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🌱 來自: Huppert’s Notes
Infectious Etiologies of Liver Disease🚧 施工中
Infectious Etiologies of Liver Disease
Hepatitis A virus (HAV), Hepatitis E virus (HAE)
• HAV: Fecal–oral transmission. Patients may be asymptomatic or present with malaise, fatigue, nausea/vomiting. Diagnosis: HAV IgM. Treatment: Supportive, does not cause chronic hepatitis.
• HEV: Fecal–oral transmission, especially waterborne. Diagnosis: HEV IgM. Treatment: 1) Acute: Supportive care; infection can be much more severe in pregnant women. 2) Chronic: Chronic infection is almost exclusively seen in immunocompromised hosts; treat with ribavirin for 12 weeks in nonpregnant patients.
Hepatitis D virus (HDV)
• Pathophysiology: Parenteral (IVDU, blood), sexual, and vertical transmission. Vertical transmission is the most common. Requires the outer envelope of HbsAg for replication; if coinfection with hepatitis B occurs, can present as acute hepatitis; if superinfection occurs, can exacerbate chronic hepatitis B
• Diagnosis: HDV RNA, HDV IgM, IgG
• Treatment: Supportive care
Hepatitis B virus (HBV)
• Transmission: Parenteral (IVDU, blood), sexual, and vertical. Adults typically do not progress to chronic hepatitis B; children very frequently progress to chronic hepatitis B.
• Detection and interpretation of serologic results: See Figures 4.8, 4.9; Tables 4.12, 4.13
• Treatment:
- Acute HBV: No treatment for acute HBV
- Chronic HBV: Therapy is often lifelong and non-curative. Indications for treatment of chronic HBV:
• Compensated cirrhosis and DNA >2000 IU/mL
• Decompensated cirrhosis or acute liver failure with any detectable DNA
• Immune active: 1) HBeAg positive: ALT ≥2× ULN and HBV>20,000 IU/mL; 2) HBeAg negative: ALT ≥2× ULN and HBV >2000 IU/mL
• Other populations: Patients on chronic immunosuppressive therapy, pregnant women with high viral loads, patients with HCC, patients with HCV coinfection who are being treated for HCV
- Agents:
• Tenofovir (TDF, TAF): Lower rates of resistance; can be used in patients with decompensated cirrhosis.
• Entecavir: Lower rates of resistance; do not use with lamivudine-resistant HBV; can be used in patients with decompensated cirrhosis.
• Lamivudine: High rates of resistance so generally less preferred; can be used in patients with decompensated cirrhosis.
• Interferon (INF-alpha): Can only be used in young patients with compensated liver disease
TABLE 4.12 • Interpretation of Hepatitis B Serologic Test Results
FIGURE 4.8: Acute hepatitis B virus infection with typical recovery serologic course. Acute hepatitis B is diagnosed by detecting hepatitis B surface antigen (HBsAg) and IgM core antibody (IgM anti-HBc), or in the window period (i.e., when neither HBsAg nor its antibody [anti-HBs] can be detected in the serum) by IgM anti-HBc alone. IgM core antibodies are lost within 24–32 weeks of the onset of illness, whereas total antibody to hepatitis B core antigen (total anti-HBc) and anti-HBs persist. The hepatitis B e antigen (HBeAg) is initially positive, and then antibody to the hepatitis E antigen can later be detected.
FIGURE 4.9: Natural course of chronic hepatitis B infection. There are several phases of chronic hepatitis B infection. During the immune tolerance phase, hepatitis B e antigen (HBeAg) is present, there are high hepatitis B virus DNA (HBV DNA) titers, and ALT is normal without evidence of active liver disease. During the immune clearance phase, HBeAg is still present. HBV DNA and ALT levels are typically both high and/or fluctuating. Due to the immune clearance phase, HBeAg is seroconverted, and then only antibody to the hepatitis B e antigen (anti-HBe) is detected during the subsequent phases. Most patients then enter a period of low viral replication, which is characterized by the absence of HBeAg, the presence of anti-HBe, low hepatitis B viral titers, low ALT, and little or no inflammation on liver biopsy. Some patients later have reactivation of their hepatitis B virus, characterized by absence of HBeAg and presence of anti-HBe (high and/or fluctuating; demonstrated as a dotted line on the right side of the figure).
TABLE 4.13 • Hepatitis B Testing Parameters
Hepatits C virus (HCV)
• Transmission: Mainly parenteral (IVDU)
• Screening: CDC and USPSTF recommend universal HCV screening at least once age 18–79 yr
• Symptoms: Most patients are asymptomatic or report non-specific symptoms (e.g., fatigue)
• Conditions associated with HCV infection:
- Cryoglobulinemia: IgM against HepC IgG that causes vasculitis of the skin (palpable purpura, Raynaud’s), kidneys (MPGN), nerves (motor-sensory axonopathy), and joints (arthralgias)
- Porphyria cutanea tarda: Fragile, photosensitive, painless vesicles on the dorsum of hand
• Diagnosis: Check HCV antibody. If positive:
- Check HCV viral load; if viremic, check genotype (1–6, 1a most common in United States [70%])
- Screen for HAV/HBV and vaccinate; provide counseling about reducing alcohol consumption and mechanisms to reduce forward transmission (e.g., avoidance of needle sharing, condom use)
- Fibrosis assessment: Affects decision for HCC screening and treatment choice
• Treatment: Treatment for HCV is curative and recommended for all patients with HCV! Treatment regimen depends on HCV genotype and whether the patient has cirrhosis
- Direct-acting antivirals (DAAs)
• Protease inhibitors (“P” = previr)
• NS5B inhibitors (“B” = buvir)
• NS5A inhibitors (“A” = asvir)
- Regimen: NS5A + NS5B inhibitor
• Velpatasvir/sofosbuvir (Epclusa): One pill daily for 12 weeks, can be used for all genotypes. First-line for treatment-naïve patients with no or compensated cirrhosis.
- Regimen: NS5A + protease inhibitor
• Pibrentasvir/glecaprevir (Mavyret): Three pills daily for 8 weeks. First line for treatment-naïve patients with no or compensated cirrhosis.
• Elbasvir/Grazoprevir (Zepatier): One pill daily for 12 weeks. First line for patients with CKD
- Monitor LFTs during treatment, as rarely patients can develop hepatic decompensation
- Sustained viral response (SVR) = Undetectable viral load 12 weeks after completion of therapy
Other viruses that cause liver injury
• Viruses: EBV, CMV, HSV, VZV. See additional details in Infectious Diseases Chapter 8