Liver Disease Flashcards
1
Q
Hepatitis
A
- Inflammatory disease localized to the liver or part of a generalized systemic process leading to hepatocellular destruction
- ACUTE: <6 mo; self limited - Etiology: viruses, drugs, alcohol
- CHRONIC: >6 mo; unresolving; often leads to cirrhosis
2
Q
Acute viral hepatitis
A
- Viral: systemic infection whose primary manifestations are hepatic.
- Serotypes: A, B, C, E, G (D (Delta) subtype of B: infection with the delta particle is dependant on concomitant infection with type B)
3
Q
Characteristics of Acute viral hepatitis
A
- The one thing to know about Hep E is that it primarily affects pregnant women
- Hep A wont make you sick on your vacation, but it will make you very sick when you get back because it has such a long incubation time
4
Q
Clinical findings of acute viral hepatitis
A
- Initial symptoms: Flu-like syndrome (fatigue, nausea, myalgias), Abdominal pain
- Clinical presentations similar for all serotypes; B & C usually more severe, higher incidence of morbidity and mortality
- 70% pts will have: Tender, palpable liver, Posterior cervical lymphadenopathy, Splenomegaly, Jaundice usually disappears 2-8 weeks after onset
- Jaundice & Icterus; Hepatomegaly
5
Q
hepatitis labs
A
- Transient anemia, lymphocytosis with atypical lymphs, increased reticulocyte count (young RBCs d/t anemia)
- Increased direct and total serum bilirubin (if the bilirubin is 10, 12, 15, 20, that person has a severe hepatitis) – you usually see jaundice with bilirubin around 10 (Level indicates severity)
- Increased serum aminotransferase: ALT/AST – the ratio will tell you if this is a viral infection (ALT typically higher than AST (if AST is higher, think alcohol), provides a rough estimate of hepatocellular injury but no prognostic value)
- Alk Phos rises early (due to liver damage) and often remains elevated after clinical recovery
- Prothrombin time: usually normal; if elevated suspect fulminant hepatitis (You always want to check, If it is elevated or prolonged, that means that the liver is so inflamed that it can’t make the clotting factors)
- *Rapid fall in serum aminotransferase from high to normal in < 1 week may be an indication of fulminant hepatitis with massive necrosis / destruction of liver parenchyma
6
Q
general managment of hepatitis
A
- Acute viral hepatitis usually resolves completely in 1-3 mo.
- Treat nausea, vomiting, anorexia (Compazine or other antiemetics)
- Benadryl, Atarax (Sedatives may precipitate hepatic encephalopathy – get ammonia buildup in the brain and they get really confused)
- Avoid ETOH and tobacco use, hepatic cleared meds until 1 month after all labs return to normal
7
Q
hepatitis A
A
- Most common type of acute hepatitis
- Epidemic outbreaks: Poor hygienic conditions, Contaminated water supply, Infected food handlers, Ingestion of contaminated shellfish, Institutions/daycare
8
Q
hepatitis A vaccine
A
- Children – Incorporated into routine childhood vaccination schedule in 2006 (2 doses starting at 12 mos, 6-12 mos apart)
- Adults – recommended for high risk individuals: Chronic liver disease, Clotting disorders, Occupational or travel exposure)
- Due to peds vaccination prevalence of disease shifting to adults
- The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has recommended hepatitis A vaccination of adults who have any of the following medical, occupational, or lifestyle risk factors (Persons with clotting-factor disorders or chronic liver disease, Men who have sex with men, IV drug users, Persons working with hepatitis A virus infected primates or HAV in a research laboratory, Persons traveling to countries with high or intermediate endemicity recommended in HIV-infected patients)
- vaccine efficacy is decreased in the setting of advanced immunosuppression
9
Q
Hep A diagnosis
A
- Serum anti-HAV IgM antibodies gold standard detecting acute illness
- Anti-HAV positive at onset of sx, peaks during convalescent phase, remains positive 4-6 mos
- Serum ALT > AST
- Bilirubin > 10 common
10
Q
Hep A treatment and prognosis
A
- Tx is supportive
- 85% have full recovery w/in 3 months and nearly all have complete recovery by 6 months
- Acute infection confers immunity
- Fatalities most common in elderly or those with chronic Hep C
11
Q
Hep B
A
- Usual transmission is blood borne
- Less common: sexual transmission
- Delta agent (Hep D): defective virus particle, same route of transmission assoc with Hep B (Causes clinical exacerbation for Hep B carriers, Implicated in fulminant hepatitis, Rapid progression to cirrhosis)
12
Q
Hep B vaccine
A
-Recommended for everyone: Given at birth, 3 doses at 0, 2, 6 months (varying schedules), Post-exposure prophylaxis, High risk individuals
13
Q
Hep B diagnosis
A
- HBsAg present 1-10 wks after acute exposure (Usually undetectable after 6 months, Persistence of HBsAg after 6 months implies chronic infection/carrier state, < 1% of immunocompetent pts will progress to chronic infection)
- Anti-HBs indicates long term immunity
- HBeAg present early and is a marker for HBV replication and degree of infectivity
- Post vaccine testing should be 1-2 months after third vaccine dose for meaningful results
14
Q
Hep B LFTs
A
- ALT & AST elevated up to 2000 in acute phase with ALT higher than AST
- PTT or PT/INR is the best predictor of prognosis
- Recovery = normalization of LFT’s in 1-4 months
- Persistent elevation of ALT > 6 months = progression to chronic hepatitis
15
Q
Chronic Hep B
A
- Persistence of Hep BsAg > 6mo after acute infection
- Incidence of progression to chronic by age: 90% perinatal, 20-50% for age 1-5 years, < 5% for adults – if you acquire hep B as an adult, about 95% will clear the infection without becoming chronic
- Symptoms: nonspecific; fatigue; acute exacerbations of infection that mimic acute hepatitis; hepatic failure
16
Q
Carrier State Hep B
A
- Patients in low or nonreplicating phase / inactive carrier state are HBeAg negative (Their envelope is negative – they are not carrying active virus)
- Persistent Positive HBsAg > 6 mo following acute infection (Carries risk of infectivity)
- Liver disease in remission as evidenced by normal serum ALT concentrations (But may progress to chronic Hep B, cirrhosis, HCC)
- HBeAg is a marker for HBV replication and degree of infectivity
17
Q
Hep B treatment
A
- Goal: suppression of viral replication
- Indications for treatment: acute liver failure, clinical complications of cirrhosis, advanced fibrosis with high serum HBV DNA, or reactivation of chronic HBV after chemotherapy or immunosuppression, INR >1.5, fulminant hepatitis)
- Antivirals: Interferon (avoid in pts w/ cirrhosis due to risk of hepatic inflammation) many serious side effects, Lamivudine, entecavir, telbivudine; negligible side effects, Adefovir, Tenofovir: nephrotoxicity
18
Q
Chronic Hep B prognosis
A
- 5 year prognosis for progression to: Cirrhosis 12 - 20%, Hepatic failure 20%, Hepatocellular Carcinoma 15%
- Lifetime mortality from liver disease = 50%
- Complete eradication rarely occurs after acute infection
- Immunocompromised pts more likely to have reactivation, progression
19
Q
Hep C
A
- Most common chronic liver disease, accounts for 8,000 to 13,000 deaths each year
- Majority of liver transplants in the US
- Acute infection often asymptomatic
- Slowly progresses; rarely causes fulminant hepatic failure
- Up to 80% progress to chronic infection leading to fibrosis and cirrhosis (3% of these develop hepatocellular CA, accounts for 30% of HCC cases in US)
20
Q
HCV screening guidelines
A
- Anyone born in the United States between 1945 and 1965
- Those with h/o illicit IVDU or intranasal cocaine use, even if only used once
- Those who received clotting factors made before 1987
- Those who received blood/organs before July 1992
- Those who have been informed that they received blood from a donor who later tested positive for HCV
- Those who were ever on chronic hemodialysis
- Those with evidence of liver disease (persistently elevated ALT level)
- Those infected with HIV
- Children born to HCV-infected mothers
- Those with a needle stick injury or mucosal exposure to HCV-positive blood
- Those who are a current sexual partner of an HCV-infected person
- Incarcerated individuals
21
Q
Hep C diagnosis
A
- Anti HCV ELISA allows detection in about 95% of pts 2 weeks after exposure
- More sensitive: HCV RNA by PCR
- LFT’s elevated 6-12wks after exposure
- Acute illness typically lasts 2-12 wks
- Difficult to distinguish acute vs chronic dz unless there is previous neg HCV RNA serology
- there is suggestive circumstantial evidence for new infection such as a history of a recent high risk exposure, new clinical features of acute hepatitis, previous absence of elevated aminotransferase levels, and absence of a prior risk for HCV infection. Although the presence of symptoms compatible with acute hepatitis can also be informative, most patients are asymptomatic during acute infection with HCV.
- A new positive HCV PCR usually followed by a positive anti-HCV within 12 weeks is generally considered definitive proof of acute HCV infection. However, this requires availability of a recent serum sample with a negative HCV PCR and anti-HCV. In the absence of such documentation, the distinction between acute hepatitis C virus infection and newly discovered chronic infection is not straightforward since in both settings patients may have detectable HCV RNA, antibodies against HCV, and elevated serum aminotransferases.
- The pattern and timing of serologic markers, including HCV RNA (usually positive within two weeks after inoculation), serum aminotransferases (usually preceding anti-HCV seropositivity), and antibodies (usually several weeks after exposure) can be helpful
22
Q
hep C diagnosis and evaluation
A
- Determination of HCV genotype is essential to making decisions about treatment
- Assessment for liver fibrosis through biopsy or noninvasive measures is helpful in guiding decisions regarding treatment and surveillance
- Testing for HIV, hepatitis B, and hepatitis A (Vaccination should be administered to those without immunity to Hep A & B)
23
Q
HCV: general mangement
A
- Antiviral therapy
- Psychologic counseling
- Alcohol avoidance
- Symptom control
- Dose adjustment of medications
- Assessment of fibrosis
- Screening for complications of cirrhosis if present
24
Q
HCV treatment
A
- The goal of treatment in patients with chronic HCV is to eradicate HCV RNA, which is associated with decreases in all-cause mortality, liver-related death, need for liver transplantation, hepatocellular carcinoma rates, and liver-related complications
- All patients with detectable viral load >6 mos should consider treatment
- Treatment selection varies by genotype and other patient factors
25
Q
HCV: cirrhosis treatment
A
- Cirrhosis: late stage of progressive hepatic fibrosis; distortion of the hepatic architecture and the formation of regenerative nodules
- Generally irreversible in advanced stages
- In earlier stages, specific treatments aimed at the underlying cause of liver disease may improve or even reverse cirrhosis
26
Q
HCV: treatment for treatment-naive pts
A
-Harvoni has 95% cure rate (no detectable virus by PCR at 6 mos post-treatment) in genotype 1; once daily dosing, ease of use, very expensive.
27
Q
HCV prognosis
A
- Recheck viral loads at 12 & 24 wks (SVR defined as undetectable viral load after 24 wks)
- Survival linked to development of cirrhosis
- Cirrhosis in about 50% of pts with chronic Hep C
- Cirrhosis = 3% per year chance developing HCC
- Host factors predictive of dz progression: Genetic, Acquisition of HCV > age 40, Acquisition of CV by blood transfusion, Coinfection with B, *Children and AA less likely to progress, ETOH abuse, W / cirrhosis, 3 yr survival = 96%, 5 yr survival = 91%, 10 yr survival = 79%
28
Q
cirrhosis
A
- Widespread hepatic fibrosis
- Extensive hepatocellular destruction
- Insidious onset with nonspecific: fatigue, anorexia, weight loss, nausea, abdominal pain
- Labs: Anemia, Thrombocytopenia, Elevated bilirubin, Decreased albumin, Increased bleeding time, Elevated ammonia
29
Q
cirrhosis disease progression
A
- Hepatocellular failure
- Jaundice
- Edema
- Ascites
- Electrolyte abnormalities
- Bleeding disorders
- Hepatomegaly
- Portal hypertension
30
Q
cirrhosis complications
A
- Hepatic encephalopathy – can see asterixis
- Bleeding from varices
- Ascites
- Spontaneous bacterial peritonitis
- Hepatocellular CA
31
Q
management of cirrhosis
A
- Diuretics
- Paracentesis
- Vitamin K
- Multivitamins
- Lactulose (reduces ammonia level)
- Avoid ETOH
- Liver transplant
- Vitamin K is essential for activity of several carboxylase enzymes within the hepatic cells, and therefore is necessary for the activation of coagulation factors VII, IX, X, and prothrombin.
32
Q
fulminant hepatitis
A
- Rare Subtype of acute Hepatitis
- Prevalence varies; hep A least common
- Presents with massive necrosis and liver failure
- Hepatic encephalopathy
- Onset within 8 weeks of disease
- High mortality
- Tx = Liver transplant
- Association with alcohol, tylenol use, methamphetamine use, hx of weight loss
33
Q
summary of serologic markers
A
- Hep A: Surface antigen/ antibody (Acute infection confirmed by + IgM Anti HAV)
- Hep B: surface antigen/ core antibody (Acute infection confirmed by + HBsAg or Anti-HBc; delta agent: Anti HDV, Anti-HBs= long term immunity to Hep B infection)
- Hep C: HCV RNA by PCR
- Hep E : HEV RNA by PCR
- 30% in US have anti-Hep A
- 90% in developing countries
34
Q
drug induced hepatitis
A
- Direct hepatotoxicity: dose dependent and reproducible (Anabolic steroids, IV tetracyline, acetaminophen)
- Idiosyncratic reaction (most common form)
- Host hypersensitivity (Phenothiazines, antibiotics, thyroid, cytotoxic, oral hypoglycemics)
- Fever
- RUQ pain
- Pruritis
- Skin rash
- Eosinophilia
- Increased transaminases
35
Q
alcoholic hepatitis
A
- Occurs after prolonged (10 yrs) heavy intake
- Anorexia, fatigue, jaundice
- Tender hepatosplenomegaly
- Fever, leukocytosis
- Elevated AST > ALT
- Definitive DX by liver biopsy
- 33% progress to cirrhosis
- Risk of hepatic encephalopathy
