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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.

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.
  • 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.

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.
  • 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.