Chronic Hepatitis: Epidemiology, Clinical Features, and Management
Introduction
- Hepatitis: Inflammation of the liver, commonly associated with viral infections but also caused by alcohol, hepatotoxins (including medications), autoimmune disorders, and fat accumulation.
- Chronic Hepatitis: Liver inflammation lasting longer than 6 months, typically indicated by persistent elevations in transaminases (AST and ALT).
- Surgical Considerations: Chronic hepatitis can complicate preoperative, intraoperative, and postoperative management due to potential hepatic decompensation, bleeding, and infections.
Chronic Hepatitis C
Epidemiology
- Hepatitis C Virus (HCV): RNA virus from the Flaviviridae family.
- Affects approximately 1.6% of the American population (~3-4 million people).
- Transmission:
- Intravenous drug use: Most common risk factor.
- Blood transfusions: Risk now ~1 in 2 million due to improved screening.
- Needle-stick exposures: Tattoos, occupational hazards.
- Sexual transmission: Low risk, higher in non-monogamous individuals.
- Vertical transmission: Occurs in 4-6% of births from HCV-infected mothers; risk increases with HIV co-infection.
Presentation
- Often asymptomatic.
- Nonspecific symptoms may include:
- Fatigue
- Myalgias
- Arthralgias
- Right upper quadrant discomfort
- Transaminases may be elevated but can be normal in up to 30% of patients.
Diagnosis
- Screening Test: Enzyme-linked immunosorbent assay (ELISA) for HCV antibodies.
- Sensitivity and specificity: 98-100% in high-risk populations.
- Confirmation: Reverse transcriptase polymerase chain reaction (PCR) to detect HCV RNA.
- Confirms active viremia.
- Genotyping:
- Six genotypes; Genotype 1 is most common in the U.S. (70% of cases).
- Genotype influences treatment response and duration.
Natural History
- Disease progression varies; often measured in decades.
- Approximately 20% develop cirrhosis after 20 years.
- Factors accelerating progression:
- Excessive alcohol use
- Older age at infection
- Co-infection with HIV or Hepatitis B virus
Treatment
- Previous Standard: Pegylated interferon (PEG IFN) and ribavirin.
- Poorly tolerated; ~45-50% response rate; treatment lasted 24-48 weeks.
- Current Therapies:
- Direct-acting antivirals (DAAs) with high efficacy and fewer side effects.
- Common Regimens:
- Sofosbuvir/ledipasvir (Genotypes 1 and 4)
- Elbasvir/grazoprevir (Genotypes 1 and 4)
- Sofosbuvir/velpatasvir (All genotypes)
- Glecaprevir/pibrentasvir (All genotypes)
- Treatment Duration: Typically 8-12 weeks.
- Response Rates: ~95% sustained virological response (SVR).
- Monitoring:
- Check viral load during treatment and 3 months post-therapy.
- An undetectable viral load at 3 months indicates a cure.
Surgery in Patients with Hepatitis C
- Non-cirrhotic patients: No special precautions needed for hepatopancreatobiliary surgery.
- Antiviral Therapy:
- Do not discontinue without consulting a hepatologist.
- Stopping therapy may necessitate restarting the full course.
- Cirrhotic patients: Require careful assessment due to increased risk of decompensation.
Hepatitis B
Epidemiology
- Hepatitis B Virus (HBV): DNA virus.
- Global Impact:
- Over 2 billion people infected at some point.
- Over 350 million chronically infected.
- Endemic Regions:
- Asia and sub-Saharan Africa: >8% HBsAg positivity.
- United States:
- Approximately 73,000 new cases annually.
- Around 1.25 million chronically infected.
Transmission
- Blood and Body Fluids:
- Sexual contact and needle-stick injuries are common transmission routes.
- Vertical Transmission:
- Rare in the U.S. due to prophylactic administration of hepatitis B immunoglobulin and hepatitis B vaccine at birth.
Presentation
- Acute HBV:
- Symptoms range from subclinical to acute liver failure.
- Severity increases with age.
- Chronic HBV:
- Often asymptomatic.
- May have nonspecific symptoms like fatigue and joint pains.
Diagnosis
- HBsAg (Hepatitis B surface antigen):
- Presence indicates acute or chronic infection.
- If negative, the patient does not have HBV.
- Additional Markers:
- HBeAg, HBeAb, and HBV DNA levels to assess viral replication.
- Genotypes:
- Eight genotypes (A-H); A and C are common in the U.S.
Natural History
- Acute HBV:
- 90% resolve spontaneously in adults.
- 10% develop chronic infection.
- Chronic HBV Phases:
- Immune Tolerant Phase:
- High viral load, normal transaminases.
- Common in perinatally infected individuals.
- Inactive Carrier State:
- Low or absent viral replication, normal transaminases.
- Active Chronic Infection:
- Elevated transaminases, active viral replication, histologic damage.
- Immune Tolerant Phase:
Treatment
- Indications:
- Elevated transaminases and significant histologic damage.
- All cirrhotic patients with chronic HBV.
- First-Line Medications:
- Nucleoside/Nucleotide Analogues:
- Entecavir
- Tenofovir
- Preferred due to potency and low resistance rates.
- Nucleoside/Nucleotide Analogues:
- Goals of Therapy:
- Suppress HBV DNA replication.
- Achieve HBeAg seroconversion.
Surgery in Patients with Chronic Hepatitis B
- Non-cirrhotic patients: Surgery can proceed without special precautions.
- Antiviral Therapy:
- Do not abruptly discontinue; risk of viral rebound and hepatic failure.
- Prophylactic Antivirals:
- Recommended if initiating immunosuppressive therapy or chemotherapy.
- Cirrhotic patients: Require careful evaluation due to increased perioperative risks.
Nonalcoholic Steatohepatitis (NASH)
Epidemiology
- Nonalcoholic Fatty Liver Disease (NAFLD):
- Prevalence: 3-23% in North America.
- Strongly linked with obesity and type 2 diabetes mellitus.
- NASH:
- Occurs in ~20% of obese individuals.
- Increasing due to the global obesity epidemic.
Presentation
- Often asymptomatic.
- Possible symptoms:
- Elevated transaminases during routine checks.
- Right upper quadrant pain or fullness.
- Associated with features of the metabolic syndrome.
Diagnosis
- Definitive Diagnosis: Liver biopsy showing fat and inflammation.
- Imaging Studies:
- Ultrasound or CT scan detects fatty infiltration when >30% of the liver is affected.
- Exclusion of Other Causes:
- Rule out alcohol use, viral hepatitis, autoimmune hepatitis, and other liver diseases.
Natural History
- Steatosis: Fat accumulation with minimal inflammation.
- NASH: Fat accumulation with inflammation and necrosis.
- Progression:
- NASH can progress to fibrosis and cirrhosis in 15-20% of cases.
- Approximately 30% may progress over 5 years.
Treatment
- First-Line Therapy: Weight loss through diet and exercise.
- Aim for a 10-15% reduction in body weight over one year.
- Bariatric surgery can be effective and improve liver histology.
- Medical Therapies:
- Thiazolidinediones (e.g., pioglitazone):
- Improve transaminases and reduce liver fat.
- Potential for weight gain; best for patients with diabetes.
- Vitamin E:
- May reduce liver inflammation.
- Long-term benefits are unclear.
- Thiazolidinediones (e.g., pioglitazone):
Surgery in Patients with NASH
- Non-cirrhotic patients: No special precautions required.
- Hepatic Resections:
- Fatty liver increases risk of postoperative liver decompensation after large resections.
- Preoperative Assessment:
- Consider liver biopsy to evaluate fibrosis and fat content.
Autoimmune Hepatitis
Epidemiology
- Incidence: Approximately 1 per 200,000 in the U.S.
- Gender: More common in women but can affect all ages and genders.
- Often associated with other autoimmune diseases (e.g., thyroid disorders, rheumatoid arthritis).
Presentation
- Variable:
- Asymptomatic with elevated transaminases.
- Symptoms of chronic liver disease or acute liver failure.
- Possible symptoms:
- Fatigue
- Malaise
- Fever
- Arthralgias and myalgias
- Skin rash
Diagnosis
- No single definitive test.
- Rule out other causes: Viral hepatitis, NASH, drug-induced liver injury.
- Autoimmune Serologies:
- Antinuclear antibodies (ANA)
- Anti–smooth muscle antibodies (ASMA)
- Anti–liver/kidney microsomal antibodies (Anti-LKM)
- Liver Biopsy:
- Interface hepatitis (piecemeal necrosis).
- Portal plasma cell infiltrate.
Natural History
- Untreated:
- Progressive disease with high mortality (40%).
- Another 40% may develop cirrhosis.
- Treated:
- High rates of remission with appropriate therapy.
- Cirrhosis still develops in some patients over time.
Treatment
- First-Line Therapy:
- Corticosteroids (e.g., prednisone 30-60 mg daily).
- High initial dose, tapered over weeks to months.
- Azathioprine (50 mg daily).
- Often started alongside steroids to maintain remission and reduce steroid dose.
- Corticosteroids (e.g., prednisone 30-60 mg daily).
- Monitoring:
- Improvement in labs and symptoms within 2 weeks.
- Histologic remission may take >12 months.
- Long-Term Management:
- Maintenance with azathioprine, possibly lifelong.
- Regular monitoring; liver biopsy may be needed before stopping therapy.
- Alternative Therapies:
- Mycophenolate mofetil if azathioprine is not tolerated.
Surgery in Patients with Autoimmune Hepatitis
- Well-Controlled Disease:
- No special precautions needed.
- Continue immunosuppressive medications perioperatively.
- Perioperative Management:
- Consider stress-dose steroids if on or recently tapered off corticosteroids.
- Restart azathioprine promptly postoperatively.
- Advanced Disease:
- Surgery in patients with acute liver failure or cirrhosis carries high risk.
- Reserve surgery for emergent, life-threatening situations.
Summary: Approach to Surgery in Patients with Liver Disease
- Prevalence: Increasing due to conditions like NAFLD.
- Risk Assessment:
- Severity of liver dysfunction correlates with perioperative risk.
- Use Child-Turcotte-Pugh (CTP) score and Model for End-Stage Liver Disease (MELD) score.
- MELD score is preferred for predicting 30- and 90-day mortality.
- High-Risk Patients:
- MELD score >10-15 indicates significantly increased perioperative mortality.
- Surgical Planning:
- Elective vs. Emergent: Consider urgency and necessity.
- Multidisciplinary Approach:
- Involve a specialty liver care center when possible.
- Optimize the patient's condition preoperatively.
- Informed Consent:
- Discuss increased risks with the patient and family.
- General Recommendations:
- Non-cirrhotic patients: Surgery can usually proceed without special precautions.
- Cirrhotic patients: Require thorough evaluation and careful perioperative management.
- Perioperative Care:
- Aim to prevent hepatic decompensation, manage coagulopathy, and reduce infection risk.
Note: Always consult a hepatologist for patient-specific management and before making any changes to antiviral or immunosuppressive therapy in the perioperative period.