Liver Disease Flashcards
What are some functions of the liver?
Synthetic functions (coagulation factors, cholesterol and triglycerides, amino acids, bile, glucose, glycogen, albumin, angiotensinogen)
Detoxification/catabolism
Drug metabolism and detoxification
Hormone degradation
Ammonia degradation
Storage (iron, copper, vitamin A, D and B12)
What are a few ways to classify liver disease?
Hepatocellular - liver injury, inflammation, and necrosis
Cholestatic (obstructive) – problem with bile flow
Mixed pattern - features of both hepatocellular and cholestatic injury
Staging or timing of liver diseases
Acute liver disease
Chronic liver disease
Cirrhosis –> final end point of most liver diseases
Liver disease common symptoms
Many are asymptomatic Fatigue Nausea Anorexia RUQ discomfort Abdominal distention Pruritus Jaundice
Risk factors for liver disease
Alcohol IDU Medications Sexual activity (Hep B) Travel Occupational exposure (e.g., needlesticks) Transfusions Family history of liver disease
What are some possible exam findings for liver disease?
Often normal
May reveal risk factors
Icterus, hepatomegaly, hepatic tenderness, splenomegaly, spider angiomata, palmar erythema, and excoriations
More signs as liver disease advances – muscle wasting, bruising, ascites, edema, dilated abdominal veins, asterixis, AMS
Lab testing for liver disease
Liver enzymes: ALT, AST
ALP
GGT
Synthetic function: Serum albumin, Prothrombin time (PT), INR
Acute liver failure (fulminant hepatic failure) characteristics
- Acute liver injury: LFTs typically > 15 times upper limit of normal
- Hepatic encephalopathy: Delirium, changes in personality, irritability, aggressive behavior, declining LOC –> coma
- Elevated PR/INR > 1.5
Which hepatitis viruses can go on to cause chronic liver disease?
HBV, HCV, and HDV
HDV require HBV
Acute viral hepatitis clinical features
A large number of infections are asymptomatic
May have jaundice and elevated liver enzymes.
Acute viral hepatitis initial phase
Incubation (inoculation) phase
Acute viral hepatitis prodromal phase
Constitutional symptoms – fever, anorexia, nausea, vomiting, diarrhea, fatigue, malaise, myalgia -
and dull RUQ pain
Precedes jaundice by 1-2 weeks
Acute viral hepatitis icteric (jaundice) phase
Heralded by onset of clinical jaundice and lasts 1-3 weeks.
The constitutional symptoms diminish.
Liver becomes enlarged and tender (RUQ pain/discomfort).
Many pts never become icteric
Acute viral hepatitis: recovery phase
Lasts from 2-12 weeks
Symptoms continue to resolve but can still have some liver enlargement and LFT abnormalities.
Complete clinical and biochemical recovery usually within 6 months
Acute viral hepatitis: Aminotransferases
AST/ALT increase during prodromal phase and precede rise of bilirubin
ALT/AST acute levels do not correlate to degree of liver cell damage or risk of developing liver failure
Typically >25 times the upper limit of normal
Peak levels of ALT/AST vary from 400-4000+ IU/L and are usually reached at time pt is icteric. If patient has markedly elevated transaminases then hepatitis should be on the list of concerns.
Acute viral hepatitis: bilirubin
With jaundice, serum bilirubin from 5-20 mg/dL
Can rise and persist after decrease in AST/ALT
Persistently elevated bilirubin associated with poorer prognosis
Acute viral hepatitis: PT
PT prolongation may indicate severe liver damage/extensive hepatocellular necrosis and poorer prognosis
Acute viral hepatitis: ALP
ALP may be normal or mildly elevated
Acute viral hepatitis: Albumin
Alb usually normal with acute, uncomplicated illness
Acute viral hepatitis: LDH
May also be elevated (1-3 times normal) but not specific
Other infectious causes of increased transaminases
EBV, CMV, VZV, rubella, measles, mumps, coxsackie B
Disseminated HSV (in immunocompromised pts)
Rickettsial infections, bacterial sepsis, Legionella, syphilis, disseminated mycobacterial, fungal infections
Yellow fever (Central and South America)
Acute viral hepatitis: Treatment
Supportive: bed rest, avoidance of hepatotoxic meds, no alcohol
Most pts do not require hospitalization and recover within 3-6 months
When should a patient be hospitalized for acute viral hepatitis
Severe dehydration
Hepatic failure
Bilirubin >15-20 mg/dL
If PT is prolonged
Acute hepatitis follow up
Transaminases, ALP, bilirubin, PT - monitored 1-2 times per week for 2 weeks initially
Then, every other week until they return to normal
Pts with fulminant hepatic failure are considered for liver transplant
Viral hepatitis immunizations
Vaccines available for hepatitis A and B
Hepatitis A epidemiology
Only leads to acute hepatitis – no chronic form of the disease
You can only get it once
Spread via oral-fecal route. Usually through contaminated food.
Rare in industrialized countries.
Incidence in US has declined drastically since vaccination.
Risk factors for hepatitis A
Most common risk factor is international travel (up to 50% of cases)
Lower SES, food and water contamination, sexual and household contact, MSM, IDU, childcare
When is hepatitis A most infectious?
Most infectious during the first 2 weeks before onset of clinical illness. Fecal shedding continues 2-3 weeks after onset of symptoms.
Hepatitis A clinical features
Malaise, fatigue, flu-like symptoms (coryza, photophobia, headache, and cough) myalgia, arthalgia, abdominal pain, N/V, anorexia, fever and jaundice
Can be silent or subclinical particularly in children (>80%)
Patients present with acute illness typically several weeks after infection.
Rarely, patients can go on to develop fulminant hepatic failure requiring liver transplant for survival
Risk of liver failure in HAV infection increases with age and other liver disease
What are the two clinical features of hepatitis A?
- Pts can have long period of jaundice after HAV infection (prolonged cholestasis)
These pts can have months of jaundice during recovery from HAV infection. These pts can also have elevated ALP levels as well
Treatment is supportive and the jaundice slowly fades over time
- Pts can have a relapse of the disease weeks or months after the initial infection
Treatment is supportive unless the pt develops fulminant hepatic failure
Hepatitis A diagnosis
Anti-HAV IgM antibodies in the serum + typical clinical presentation is diagnostic
May be positive in 5-10 days prior to onset of sxs
Detectable up to 6 months after exposure
Aminotransferases are elevated (10-100 times the upper limit of reference range) – usually >1,000 IU/dL.
Resolution of the illness is associated with emergence of anti-HAV IgG antibodies
Change from detection of IgM antibodies to IgG antibodies distinguishes acute from convalescent infection
IgG confers life-long immunity
Hepatitis A treatment
Supportive
Hepatitis A prevention
HAV vaccine
Good hygiene
Who should receive routine vaccination for Hep A?
All children at one year of age (12-23 months)
MSM
Chronic liver disease
Illicit drug users (injection and non-injection
Household contacts of child adopted from endemic country
Homeless
Vaccination for international travel to high risk areas
< 40= I dose HAV and booster within 6-12 months
>40 or immunocompromised, chronic disease: 2 full dose schedule before departure
If not enough time before travel give initial vaccine dosage with immune globulin.
Post exposure prophylaxis- within 2 weeks of exposure
- 1- 40 years and healthy: HAV vaccine
- > 40 years: HAV vaccine +/- immune globulin
- <1 year, immunocompromised, chronic liver disease: HAV vaccine + immune globulin
- <1 year or allergic to vaccine: immune globulin
Prevaccination testing for anti-HAV antibodies
Consider cost, delay of vaccination:
Can test populations expected to have high rates of previous HAV infection and natural immunity:
1. Adults >40 years of age
2. Adults in certain populations – American Indian, Alaska Native, Hispanic
3. Adults born in or lived in endemic regions
4. Risk groups with high HAV seroprevalence, (eg, IDU, MSM, or HIV-infected)
Hepatitis A prognosis
Usually self-limited infection
Most symptoms and labs resolve by 3-6 months
Prolonged or relapsing symptoms possible
Acute liver failure is rare but risk increases with age and other comorbid chronic liver disease
No chronic disease or cirrhosis
Acute hepatitis B epidemiology
Major cause of acute viral hepatitis and most common cause of chronic viral hepatitis worldwide
Rare in Western, developed countries – 2% of population
In U.S., <2% prevalence
Sexual transmission
High risk individuals for acute hepatitis B
H/o multiple transfusions IDU Hemodialysis Risky sexual behavior MSM Household and heterosexual contacts of hepatitis B carriers Residents and employees of residential care facilities Travelers to endemic areas
Acute hepatitis B clinical presentation
Incubation period 60-160 days. Symptoms developing months after infection - varies from mild to acute liver failure
Subclinical disease possible, especially in children but most should be vaccinated.
More insidious onset and more prolonged course than HAV
Malaise, fatigue, jaundice, pruritus, headache, RUQ abdominal pain, N/V, anorexia, dark urine.
These symptoms all decrease rapidly after the onset of jaundice
Most acute HBV infections are self-limited in adults
Hepatitis B serum sickness-like illness
~10% of pts with acute HBV can present with a serum sickness-like illness (fever, maculopapular rash or urticarial, migratory arthritis)
Hepatitis B diagnosis
Liver chemistries- AST, ALT, Alkaline phosphatase, total bilirubin are typically elevated.
ALT and AST - typically up to 1000-2000 units/L.
Hepatitis B surface antigen: HBsAg
HBsAg appears in serum 1-10 weeks after exposure, prior to onset of symptoms or elevation of serum ALT
In pts who recover, HBsAg becomes undetectable in 4-6 months
Persistence of HBsAg for >6 months implies chronic infection
Hepatitis B e antigen; HBeAg
Hepatitis B envelope antigen
Serves as a marker for hepatitis B replication and infectivity
The presence of HBeAg indicates high HBV DNA and high rates of transmission
Hepatitis B surface antibody: HBsAb
Appears when HBsAg declines in pts who mount a protective immune response. A person who clears the virus through having it or by having vaccine.
It confers immunity in patients with recovered hepatitis B or with previous vaccination. No one with HBsAb will actively have the disease.
Hepatitis B core antibory: HBcAb
Suggests HBV infection
IgM HBcAb could be the only positive antibody in the “window period”
Period of acute HBV infection when both HBsAg and HBsAb may be negative
Transient presence of IgM anti-HBc forms an important basis for diagnosis of acute infection
Hepatitis B e antibody: HBeAb
Development is a marker for low HBV DNA and lower rates of transmission in pts without protective immunity
HBV viral DNA
The most accurate marker of viral replication. Risk of transmission during acute infection is very high during the incubation period because of high viral load.
Treatment of acute HBV
Supportive watching to liver failure (rare) and progression of the disease.
HBV preexposure prophylaxis
HBV vaccine for everyone
HBV postexposure prophylaxis
Infants for HBsAg positive should receive HBV vaccine and hepatitis B immune globulin within 12 hours.
Susceptible sexual partners of individuals with HBV and needle-stick injury should receive immune globulin within 24 hours.
HBV prognosis
Can have spontaneous resolutions or progression to chronic disease.
5-10% of adults with develop chronic HBV. Should take about 4 months for aminotransferases to go down but it greater than 6 months then assume chronic hepatitis.
Hepatitis C epidemiology
Usually presents as a chronic infection
Primary route of transmission is blood exposure (eg, transfusion or IDU)
80% of pts infected with HCV has no signs or symptoms of the infection.
Risk factors for hepatitis C
IDU, HIV, hemodialysis, incarceration, blood transfusion (rare)
Acute hepatitis C clinical presentation
20% with acute infection have jaundice; if sxs, may have nausea, malaise
Most patients who are acutely infected with HCV are asymptomatic.
Symptomatic patients may experience jaundice, nausea, dark urine, and right upper quadrant pain, with a mean onset of symptoms at seven to eight weeks after infection.
HCV diagnosis
HCV RNA by PCR and anti-HCV antibody testing by enzyme-linked immunosorbent assay (ELISA)
Screening test is the HCV antibody. The presence of HCV antibody suggests prior exposure to HCV but does not convey immunity so you would have to do further testing if it was positive to confirm.
HCV RNA positive and HCV antibody positive confirms HCV infection.
Can also check LFTs, HIV, and tests to exclude other disorders.
Hepatitis prevention and screening
No vaccine or postexposure prophylaxis
CDC testing guidelines recommend a 1-time test for HVC in baby boomers without assessing HCV risk.
Hepatitis C treatment
Some patients are able to clear acute hepatitis C virus spontaneously. Tratment can be delayed to 6 months or more to allow for spontaneous resolution.
- Interferon based regimens
- Direct-acting antivirals (DAA)
DAAs are highly effective in treating chronic infection and can lead to higher cure rates.
Recheck HCV RNA & anti-HCV antibody in 12 weeks.
All patients with virologic evidence of chronic HCV infection for over 6 month period should be considered for treatment.
Goal of treatment is sustained virologic response (SVR)
Hepatitis D epidemiology
Requires HBsAg to enable replication and infection so HDV always occurs in associated with HBV infection.
Endemic in Mediterranean, Middle East, and parts of south america
Hepatitis D “superinfection”
Superinfection results in chronic HDV infection along with chronic HBV infection
HDV tends to be a severe illness with high mortality (2-20%)
Often a protracted course that leads to cirrhosis
Hepatitis D clinical features
Typical hepatitis sxs: jaundice, abdominal pain, anorexia, fatigue, N/V, arthralgia
Hepatitis D diagnosis
Test include HDV RNA and Anti-HDV antibody
Testing done only when evidence of HBV infection (HBsAg+).
Hepatitis D treatment
Mostly supportive care
No evidence of benefit of interferon Rx for coinfection or superinfection in acute phase
Hepatitis E epidemiology
HEV resembles HAV – fecal-oral transmission
Most occur in developing countries (India, Southeast Asia, Africa, Mexico)
US cases typically with history of travel to endemic area
Hepatitis E diagnosis
Anti-HEV
PCR and serologic testing through CDC
Chronic viral hepatitis
Defined as the presence of liver inflammation persisting for ≥6 months and associated with HBV, HCV, or HDV infection
Chronic viral hepatitis physical exam
Findings occur late in the disease process and are due to cirrhosis:
spider angiomata, hepatomegaly, splenomegaly, ascites, jaundice, gynecomastia, testicular atrophy, asterixis, loss of body hair
Chronic hepatitis diagnosis
- Serology testing for HBV and HCV:
HBsAg, anti-HBsAb, anti-HBcAb, HBeAg, anti-HBeAb and Anti-HCVAb - Transaminases, bilirubin, alkaline phosphatase, PT, albumin. AST/ALT usually 2-5 times normal (ALT>AST)
ALP usually minimally elevated unless cirrhosis - Liver biopsy may be done for diagnosis confirmation and to determine the severity of disease. Liver fibrosis historically the gold standard for assessing the liver stage and predicting the prognosis.
HBV acute infection leads to chronic HBV in:
90% of newborns of HBeAg positive mother
25% of infants/children
5-10% of adults
Resolved hepatitis B
Infection controlled evidenced by resolution of symptoms, normalization of liver enzymes and clearance of HBsAg - with associated antibodies to hepatitis B surface antigen (anti-HBs)
The presence of anti-HBs following acute infection generally indicates recovery and protective immunity against re-infection
In addition, patients with resolution of infection have disappearance of HBeAg and development of antibodies to hepatitis B e antigen (anti-HBe).
Chronic hepatitis B e antigen
HBsAg and anti-HBc (IgG antibodies) generally persist for life and HBV DNA can usually be detected. But e antigen can either be positive or negative:
The continued presence of HBeAg generally reflects higher HBV DNA levels and greater infectiousness (chronic hepatitis B e antigen positive)
Some patients with chronic HBV infection may have resolution of their HBeAg along with appearance of anti-Hbe (chronic hepatitis B e antigen negative)
Inactive hepatitis B (HBsAg carrier)
Persistent HBsAg >6 months after acute infection without any necroinflammation
Normal liver enzymes
Nondetectable HBV DNA levels (< 2000)
Transmission to others still possible
Much less incidence of cirrhosis, ESLD, liver cancer than with chronic hepatitis B e antigen positive or e antigen negative.
Chronic hepatitis B giagnosis
HBV – ALT (made only by hepatocytes) and HBV DNA (via PCR) are also important markers of severity and prognosis.
Chronic hepatitis B risk factors for progression to cirrhosis
Older age HBV genotype C High levels of HBV DNA Alcohol consumption Concurrent infection with HCV, HDV, or HIV
Chronic liver disease lab testing
CBC, LFTs (AST, ALT, total bilirubin, alkaline phosphatase, albumin), PT, and tests for HBV replication (HBeAg, anti-HBe, HBV DNA).
Want to check for immunity to Hep A, evaluation for other causes of liver disease.
Chronic hepatitis B treatment
Refer!
Complex and depends on multiple factors including:
Clinical variables (eg, the presence or absence of liver inflammation and/or cirrhosis)
Patient’s immunologic response to infection (eg, hepatitis B e antigen status)
HBV viral load and genotype
Risk factors for disease progression (eg, age >40; FHx of hepatocellular carcinoma)
Interferon alpha, Nucleoside and nucleotide analogs –> both aimed at inhibiting HBV replication.
Chronic hep B goals of treatment
Reduced risk of end stage liver disease (ESLD) and cancer
Sustained suppression of HBV DNA
HBsAg and HBeAg seroconversion (transition to resolution)
Decreased ALT/AST
Decreased necroinflammation (transition to inactive hepatitis B)
Reduce transmission
Treatment response measure by:
- loss of HBeAg
- development of HBeAb and
- cessation of viral replication in HBeAg positive patients or
- viral suppression in HBeAg negative patients
Hepatitis C is a ____ disease based on genotype
Curable in up to 82% of patients with treatment
Hepatitis C predictors of poor response to treatment:
Cirrhosis Male Advanced age HIV HCV genotype 1 or 4
Chronic Hep C diagnosis
Screening: HCV Ab (hepatitis C antibody)
> 90% sensitivity
Confirm with HCV RNA (also used to determine more acute infection when HCV Ab negative early on; also used to assess Rx response)
HCV RNA genotype/subtype (and HCV viral load) help predict response to treatment
Hep C treatment goals
HCV RNA eradication (cure)
sustained virologic response (SVR), defined as an undetectable RNA level 12 weeks following the completion of treatment.
Hep C treatment
Refer!
Antiviral therapy of HCV has been rapidly evolving
Choice of medication depends on patient factors and genotype. Genotype 1 most common in US.
Direct-acting antivirals (DAAs)
Interferon alfaq
Chronic Hepatitis D
Occurs only in presence of chronic HBV
Limited therapy options with limited efficacy.
