Module 6.2 - Liver Disease Flashcards
(42 cards)
1
Q
What is hepatitis?
A
- An inflammation of the liver that can be caused by toxins, medications, and viruses
- Initially screened for by performing liver function tests , specifically ALTand AST in response to presenting symptoms
2
Q
What causes Hepatitis A?
A
- Transmitted fecal-oral route, including contaminated food sources, water and shellfish
- Poor sanitation and crowding facilitates spread of virus
- Maximum infectivity occurs 2 weeks before symptoms of clinical illness
- Mortality rate is low and fulminant hepatitis A is uncommon
3
Q
How is Hepatitis A diagnosed?
A
- IgM anti-HAV – excellent diagnostic test; occurs during the first week of clinical disease
- IgG anti-HAV – appears as IgM anti-HAV declines (within 3-6 months) and persists for years, conferring long-term immunity; an effective vaccine is available.
4
Q
How is hepatitis A managed?
A
- Supportive care- bed rest until jaundice resolves, no heavy lifting/activity
- High-calorie diet- small, frequent meals with supplements, low protein, high carbohydrates, no fatty foods
- Avoid potentially hepatotoxic medications
- Alcohol restriction
- Hospitalization only if fulminant hepatic failure is suspected ( encephalopathy and severe coagulopathy)
- Anti-emetics for nausea and vomiting
5
Q
What vaccinations are available for hepatitis A?
A
- Hepatitis A vaccine – consists of inactivated HAV
- Recommended for all children 1 year of age and older.
6
Q
What causes Hepatitis B?
A
- Blood-borne virus; present in saliva, semen and vaginal secretions
- Over 2 billion people worldwide infection with 400million having chronic infections
Mode of transmission varies geographically-
- High-prevalence areas (Asia, Africa)- mainly during childbirth
- Intermediate-prevalence regions (Southern and Easter Europe) – mainly through trauma
- Low-prevalence regions (US and Western Europe)- mainly through IV drug abuse and unprotected intercourse
7
Q
Who is at high risk for hepatitis B infection?
A
- Persons with HIV or HCV
- Injection drug users
- Men who have sex with men
- Individuals with multiple sexual partners or a history of sexually transmitted diseases
- Hemodialysis patients
- Inmates of correctional facilities
- From a region with high or intermediate prevalence rates
- Persons needing immunosuppressive therapy
- All pregnant women
- Individuals with chronically elevated ALT or AST
8
Q
How is Hepatitis B diagnosed?
A
Diagnosis of HBV infection can be made through serologic detection of Hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg), and Hepatitis B surface antibody (anti-HBs).
9
Q
How do patients’s susceptible to Hepatitis B serologically present?
A
- Anti-HBc: Negative
- Anti-HBs: Negative
10
Q
How do patients who are immune to Hepatitis B due to natural infection serologically present?
A
- HBsAg: Negative
- Anti-Hbc: Positive
- Anti-HBs: Positive
11
Q
How do patients who are immune to Hepatitis B due to HBV Vaccination serologically present?
A
- HBsAg Negative
- Anti-HBc Negative
- HBsAg Negative
- Anti-HBs Positive
12
Q
How do patients who are actively infected with Hepatitis B serologically present?
A
- HBsAg Positive
- Anti-HBc Positive
- IgM anti-HBc Positive
- Anti-HBs Negative
13
Q
How do patients who are chronically infected with Hepatitis B serologically present?
A
- HBsAg Positive
- Anti-HBc Positive
- IgM anti-HBc Negative
- Anti-Hbs Negative
14
Q
When is treatment for hepatitis B initiated?
A
- Treatment of chronic HBV is indicated if risk of liver-related morbidity or mortality in 5-10 years and the likelihood of achieving viral suppression are high
- Treatment is NOT indicated if the risk of liver-related morbidity or mortality in the next 20 years and the likelihood of achieving viral suppression are low.
- Considerations for safety, efficacy and cost should be taken when choosing anti-viral therapy
15
Q
What are the treatment options for Hepatitis B?
A
1st line therapy:
- Peg interferon alpha: 180mcg SQ weekly x 48 weeks; many side effects; efficacy is limited
- Entecavir: 0.5-1 mg po daily; adjust dose for renal impairment
- Tenofovir: 300mg po daily
2nd line therapy:
- Adefovir: 10mg po daily; adjust does in renal impairment; less potent than other agents and linked to increasing rate of antiviral resistance; use as 2nd line drug following 1st year of therapy
- Lamivudine: 100mg po daily; not preferred due to resistance; adjust dose in renal impairment
- Telbivudine: 600mg po daily; renal impairment dosing; not preferred due to resistance
- Can be complicated by cirrhosis or hepatocellular carcinoma necessitating consideration for liver transplantation*
- Periodic testing of alpha-fetoprotein (AFP) levels and an ultrasound of the liver should be performed in patients with chronic HBV to monitor for hepatocellular carcinoma*
16
Q
How does the hepatitis B vaccination work?
A
- Vaccine contains HBsAg, the primary antigenic protein in the viral envelope
- Promotes synthesis of specific antibodies directed against HBV
- Vaccines are made from a viral component rather than from a live virus; therefore, cannot cause disease.
- Vaccines administered in 3 doses (1st dose, 2nd dose one month later, 3rd dose 6 months later)
- Post exposure prophylaxis with immune globulin can be used to prevent HBV infection (perinatal transmission, needle sticks, etc.).
17
Q
Who is at risk for Hepatitis C infection?
A
- HCV is a blood borne virus
- Primary risk groups are IV drug abusers; risk of sexual and perinatal transmission is small.
- Most people are asymptomatic, so they are unaware of infection
18
Q
How is hepatitis C diagnosed?
A
- Anti-HCV (anti HCV antibody) – first line test for detection of HCV
- HCV PCR used to confirm HCV infection- gold standard for confirmation of infection; detects actual virus, not antibodies, differentiates between prior exposure from current viremia
19
Q
How is hepatitis C managed?
A
- Chronic HCV : new antiviral medications have recently become available; however the cost of these new agents prevents universal delivery of antiviral therapy
- Virological cure is when HCV PCR is negative at 6 months post-treatment
- Evaluation of HCV infected patients includes assessing extent of their liver disease, other viral and host factors (viral genotype, liver fibrosis stage, history of prior antiviral treatment, renal function, medication use, identification of co-morbidities (HIV, HBV infections)
- Additional management of HCV infected patients is warranted for advanced fibrosis or cirrhosis- medication dose adjustment, avoidance of hepatotoxic medications, twice yearly ultrasonography of the liver for hepatocellular carcinoma screening and upper endoscopy for screening for esophageal varices.
- All patients with virologic evidence of chronic HCV (detectable HCV viral level over a 6 month period) should be considered for antiviral treatment.
20
Q
How does a Hepatitis D infection occur?
A
- HDV is an uncommon incomplete RNA virus
- HDV can ONLY develop when there is a concomitant HBV infection.
- Acute co-infection by HBV and HDV leads to hepatitis that can range from mild to fulminant, but chronicity rarely develops.
- High prevalence (20-40%) of HDV in Africa, Middle East, Italy and the Amazon basin, uncommon in the U.S., Southeast Asia and China
There is NO vaccination or specific treatment for HDV, but it can be prevented with HBV vaccination.
21
Q
What are the signs and symptoms associated with hepatitis?
A
Prodromal phase:
- Malaise, myalgia, arthralgia, fatigue
- Upper respiratory symptoms
- Anorexia, nausea/vomiting
- Diarrhea or constipation may occur
- Aversion to smoking (HBV)
- Skin rashes, arthritis, serum sickness in early HBV
- Fever (<103F, 39.5C)- more common in HAV
- Mild, constant RUQ abdominal pain/mid-epigastrium pain- aggravated by exertion
Icteric phase:
- Clinical jaundice occurs 5-10 days after prodromal phase- but can occur earlier
- Most patients never develop clinical icterus
- Prodromal symptoms usually worsen with the onset of jaundice
- Dark urine and clay-colored stools
22
Q
What are some physical exam findings seen with viral hepatitis?
A
- Jaundice
- Tender hepatomegaly
- Splenomegaly
- Rash (HBV)
23
Q
What are some lab changes seen with hepatitis?
A
- WBC – normal or low
- Urinalysis – proteinuria is common, bilirubinuria may occur prior to jaundice
- Increased ALT and AST levels (greater than 500 IU/L; normal range is 0-35 IU/L)- commonly this is what causes the clinician to consider the differential diagnosis of viral hepatitis
- Increased Bilirubin and alkaline phosphatase levels; may remain elevated after ALT and AST have normalized
- Prothrombin time (PT) and glucose levels are usually normal; increased PT and decreased glucose levels indicate severe liver damage.
24
Q
Define chronic hepatitis
A
Chronic hepatitis is defined as symptomatic disease (fatigue, malaise, jaundice) with biochemical or serologic evidence of ongoing hepatic damage for more than 6 months.
25
What is fulminant hepatitis?
Defined by hepatic insufficiency with hepatic encephalopathy occurring within 2-3 weeks after symptoms onset; viral hepatitis accounts for 12% of fulminant liver failure; more than half the cases are due to drug or chemical toxicities; mortality rate is 80% without transplantation and 35% with transplantation.
26
What causes autoimmune hepatitis?
* A chronic, progressive hepatitis attributed to T-cell mediated autoimmunity (T-cell mediated immune attack of the liver)
* AIH can be triggered by viral infections or drugs, or it may be a component of other autoimmune disorders (rheumatoid arthritis, Sjogren syndrome, ulcerative colitis, etc.)
* **Women (78% of cases) more frequently affected than men**
27
What labs & diagnostic tests are used to diagnose autoimmune hepatitis?
* Elevated serum IgG levels (\> 1- 1.5 times normal), but no serum markers of viral infection
* Abnormal serum aminotransferases, low to normal alkaline phosphatase
* Positive ANA, SMa or LKM 1 antibodies at titers greater than 1:80
* **Diagnosis of AIH should be considered in all patients with acute or chronic hepatitis of undetermined cause.**
28
What treatment options are available for autoimmune hepatitis?
1. Prednisone monotherapy
2. Prednisone and azathioprine
* Conventional therapy continued until remission, treatment failure, incomplete response or drug toxicity
* May lead to liver transplantation in both the acute and chronic settings.
29
What is Non-alcoholic Fatty Liver Disease (NALFD)?
Non-alcoholic fatty liver disease (NAFLD) is a group of disorders characterized by hepatic steatosis in the absence of heavy alcohol consumption, medication or hereditary disorders. There is presence of steatosis with **NO evidence of hepatocellular injury in the form of ballooning of hepatocytes.**
* Increased incidence in U.S. due to increasing prevalence of obesity
* 70% of overweight individuals have some form of NAFLD.
* Probably a consequence of hepatocyte fat accumulation and increased hepatic oxidative stress, leading to increased lipid peroxidation and ROS generation.
30
What is Non-alcoholic Steatohepatitis (NASH)?
* Type of NALFD- the most pathologic disorder of the group
* **Presents WITH steatosis PLUS hepatocytes damage and inflammation.**
* Progresses to cirrhosis in 10-20% of cases
* **Strongly associated with the metabolic syndrome of dyslipidemia, hyperinsulinemia and insulin resistance.**
* Patients frequently asymptomatic; some experience fatigue, RUQ discomfort, malaise.
31
How is Non-alcoholic Steatohepatitis (NASH) diagnosed?
* Elevated Serum aminotransferase levels present
* Imaging ( U/S, CT scan or MRI) can be used as initial screening tests, but are not reliable to determining steatohepatitis or fibrosis
* **Liver biopsy – The gold standard test to determine if hepatic inflammation or fibrosis is present.**
32
How is Non-alcoholic Steatohepatitis (NASH) managed?
* **Lifestyle intervention -** weight loss and exercise with the recommendation of losing at least 10% of body weight.
* Medications: Vitamin E 800 IU/day has been shown to improve liver histology in non-diabetic patients with biopsy-proven NASH.
* Treatment is targeted at correcting the associated obesity, hyperlipidemia and insulin resistance.
* May lead to cirrhosis and need for liver transplantation.
33
What is Hereditary Hemochromatosis?
* It is a homozygous recessive heritable disorder caused by excessive iron absorption; characterized by excessive iron accumulation in the parenchymal cells of various organs, **particularly liver and pancreas- tissue damage is attributed to direct iron toxicity.**
* **Most common genetic disorder in Caucasians; more prevalent in northern European origin (especially Nordic or Celtic ancestry)**
* Genetic predisposition increases the inappropriate absorption of dietary iron that can lead to cirrhosis, hepatocellular carcinoma, diabetes and heart disease.
34
How is Hereditary Hemochromatosis diagnosed?
* Diagnosis based on increased iron stores demonstrated by elevated ferritin levels and increased hepatic iron content.
* Hemochromatosis gene detection can further define the diagnosis.
**3 stages of progression identified:**
1. Stage 1 – patients with genetic disorder, with NO increase in iron stores
2. Stage 2 – patients with genetic disorder, with evidence of iron overload, with NO evidence of tissue or organ damage.
3. Stage 3 – Patients with genetic disorder with iron overload and deposition to the degree that tissue and organ damage has occurred.
35
How do you treat Hereditary Hemochromatosis?
* For patients with iron overload- therapeutic phlebotomy weekly is performed. Total ferritin target level is 50-100 micrograms/L
* Avoid vitamin C and Iron supplements.
* Dietary restrictions are unnecessary.
* For patients with hemochromatosis cirrhosis- screening is recommended for hepatocellular carcinoma
* Family screening is recommended for all first degree relatives, to include: iron studies, ferritin and hemochromatosis gene mutation analysis.
36
What is and what causes Wilson Disease?
* A familial autosomal recessive disorder **causing copper to be accumulated in the liver,** which results in hepatic injury through ROS generation; lethal if not treated.
* Eventually copper is released into the bloodstream and deposited in brain, kidneys and corneas.
* Nearly all patients with neurological involvement will develop eye lesions, called Kayser-Fleischer rings- green-brown copper deposits in Descemet’s membrane of the corneal limbus.
37
How is Wilson Disease diagnosed?
* Diagnosis is based on decreased serum Ceruloplasmin, increased hepatic copper content and increased urinary copper excretion.
* Abnormal aminotransferase generally.
* Serum Ceruloplasmin that is significantly low, \< 50 mg/L, is a strong indicator of Wilson’s disease
* A 24 hour urine copper should be obtained on all patients with suspicion of Wilson disease. Findings greater than 40 micro-grams may indicate Wilson’s disease.
* **Liver biopsy for hepatic copper content– Gold standard for diagnosis**- content \> 250 micro-grams/gram dry weight in indicative of Wilson’s disease.
* **Serum copper levels are of NO diagnostic value.**
38
What are the treatment options for patients with Wilson Disease?
* **Copper chelation is standard therapy**
* **Liver transplantation may be necessary.**
* Avoid intake of food and water high in copper
* Zinc 50mg po tid – blocks intestinal absorption of copper
* Treatment is life long, unless liver transplantation is performed
* All first degree relatives should be screened.
39
What is Alcoholic Liver Disease (ALD)?
* The leading cause of liver pathology in most Western countries; accounts for 40% of deaths from cirrhosis in the U.S.
* **Amount of alcohol is a factor, but there is not a linear correlation with the amount consumed and the amount of liver disease present**
* **Women are twice as sensitive to** **alcohol mediated** **hepatotoxicity and may require less alcohol intake to lead to severe liver disease.**
* Binge drinking (5 or more drinks per sitting) increases risk of ALD.
* Genetic factors predispose individuals to alcoholism and ALD.
40
What are the 3 stages of Alcoholic Liver Disease?
**1. Hepatic steatosis (fatty liver) –** marked micro-vesicular lipid droplets within hepatocytes; liver becomes enlarged, soft greasy and yellow; little to no fibrosis; condition is reversible.
**2. Alcoholic hepatitis –** characterized by ballooning degeneration and hepatocyte necrosis; neutrophilic reaction to degenerating hepatocytes, portal and peri-portal mononuclear inflammation and fibrosis
**3. Alcoholic cirrhosis –** final stage; largely irreversible; liver is transformed from fatty and enlarged to brown, shrunken and non-fatty; regenerative nodules prominent and/or obliterated by dense fibrous scar
41
What lab tests / diagnostic tests are used to diagnose Alcoholic Liver Disease?
* **Based on** **history** **of significant alcohol** **intake ,** **clinical evidence of liver disease and supporting lab abnormalities**
* Various questionnaires developed (CAGE, MAST, AUDIT)
* **No single lab value definitely establishes ALD**
* AST/ALT ratio is frequently higher than 2; indicative of ALD in 70% of patients.
* Maddrey’s discriminant function- prognostic scoring system to stratify the severity of illness
42
How do you treat Alcoholic Liver Disease?
* **Abstinence is** **most** **important treatment for ALD**
* Alcoholic hepatitis treatment:
* Treat for nutritional deficiencies
* Consider glucocorticoids x 4 week course
* If steroids contraindicated, pentoxifylline 400mg tid for 4 weeks for severe cases
* ALD is the 2nd most common indication for liver transplantation for chronic liver disease in the Western world.
