Liver Disorders Flashcards
Exam II
Hepatitis pathophysiology
Inflammation triggers a fibrogenesis process, where hepatic stellate cells become activated and cause scarring, which leads to fibrosis
Fibrosis progresses through standardized stages and can lead to cirrhosis (advanced, irreversible fibrosis)
Regenerative nodules can produce dysplastic cells, causing hepatocellular carcinoma (HCC)
Two types of liver injury
- Hepatocellular injury
- Cholestatic injury (biliary tree)
Transaminases
AST and ALT
ALT is more specific for liver damage
IgM
Indicates an acute infection
M for “miserable”
IgG
Indicates a past exposure
G for “gone”
PCR testing
Looks for viral load
Always choose quantitative testing, not qualitative
Antibody testing
looking for immunity
Antigen testing
looking for virus
Hepatitis A presentation
Acute infectious hepatitis
Hepatitis A transmission
Fecal-oral
HAV bile excretion with shedding in stool occurring 2 weeks prior to and 1 week after onset of sx/clinical illness
Hepatitis A pathophysiology
Viruses replicate and proliferate within the liver cells
- Hepatocyte viral uptake via a receptor on plasma cell membrane
- Viral replication within hepatocytes
- RNA is uncoated and ribosomes bind to form polysomes
- Viral proteins are synthesized
- Genome is copied by polymerase
- Assembled virus particles are shed into the biliary tree and excreted into feces
Hepatocellular injury leading to diffuse liver necrosis and portal triad membrane changes
Prominent centrilobular damage, increased portal cellularity, and regional lymph node enlargement
Impaired synthetic liver function
Decreased albumin
Prolonged PT
Cholestasis
Injury to bile ducts causing leaking of bile into the blood stream
Causes jaundice and hyperbilirubinemia in more severe case
Hepatitis A vaccinations
Mandatory pediatric vaccinations and given for at risk populations (military, international travelers, people moving to endemic areas, illicit drug users, male homosexuals, institutionalized individuals)
Serum (HAV) immunoglobulin
Given to those exposed
Pre-exposure prophylaxis: ex. leaving too soon for travel for standard vaccine
( <2 week trip, >2 yo)
=Post-exposure prophylaxis:
(Up to 2 weeks post-exposure)
Hepatitis A incubation period
Incubation period of 28 days (15-50 range)
Hepatitis A symptoms
70% of infections in children <6 yo are asymptomatic
Most cases are symptomatic in adults and older children, with individuals normally only having flu-like symptoms and seeking care following jaundice presentation
§ Fever
§ Fatigue
§ Loss of appetite
§ N/V
§ Abdominal px
§ Dark urine
§ Diarrhea
§ Clay-colored stools
§ Joint pain
§ Jaundice
HAV treatment
supportive measures
HAV Ab IgG
Chronic marker (past infection)
HAV Ab IgM
acute marker (current infection)
HAV Ab total
Assessing immune status, no concern for acute infection
(+) means previous exposure or vaccination (immunity)
Hepatitis B presentation and natural hx
Acute and chronic infectious hepatitis
Adult infections: 95% of individuals clear the infection and develop lifelong immunity
Neonate: 90% chronicity
Children <6 yo: 25-50% chronicity
Acute HBV is a “common” form of acute hepatic failure
Can progress to Cirrhosis and HCC
HBV pathophysiology
Following exposure to HBV, a cell-mediated immune response is triggered
HBV replicates in the cell nucleus (cccDNA), and virus is constantly being shed into the blood
- Attachment–virus binds to receptor
- Cytotoxic T cells and NKC are sent to the
virus and release inflammatory cytokines - Hepatocytes are attacked by the cytokines and infiltrated by HBV
- Penetration–viral membrane merges with the host cell membrane, then sends DNA and other proteins into the cell cytoplasm
- Uncoating–HBV uses RNA to replicate
- Assembly–virions are formed and returned to the nucleus where they are recycled and make additional virions
- Release–DNA is synthesized via reverse transcription and new virus is sent into the cytoplasm, then towards the cell membrane where it is released
Ground glass appearance under microscope
HBV transmission
Blood-to-blood transmission
Mucosal contact with infected blood or body fluid (aka semen, saliva [contains some blood])
Perinatal infection is also common (maternal-fetal/vertical transmission)
Virus can survive for 7 days outside the body and still cause infection
HBV risk factors
○ Hemodialysis (HD)
○ Blood transfusions (ask about hx of transfusions outside of the US)
○ Perinatal
○ Sexual
○ Household
○ Occupational
○ IV drug use
○ Nosocomial
○ UNK
HBV vaccination
routine childhood vaccinations since 1982
( 95% effective at preventing infection and the development of chronic disease)
Vaccinate those at exposure risk and families of those with chronic disease
ex. Hemodialysis patients are at risk and will get “double dosed” with vaccine–different than the standard childhood vaccination
HBV factors increasing cirrhosis risk
Host: >40 yo, Male sex, Immunocompromised
Viral: High serum HBV DNA (>2,000 IU/mL), Elevated ALT, Prolonged time to HBeAg serocoversion, Development of HBeAg neg CHB, Genotype C
Environmental: Concurrent viral infections (HIV, HCV, HDV), Heavy alcohol use, Metabolic syndrome
HBV factors increasing HCC risk
Host: cirrhosis risks PLUS familial hx and born in sub-saharan africa
Viral: Cirrhosis risks PLUS presence of cirrhosis
Environmental: Cirrhosis risks PLUS aflatoxin and smoking
Acute HBV symptoms
□ General illness
□ Loss of appetite
□ N/V
□ Body aches
□ Mild fever
□ Dark urine
□ Jaundice
Acute HBV relevant history
Exposure to infected fluids/blood in the past few months
Chronic HBV s/sx
Can be asymptomatic
Prodromal period (1-4 months):
Serum sickness
RUQ abdominal px 2/2 hepatomegaly
Fatigue
Joint px
Hepatosplenomegaly
Spider telangiectasias
Jaundice
Ascites
Peripheral edema
Chronic HBV relevant history
Risk factor &/or serological testing + for 6 months
Tattoos, military vaccinations, etc.
Acute HBV tx
Watch and wait
Oral meds are controversial as they are mostly used for chronic and there is not much data
(Treating viral replication; can develop resistance)
Transplantation
Chronic HBV tx
When to treat:
Viremia (+ viral load >2,000 or 20,000 IU/mL)
FHx of HCC
>40 yo
ALT elevation >2x upper limit of normal (ULN)
Liver biopsy/non-invasive fibrosis measure showing advanced fibrosis or cirrhosis (F3 or F4)
Who not to treat:
Contradictions to interferon therapy:
SI, severe depression
Previous significant side effects (IFN retinopathy, etc.)
Autoimmune disease
Cytopenias
Severe cardiac disease
Uncontrolled seizures
Decompensated cirrhosis
Immune tolerant HBV (need close f/u q6 mo for reassessment)
Carriers (have low level of virus)
Pediatric and CKD oral med restrictions
(though some can be renally dose)
Transplantation considerations
Suppress the virus if going to be transplanted
The new liver will be infected
Post transplantation immunosuppression
HBsAg
First detectable viral antigen (protein on the surface of the HBV)
Marker of active (infectious) acute or chronic disease
Window period–may be (-)
HBcAb Total
Core protein (from the nucleus)
Indicates ongoing or past infection
**NOT a marker for active disease
Remains (+) for life
IgM anti-HBc
Acute infection marker
Helps r/o acute vs. chronic disease
Indicator of recent infection (<6 mo)
HBsAb
Marker of immunity—the body has mounted an antibody to HBV
(+) following vaccination
Window period–may be negative
HBeAg
Advanced testing during tx
A secreted product of the nucleocapsid gene of HBV that is chronic hepatitis B
Marker of active viral replication
Infectivity state?
Non-mutant strains?
HBeAb
Advanced testing during tx
marker of seroconversion
HBV DNA PCR quantitative
viral load testing
Hepatitis C presentation
Primarily a chronic disease (one of the most common forms of chronic liver disease)
85% of cases result in chronic infection
15% of cases occur as acute hepatitis, with individuals mounting an immune response and clearing the virus (rare)
Acute disease is not often detected
HCV transmission
Blood to blood
HCV risk factors
HD
Transfusions
Perinatal
Nasal cocaine
Sexual?? Non-monogamy
Unregulated tattoos (non-single use only dye)
Nosocomial
IVDU
HCV disease progression
2-22 week incubation period
