-appearing, jaundiced
- HEENT: Icteric sclera
- Cardiovascular: Regular rhythm, no murmurs
- Abdomen: Distended, fluid wave positive, shifting dullness, caput medusae, no tenderness
- Extremities: 3+ pitting edema to knees, spider angiomata on chest
- Neurologic: Alert, no asterixis

### Laboratory Results
- **Sodium**: 128 mEq/L
- **Creatinine**: 1.4 mg/dL (baseline 1.0)
- **Albumin**: 2.6 g/dL
- **Total bilirubin**: 4.8 mg/dL
- **INR**: 1.6
- **Platelets**: 78,000/μL
- **Diagnostic paracentesis**: SAAG 1.8 g/dL, total protein 1.2 g/dL, WBC 180/μL (25% PMNs)

### Clinical Image
![Ascites Physical Exam](image_01.png)
*Figure 1: Clinical photograph demonstrating tense ascites with umbilical eversion and caput medusae, signs of portal hypertension in decompensated cirrhosis.*

**Image Source**: Educational illustration for teaching purposes.

### Questions

1. **What does the SAAG (Serum-Ascites Albumin Gradient) indicate in this patient?**
   - A) SAAG <1.1 indicates portal hypertension
   - B) SAAG ≥1.1 indicates portal hypertension
   - C) SAAG indicates infection
   - D) SAAG is not useful in cirrhosis

2. **Calculate this patient's MELD-Na score and what does it indicate?**
   - A) 10 - low mortality
   - B) 18 - moderate mortality, consider transplant evaluation
   - C) 25 - high mortality, urgent transplant evaluation
   - D) Cannot calculate

3. **Does this patient have spontaneous bacterial peritonitis (SBP)?**
   - A) Yes, any WBC in ascites indicates SBP
   - B) No, PMN count <250/μL rules out SBP
   - C) Yes, based on symptoms alone
   - D) Need culture results to determine

4. **What is the appropriate management of this patient's ascites?**

5. **What is the indication for SBP prophylaxis and what regimen is used?**

### Answers

1. **B) SAAG ≥1.1 indicates portal hypertension** - SAAG = serum albumin - ascites albumin. SAAG ≥1.1 g/dL indicates portal hypertension (97% accuracy). Causes: cirrhosis, heart failure, portal vein thrombosis, Budd-Chiari. SAAG <1.1 suggests non-portal hypertensive causes: malignancy, TB, nephrotic syndrome.

2. **Approximate MELD-Na calculation**:
   - MELD = 3.78 × ln(bilirubin) + 11.2 × ln(INR) + 9.57 × ln(creatinine) + 6.43
   - With sodium adjustment for Na <137
   - **Estimated MELD-Na: ~18-20** - indicates significant liver disease, should be evaluated for liver transplant, 3-month mortality approximately 6%

3. **B) No, PMN count <250/μL rules out SBP** - SBP diagnosis requires ascitic fluid PMN count ≥250/μL. This patient has 180 × 0.25 = 45 PMNs/μL, below threshold. However, if clinical suspicion high, consider empiric treatment pending culture.

4. **Management of cirrhotic ascites**:
   - **Sodium restriction**: 2 g/day (88 mEq/day)
   - **Diuretics**: Spironolactone 100 mg + furosemide 40 mg (maintain 100:40 ratio); increase as needed to max spironolactone 400 mg + furosemide 160 mg
   - **Fluid restriction**: Only if sodium <120-125 mEq/L
   - **Therapeutic paracentesis**: If tense ascites; give albumin 6-8 g/L removed if >5L removed
   - **Alcohol abstinence**: Essential
   - **TIPS**: Consider if refractory ascites
   - **Transplant evaluation**: Required given decompensation

5. **SBP prophylaxis indications and regimen**:
   - **Indications**:
     - Prior SBP episode (secondary prophylaxis)
     - GI bleeding in cirrhosis
     - Ascitic fluid protein <1.5 g/dL with renal dysfunction or liver failure (MELD ≥15, Na ≤130, Cr ≥1.2, BUN ≥25, bilirubin ≥3)
   - **Regimen**:
     - Norfloxacin 400 mg daily OR
     - Ciprofloxacin 500 mg daily OR
     - TMP-SMX DS daily
   - This patient has low ascitic protein (1.2 g/dL) and liver dysfunction - qualifies for primary prophylaxis

---

## Case 2: Hepatic Encephalopathy

### Patient Presentation
A 62-year-old woman with cirrhosis secondary to nonalcoholic steatohepatitis (NASH) is brought in by her family for confusion and erratic behavior over the past 3 days. They report she has been sleeping during the day, awake at night, and yesterday did not recognize her grandchildren. She missed her last GI appointment and ran out of lactulose 1 week ago.

### Vital Signs
- Blood Pressure: 112/68 mmHg
- Heart Rate: 78 bpm
- Respiratory Rate: 16/min
- Oxygen Saturation: 97% on room air
- Temperature: 36.9°C

### Physical Examination
- General: Somnolent but arousable, disheveled
- HEENT: Icteric, fetor hepaticus
- Cardiovascular: Normal
- Abdomen: Moderate ascites, splenomegaly
- Neurologic: Disoriented to time and place, asterixis present, slow responses, no focal deficits
- Skin: Spider angiomata, palmar erythema

### Laboratory Results
- **Ammonia**: 142 μmol/L (elevated, normal <35)
- **Sodium**: 132 mEq/L
- **Creatinine**: 1.3 mg/dL
- **Blood glucose**: 98 mg/dL
- **Urinalysis**: Negative for infection
- **CBC**: WBC 5,200/μL, normal differential

### Clinical Image
![Asterixis](image_02.png)
*Figure 2: Demonstration of asterixis (flapping tremor) - intermittent lapses of sustained posture when wrists are dorsiflexed, characteristic of hepatic encephalopathy.*

**Image Source**: Educational illustration for teaching purposes.

### Questions

1. **What is the West Haven criteria grade of this patient's hepatic encephalopathy?**
   - A) Grade I - mild
   - B) Grade II - moderate
   - C) Grade III - severe (somnolent but arousable)
   - D) Grade IV - coma

2. **What are common precipitants of hepatic encephalopathy?**
   - A) Hyperglycemia only
   - B) GI bleeding, infection, constipation, medications (sedatives, opioids), electrolyte abnormalities, dehydration, dietary protein excess, medication non-adherence
   - C) High carbohydrate diet
   - D) Exercise

3. **What is the first-line treatment for hepatic encephalopathy?**
   - A) Antibiotics alone
   - B) Lactulose (titrate to 2-3 soft bowel movements daily)
   - C) Protein restriction
   - D) Benzodiazepines

4. **What is the role of rifaximin in hepatic encephalopathy?**

5. **Should dietary protein be restricted in hepatic encephalopathy?**

### Answers

1. **C) Grade III - severe (somnolent but arousable)** - West Haven criteria:
   - **Grade I**: Mild confusion, short attention span, sleep-wake reversal
   - **Grade II**: Lethargy, moderate confusion, disorientation, asterixis
   - **Grade III**: Somnolent but arousable, marked confusion, incoherent speech
   - **Grade IV**: Coma, unresponsive
   - This patient is somnolent but arousable with disorientation = Grade III

2. **B) GI bleeding, infection, constipation, medications (sedatives, opioids), electrolyte abnormalities, dehydration, dietary protein excess, medication non-adherence** - Always search for precipitants:
   - GI bleeding (increased nitrogen load)
   - Infection/SBP
   - Constipation
   - Medications (benzodiazepines, opioids)
   - Hypokalemia, hyponatremia
   - Dehydration/AKI
   - Dietary indiscretion
   - Non-adherence to lactulose (this patient)

3. **B) Lactulose (titrate to 2-3 soft bowel movements daily)** - Lactulose mechanism:
   - Non-absorbable disaccharide
   - Acidifies colonic contents (traps ammonia as NH4+)
   - Cathartic effect (removes nitrogen)
   - Dose: 25-30 mL (15-30 g) every 1-2 hours until bowel movement, then titrate
   - Maintenance: 25-30 mL 2-4 times daily for 2-3 soft stools/day

4. **Role of rifaximin**:
   - Non-absorbable antibiotic targeting gut flora
   - Added to lactulose for prevention of recurrent HE (secondary prophylaxis)
   - Dose: 550 mg twice daily
   - RFHE trial showed 50% reduction in recurrent HE
   - Expensive; generally reserved for recurrence despite lactulose
   - Not typically used for acute HE treatment alone

5. **Protein restriction is NOT recommended**:
   - Historical practice of protein restriction is harmful
   - Cirrhotic patients are often malnourished and catabolic
   - Protein restriction worsens muscle wasting and outcomes
   - **Recommended intake**: 1.2-1.5 g/kg/day protein
   - Vegetable and dairy protein may be better tolerated than animal protein
   - Branched-chain amino acids (BCAA) supplements may help if intolerant

---

## Case 3: Hepatorenal Syndrome

### Patient Presentation
A 55-year-old man with alcohol-related cirrhosis (Child-Pugh C) presents with oliguria for 2 days. He was recently hospitalized for SBP and completed antibiotic treatment 1 week ago. He has refractory ascites requiring weekly paracenteses. He denies diarrhea, vomiting, or NSAID use. He has been compliant with his medications.

### Vital Signs
- Blood Pressure: 92/58 mmHg
- Heart Rate: 96 bpm
- Respiratory Rate: 18/min
- Oxygen Saturation: 96% on room air

### Physical Examination
- General: Cachectic, jaundiced
- Cardiovascular: Hypotensive, no JVD
- Abdomen: Tense ascites
- Extremities: Minimal edema (third-spacing)
- Skin: Multiple spider angiomata

### Laboratory Results
- **Creatinine**: 3.2 mg/dL (was 1.2 two weeks ago)
- **Sodium**: 124 mEq/L
- **BUN**: 58 mg/dL
- **Urinalysis**: Bland (no casts, no protein, SG 1.020)
- **Urine sodium**: 6 mEq/L
- **Urine output**: 250 mL in 24 hours

### Clinical Image
![HRS Pathophysiology](image_03.png)
*Figure 3: Diagram illustrating the pathophysiology of hepatorenal syndrome: splanchnic vasodilation leads to decreased effective arterial blood volume, activating vasoconstrictors that cause renal vasoconstriction.*

**Image Source**: Educational illustration for teaching purposes.

### Questions

1. **What defines hepatorenal syndrome-acute kidney injury (HRS-AKI)?**
   - A) Any AKI in a cirrhotic patient
   - B) AKI in cirrhosis without improvement after diuretic withdrawal and volume expansion, no shock, no nephrotoxin exposure, no parenchymal kidney disease
   - C) Creatinine >2 mg/dL
   - D) Oliguria alone

2. **What should be the initial diagnostic and therapeutic approach to AKI in cirrhosis?**
   - A) Immediate dialysis
   - B) Hold diuretics, volume expand with albumin (1 g/kg x 2 days), rule out other causes
   - C) Start vasoconstrictors immediately
   - D) Liver transplant evaluation only

3. **What is the treatment for HRS-AKI?**
   - A) Diuretics
   - B) Albumin plus vasoconstrictors (terlipressin, norepinephrine, or midodrine + octreotide)
   - C) NSAIDs
   - D) Fluid restriction only

4. **What is the prognosis of HRS-AKI and what is the definitive treatment?**

5. **How is HRS differentiated from other causes of AKI in cirrhosis?**

### Answers

1. **B) AKI in cirrhosis without improvement after diuretic withdrawal and volume expansion, no shock, no nephrotoxin exposure, no parenchymal kidney disease** - HRS-AKI criteria (revised 2015):
   - Cirrhosis with ascites
   - AKI (creatinine increase ≥0.3 mg/dL or ≥50%)
   - No improvement after diuretic withdrawal and albumin challenge (1 g/kg x 2 days)
   - Absence of shock, nephrotoxins (NSAIDs, aminoglycosides, contrast)
   - No evidence of parenchymal kidney disease (proteinuria <500 mg/day, normal urine sediment, no obstruction)

2. **B) Hold diuretics, volume expand with albumin (1 g/kg x 2 days), rule out other causes** - Initial approach:
   - Stop diuretics and nephrotoxins
   - Albumin 1 g/kg (max 100 g) for 2 consecutive days
   - Assess response at 48 hours
   - If no improvement, likely HRS - start vasoconstrictor therapy
   - Check urinalysis to exclude parenchymal disease
   - Rule out obstruction (renal ultrasound)

3. **B) Albumin plus vasoconstrictors (terlipressin, norepinephrine, or midodrine + octreotide)** - Treatment regimens:
   - **First-line**: Terlipressin + albumin (not available in US until recently)
   - **Alternative**: Norepinephrine + albumin (ICU setting)
   - **Alternative**: Midodrine (7.5-15 mg TID) + octreotide (100-200 mcg TID) + albumin (non-ICU)
   - Albumin: 20-40 g/day
   - Continue until creatinine <1.5 mg/dL or max 14 days

4. **Prognosis and definitive treatment**:
   - HRS-AKI has very poor prognosis: median survival weeks to months without intervention
   - Response to medical therapy: 40-50% with terlipressin, lower with other regimens
   - **Definitive treatment**: Liver transplantation
   - HRS patients receive MELD exception points for transplant prioritization
   - TIPS may be considered as bridge to transplant in select cases
   - RRT may be needed as bridge to transplant but does not treat underlying HRS

5. **Differentiating HRS from other AKI causes in cirrhosis**:
   - **Prerenal (hypovolemia)**: Responds to volume expansion
   - **ATN**: Muddy brown casts, FENa >2%, granular casts (HRS has bland sediment, FENa <1%)
   - **Drug-induced**: Recent nephrotoxin exposure
   - **Post-renal**: Obstruction on imaging
   - **Parenchymal disease**: Proteinuria, hematuria, abnormal sediment
   - HRS = diagnosis of exclusion after ruling out other causes and no response to albumin

---

## Learning Points

1. **SAAG ≥1.1 g/dL** indicates portal hypertension; diagnostic paracentesis is essential for new-onset or worsening ascites.

2. **SBP** is diagnosed by ascitic fluid PMN ≥250/μL; treatment is ceftriaxone plus albumin; prophylaxis indicated for high-risk patients.

3. **Hepatic encephalopathy** is treated with lactulose (titrate to 2-3 stools/day); rifaximin added for recurrence; protein restriction is NOT recommended.

4. **HRS-AKI** is diagnosed after excluding other AKI causes and no response to albumin challenge; treatment includes vasoconstrictors plus albumin.

5. **Liver transplant evaluation** is essential for patients with decompensated cirrhosis (ascites, HE, variceal bleeding, HRS).