# Clinical Cases: Liver Diseases

## Case 1: Acute Hepatitis B

### Patient Presentation
**Demographics:** 28-year-old male

**Chief Complaint:** Fatigue, nausea, and dark urine for 10 days

**History of Present Illness:** The patient developed progressive fatigue, loss of appetite, and nausea over the past 2 weeks. He noticed his urine became dark "like cola" 10 days ago, followed by yellowing of his eyes. He reports right upper quadrant discomfort and low-grade fever. He has no prior history of liver disease.

**Past Medical History:** None

**Social History:** Reports unprotected sexual contact with new partner 3 months ago; denies IV drug use; no tattoos

### Physical Examination
- **Vital Signs:** Temperature 37.8C, HR 78 bpm, BP 118/72 mmHg
- **General:** Ill-appearing jaundiced male
- **HEENT:** Icteric sclerae, mild pharyngeal erythema
- **Abdomen:** Tender hepatomegaly (liver edge 4 cm below costal margin), no splenomegaly, no ascites
- **Skin:** Jaundice, no spider angiomata

### Workup and Results
- **Liver Function Tests:** AST 1,850 U/L, ALT 2,240 U/L (markedly elevated), Total bilirubin 8.4 mg/dL, Direct bilirubin 6.2 mg/dL, ALP 180 U/L
- **INR:** 1.2 (mildly elevated)
- **Albumin:** 3.6 g/dL
- **Hepatitis Serologies:**
  - HBsAg: Positive
  - Anti-HBc IgM: Positive (indicates acute infection)
  - HBeAg: Positive (high replication)
  - Anti-HBs: Negative
  - HBV DNA: 8.2 x 10^7 IU/mL

![Hepatitis B Serology](case_01_image.jpg)
*Hepatitis B serologic markers over time during acute infection, showing the appearance and disappearance of HBsAg, anti-HBc IgM, HBeAg, and the eventual development of protective anti-HBs in patients who clear the infection.*

**Image Source:** Wikimedia Commons, Public Domain

### Diagnosis
**Acute Hepatitis B Infection**

### Clinical Correlation
Hepatitis B virus is a partially double-stranded DNA virus transmitted through blood and body fluids. The incubation period is 6 weeks to 6 months. Acute infection is diagnosed by presence of HBsAg (surface antigen indicating active infection) and anti-HBc IgM (core antibody indicating acute infection). High HBeAg and HBV DNA levels indicate active viral replication. In immunocompetent adults, 95% clear the virus spontaneously. The marked transaminase elevation reflects immune-mediated hepatocyte destruction. Monitoring INR and mental status is critical to detect progression to acute liver failure, which occurs in <1% of acute HBV but has high mortality.

### Treatment
- Supportive care for most acute HBV (high spontaneous clearance rate)
- Avoid hepatotoxic substances (alcohol, acetaminophen)
- Monitor for signs of acute liver failure: worsening coagulopathy (INR >1.5), hepatic encephalopathy
- Antiviral therapy (entecavir or tenofovir) indicated only if severe/fulminant course
- Sexual contacts and household members should be tested and vaccinated
- Follow-up serology at 6 months to confirm clearance (HBsAg negative, anti-HBs positive)
- If HBsAg persists >6 months: chronic hepatitis B requiring treatment evaluation

---

## Case 2: Non-Alcoholic Steatohepatitis (NASH) with Cirrhosis

### Patient Presentation
**Demographics:** 58-year-old female

**Chief Complaint:** Fatigue, abdominal distension, and leg swelling for 3 months

**History of Present Illness:** The patient has experienced progressive fatigue, abdominal bloating, and bilateral leg swelling over the past 3 months. She has gained 15 pounds, mostly in her abdomen. She has noticed easy bruising. She has no history of alcohol abuse and denies IV drug use.

**Past Medical History:** Type 2 diabetes (12 years), hypertension, hyperlipidemia, obesity (BMI 38), obstructive sleep apnea

**Medications:** Metformin, lisinopril, atorvastatin

**Social History:** Never drinks alcohol, non-smoker

### Physical Examination
- **Vital Signs:** BP 138/82 mmHg, HR 84 bpm
- **General:** Obese female with central adiposity
- **HEENT:** Mild scleral icterus
- **Abdomen:** Distended with shifting dullness (ascites), hepatomegaly, no splenomegaly initially detected due to body habitus
- **Extremities:** 2+ pitting edema bilaterally
- **Skin:** Multiple spider angiomata on chest, palmar erythema

### Workup and Results
- **Liver Function Tests:** AST 68 U/L, ALT 52 U/L (AST:ALT ratio <1), ALP 145 U/L, Total bilirubin 2.8 mg/dL
- **Albumin:** 2.6 g/dL
- **INR:** 1.4
- **Platelet Count:** 98,000 (low, suggesting portal hypertension)
- **HbA1c:** 8.2%
- **Hepatitis B and C Serologies:** Negative
- **Autoimmune Markers:** ANA, ASMA negative; normal ceruloplasmin, ferritin/transferrin saturation
- **FIB-4 Score:** 4.8 (high, suggesting advanced fibrosis)
- **Transient Elastography (FibroScan):** 28 kPa (cirrhosis range)
- **Abdominal Ultrasound:** Nodular liver contour, splenomegaly, moderate ascites

![NASH Liver Biopsy](case_02_image.jpg)
*Liver biopsy in NASH showing macrovesicular steatosis (large fat droplets displacing nuclei), ballooning hepatocyte degeneration, and early bridging fibrosis. These findings distinguish NASH from simple steatosis.*

**Image Source:** Wikimedia Commons, CC BY-SA 3.0

### Diagnosis
**NASH-related Cirrhosis (Decompensated - Ascites)**

### Clinical Correlation
Non-alcoholic fatty liver disease (NAFLD/MASLD) exists on a spectrum from simple steatosis to steatohepatitis (NASH/MASH) to cirrhosis. NASH is distinguished by hepatocyte injury (ballooning degeneration) and inflammation in addition to steatosis. Risk factors align with metabolic syndrome: obesity, type 2 diabetes, dyslipidemia, and hypertension. NAFLD has become the most common liver disease worldwide and a leading indication for liver transplantation. The transition to decompensated cirrhosis (ascites, variceal bleeding, encephalopathy, jaundice) marks a significant prognostic threshold. Insulin resistance drives the pathophysiology through increased hepatic lipogenesis and oxidative stress.

### Treatment
- Ascites management: Sodium restriction (<2g/day) + spironolactone (with furosemide if needed)
- Weight loss target 7-10% (improves histology even in cirrhosis)
- Optimize diabetes control (consider pioglitazone for NASH without decompensation)
- Statin continuation is safe and may be beneficial
- Consider GLP-1 receptor agonists (weight loss + potential hepatic benefit)
- Screen for esophageal varices (upper endoscopy)
- HCC surveillance: Ultrasound every 6 months
- Liver transplant evaluation given decompensation
- Vaccinations: Hepatitis A, Hepatitis B, pneumococcal, influenza

---

## Case 3: Acute Liver Failure from Acetaminophen Overdose

### Patient Presentation
**Demographics:** 19-year-old female

**Chief Complaint:** Brought to ED by parents with confusion and vomiting

**History of Present Illness:** The patient was found by her parents appearing confused with multiple episodes of vomiting. Empty acetaminophen bottles were found in her room. She reportedly has been depressed after a recent breakup. Her roommate states she may have ingested pills "a couple days ago." Initial presentation was 48 hours after ingestion.

**Past Medical History:** Depression, anxiety

**Medications:** Sertraline 100 mg daily

### Physical Examination
- **Vital Signs:** BP 92/58 mmHg, HR 118 bpm, Temperature 36.2C, RR 24/min
- **General:** Somnolent, jaundiced young female
- **HEENT:** Icteric sclerae, poor oral hygiene
- **Cardiovascular:** Tachycardic, regular
- **Abdomen:** Tender right upper quadrant, liver edge not palpable (liver shrinkage)
- **Neurologic:** Confused, slow to respond, asterixis present; GCS 12 (E3V4M5)

### Workup and Results
- **Liver Function Tests:** AST 8,420 U/L, ALT 6,850 U/L (massively elevated), Total bilirubin 4.8 mg/dL
- **INR:** 6.8 (severely elevated)
- **Arterial pH:** 7.22 (acidosis)
- **Lactate:** 8.4 mmol/L
- **Creatinine:** 2.8 mg/dL (acute kidney injury)
- **Ammonia:** 185 mcmol/L (elevated)
- **Acetaminophen Level:** 18 mcg/mL (may be low or undetectable in late presentation despite toxicity)
- **Blood Glucose:** 58 mg/dL (hypoglycemia from impaired gluconeogenesis)

![Acetaminophen Hepatotoxicity](case_03_image.jpg)
*Diagram showing acetaminophen metabolism pathway: at therapeutic doses, glucuronidation and sulfation predominate; in overdose, CYP2E1 generates toxic NAPQI which depletes glutathione and causes hepatocyte necrosis. N-acetylcysteine (NAC) replenishes glutathione.*

**Image Source:** Wikimedia Commons, CC BY-SA 3.0

### Diagnosis
**Acute Liver Failure due to Acetaminophen Overdose**

### Clinical Correlation
Acute liver failure is defined by coagulopathy (INR >/=1.5) and hepatic encephalopathy in a patient without pre-existing liver disease. Acetaminophen is the leading cause (50% in US). Acetaminophen is normally metabolized by glucuronidation and sulfation. In overdose, these pathways saturate, and CYP2E1 generates the toxic metabolite NAPQI. NAPQI is normally detoxified by glutathione, but glutathione depletion allows NAPQI to cause massive hepatocyte necrosis. Late presentation (>24 hours) is concerning because the acetaminophen level may be low despite massive liver injury already underway. King's College Criteria guide transplant listing: pH <7.3 after resuscitation, OR combination of grade 3-4 encephalopathy + INR >6.5 + creatinine >3.4 mg/dL.

### Treatment
- **ICU admission immediately**
- **N-acetylcysteine (NAC):** Essential even in late presentation; replenishes glutathione, improves outcomes
  - IV NAC: 150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours
- Glucose infusion to prevent/treat hypoglycemia
- Monitor for cerebral edema: Head elevation, avoid agitation, hypertonic saline/mannitol if needed
- Fresh frozen plasma ONLY for invasive procedures or active bleeding (not to correct INR - it obscures prognosis)
- Contact liver transplant center immediately
- **King's College Criteria assessment** - this patient meets criteria (pH <7.3, encephalopathy, elevated INR and creatinine)
- Renal replacement therapy if needed
- Psychiatric evaluation when stable