L9: Liver Diseases: Viral Infections and their Complications

Learning Objectives

• list the etiologies of hepatitis, describe

  the routes of transmission (in viral hepatitis), pathology and complications.

• describe the etiologies of cirrhosis, complications and their pathogenetic basis.

• tell the epidemiology of HCC, its risk factors, and pathology.

Hepatitis

Etiology

• hepatitis virus

• alcoholism

  • spectrum: steatosis (fatty liver), alcoholic hepatitis, liver fibrosis and cirrhosis

  • steatosis is reversible but cirrhosis is not

• obesity or metabolic

  • MASLD: metabolic-dysfunction associated steototic disease

  • NASH: non-alcoholic steohepatitis

  • fatty liver disease: inflammation with concurrent fat accumulation in liver

• drugs

  • metabolised drugs: toxic to liver

• autoimmune diseases

• metabolic diseases (Wilson’s disease)

Transmission

Hepatitis A virus

• fecal-oral route

  • not well cooked shellfish

  • infected subject

• 15-40 days incubation period

• no carrier state or chronicity

• 99% full recovery

• direct cytopathic effect

Hepatitis E virus

• major cause of acute hepatitis in HK but not globally

• fecal-oral route (not parenteral)

• subclinical infection is common

• no chronic infection

Hepatitis B virus

• parenteral route

  • blood and blood products: drug injection, transfusion, transplant

  • sexual contact: permucosal

  • vertical transmission from mother to child at the time of birth

• acute and chronic hepatitis with carrier state

• 90% recovery for acute hepatitis; might lead to cirrhosis and HCC for chronic hepatitis

• vaccine available but no curative anti-viral drug

• HBV life cycle

  • infection of HBV viron

  • rcDNA integrate with host DNA in nucleus → cccDNA

    • cccDNA remain permenantly in nucleus

    • relative quantity of cccDNA: indicator for HBV treatment

  • trancribed mRNA → HB protein and pgRNA (encapsidation → DNA by reverse transcription)

  • form new viron in ER and released to bloodstream

• HBV DNA and serology

  • immune tolerance

    • minal host reaction

    • high HBV DNA

    • normal AST and ALT

  • immune clearance

    • killing of infected hepatocytes by cytotoxic T cell

    • fluctuating HBV DNA and ALT

    • active hepatitis

  • residual

    • low HBV DNA

    • frequent cirrhosis or HCC

Hepatitis C virus

• acute and chronic hepatitis with carrier state

• serological markers: anti-HCV (not protective) and HCV RNA

• parenteral route via blood or body fluid

• no availabe vaccine but have currative anti-viral drug

Manifestation

Acute hepatitis

• jaundice: yellow skin and eye

• malaise: generalised weakness

• anorexia: loss of appetite

• apoptotic or acidophil bodies

Chronic hepatitis

• apoptotic or acidophil bodies

• submassive or massive necrosis

Cirrhosis

Characteristics

• end-stage liver disease

• only curative treatment: liver transplant

• diffuse process affecting the entire liver

• regenerative nodules surrounded by fibrous connective tissue

Etiology

• hepatitis viruses: HBV, HCV, HDV

• alcohol, drugs, toxins

• MASLD/NASH

• autoimmune hepatitis

• primary biliary cirrhosis

• hereditary disease (Wilson’s disease)

• crytogenic cirrhosis

Complications

• portal hypertension

  • esophageal varices

  • ascites (accumulated fluid in peritoneal cavity)

  • porto-systemic shunting → hepatic encephalopathy

    • CNS syndrome: confusion, coma, flapping tremor

    • due to failure of liver to eliminate nitrogen-metabolites

  • splenomegaly

• hepatocellular carcinoma

Hepatocellular carcinoma

Etiology

• chronic HBV or HCV infection

• chronic alcoholism → cirrhosis

• MASLD

  • + obesity or type 2 diabetes or metabolic disorder → cirrhosis → HCC

• aflatoxin

• metabolic disorders

Epidemiology

• 500k-1million per year

• > 50% cases occur in China

• top 2nd and 3rd most common fatal cancer

• in HK

  • 60-80% casesassociated with cirrhosis

  • > 80% related to HBV

  • male : female = 3.5:1

  • insidious onset

Mansifestation

• hemorrhagic with frequent necrosis

• soft due to high vacularity and minimal supportive stroma

• prone to hemorrhage, rupture and peritoneal bleading