Exam 2: Hepatitis Flashcards
1
Q
Define Hepatitis
A
- Non- specific inflammation of the hepatocytes, liver cells
- etiology can be single or multifactorial
2
Q
the pathophysiology of hepatitis
A
- inflammation triggers fibrogenesis
-hepatic stellate cells are activated, which cause fibrosis - fibrosis can lead to cirrhosis
3
Q
what does inflammation in the liver cells activate?
A
it activates stellate cells and these cells make fibrosis
4
Q
can cirrhotic be reversed?
A
no, once cirrhotic, it cannot be reversed. there is no cure.
-early stages of cirrhosis, may be reversed with anti-fibrotic agents
4
Q
what can cause hepatitis? (5)
A
-heavy alcohol use
-toxins
-some medications
-certain medical conditions
-virus
5
Q
the common hepatitis viruses in the US
A
-hepatitis A virus
-hepatitis B virus
-hepatitis C virus
5
Q
what is the portal triads composed of?
A
composed of three major tubes
- hepatic artery
-portal vein
-bile duct
5
Q
function of the hepatic artery
A
carry oxygenated blood to the hepatocytes
6
Q
function of the portal vein
A
carry blood with nutrients from the small intestines
7
Q
function of the bile duct
A
carries bile products away from the hepatocytes, to the larger ducts and gallbladder
8
Q
Serologic Markers (5)
A
- IgM
o means “Miserable NOW= acute”
if you are worried for an acute infection, you order this! - IgG
o Means “good to go, Gone= chronic”
Exposed at some point in your life - Either by vaccine or actual infection
- Antibody (Ab) Total
o Just checks immunity
When it comes back + = exposed, or vaccinated.
You have immunity towards the virus! - ALT
o More specific for Liver damage
Important lab to follow and monitor! - Antigen (Ag)
o Looking for something infecting, acute!
Surface (sAg) - Outside of the virus
Envelope (eAg) - Around the virus
Core (cAg) - Inside the virus
9
Q
what is Nonalcoholic Steatohepatitis (NASH)
A
- Significant form of chronic liver disease in adults and children
- Presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis
o Fat in liver, with inflammation surrounding it. Liver cells blow up like a balloon, then can progress to fibrosis
o Only diagnosed by biopsy - Seen as early as 8 years of age, most common liver abnormality in children from 2 to 19 yrs
10
Q
the pathogenesis of NASH
A
o NASH is hepatocellular injury, inflammation, and fibrosis
The most severe forms of NASH progress to cirrhosis, end stage liver disease, and increased risk for hepatocellular carcinoma
o Insulin resistance
o Change in lipogenesis
o Mitochondrial dysfunction
o Cytokine and adipokine association –liver damage and alterations in repair in the fatty liver
o 2 “hit” model or theory
steatosis can be reversible process
“Hit” 1 is excessive hepatocyte triglyceride accumulation resulting from insulin resistance
“Hit” 2 involves an inflammatory injury to the liver possibly by oxidative stress, associated with lipid peroxidation and cytokines
11
Q
What is Hepatitis A? And what injuries can you get from it?
A
o Only an ACUTE illness!!!
o A highly contagious, short-term liver infection, caused by the virus Hep A.
o You can get two type of injuries; hepatocellular injury or Cholestasis
12
Q
what is hepatocellular injury?
A
- “Basically, injury to the actual liver cells”
- Diffuse liver necrosis
- Prominent Centrilobular damage
- Increased portal cellularity
- Regional lymph node enlargement
13
Q
what is cholestasis?
A
- “causing injury to bile ducts, therefore bile leaks out, gets absorbed in the blood, causing jaundice”
- Jaundice, this is a more severe case of Hep. A
- Hyperbilirubinemia
Impaired Synthetic Function - Prolonged PT
- Decreased albumin
14
Q
pathophysiology of hepatitis A
A
Viral replication on the liver cells
After entry into cell (virus), RNA is uncoated and ribosomes bind to form polysomes
* -> viral proteins are then synthesized
* -> genome is copied by polymerase
* -> assembled virus particles are shed into biliary tree and excreted into the feces
15
Q
incubation period for hepatitis A
A
28 days
-symptoms last about 4-6 weeks
16
Q
transmission of hepatitis A
A
o Fecal-oral
Hep A virus bile excretion with shedding in stool occurring 2 weeks prior to and 1 week after onset of symptoms/illness
17
Q
pertinent patient hx (hep A)
A
recent travel outside of US
18
Q
presentation of Hepatitis A (8)
A
o Flu-like symptoms
o Anorexia
o Headache
o Abdominal pain
o Myalgia
o Dark urine
o Clay colored stools
o Jaundice (common)
19
Q
Abnormal Liver Enzymes/Serologic Markers: hepatitis A
A
o AST/ ALT usually elevated >500 in acute infection
o Serological testing
HAV Ab IgG- chronic marker- + test = immune/cleared
HAV Ab IgM- acute marker- + test = acute
HAV Ab Total- does not differentiate between the two tests
* It is helpful to determine immunity, not active acute infection
* May have acquired immunity
20
Q
complications of hepatitis A
A
-extremely rare
-transplantation
21
Q
preventative measures for hepatitis A
A
o HAV vaccine!!
Available for adults and children
Given to “risky” population
* Military, travelers, moving to endemic areas, illicit drug users, gays
• Serum immunoglobulin is given to
those exposed (HAV Immunoglobulin)
− Pre-exposure prophylaxis
• < 2 week trip
• < 2 y/o
− Post-exposure prophylaxis
• Up to 2 weeks post exposure
• Household, sexual contact, daycare, food
handlers etc.
22
what is hepatitis B
o Liver infection caused by Hep. B virus
o Member of the hepadnavirus family
o Acute and chronic infection
Some people are sick for a few weeks, others the disease progresses to a serious lifelong illness, chronic HBV.
30% acute, 15% chronic
* 95% clear the infection and develop a lifelong immunity
o **rmbr it is not curable, you can stop the activity, but since it is replicated in the nucleus you cannot get rid of the virus’ DNA
23
pathophysiology of hepatitis B
Once the body is exposed to HBV, a cell-mediated immune response is triggered
Cytotoxic T cells and natural killer cells are sent to the virus and release inflammatory cytokines
Liver cells are attacked and are infiltrated by HBV
* Ground glass appearance
Virus is constantly being shed into the blood
Replication TAKES PLACE IN NUCLEUS OF THE CELL. “DEEP IN THE CELL” THEREFORE THERE IS NO CURE!
24
incubation period for hepatitis B
30-60 days
-can survive 7 days outside of the body and still cause infection
25
transmission of hepatitis B
o Mother to child
20% transmission rate, if HBs Ag positive
90% transmission rate, if HBe Ag positive
o Blood to blood
Mucosal contact with infected blood or body fluid
* Hemodialysis patients are always at risk
Can be transmitted sexually, if mucosal gets torn
* Sometimes semen or saliva has blood
* Having sex on your menstrual cycle
* Perinatal infection is common
26
pertinent patient hx (risk factors) for hepatitis B
o Are they getting HD
o Have they had transfusion, outside of US
o Sexual encounters
o Someone at home who has it
o Are they IV drug users
o What kind of work do they do
27
what are three initial testing for HBV
-HBsAg (surface antigen): it is the marker of active disease--first detectable viral antigen
-HBcAb Total (core total): the core protein is part of the nucleus, it will remain positive for life, if they have been exposed or had it
-HBsAb (surface antibody): marker of immunity--it will be (+) if you have had vaccine
28
complications of HBV
o HBV can progress to CIRRHOSIS if not treated
o HUGE Risk for hepatocellular carcinoma (HCC), even without cirrhosis
Some people die of liver cancer without knowing they had hep B
o Common form of fulminant hepatic failure
Massive necrosis of the liver parenchyma and decrease in liver size
o Watch and wait
may need transplantation
29
preventive measures for HBV
vaccine!
- some populations need a second dose/booster
30
what is hepatitis C
o Liver disease, caused by Hep C virus
o Curable disease
o Primarily a chronic infection (85%)
Acute disease not often detected
o SLOW, with varying progression rates
Predictors for progression; >40 years old, alcoholic, male, steatosis, HIV+, HBV+
Can lead to cirrhosis, but again, it takes a long time to get to that stage!
o Species is classified into 7 genotypes and several subtypes
31
pathophysiology of hepatitis c
Replicated in the cytoplasm, NOT nucleus
* That is why it is curable, powerful drugs stop replication all together
* Treatment averages 12 weeks
32
incubation period for hepatitis c
o 14 to 160 days (2 to 22 weeks)
Can remain outside the body
* 16 days at 77F 2 days at 98.6F, 4 weeks at
33
transmission of hepatitis c
parental transmission, blood to blood
34
what should people with cirrhotic liver be screen for?
for liver cancer for the rest of their life
35
pertinent patient hx for HCV
o HISTORY IS IMPORTANT TO ESTBALISH A TIME FRAME!
o May have no known or won’t admit their risk factors
Are they HIV +?
Do they have a past or current injection drug use or intranasal drug use
Hemophilia with receipt of clotting factor concentrates before 1987, long term hemodialysis, persistently abnormal ALT
Received organ transplant/transfusion before July 1992 or received blood from a donor who later tested HCV positive
They cocaine users
Where they Incarcerated
Recognized exposure
* health care workers exposed after needle sticks, sharps or mucosa,
* exposures to HCV positive blood, children born to HCV positive mothers
* Received tattoo with unsterile instruments
36
patient screening for HCV (2)
Birth Cohort Screening-
* Person born between 1945 and 1965
* ONE time screening/blood test, may identify infected patients at earlier stages of disease
Risk Factor-Based Screening-
* ^^^all of the risk factors from above^
o Let’s say someone comes for birth cohort screening, and hep C is negative, but then comes back 8 months later and wants to be screened again because they tried IV heroin, you now do the RISK FACTOR BASED SCREENING. Not the birth cohort one.
37
presentation for hcv
o 75% asymptomatic
o Jaundice (uncommon)
o Fatigue, RUQ pain**
Usually has chronic fatigue
o May present initially with variceal bleed
o May present with elevated LFT’s and/or HCV Ab Positive test
Found common after insurance physicals/blood donations
38
diagnosis and serological testing for HCV (6)
*Hepatitis C virus antibody
Can’t tell you if you have active viral infection
Can only tell you exposure, can take 6 months to become positive
* If you think someone was truly exposed and it initially came back negative, you have to repeat the test, since it takes up to 6 months to become positive.
*Hepatitis C virus RNA Polymerase Chain Reaction (PCR) QUANTitative result
Viral load!!!
Positive 1-2 weeks after infection
Threshold is low most <15 or <29
* If the antibody test is positive, next thing you draw is the HCV PCR QUANT!!
*HCV Ab with reflex PCR
If you have someone at risk, you do a REFLEX to know antibody and PCR (viral load)
* This is the one you will order!!!
*HCV PCR qualitative
Positive or negative result
Not utilized, since the QUANT is more sensitive
*HCV genotype
This is done when someone is positive for further characterize the virus
when looking at treatment options
*Hepatitis C virus RIBA
Determines exposure to the virus vs a false positive Ab
* Not used anymore usually do a DNA virus test instead
39
complications of hepatitis c virus
o May develop Hepatocellular Carcinoma (HCC), once cirrhotic though
o Cirrhosis
How to tell if someone is cirrhotic?? You draw;
* Albumin, INR level, platelet count
40
preventative measures for HCV
o There is no vaccine
o Latex condoms of multiple partners
o Avoid sharing toothbrushes, razors, combs
o Cover open wounds
41
treatments for HCV
o Curable with 12 week PO treatment
YOU ARE CURED BUT *RMBR- YOU HAVE NO IMMUNITY TO IT
* If you get re exposed, you can get it again
After 4 weeks people have cleared the virus, but there is no evidence that says that is really how much time you need.
* Therefore, if someone stops taking meds prematurely, perform a PCR blood test at 12 weeks to confirm they are “cured”
o Before you start treatment for HCV, you NEED TO CHECK FOR HEP B
“black box warning” PO meds for Hep C can “reactivate” Hep B
* Those people who are positive for both, need to also start treatment for hep B, to prevent the acute phase.
42
what is hepatitis d?
o Also known as “DELTA”, a liver infection caused by the hepatitis D virus
o Can only occur in people who are also infected with hepatitis B
“parasitic virus” cannot infect on its own, needs HBV
o Similar to HBV
o Inflammatory infiltrates causing interface hepatitis (necrosis cells)
Periportal fibrosis or bridging necrosis may be present with the process of bridging necrosis places the patient at increased risk of cirrhosis
43
what are the two types of hepatitis delta?
Co-infection
* Simultaneous infection with hepatitis B and D at the same time (both acute)
o You can become cirrhotic much quicker!
Superinfection
* Acute hepatitis Delta infection of someone with chronic Hep B
o You have had Hep B for a while (chronic), then all of sudden get really sick quick, while being complaint with your HBV medications
* Leads to chronic HDV infection in up to 80% of patients
* If associated with fulminant acute hepatitis and severe chronic active hepatitis that can often progress to cirrhosis
o fulminant hepatic failure- Massive necrosis of the liver parenchyma and decrease in liver size
* severe acute hepatitis with a short incubation period
44
incubation period for hepatitis d
o 3 to 7 weeks
Requires an associated HBV infection
45
transmission for hepatitis d
o Parenteral
IV drug use, is a common way
46
pertinent patient hx for hepatitis D
o High prevalence Mediterranean basin, middle east, central Asia, west Africa and amazon basic of S. America and some south pacific islands
47
presentation for hepatitis D
o Jaundice (common)
o Pre-icteric (prodromal- nonspecific symptoms occur) begins with fatigue, lethargy, anorexia, nausea
Lasts 3-7 days
AST/ALT abnormal
Jaundice typical
Clay colored stools and dark urine
Total bili abnormal
o Once symptoms resolve disease usually in convalescence (gradual recovery)
o Superinfection
Hepatic encelopathy can develop
48
diagnosis for hepatitis D
-consider evaluation in all patients who are HBsAg positive or recent HBV infection
-antibody (IgM IgG), PCR testing
**anyone who has HBV rather its historically or currently but its controlled and they get worse, look at them for HDV!
**faster progression to cirrhosis when coinfected vs hbv infection alone
49
DESCRIBE THE GENERAL SIGNS AND SYMPTOMS OF ACUTE VIRAL HEPATITIS
* 70% of infections in children <6 are not accompanied by symptoms
* Immunological response to virus
o Fever, fatigue, loss of appetite, N/V, ab pain, dark urine, diarrhea, clay-colored stools, joint pain, jaundice
* Flu like symptoms
50
DISCUSS THE IMPLICATIONS OF CHRONIC VIRAL HEPATITIS
* Inflammation triggers fibrinogenesis
* During inflammation stellate cells become active and make fibrosis, cirrhosis is advanced fibrosis
* Once cirrhotic, cannot be reversed
51
How is HBV transmitted?
o HBV is transmitted through activities that involve percutaneous (i.e., puncture through the skin) or mucosal contact with infectious blood or body fluids (i.e., semen, saliva), including blood and semen
Sex with an infected partner
Injection drug use that involves sharing needles, syringes, or drug-preparation equipment
Birth to an infected mother
Contact with blood or open sores of an infected person
Needle sticks or sharp instrument exposures
Sharing items such as razors or toothbrushes with an infected person
HBV is not spread through food or water, sharing eating utensils, breastfeeding, hugging, kissing, hand holding, coughing, or sneezing
52
How long does HBV survive outside the body?
HBV can survive outside the body at least 7 days and still be capable of causing infection
53
What should be used to remove HBV from environmental surfaces?
o Any blood spills — including dried blood, which can still be infectious — should be cleaned using 1:10 dilution of one part household bleach to 10 parts of water for disinfecting the area.
o Gloves should be worn when cleaning up any blood spills
54
Who is at risk for HBV infection?
Infants born to infected mothers
Sex partners of infected persons
Men who have sex with men
Injection drug users
Household contacts or sexual partners of known persons with chronic HBV infection
Health care and public safety workers at risk for occupational exposure to blood or blood-contaminated body fluids
Hemodialysis patients
55
IDENTIFY THE FACTORS THAT PROMOTE THE PROGRESSION AND SEVERITY OF HEPATITIS C.
* 75% are asymptomatic with vague symptoms until more chronic stages
* Only half people infected know they are infected
* People aren’t compliant with treatment
* Medications are expensive
56
DISCUSS REASONS FOR AND IMPLICATIONS OF, THE CHRONICITY OF HEP C. (What does it impact)
* Impacts more than just the liver-
o neuropathy, insulin resistance, cutaneous manifestations, glomerulonephritis, lymphoproliferative disorders, vasculitis
* 70-80% of people have no signs and symptoms of an acute infection.
57
the definition of Nonalcoholic fatty liver disease (NAFLD)
defined as the presence of fat in the liver (hepatic steatosis) either in imagining or on liver histology after the exclusion of secondary causes of fat accumulation in the liver
o Triglycerides are the primarily form of fat
o (e.g., significant alcoholic consumption, certain medications, and other medical conditions, or hereditary disorders)
58
what does the most severe form of NASH progress to? (3)
-cirrhosis
-end stage liver disease
-increased risk for hepatocellular carcinoma
59
risk factors associated with NAFLD: Conditions with established association (4)
o Obesity
o DM2
o Dyslipidemia (high levels of triglycerides and cholesterol)
o metabolic syndrome
**with NAFLD, its not trying to get to ideal body weight. a lot of these patients, a 10% reduction of their body weight will lead to improvement in their liver test
60
metabolic syndrome criteria
(elevated BP, HDL/LDL/triglycerides out of wack)
Presence of 3 or more of the following features;
* Waist circumference >102 cm in men >88 cm in women
o APPLE vs pear
* Triglyceride level 150 mg/dL or >
* High-density lipoprotein (HDL) cholesterol level < 40 mg/dL in men and < 50 mg/dL in women
* SBP 130 mmHg or greater or DBP 85 mmHg or greater
* Fasting plasma glucose level 110 mg/dL or greater
61
risk factors associated with NAFLD: Conditions with emerging association
o Polycystic Ovary Syndrome (PCOS)
o Hypothyroidism
o Obstructive Sleep Apnea (OSA)
o Hypopituitarism
o Hypogonadism
o Pancreato-duodenal resection
* Seen in children as young as 2 years of age
62
what does adipose tissue lead to?
- it is metabolically active and leads to insulin resistance
also leads to:
-thrombophilia
-HTN
-hyperuricemia
-dyslipidemia
-hyperglycemia
-macrovascular disease
-central obesity
63
what does an increased influx of free fatty acids to the liver and mitochondria lead to?
oxidative stress and liver damage
o Despite increased mitochondrial oxidation, the liver is unable to adapt to the chronic substrate oversupply
64
functions of adipose tissue:
- plays a central role in energy metabolism through its ability to store energy in the fed state and to release it in the fasting state
-influence systemic energy homeostasis through the endocrine system
65
Visceral adipose tissue generates multiple signals that alter lipid and glucose metabolism can lead to what?
-lead to hepatic fat accumulation
-creates a pro inflammatory environment that triggers cellular injury in the liver and other tissues
The inability to suppress injurious processes, such as oxidative stress, dysregulation of the unfolded protein response (leading to endoplasmic reticulum stress), lipotoxicity, and apoptotic pathways, contribute to liver damage, progressive fibrosis that can lead to cirrhosis, and the development of hepatocellular cancer in some patients
66
list other causes of NAFLD
* Modern diets, insufficient activity/play, Obstructive sleep Apnea, altered gut microbiome
* Macro vesicular Steatosis
o Excessive alcohol consumption
o Hep C Genotype 3
o Wilson’s Disease
o Lipodystrophy
o Parenteral nutrition
o Abetalipoproteinemia
o Medications (amiodarone, methotrexate, tamoxifen, corticosteroids)
* Micro vesicular Steatosis
o Reye’s syndrome
o Medications (valproate, anti-retroviral medications)
o Acute fatty liver of pregnancy
o HELLP syndrome
o Inborn errors of metabolism
67
IDENTIFY THE MOST COMMON CLINICAL MANIFESTATIONS OF NAFLD IN PEDIATRIC AND ADULT PATIENTS
* Non-specific or asymptomatic
o Some report RUQ pain
o Apple obesity (central)
o Hepatomegaly
o Dorsocervical hump
* Once cirrhosis develops-
o Palmar erythema, spider angiomata, gynecomastia, upper abdominal veins
More severe- ascites, icterus, nail changes, splenomegaly, asterixis (shaking of the hands)
68
diagnosis of NAFLD
-US
-CT
-MRI
-Fibro scan
69
Diagnosis of NASH
liver biopsy
70
Diagnosis for Advanced fibrosis
o FIB4 index, APRI, ALT/AST, NAFLD fibrosis score
Fibrosis score is a blood test where is the fibrosis and the level of it
o FibroScan
o MR elastography
o Liver biopsy
71
Physical finding of chronic hepatitis b (5)
- hepatosplenomegaly
- spider telangiectasias (vascular abnormality not exclusive to liver disease but often correlates)
- jaundice
- ascites
- peripheral edema
72
Decompensated cirrhosis in HCV (4)
- hepatic encephalopathy
- esophageal varices
- ascites
- cancer
