Many drugs can harm the liver. Important associations given below:

Acute hepatocellular injury: Acetaminophen, Isoniazid

Cholestatic injury: Contraceptive steroids, Chlorpromazine

Granulomatous hepatitis: Allopurinol, phenylbutazone,sulfonamides

Chronic hepatitis: methotrexate, nitrofurantoin, methyldopa

Neoplastic lesions: oral contraceptive steroids

Angiosarcoma: Vinyl chloride, thorotrast

Cirrhosis: Amiodarone

Fulminant hepatitis: Halothane

–Autoimmune hepatitis is a chronic disorder characterized by continuing hepatocellular necrosis and inflammation.

-It can progress to cirrhosis and liver failure.

-Though usually a disease of young women (70% of cases occur in females), autoimmune hepatitis can occur in either sex at any age.

-most common in whites and Northern Europeans.

–The cause is unknown, but believed to be autoimmunity.

–Two subtypes of disease have been described based on the autoantibodies present: type 1 AIH—ANA and/or ASMA (anti-actin); type 2 AIH—anti-LKM (anti–liver kidney microsomal).

-Affected younger persons are often positive for HLA-B8 and -DR3; older patients are often positive for HLA-DR4

Symptoms & Signs:

Clinical Manifestations: Fever, Fatigue, anorexia, jaundice, abdominal pain, epistaxis, cirrhosis.

Extrahepatic Manifestations: Rash, erythema nodosum,pleurisy, pericarditis, anemia, arthralgias, keratoconjunctivitis sicca, xerostomia, thyroiditis, hemolytic anemia, nephritis.

Diagnosis: Diagnosis is based on many factors.

Demographics: 70% of cases in females.

History: Exclude other known causes of liver disease

Serology: presence of specific autoantibodies, which include antinuclear antibodies (ANAs), smooth-muscle antibodies (SMAs), antibodies to liver and kidney microsome type 1 (anti-LKM1), and anti-liver cytosol type 1 (anti-LCI), perinuclear antineutrophil cytoplasmic antibodies (aANCAs)

Biochemistry: Elevated aminotransferases and serum IgG, hypergammaglobulinemia

Clinical: response to immunosuppressive treatment

Histology: portal tract inflammation that extends into the parenchyma (interface hepatitis, plasma cells, rosettes,bridging necrosis)

 

Treatment:

Medications: Immunosuppressive therapy with either steroids (prednisone, budesonide) or/and azathioprine

Surgery: Liver transplantation

Immunization: Vaccinate against hepatitis A and B.

Prognosis:

-Approximately 50% of patients with autoimmune hepatitis will die within 5 years without treatment. Death may result from complications of cirrhosis, hepatic failure or hepatic coma.

-The majority of patients (90%) with autoimmune hepatitis achieves complete remission within 3 months

1. Describe the typical patient with autoimmune hepatitis. Young, white female, third to fifth decade
2. What is the gold standard in the diagnosis of autoimmune hepatitis? Liver biopsy.

-The hepatitis C virus (HCV) is a single-stranded RNA virus (hepacivirus)

-HIV leads to more rapid progression of chronic hepatitis C to cirrhosis

-the most common chronic bloodborne infection in the United States

-The incubation period averages 6–7 weeks

Transmission: Primarily transmitted by parenteral route usually through use of injected drugs with needle sharing accounting for more than 40% of the cases;  rarely sexually transmitted

-Transmission via breastfeeding has not been documented.

-HCV pathogenesis (average incubation period 6-12 weeks) is mainly immune mediated, in which the liver damage is caused by cytotoxic CD8 T cells and proinflammatory cytokines.

-No immunizations are currently available for HCV infections.

Symptoms & Signs:

-Most primary infections are asymptomatic or clinically mild

-can present with jaundice, anorexia, malaise, and abdominal pain

Diagnosis

Two types of diagnostic tests are available to detect HCV infection; HCV antibodies (ELISA) and confirming by HCV RNA (RT-PCR)

-Testing for antibodies to HCV (anti-HCV) is recommended for screening of asymptomatic persons based on risk factors or exposure.

-Waxing and waning aminotransferase elevations

 

Treatment

-No effective treatment for acute disease

-Treatment for chronic disease includes interferon, pegylated interferon, ribavirin, or HCV direct-acting antiviral agents.

-There are four current classes of direct-acting antiviral agents (DAAs): nonstructural protein (NS) 3/4A protease inhibitors, NS5B nucleoside polymerase inhibitors, NS5B non-nucleoside polymerase inhibitors, and NS5A inhibitors.

Complications

-Alcohol abuse and smoking can influence hepatitis severity.

-HCV is a pathogenic factor in mixed cryoglobulinemia and membranoproliferative glomerulonephritis.

Prognosis

-In most patients, clinical recovery is complete in 3–6 months

-Vertical transmission is around 5% in mothers who are positive for HCV RNA.

-In contrast to HAV and HBV, most people infected with HCV (85%) develop a chronic infection. Of these, up to 70% will develop chronic liver disease; Cirrhosis occurs in up to 50% of chronically infected patients.

Prevention

-Prevention consists mainly of reduction of risk factors, including screening of blood and blood products, preventing percutaneous injuries, and reducing intravenous drug use.

1. What is the most sensitive indicator to detect HCV infection? HCV RNA by the polymerase chain reaction (PCR)
2. Is breastfeeding contraindicated in women infected with hepatitis C? No

 

IV drug use with needle sharing + Single-stranded RNA virus + Chronic liver disease = Hepatitis C