Quiz 2

(Ref: Harrison 20th edition p 2400)
 GGTP is not specific to alcohol since it is easily inducible and elevated in all forms of fatty liver.
 AST and ALT are increased 2 – 7 times with AST/ALT ratio > 1 in alcoholic hepatitis
 ALP is used for evaluation of obstructive jaundice LDH is elevated in hemolytic anemia and malignancy.

(Ref: Trends in biomarkers in disease and pubmed index number: PMC5729599 p 57) Serum Hyaluronic acid is a glycosaminoglycan and is a component of ECM that is produced by hepatic stellate cells. The degradation of same occurs in sinusoidal
endothelial cells. The serum concentration of Hyaluronic Acid is elevated in patients of hepatic fibrosis and can serve as a non-invasive surrogate for liver biopsy.
Extra mile
1. Fibrosure/ Fibro Test
■ Incorporates haptoglobin, bilirubin, GGT and Apolipoprotein A-1 and α2 macroglobulin.
■ High level of positive and negative predicitive values for diagnosing advanced fibrosis. 2. Fibro scan/ Transient Elastography Evaluates hepatic stiffness
3. Magnetic resonance Elastography

(Ref: Harrison 20th edition, p 2361)
 In Chronic HBV infection, possibilities are:
1. HBsAg remains detectable beyond six months
2. Anti-HBc is primarily of the IgG class
3. Anti-HBs is either undetectable or detectable at low levels
 During early chronic HBV infection, HBV DNA can be detected both in serum and in hepatocyte nuclei, where it is present in free or episomal form.
 HBeAg is a qualitative marker and HBV DNA a quanti-tative marker of replicative phase
 In chronic hepatitis B is the degree of hepatitis B virus (HBV) replication is more important than histology alone.
 In both HBeAg-reactive and HBeAg negative chronic hepatitis B, the level of HBV DNA correlates with the level of liver injury and risk of progression.
 The level of HBV replication is the most important risk factor for the ultimate development of cirrhosis and HCC in both HBeAg-reactive and HBeAg-negative patients.

(Ref: Nelson 20th edition, p 1547; CMDT 2019 edition, p 695)
The following infants are considered "high-risk" and should receive both vaccine and HBIG.
1. Mother is HBsAg seropositive and HbeAg positive
2. Mother is HBsAg seropositive and HbeAg/anti-HBe, negative
3. Mother is HBsAg seropositive and e markers are not available
4. Mother has acute hepatitis B in pregnancy
5. Mother is HBsAg seropositive and infant in born weighing 1500g or less

(Ref: Harrison 20th edition, p 277; Harrison 19th edition p 280)
Total serum bilirubin = Direct bilirubin + Indirect bilirubin + Delta Bilirubin
 Delta bilirubin is a part of the direct-reacting (conjugated) bilirubin that is covalently linked to albumin, is known as delta fraction, or bili-protein.
 Because of tight binding to albumin, the clearance rate of albumin-bound bilirubin from serum approximates the half-life of albumin, 12-14 days, rather than the short half-life of bilirubin, about 4 hours.
 It represents an important fraction of total serum bilirubin in patients with cholestasis & hepatobiliary disorders.
 The prolonged half-life of albumin-bound conjugated bilirubin explains why do?
1. Some patients with conjugated hyperbilirubinemia do not exhibit bilirubinuria during the recovery phase of their disease because the bilirubin is covalently bound to albumin and therefore not filtered by the renal glomeruli
2. Elevated serum bilirubin level declines more slowly than expected in some patients who otherwise appear to be recovering satisfactorily.
3. Late in the recovery phase of hepatobiliary disorders, all the conjugated bilirubin may be in the albumin-linked form. Its value in serum falls slowly because of the long half-life of albumin.

(Ref: CMDT 2019 p 727, Harrison 19th p 673)
The cause for the disease cannot be found in about half of the patients.
 Primary Budd-Chiari syndrome (75%): thrombosis of the hepatic vein
 Secondary Budd-Chiari syndrome (25%): compression of the hepatic vein by an outside structure (e.g. a tumor)
 Hepatic vein thrombosis is associated with the following in decreasing order of frequency:
1. Polycythemia vera
2. Pregnancy
3. Post partum state
4. Use of oral contraceptives
5. Paroxysmal nocturnal hemoglobinuria
6. Hepatocellular carcinoma
7. Lupus anticoagulants

(Ref: Harrison 20th edition, p 2413; Harrison 19th p 441e-42f)
Specific treatment of hepatic encephalopathy is aimed at
1. Elimination or treatment of precipitating factors and
2. Lowering of blood ammonia (and other toxin) levels by decreasing the absorption of protein and nitrogenous products from the intestine.
 In the setting of acute gastrointestinal bleeding, blood in the bowel should be promptly evacuated with laxatives (and en-mas if necessary) in order to reduce the nitrogen load.
 Protein should be excluded from the diet, and constipation should be avoided.
 Ammonia absorption can be decreased by the administration lactulose, a non-absorbable disaccharide that acts as an osmotic laxative.
 Metabolism of lactulose by colonic bacteria may also result in an acid pH that favors conversion of ammonia to the poorly absorbed ammonium ion.

(Ref: Harrison 20th edition, p 2043)
 Initial resuscitation requires rapid re-expansion of the circulating intravascular blood volume along with interventions to control ongoing losses.
 Continuing acute blood loss, with hemoglobin concentrations declining to < 100 g/L (10 g/dL), should initiate blood transfusion, preferably as fully cross matched recently banked (< 14 days old) blood.
 Resuscitated patients are often coagulopathic due to deficient clotting factors in crystalloids and banked packed red blood cells (PRBCs). Early administration of component therapy during massive transfusion [fresh-frozen plasma (FFP) and platelets] approaching a 1:1 ratio of PRBC/FFP appears to improve survival. In extreme emergencies, type-specific or O-negative packed red cells may be transfused. Following severe and/or prolonged hypovolemia, inotropic support with norepinephrine, vasopressin, or dopamine may be required to maintain adequate ventricular performance.
 Once hemorrhage is controlled and the patient has stabilized, blood transfusions should not he continued unless the hemoglobin is < ~7g/dL.