LIVER DISORDERS AND ENZYMES Flashcards

Question

what is the upper limit of normal for ALK?

Answer 1

elevated AST/ALT marker of injury, inflammation, necrosis of hepatic parenchyma

Answer 2

elevated alk phos +/- increased total bilirubin

Answer 3

both hepatocellular and cholestatic injury

Answer 4

NAFLD/NASH hep c hep b alcohol liver disease

Answer 5

wilsons dz alpha 1 antitrypsin deficiency

Answer 6

meds alcohol hepatitis hep a hep b

Answer 7

primary biliary cholangitis primary sclerosing cholangitis malignancy medications

Answer 8

biliary obstruction ABV/CMV/HSV pregnancy

Answer 9

sarcoidosis autoimmune cholangiopathy amyloidosis

Answer 10

thyroid dz muscle injury celiac dz chronic pancreatitis AI hemolysis bone disorders CF right HF malignancy systemic infection AIDS cholangiopathy

Answer 11

IgM anti HAV

Answer 12

IgM anti Bc IgM anti Bs

Answer 13

IgM ant HCV HCV RNA

Answer 14

anti smooth muscle antibody, ANA, increased GGT

Answer 15

ferritin, Fe high. Iron infiltrates organs (pituitary, pancreas, heart)

Answer 16

low ceruloplasmin, hemolysis

Answer 17

low serum A1AT

Answer 18

viral replication asx labs show serologic nd enzyme markers of hepatitis

Answer 19

prodromal anorexia N/V alterations in taste arthralagias malaise fatigue urticaria and pruritus aversion to cig smoke in this stage often dx w/ gastroenteritis or viral syndrome

Answer 20

icteric dark urine pale-colored stools x GI sx and malaise become icteric and may develop RUQ pain w/ hepatomegaly

Answer 21

convalescent sx and icterus resolve liver enzymes return to normal

Answer 22

traveling or working in countries w/ high or intermediate rates of HAV illegal drugs (injection or not) occupational risk exposures close personal contact w/ international adoptee unvax ppl in outbreaks settings that provide service to HAV ppl

Answer 23

oral fecal- overcrowding and poor sanitation contaminated water or food- inadequately cooked shellfish biggest RF is international travel

Answer 24

excreted in feces up to 2 weeks before clinical illness

Answer 25

before clinical illness occurs

Answer 26

concomitant chronic hep C

Answer 27

adults-> self limited symptomatic >70% sx uncommon in children <6 y/o abrupt onset fever, N/V, anorexia, abd pain, malaise within days to weeks-> dark urine (bilirubinuria) acholic stools jaundice and pruritus early s/sx diminished when jaundice appears; jaundice peaks in 2 weeks

Answer 28

Jaundice, scleral icterus, hepatomegaly (80%), RUQ tenderness to palpation. Less common: splenomegaly and extrahepatic manifestations such as skin rash and arthralgias. Pregnancy: infection has been associated with increased risk of preterm labor. No specific disease manifestations in immunocompromised hosts

Answer 29

Labs  WBC count usually low in preicteric phase  Mild proteinuria  High elevations of AST and/or ALT occur early  Hyperbilirubinemia may precede jaundice

Answer 30

Detection of IgM anti-HAV antibodies. Serum IgM antibodies are detectable at the time of symptom onset, peak during the acute or early convalescent phase of the disease, and remain detectable for 3-6 months. Detection of serum IgM antibodies in the absence of clinical symptoms may reflect prior HAV infection with prolonged persistence of IgM, a false-positive result, or asymptomatic infection (more common in children <6 years of age than in older children/adults). Serum IgG antibodies appear early in the convalescent phase of the disease, remain detectable for decades, and are associated with lifelong protective immunity

Answer 31

know course of HAV graph

Answer 32

Usually self-limited: supportive care. Full clinical and biochemical recovery is observed within 3 months in 85%. Prevention: vaccination, immune globulin, attention to hygienic practices.

Answer 33

prodrome of anorexia, N/V, malaise, aversion to smoking fever, enlarged tender liver, jaundice normal to low WBC count, high aminotransferase early on liver bx-> hepatocellular necrosis and mononuclear infiltrate but is rarely indicated

Answer 34

Modes of transmission - Inoculation of infected blood or blood products or by sexual contact - Present in saliva, semen, and vaginal secretions - HBsAG-positive mothers can transmit @ delivery - Risk of chronic infection to infant is ~90%

Answer 35

MSM  IVDU  Patients/staff at hemodialysis centers  Physicians/PAs/Dentists/Nurses/Lab and blood bank workers

Answer 36

heterosexual transmission

Answer 37

Incubation period 6 weeks to 6 months

Answer 38

Usually insidious in onset

Answer 39

Aminotransferase levels usually higher in HBV than in HAV

Answer 40

Similar to all viral hepatitis, variable  Ranges from asymptomatic infection to fulminating disease and death in a few days  Fever is common and low grade  Defervescence and fall in pulse rate coincide with jaundice onset

Answer 41

HBsAg (surface antigen)  1st evidence of infection  Before biochemical evidence of liver disease  Persistence >6 months signifies chronic HBV Anti-HBs (antibody to surface antigen)  Two sources  Clearance of HBsAg by immune system  Successful vaccination  Disappearance of HBsAg and appearance of anti-HBs signals recovery, non-infectivity, and immunity Anti-HBc  Appears right after HBsAg  Never appears alone  In the setting of acute hepatitis B, IgM anti-HBc makes the diagnosis  IgG anti-HBc persists indefinitely  Both in recovered patients and in chronic HBV infections HBeAg  Secretory form of HBcAg  Appears during incubation period after HBsAG  Indicates viral replication and infectivity  Persistence >3 months increases chances of chronic infection state  Disappearance often followed by appearance of anti-HBe  Signifies ↓ viral replication and ↓ infectivity

Answer 42

Detectable only with PCR  Presence parallels presence of HBeAg  HBV DNA is more sensitive and precise marker of viral replication and infectivity  Some patients who have recovered have low level HBV DNA in liver and serum, but most are not infectious

Answer 43

 Vaccination  Isolation from unvaccinated individuals  Hand hygiene  Universal precautions  Hepatitis B immune globulin (HBIG)  Protective/lessens severity if given within 7 days of exposure  Followed by vaccine

Answer 44

 Supportive as for acute hepatitis A  Encephalopathy or severe coagulopathy indicates impending acute hepatic failure  Transfer to liver transplant center  Antivirals used in severe, but not mild cases  Clinical recovery complete in 3 to 6 months  Mortality is 0.1-1%  Worse with superimposed Hepatitis D

Answer 45

Acute illness subsides over 2-3 weeks - Clinical and laboratory recovery by 16 weeks May become chronic - Defined as elevated aminotransferase levels >6 months * 40% will develop cirrhosis * Especially if coinfected with hepatitis C and/or HIV * Those with cirrhosis at increased risk for hepatocellular carcinoma

Answer 46

* Body piercing * Tattoos * Hemodialysis * Incarceration

Answer 47

* Multiple sexual partners * HIV coinfection * Unprotected receptive anal intercourse * Sex while high on methamphetamine

Answer 48

Incubation period 6 – 7 weeks

Answer 49

Clinical illness is usually mild or asymptomatic  Jaundice more likely during acute illness  Waxing and waning aminotransferase elevations  >80% chance of becoming chronic

Answer 50

Aminotransferases often normalize during pregnancy despite continued viremia  Elevate again after delivery

Answer 51

 Enzyme immunoassay (EIA) detects antibodies to HCV  Antibodies are not protective  Negative antibody test indicates no chronic HCV infection, no need for further evaluation.  Other confirmatory tests  HCV RNA measurement

Answer 52

 Systemic disorders:  Membranoproliferative glomerulonephritis  Possible relationships:  Lichen planus  Autoimmune thyroiditis  Idiopathic pulmonary fibrosis  Increased risk of non- Hodgkin lymphomas  Insulin resistance

Answer 53

 Test donated blood  Birth cohort screening born 1945-1965 recommended  HCV-infected persons should practice safe sex  Little evidence that HVC is spread easily by sexual contact or perinatally  NO specific measures are recommended for persons in a monogamous relationship or for pregnant women  Vaccination against HAV and HBV in patients with chronic HVC

Answer 54

 Evolving rapidly  Spontaneous resolution in 15% - 50%. Monitoring for spontaneous clearance for a minimum of 6 months before initiating treatment is therefore recommended.

Answer 55

 Two goals.  Achieve sustained eradication of HCV  Prevent progression to cirrhosis, hepatocellular carcinoma, and decompensated liver disease requiring liver transplantation.

Answer 56

 Antiviral therapy should be determined on a case-by-case basis.  However, treatment recommended for patients with elevated serum alanine aminotransferase (ALT) levels who meet the following criteria:  Older than 18 years  Positive HCV antibody and serum HCV RNA test results  Compensated liver disease (eg, no hepatic encephalopathy or ascites)  Acceptable hematologic and biochemical indices (hemoglobin at least 13 for men and 12 for women; neutrophil count >1500/mm 3, serum creatinine < 1.5 mg/dL)  Willingness to be treated and to adhere to treatment requirements  No contraindications for treatment

Answer 57

 Psychologic counseling  Alcohol avoidance  Symptom control  Dose adjustment of medications  Assessment of fibrosis  Screening for complications of cirrhosis if present

Answer 58

 Defective RNA virus capable of causing hepatitis in association with HBV  Requires HBsAg  Clears when HBsAg clears  Can cause superinfection in patients with chronic HBV  Fulminant hepatitis or severe chronic hepatitis that progresses rapidly to cirrhosis  In US, new cases are infrequent because of control of HBV infection  Immigrant population at highest risk (endemic areas, including Africa, central Asia, Eastern Europe, Amazon region of Brazil)  Diagnosis is by detection of anti-HDV and, where available, hepatitis D antigen (HDAg) or HDV RNA in serum.

Answer 59

 Major cause of acute hepatitis throughout Central and Southeast Asia, the Middle East, and North Africa  Consider in those traveling to endemic areas  In industrialized countries, may be spread by swine; having pet in the home and consuming undercooked organ meats or infected cow’s milk are risk factors.  Risk increased in patients undergoing hemodialysis.  In endemic areas, mortality rate is high in pregnant women.  Generally is self-limited, no carrier state. Risk of hepatic decompensation and death increased if underlying chronic liver disease.  Problematic in transplant situation

Answer 60

Diagnosis by testing for IgM anti-HEV in serum, although available tests may not be reliable. A 3-month course of treatment with oral ribavirin has been reported to induce sustained clearance of HEV RNA in patients with persistent HEV infection and may be considered in patients with severe acute hepatitis E

Answer 61

- Obesity - Diabetes mellitus - Hypertriglyceridemia - Risk 4 to 11 x higher in those with metabolic syndrome/insulin resistance - Physical activity may be protective

Answer 62

One of the cardinal features of portal hypertension. The appearance is due to cutanous portosystemic collateral formation between distended and engorged paraumbilical veins that radiate from the umbilicus across the abdomen to join systemic veins.

Answer 63

- Asymptomatic or mild RUQ discomfort - Hepatomegaly ~75% - May or may not be stigmata of chronic liver disease - Signs of portal hypertension if advanced fibrosis/cirrhosis - NAFLD Fibrosis Score (http://nafldscore.com)

Answer 64

 May be mild or moderate elevations in AST and ALT.  Degree of aminotransferase elevation does not predict degree of hepatic inflammation or fibrosis  Normal levels do not exclude NAFLD.  When elevated, AST and ALT typically 2x to 5x upper limit of normal, with AST/ALT ratio of <1 (unlike alcoholic fatty liver disease, which typically has AST/ALT ratio >2).  Alkaline phosphatase may be elevated to 2x to 3x upper limit of normal.  Serum albumin and bilirubin levels are typically within the normal range.  May be elevated serum ferritin or transferrin saturation.

Answer 65

 US: hyperechoic texture/bright liver because of diffuse fatty infiltration.  Biliary dilatation suggests extrahepatic cholestasis due to gallstones, strictures, or malignancy. Absence of biliary dilatation suggests intrahepatic cholestasis.  CT and MRI can identify steatosis but not inflammation or fibrosis.  Magnetic resonance spectroscopy (MRS) is quantitative, but not widely available.  Study compared MRS with liver biopsy: correlation between measurement of intrahepatocellular lipid by MRS and histologic assessment of cirrhosis.

Answer 66

 Requires all of these:  Hepatic steatosis by imaging or bx  Exclusion of significant alcohol consumption  Exclusion of other causes of hepatic steatosis  Absence of coexisting chronic liver disease  Radiologic findings can make diagnosis if other causes of hepatic steatosis have been excluded.  Liver biopsy if diagnosis not clear or to assess degree of hepatic injury.  Bx is only method to differentiate NAFLD from NASH.

Answer 67

 Lifestyle changes  Drugs  Vitamin E, 800 U?  Metformin (may not improve liver histology)  TZDs, GLP-1  Liver transplant  For advanced cirrhosis

Answer 68

 Result of injury that leads to both fibrosis and regenerative nodules.  May be reversible if cause is removed.  The clinical features result from hepatic cell dysfunction, portosystemic shunting, and portal hypertension

Answer 69

 Most common:  Chronic alcoholism  Chronic viral hepatitis (B/C)  Hemochromatosis  NAFLD/NASH

Answer 70

 Autoimmune hepatitis  Primary and secondary biliary cirrhosis  Primary sclerosing cholangitis  Medications (methotrexate, isoniazid)  Wilson disease  Alpha-1 antitrypsin deficiency  Celiac disease

Answer 71

 Hepatocyte dysfunction  Inability of hepatocyte to perform normal tasks  Portosystemic shunting  Portal vein blood flow not flowing through liver  Blood not presented to hepatocytes for processing  Portal hypertension  Portal system, like pulmonary system, is low pressure  Obstructed liver blood flow results in “back pressure”

Answer 72

 May have no symptoms for long periods.  Symptom onset usually insidious.  Fatigue, disturbed sleep, muscle cramps, weight loss are common.  Advanced cirrhosis:, anorexia may be extreme, with associated N/V, reduced muscle strength/exercise capacity.  May be abdominal pain.  Menstrual abnormalities (amenorrhea), erectile dysfunction, loss of libido, gynecomastia  Hematemesis is presenting symptom in 15–25%

Answer 73

 Esophageal varices - Hematemesis  Gastric varices - Melena  Splenomegaly - Dilated abdominal veins  Rectal varices - Hemorrhoids  Ascites - Increased hydrostatic pressure  Hepatic encephalopathy  Accumulation of serum ammonia in the brain due to lack of excretion by liver  Precipitating Factors: infection, GI bleeding, hyponatremia, hypovolemia, sedating drugs  Clinical Findings: decreased mental function, poor concentration, Asterixis, stupor  Diagnosis: no gold standard  Clinical findings/psychometric testing  Serum ammonia levels not useful  Management:  Non-absorbable disaccharides: Lactulose  Non- absorbable antibiotics: Rifaxamin (suppresses bowel flora, decreasing ammonia production)

Answer 74

 Non-absorbable disaccharide syrup  Digested by colonic bacteria  Acidifies colon contents  Favors formation of non-absorbable ammonium ion (NH4+)  Favors change in bowel flora: fewer ammonia-forming organisms  Continued use after acute episode may reduce frequency of recurrences

Answer 75

 Hepatorenal Syndrome  Deterioration of kidney function due to alterations in blood flow  High mortality rate  Liver transplant definitive therapy  Hepatopulmonary Syndrome  Hypoxemia secondary to vasodilation in lungs  Symptoms: Platypnea-orthodeoxia (dyspnea and deoxygenation when changing from a recumbent to an upright position)  Management: Supplemental O2, liver transplant

Answer 76

 Bleeding from varices  Hepatic failure  Increased risk of hepatic cancer  Increased risk of infection/sepsis

Answer 77

Rapid development of hepatocellular dysfunction with associated coagulopathy and mental status changes in patient without known prior liver disease

Answer 78

- Medications: most common in US is acetaminophen - Alcohol - viral Hepatitis - Acute fatty liver of pregnancy - Wilson disease - Autoimmune hepatitis

Answer 79

- Confusion, jaundice, ascites - High mortality

Answer 80

 History = hepatic encephalopathy  Blood work: elevated transaminases (often with abnormal bilirubin and alk phos); prolonged prothrombin time (INR ≥1.5)  CT head

Answer 81

 ICU monitoring  Supportive treatment: fluid balance, mechanical ventilation, treatment of underlying cause  Liver transplant if no improvement

Answer 82

 May be normal in early disease  Alcohol suppresses marrow production of all cell lines.  Thrombocytopenia, most common cytopenia, due to sepsis, folate deficiency, or splenic sequestration.  Anemia, frequent, often macrocytic  Causes include folate deficiency, hemolysis, hypersplenism, occult/overt GI blood loss  WBC may be low, reflecting hypersplenism, or high suggesting infection.  Prolonged PT from reduced levels of clotting factors.  Abnormalities of fibrinolysis: increased risk of venous thromboembolism.  Hepatocellular injury/dysfunction: modest elevations of AST and alkaline phosphatase, progressive elevation of bilirubin.  Serum albumin decreases as disease progresses; gamma-globulin levels are increased.  Risk of DM increased, esp when HCV infection, alcoholism, hemochromatosis, NAFLD.  Vitamin D deficiency common.

Answer 83

 US  Assess liver size  Detect ascites  Detect hepatic nodules  Combined with Doppler may establish patency of splenic, portal, and hepatic veins  Contrast-enhanced CT good for characterizing nodules  CT or ultrasound guided biopsy if malignancy is suspected

Answer 84

 Esophagogastroduodenoscopy (EGD)  Confirms presence of varices  Detects specific causes of bleeding

Answer 85

GOLD STANDARD FOR DX FibroTest (FibroSure in the US): biomarker test that uses six blood serum tests to generate a score correlated with degree of liver damage. May eventually have same prognostic value as liver biopsy

Answer 86

 Review treatment of esophageal varices  Abstinence from alcohol.  Palatable diet, with adequate calories and protein and, if fluid retention, sodium restriction.  In hepatic encephalopathy, protein intake should be reduced to no less than 60–80 g/day.  Vitamin supplementation.  HAV, HBV, pneumococcal vaccines, yearly influenza vaccine, COVID vaccine.

Answer 87

 Results from portal hypertension:  With increased hydrostatic pressure, this results in hypoalbuminemia, decreasing oncotic pressure.  Peripheral vasodilatation, impaired hepatic inactivation of aldosterone; and increased aldosterone secretion secondary to increased renin production.

Answer 88

 Diagnostic paracentesis for ascites  Cell count and culture, ascitic albumin level (serum albumin minus ascitic fluid albumin ≥ 1.1suggests portal hypertension).

Answer 89

 Evaluation should be considered once a patient with cirrhosis has experienced a complication such as ascites, hepatic encephalopathy, or variceal hemorrhage or hepatocellular dysfunction  Comprehensive medical, surgical and psychiatric evaluation  Cardiac, pulmonary, dental, cancer screening  Transplant priority based on severity of hepatic dysfunction based on MELD-Na (Model of End Stage Liver Disease score) https://www.mdcalc.com/meldna-meld-na-score-liver-cirrhosis  Exclusion criteria include: severe pulmonary HTN, extrahepatic malignancy, severe cardiopulmonary disease, severe vascular disease, uncontrolled infection, active substance abuse, lack of adequate social support, poorly controlled psychiatric illness

Answer 90

 CTP score is obtained by adding the score for each parameter  CTP class:  A = 5-6 points  (100% survival)  B = 7-9 points  (80% survival)  C = 10-15 points  (45% survival)

Answer 91

Major cause of liver disease in United States  15-20% chronic heavy drinkers develop hepatitis or cirrhosis  Defined as 60-80 g/day for men and 20g/day for women Risk Factors * FHx, Hx substance abuse, underlying depression or anxiety disorder Signs and Symptoms * Acute hepatitis can present with signs of liver failure: jaundice, ascites, etc. Diagnosis * History, history, history** * 2:1 ratio of AST/ALT * Serum alcohol level, ethyl gluconuride * Iron Studies ( ferritin, iron, TIBC), Folate, Vitamin B12 * Liver biopsy not warranted Treatment * Abstinence and counseling * Steroid taper in acute alcoholic hepatitis?

Answer 92

 Syndrome in which a clot causes narrowing or blockage of the hepatic veins  Primary venous process vs. Secondary compression process  Risk Factors  Hypercoagulable state – pregnancy, oral contraception, sickle cell disease, polycythemia, etc.  Signs and Symptoms  Acute vs. chronic blockage  RUQ pain, fatigue, tenderness, abdomen fullness, jaundice, ascites/ lower extremity edema  Diagnosis  Ultrasound with doppler is gold standard  CT/MRI/Venography  Treatment  Correcting underlying disorders  Anticoagulation  Angioplasty/liver transplant for those who have progressed

Answer 93

 Small intrahepatic bile ducts  Labs: ALK > > AST/ALT; Anti mitochondrial Antibody (AMA) +  Common in woman  Dx: US evaluation to rule out obstruction; Liver Biopsy to confirm Dx if AMA  Sx: itching, sjogren’s syndrome, fatigue  Treatment: Ursodeoxycholic acid (UDCA)

Answer 94

 Labs:  AST/ALT >> ALK Phos  Antinuclear Antibody (ANA) +  Elevated Gamma Globulins (IgG)  Anti-smooth Muscle antibody (SMA) +  More common in woman  Dx: Liver biopsy to confirm Dx  Sx: fatigue/flu-like  Can present as fulminant hepatic failure  Treatment includes Prednisone taper and Azathioprine

Answer 95

 Leads to narrowing of intra- and extrahepatic bile ducts  Labs: Alk phos = ALT/AST, Elevated Total Bilirubin  Association with Ulcerative Colitis  Sx: jaundice, itching  Risk of cholangitis  Tx: MRCP/ERCP with stenting  Increased risk for Cholangiocarcinoma

Answer 96

Hemochromatosis *Iron Overload leading to iron accumulation within liver *Patients of northern European descent *Labs: Iron/ferritin/TIBC if clinical suspicion, If iron saturation >45%, check genetic testin *Dx: Liver biopsy with hepatic iron index, Imaging: MRI *Treatment includes phlebotomy or iron chelation therapy Alpha 1 Antitrypsin Deficiency *Genetic disorder leading to defective production of A1AT *Can affect lungs and liver, Suspect with early onset COPD *Labs: Serum A1AT level, A1AT phenotype *Tx: A1AT infusion for lung related disease, Supportive care/transplant for liver related disease Wilson Disease *Autosomal recessive disorder related to ineffective copper metabolism *Young patients with neuropsychiatric symptoms *Labs: Serum ceruloplasmin, 24 hour urine copper *Dx: Slit lamp exam for Kayser- fleischer rings *Management includes genetic counseling and copper chelation

Answer 97

 AST/ALT are associated with hepatic inflammation, not hepatic synthetic function. INR, albumin, and bilirubin are associated with hepatic synthetic function  To confirm hepatitis C with active viremia, one must have a positive Hepatitis C RNA  Presence of Positive HBV surface Ab in absence of other positive markers is consistent with immunization  Thrombocytopenia can indicate cirrhosis with portal hypertension (sequestration of platelets in enlarged spleen)  Screen all patients with advanced fibrosis/cirrhosis for cancer