A.30 Chronic Hepatitis. Drug Induced Liver Disorder Flashcards
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HBV Epidemiology
- Over 248 million people worldwide are chronically infected with HBV.
- High prevalence is observed in Asia, Africa, and the American continent.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HBV Etiology
- Virus: Hepatitis B virus (HBV)
- Transmission:
- Sexual contact
- Parenteral: Needlestick injuries, contaminated instruments, shared needles, contaminated blood products
- Perinatal
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HBV Pathophys
- HBV primarily infects liver cells, leading to immune-mediated inflammation and cell injury, characterized by a significant response from CD8+ cytotoxic T cells.
- This immune response impacts both infected hepatocytes (liver cells) and the ongoing regeneration processes in the liver.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HBV Clinical
Infections lasting over 6 months, characterized by the detection of HBsAg and potentially accompanied by signs of liver damage.
* The majority of patients are inactive, non-contagious carriers.
* There is a risk of reactivation of chronic inactive hepatitis, leading to acute hepatitis or exacerbation of liver function.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HBV Complications
- Extrahepatic manifestations occur in 25% of cases, including:
- Polyarteritis nodosa
- Membranous glomerulonephritis
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HBV Serology
HBsAg:
* Antigen found on the surface of HBV, indicating ongoing infection.
Anti-HBs:
* Antibody to HBsAg; usually signifies successful vaccination or recovery from infection.
HBcAg:
* Antigen associated with the core of HBV.
Anti-HBc:
* Antibody to HBcAg; can indicate acute or chronic infection, distinguishing between active infection and resolved infection.
HBeAg:
* Indicates active viral replication and higher infectivity.
Anti-HBe:
* Antibody to HBeAg, suggesting lower transmissibility.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HBV Labs
Liver Function Tests:
* Elevated AST, ALT, and bilirubin levels.
Acute hepatitis: AST/ALT ratio of < 1 in fulminant infection.
Chronic hepatitis: Variable values with an AST/ALT ratio of ≥ 1.
Other Tests:
* γ-GT, GLDH, and/or ALP levels.
* Assess serum levels of albumin and cholesterol.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HBV Pathology
- Features piecemeal necrosis and periportal liver cell necrosis with lymphocytic infiltration, indicating chronic inflammation.
- Presence of fibrous septa.
- Observation of “ground glass” hepatocytes (specific to hepatitis B).
- Definition: Hepatocytes exhibiting swollen transparent cytoplasm due to endoplasmic reticulum hyperplasia.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Chronic HBV TX
Antiviral Therapy:
* Options include Nucleoside/nucleotide analogs, Tenofovir (DOC), Entecavir, and PEG-IFN-α.
Indication: For chronic hepatitis B with evidence of liver inflammation (ALT ≥ 2 times upper limit).
Goals: Reduce HBV DNA levels below detectable limits and achieve seroconversion of HBeAg to anti-HBe.
Supportive Care:
* Focus on managing symptoms and monitoring liver function.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Complications: HDV infection
- About 5% of individuals with chronic HBV infection are carriers of HDV.
Pathogen:
- HDV is an incomplete viral particle that resembles a viroid.
- It utilizes the HBsAg coat of HBV for its replication.
Transmission:
- Primary routes include sexual contact and, less frequently, via blood exposure (in combination with HBV).
Course:
- Coinfection: Typically manifests as acute hepatitis, with a 90% risk of liver complications.
- Superinfection: Can lead to chronic HBV infection, resulting in severe liver cirrhosis.
Long-term Complications of Hepatitis B:
- Liver cirrhosis.
- Hepatocellular carcinoma (HCC).
- Reactivation of previous infections can occur due to immune system compromise.
Treatment:
- Best managed with PEG-IFN-α.
Prevention:
- Vaccination is recommended for all unvaccinated individuals.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HCV Epidemiology
- Prevalence: Up to 2% of the U.S. population is affected by chronic HCV infection.
- Clinical Progression: Approximately 75% to 85% of individuals with HCV infection may progress to develop chronic disease.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HCV Etiology
The risk of chronic infection is multifactorial and depends on the host’s ability to clear the pathogen. There are six genotypes, and reinfection with another HCV genotype is possible.
Transmission:
- Parenteral:
- Needle sharing among IV drug users, needlestick injuries, and exposure through healthcare workers.
- Blood transfusion and dialysis.
- Sexual: Rare, primarily in conjunction with HBV and HIV.
- Perinatal: Vertical transmission from mother to child.
High-Risk Groups for HCV Infection:
- IV drug users
- HBV or HIV-positive individuals
- Prison inmates
- Individuals born between 1945 and 1965
- Recipients of blood transfusions or organ transplants before 1992
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HCV CLinical
Incubation Period:
2 weeks to 6 months
Asymptomatic:
- Present in 80% of cases
- Common symptoms include fatigue, fever, myalgias, arthralgias, rash, and nausea, along with liver involvement that may go unnoticed.
Findings in symptomatic individuals (up to 85% of the time):
- Symptoms may include jaundice, possible hyperbilirubinemia, and tender hepatomegaly.
Extr hepatic features (common):
Hematological:
- Lymphoma (especially B-cell)
- Immune thrombocytopenic purpura (ITP)
- Aplastic anemia
Renal:
- Membranoproliferative glomerulonephritis
- Membranous glomerulonephritis
Rheumatological:
- Polyarteritis nodosa
- Sjögren’s syndrome
- Endocrine:
Diabetes mellitus
Thyroiditis (may be mild or asymptomatic)
Vascular:
- Leukocytoclastic vasculitis
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HCV DX
Detection of Antibodies:
- EIA/ELISA: Standard immunoassays for detecting anti-HCV antibodies in cases of acute and chronic infection.
- PCR: Used for HCV RNA detection if antibodies are absent.
- Positive PCR: Indicates active HCV infection.
- If positive, confirm infection but prior infection is not confirmed.
- Determines HCV genotype and guides patient management and monitoring.
Liver Function Tests:
increase in Transaminases
AST/ALT levels:
<1: Acute hepatitis
> 2: Chronic hepatitis
decrease Total Protein/Albumin (TP/Alb):
- Cholestasis Parameters:
increase γ-GT, ALP, Bilirubin
Inflammation Markers:
Leukocytosis
increase ferritin levels
Liver Biopsy Indicators: If diagnosis is uncertain.
- Useful for evaluating fibrosis in patients with chronic HCV
U.S. Recommendations:
- Assess for cirrhosis and neoplasia, including HCC.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HCV TX
General Recommendations:
- Avoid hepatotoxic medications (e.g., acetaminophen) and alcohol.
Acute Hepatitis C:
- Prevent Progression to Chronic Infection:
- Antiviral therapy: Initiate promptly for HCV infection.
- Treatment is not required if HCV is eliminated.
- Monitor HCV RNA levels every 4–8 weeks for response.
Chronic Hepatitis C:
Treatment Goals: Achieve complete viral eradication.
Treatment Regimens:
- Selected based on viral genotype (most relevant for response), viral load, and liver health.
- Chronic HCV infection generally necessitates a multidrug approach.
Typical regimen includes:
- Ledipasvir + Sofosbuvir (for genotypes 1 and 4–6)
- Sofosbuvir + Velpatasvir (for all 6 genotypes) for 12 weeks.
- Interferon + Ribavirin:
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
HCV Complications
Complications
- Rarely, fulminant hepatitis
- Liver cirrhosis
- Hepatocellular carcinoma
- Secondary hemochromatosis
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Autoimmune Hepatitis Epidemiology
- Prevalence: 0.1 per 100,000 white adults in the U.S.; even lower in other ethnicities
- Bimodal Distribution: Ages 10–20 years and 45–70 years
- Sex Ratio: Female to Male ratio is approximately 4:1
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Autoimmune Hepatitis Etiology
- Idiopathic: The exact cause is unknown.
- Autoimmune hepatitis (AIH) is frequently associated with other autoimmune conditions, such as type 1 diabetes mellitus, Hashimoto’s thyroiditis, and celiac disease.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Autoimmune Hepatitis Clinical Features
AIH typically has a gradual onset, with symptoms ranging from mild to severe, including asymptomatic presentations and acute liver failure.
- Nonspecific Symptoms: Fatigue, abdominal pain, weight loss
- Signs of Acute Liver Failure (in ⅓ of cases): Jaundice, right upper quadrant (RUQ) pain, fever
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Autoimmune Hepatitis DX
- Liver Function Tests: Elevated ALT and AST
- Autoantibodies: Presence of antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA)
- Hypergammaglobulinemia: Elevated IgG levels
Liver Biopsy
A biopsy should be conducted to confirm the presence of AIH antibodies and establish the diagnosis.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Autoimmune Hepatitis TX
Immunosuppressive Medications
- Initial Therapy: Combination of prednisone and azathioprine
- Maintenance Therapy: Azathioprine or prednisolone
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Autoimmune Hepatitis Progonsis
- 10-Year Survival Rate with Treatment: Approximately 90%
- Lifelong Therapy: Generally necessary
- Increased Risk: Development of hepatocellular carcinoma (HCC)
- Untreated Condition: Higher risk of liver cirrhosis
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Drug Induced Liver Injury define
A type of hepatocellular and/or cholestatic injury resulting from drug exposure.
A.30 Chronic Hepatitis. Drug Induced Liver Disorder
Drug Induced Liver Injury symptoms
Often asymptomatic but may present with fatigue, anorexia, nausea, vomiting, and abdominal pain, along with abnormal liver function tests.
