Liver disorders Flashcards
Common causes of abnormal LFTS impossible to explain
- drugs -eg stat……
- Gall sto…….
- alc……. excess
- Fatty …… disease
- Viral (e.g. hepatitis) infe………
- Haemach…………..
- Wil…… disease
Transient mild abnormalities which are simply impossible to explain Drugs – eg Statins Gall stones Alcohol excess Fatty Liver Disease Viral (e.g. hepatitis) infections Haemachromotasis Wilson’s disease
Typical patterns of liver dysfunction
Liver dysfunction
- Hepat……. inte……
- Chole……..
- Liver function mass changes ie impaired synthetic capa…..
Biochemical markers
- AST, ALT, GGT, conjugated bilirubin
- ALP, GGT, conjugated bili……..
- Prothrombin time, Albumin, liver enzymes may ………
Typical patterns of liver dysfunction
Liver dysfunction
- Hepatocyte integrity
- Cholestasis
- Liver function mass changes ie impaired synthetic capacity
Biochemical markers
- AST, ALT, GGT, conjugated bilirubin
- ALP, GGT, conjugated bilirubin
- Prothrombin time, Albumin, liver enzymes may be raised or normal/low
Hepa titis - causes
Caused by:
- Infectious agents:
-
-
Non-infectious agents:
Ioni…. radiation, Dru…, Herbal reme….., Alco…., Autoim……. diseases, Metal …toxicity (iron ,copper)
Hepatitis: Liver cell Inflammation
Caused by:
Infectious agents:
Bacterial
Viral
Noninfectious agents:
Ionizing radiation, Drugs, Herbal remedies, Alcohol, Autoimmune diseases, Metal ion toxicity (iron, copper)
Hepatitis -Types
Acute hepatitis: Inflammation develops quickly and lasts for a short period.
- Viral (Type ..,..,..also E..,C..,sometimesC) – Characterised by …… cell injury with swelling and spotty ……..
- Alcohol-related – Characterised by cellular …….., spotty necrosis and ……. bodies with a variably intense ………. infiltrate.
Chronic Hepatitis: Lasts for more than 6 months
Viral (Type ..,..,..), autoimmune, alcohol.
Acute Hepatitis: Inflammation develops quickly and lasts for a short period.
Viral (Type A,B, E,also EBV,CMV,sometimesC) – Characterised by diffuse cell injury with swelling and spotty necrosis.
Alcohol-related – Characterised by cellular swelling, spotty necrosis and Mallory bodies with a variably intense neutrophil infiltrate.
Chronic Hepatitis: Lasts for more than 6 months
Viral (Type B, C, D), autoimmune, alcohol.
Viral Causes
Hepatitis viruses primarily infect the liver.
…&.. - food borne
(Acute infection short incubation)
..,..,.. Blood borne
(Acute and …….. infection, longer incubation)
Viral Causes
Hepatitis viruses primarily infect the liver.
A&E - food borne
(Acute infection short incubation)
B,C,D Blood borne
(Acute and chronic infection, longer incubation)
Hepatitis A
- Also known as ……… hepatitis and …..-……. hepatitis
Transmitted by:
- Close Personal Contact (e.g. household contact, sexual …….
- Contaminated ….. and …….
- Blood exposure (rare) e.g. ………. drug use, rarely by ………
Hepatitis A
- Also known as infectious hepatitis and short - incubation hepatitis
Transmitted by:
- Close Personal Contact (e.g. household contact, sexual contact
- Contaminated Food and Water
- Blood exposure (rare) e.g. injection drug use, rarely by transfusion
Hepatitis A - Clinical Features
….NA virus, single ….type
Acute disease and asy……… infection
W………. distribution
Inf…./Chi…….
Faecal shedding of hepatitis antigen (Ag), but appearance of Ag is ….. and disappears as liver enzymes ….. (virus in stool 2- 3 weeks before and. ….. week after onset of jaundice)
Jaundice: …-80%
Incubation period:
Average ……. days
(range 15-50 days)
Rare complications:
Fulm………….. hepatitis
Chol……. hepatitis
relap….. hepatitis
RNA virus, single serotype
Acute disease and asymptomatic infection
Worldwide distribution
Infants/Children
Faecal shedding of hepatitis antigen (Ag), but appearance of Ag is transient and disappears as liver enzymes peak (virus in stool 2-3 weeks before and 1 week after onset of jaundice).
Jaundice: 70-80%
Incubation period: Average 30 days
(range 15-50 days)
Rare Complications: Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
Hepatitis A
In HepA, elevations in … (2-5 weeks after exposure) precedes the development of jaundice (4-6 weeks after exposure).
Diagnosis: Serologic detection of hepatitis A anti…… using EI.. or sto….analysis.
IgM and IgG appear in stool at different times of infection.
IgM appearance in stool: Signs of … infection 4 - … weeks and declines by week 1….
IgG appears at week 5-]…. and stays high for a long time – Sign of the past infe……..
In HepA, elevations in AST (2-5 weeks after exposure) precedes the development of jaundice (4-6 weeks after exposure).
Diagnosis: Serologic detection of hepatitis A antibody using EIA or stool analysis.
IgM and IgG appear in stool at different times of infection.
IgM appearance in stool: Signs of acute infection 4 - 7 weeks and declines by week 10.
IgG appears at week 5-6 and stays high for a long time – Sign of the past infection.
Concentration of Hepatitis B virus in Various Body fluids
-
-
- -
Low/Not detectable - - - - -
Concentration of Hepatitis B virus in Various Body fluids
High
- blood serum
- serum
- wound exudates
Morderate
- semen
- vaginal fluid
- saliva
Low/Not detectable
- urine
- faeces
- sweat
- tears
- breast milk
Hepatitis B
The virus consists of a 42-cm double-shelved spherical particle with a central core of … surrounded by a protein …..
Incubation 8-…. weeks Average …. days (45-180 days).
~ 2/3rd cases may be asy……. or produce mild …. like symptoms.
1/3rd patients - mal…., irregular f……, tenderness in the right upper abdomen, jau….., dark urine.
~90% patients recover within …. months. Mortality in ~ …%.
10% patients develop …… hepatitis.
The virus consists of a 42-cm double-shelved spherical particle with a central core of DNA surrounded by a protein coat.
Incubation 8-26 weeks Average 60 days (45-180 days).
~ 2/3rd cases may be asymptomatic or produce mild flu like symptoms.
1/3rd patients - malaise, irregular fevers, tenderness in the right upper abdomen, jaundice, dark urine
~90% patients recover within 6 months. Mortality in ~ 1%.
10% patients develop chronic hepatitis
HBV infection
Acute
- Fu………then >
Death/ Recovery
- Re…….
Chronic
- Mild> ……..
Severe > …………..
HBV infection
Acute
- Fulminant then >
Death/ Recovery
- Recovery
Chronic
- Mild> Cirrhosis
Severe > Cancer
Hepatitis D
Also known as ……. hepatitis.
Causes disease in patients who have …… virus infected disease present.
A defective ……virus that has a ba.. pa.. homology with Hep.. virus and uses it for repli…….
Patients with co-infection of HepB and HepD infection show a high rate of progression to chronic hepatitis.
High risk of chronic ….. disease.
Hepatitis D
Also known as delta hepatitis.
Causes disease in patients who have HepB virus infected disease present.
A defective RNA virus that has a base pair homology with HepB virus and uses it for replication.
Patients with co-infection of HepB and HepD infection show a high rate of progression to chronic hepatitis.
High risk of chronic liver disease.
Hepatitis C
- Hepatitis C unstable …virus with multiple types and subtypes
- HepC is different from A and B in that people with HepC …….. of developing ……… do not get complete ……………
Hepatitis C
Hepatitis C unstable RNA virus with multiple types and subtypes.
HepC is different from A and B in that people with HepC inspite of developing antibodies do not get complete protection.
Exposures Known to be Associated With HCV Infection
- Iatrogenic, Infected …… (injecting drug use, tattoos, body piercing)
- Transfusion, transplant from infected …………
- Occupational ………… to ………. - Mostly needle sticks
- Birth to ……….- …….. mother
- sex with i………. ……. - multiple sex partners
Exposures Known to Be Associated With HCV Infection
Iatrogenic, Infected needles (Injecting drug use, tattoos, body piercing).
Transfusion, transplant from infected donor.
Occupational exposure to blood- Mostly needle sticks
Birth to HCV-infected mother
Sex with infected partner
Multiple sex partners
Features of Hepatitis C virus Infection
-
Acute illness (jaundice) - MIld ...%
Case fatality rate ..-..%
Chronic infection ..-..%
Chronic hepatitis ..-..%
Cirrhosis ..-..%
Mortality from CLD..-..%
Incubation period Average 6-7 weeks
Range 2-26 weeks
Acute illness (jaundice) Mild (<20%)
Case fatality rate Low Chronic infection 60%-85% Chronic hepatitis 10%-70% Cirrhosis <5%-20% Mortality from CLD 1%-5%
Chronic Hepatitis C Factors Promoting Progression to severity
Increased …….. intake
Age > …..years at time of infection
HIV co-infection
Other
- …. gender
- Chronic ….. co-infection
Chronic Hepatitis C Factors Promoting Progression to severity
Increased alcohol intake
Age > 40 years at time of infection
HIV co-infection
Other
- male gender
- Chronic HBC co-infection
Hepatitis C
- HepC ab however is not detectable in first ….. ……. of infection but is ……. present in later stages
- Clinically acute hepatitis C is usually mild, however, infection has a …… rate of ……… to chronic hepatitis, cirrh…. and car……..
HepC Ab however is not detectable in first few months of infection but is always present in later stages.
Clinically acute hepatitis C is usually mild, however, infection has a high rate of progression to chronic hepatitis, cirrhosis and carcinoma.
Chronic hepatitis
When transaminases are persistently elevated for more than 6 months, chronic hepatitis is said to exist
caused by virus, d….. and ……..
Increases the risk of:
- Cirr…… and hepa……. car……..
Patients with high antigen levels are highly infectious and those with high antibodies suggest recovery
Symptoms include:
- Hyperbili……
- bouts of ……
- fatig…..
- Ma…..
- An………
- Mild h…….. tenderness
- Persistent elevation of ……enzymes (….,….)
Chronic hepatitis
When transaminases are persistently elevated for more than 6 months, chronic hepatitis is said to exist
caused by virus, drugs and alcohol
Increases the risk of:
- Cirrhosis and hepatocellular carcinoma
Patients with high antigen levels are highly infectious and those with high antibodies suggest recovery
Symptoms include:
- Hyperbilirubinemia
- bouts of jaundice
- fatigue
- Malasia
- Anorexia
- Mild hepatic tenderness
- Persistent elevation of serum enzymes (AST.ALT)
Summary Viral Hepatitis
- Acute hepatitis caused by Hepatits virus A,B,C and E
- Jaundice frequently associated with the disease
- Hepatitis is associated with elevation in …. and …. . In Hep A, transaminases peak between week ..-.. after infection, in HepB, transaminases peak between peak between weeks …-…following infection. AST:ALT ratio <1
Chronic hepatitis exists in Hep .., .., and infection
Primary mode of transmission is ……-……. for A and E, parental and …… for B, C and D
Acute hepatitis caused by Hepatitis virus A, B, C and E.
Summary Viral Hepatitis
Jaundice frequently associated with the disease.
Hepatitis is associated with elevation in AST and ALT. In Hep A, transaminases peak between week 4-5 after infection, in HepB, transaminases peak between weeks 12-15 following infection. AST:ALT ratio <1.
Chronic hepatitis exists in Hep B, C and D infection.
Primary mode of transmission is Faecal-oral for A and E, parenteral and sexual for B,
Viral Hepatitis
Hepatitis A
Source of virus - Fa..... Route of transmission - fec..-.... Chronic infection - .... Prevention - Food and ..... ..... - Vac..... - Imm... .......
Hepatitis B
Source of virus - Blood/bo.. ..... Route of transmission - Chil.... - Nee..... - S...... - Tran..... Chronic infection - ... Prevention - v...... - Imm...... ......
Hepatitis c
Source of virus - Blood Body fl..... Route of transmission - N...... - Tr...... -S.... - Chil...... Chronic infection - .... Prevention - Blood dono.... ...... - Ri... ......... - Ed...........
Viral Hepatitis
Hepatitis A
Source of virus - Faeces Route of transmission - fecal- oral Chronic infection - No Prevention - Food and water safety - Vaccine - Immune globulin
Hepatitis B
Source of virus - Blood/body fluids Route of transmission - Children - Needles - Sex - Transfusion Chronic infection - Yes Prevention - Vaccine - Immune globulin
Hepatitis c
Source of virus - Blood Body fluids Route of transmission - Needles - Transfusion -Sex - Childbirth Chronic infection - Yes Prevention - Blood donor screening - Risk management - Education
Hepatitis D
Source of virus - Bl...... .......... Route of transmission - N...... - S..... - tran( requires H co-infeciton) Chronic infection - ........ Prevention - H......
Hepatitis E
Source of virus - Fa...... Route of transmission - fecal..... Chronic infection - Prevention - Ensure .... ...... ....
Hepatitis D
Source of virus - Blood/body fluids Route of transmission - Needles - Sex - transfusion ( requires HBV co-infeciton) Chronic infection - Yes Prevention - HBV vaccine
Viral Hepatitis
Hepatitis E
Source of virus - Faeces Route of transmission - fecal- oral Chronic infection - No Prevention - Ensure safe drinking water
Hepatitis Treatment
Inter…… (IFN) can be used for treatment
- Antiviral and immune modulating effect, less eff…… alone
Riba….. (RBV)
- Nucleoside analogue with …..-….. properties
- Alone gives transient biochemical response
…. + … combined
- More effective
Lamivudine for HepB
For HepC: Simeprevir; sofosbuvir; a combination of ledip….and sofo…… for 8-.. weeks
Hepatitis Treatment
Interferon (IFN) can be used for treatment
- Antiviral and immune modulating effect, less effective alone
Ribavirin (RBV)
- Nucleoside analogue with anit-viral properties
- Alone gives transient biochemical response
IFN + RBV combined
- More effective
Lamivudine for HepB
For HepC: Simeprevir; sofosbuvir; a combination of ledipasvir and sofobuvir for 8-12 weeks
Alcohol Hepatitis
Centrolobular necrosis of hepato….
Hyaline incl……. (Mallory bodies).
Fatty change - also in obesity,, diabetes
- .. accumulation
Minimal elevations of …. and ….. often occur
AST/ALT ratio is greater than ….
Laboratory values can appear chole…., chole…….
Patients can present with jaundi.., abdo….pain, fe….,
Carbo…… deficient tran…… - A specific serum ma…… for alcohol abuse
Centrolobular necrosis of hepatocytes.
Hyaline inclusions (Mallory bodies).
Fatty change – also in obesity, diabetes
TG accumulation
Minimal elevations of AST and ALT often occur.
AST/ALT ratio is greater than 1.
Laboratory values can appear cholestatic, cholecystitis.
Patients can present with jaundice, abdominal pain, fever.
Carbohydrate deficient transferrin- A specific serum marker for alcohol abuse.
Autoimmune Hepatitis
Vulnerable areas are peri…… region. Marked portal and periportal inflammation. ….. duct lesions may be present
Biochemical test - Elevated tran………, and gamma …….
Serological test - Presence of antibodies (antinuclear, antismooth muscle), anti - s…. ….. …… (SLA)
Accounts for. …..% of all chronic hepatitis
Responds well to st……, treated by cortico……
May progress to cir…..
Vulnerable areas are periportal region. Marked portal and periportal inflammation. Bile duct lesions may be present.
Biochemical test – Elevated transaminases, and gamma globulins.
Serological test – Presence of antibodies (antinuclear, antismooth muscles) , anti-soluble liver antigen (SLA).
Accounts for 20% of all chronic hepatitis.
Responds well to steroids, treated by corticosteroids.
May progress to cirrhosis.
Drug induced Hepatitis
Toxic exposure to certain medications, herbal remedies or food supplements can also lead to …….. of the liver.
Toxicity occurs after prolonged … or ………..
Symptoms include: fev…, r… or it…. red hives on sk…., jo…. pain, sore muscles, jau…., decre….., appe…., nau…., vom…. etc,
Diagnosis: liv….function tests, ble…. time tests for chem….in the body. ultr…., liver , biopsy etc
Treatment - Discontinue the cause, and …. ……… closely during recovery
Drug induced Hepatitis
Toxic exposure to ce5rtain medications, herbal remedies or food supplements can also lead to inflammation of the liver.
Toxicity occurs after prolonged use or overdoes
Symptoms include: fever, rash or itchy red hives on skin, joint pain, sore muscles, jaundice, decreased, appetite, nausea, vomiting etc,
Diagnosis: liver function tests, bleeding time tests for chemicals in the body. ultrasound, liver , biopsy etc
Treatment - Discontinue the cause, and monitor liver closely during recovery
Check history of liver disease risk factors
Alcohol intake, Blood transfusion, IV drug use,
Hepatotoxic medications/herbs, Family history of liver disease
if yes …..
Discontinue alc…./other hepato…….
and retest in 1–….. months
- if abnormal …. Retest 6-.. months
- if normal …. Retest 6-… months
- if AST/ALT raised Hep .., ... serology test Transferrin satu...... (iron) Caerulop....... (copper) Antism..... muscle/Antin..... Ab Liver ult...... α-anti........
- if ALP raised Check for GGt if then both GGT and ALP raised Check Antimitoch........ antibody Conj Biliru......, ultrasound for bile duct d........
if no …..Repeat liver function test to
confirm the abnormality
- Normal …..Retest 6-12 months
Consider liver ……….
Check history of liver disease risk factors
Alcohol intake, Blood transfusion, IV drug use,
Hepatotoxic medications/herbs, Family history of liver disease
if yes …..
Discontinue alcohol/other hepatotoxins
and retest in 1–3 months
- if abnormal …. Retest 6-12 months
- if normal …. Retest 6-12 months
- if AST/ALT raised Hep B, C serology test Transferrin saturation (iron) Caeruloplasmin (copper) Antismooth muscle/Antinuclear Ab Liver ultrasound α-antitrypsin
- if ALP raised Check for GGt if then both GGT and ALP raised Check Antimitochondrial antibody Conj Bilirubin , ultrasound for bile duct dilation
if no …..Repeat liver function test to
confirm the abnormality
- Normal …..Retest 6-12 months
Consider liver biopsy
Tests for Liver Function vs Damage
Liver function
- Production of ……..
e. g. pla….. alb…., u…. etc
Clearance of en………. compounds
e.g biliru….., am…., hor….
Clearance of ……. substances
eg drugs, toxins
Imaging, Bio…….
Tests for Liver Function vs Damage
Liver function
- Production of metabolites
e. g.plasma albumin, urea etc
Clearance of endogenous compounds
e.g bilirubin, ammonia, hormones
Clearance of Exogenous substances
eg drugs, toxins
Imaging, Biopsy
