Gastroenterology

Question 1

2 regulatory sequences within HBV gene

Answer 1

• GRE glucocorticoid responsive element
• enhancer
  GRE regulates enhancer

Question 2

which gene produces HBsAg?

Answer 2

Gene S

Question 3

Function of HBV enhancer I

Answer 3

stimulates protein expression esp.

the core protein

Question 4

Function of HBV region X

Answer 4

encodes products for transactivation (integrating genome into host genome),
? related to carcinogenesis

Question 5

Function of HBV Enhancer II

Answer 5

stimulates surface gene promoters

Question 6

Function of HBV Direct repeat II DRII

Answer 6

initiates short +ve strand synthesis, preferential sites for integration

Question 7

Function of HBV DRI direct repeat I

Answer 7

initiates long -ve strand synthesis,

preferential sites for integration

Question 8

Where is HBcAg found? Which gene encodes it?

Answer 8

found in virus or hepatocytes

GeneC

Question 9

Where is HBeAg found?

Answer 9

Serum

Question 10

clinical significance of pre-C protein in HBV

Answer 10

Mutant strain with stop codon (TAG) causes
inability to produce HBeAg even if virus is still rapidly replicating
Mutation detected around e-seroconversion,
probably because immune factors
selecting against HBeAg-producing virus,
so HBeAg-deficient mutants emerge.
These pts will be HBeAg -ve, anti-HBe +ve,
HBV DNA +ve

Question 11

Function of HBV Gene P

Answer 11

Encodes polymerase and reverse transcriptase

Question 12

Steps of HBV replication

Answer 12

1. adsorption
2. release of relaxed circular partially dsDNA
3. completion of +ve strand DNA
4. transport to nucleus
5. conversion to supercoiled cccDNA
6. transcription of mRNA
7. transportation of mRNA to cytoplasm
   8a. translation of mRNA to viral proteins

8b. translation of pregenomic RNA to DNA pol/RT
9b. encapsidation of DNA pol bound to pregenomic RNA
10b. RT of pregenomic RNA to full length -ve strand DNA
11b. +ve strand DNA synthesis by DNA pol into relaxed circular partial dsDNA
12b. amplification and replenishment of cccDNA

Common pathway after 8a/11b:

9a. migration to ER
10a. acquisition of envelopes
11a. exocytosis

Question 13

2 types of jaundice

Answer 13

unconjugated/indirect hyperbilirubinemia (prehepatic)

conjugated/direct hyperbilirubinemia (hepatic or post-hepatic)

Question 14

Causes of unconjugated hyperbilirubinemia/ prehepatic jaundice

Answer 14

1. increased bilirubin production - hemolysis (G6PD deficiency, thalassemia)
2. decreased hepatic uptake - drugs (rifampicin)
3. decreased conjugation - congenital (Gilbert’s syndrome, Criggler-Najjar syndrome)

Question 15

Raised ALP and GGT

Answer 15

• cholestatic conditions

- SOL in liver except polycystic liver

Question 16

Isolated GGT elevation

Answer 16

• alcohol
• Fatty liver
• drugs (rifampicin, antiepileptics - phenytoin carbamazepine barbituates)

Question 17

Isolated ALP elevation

Answer 17

• bone conditions (bone CA, Pagets, osteomalacia, MM)
• puberty
• pregnancy

Question 18

Causes of conjugated hyperbilirubinemia

Answer 18

hepatic: (diffuse hepatic injury)
- hepatitis
- late stage cirrhosis
post-hepatic:
intrahepatic - hepatocyte secretory defect eg cholestatic phase of viral hepA and E; bile canaliculi eg PBC PSC
extrahepatic obstruction - CBD stones, cholangitis, malignancy

Question 19

reasons for elevated globulin in cirrhosis

Answer 19

• portosystemic shunting
• not degraded properly in the liver
• abnormal antigen produced in cirrhotic liver

Question 20

reversed A:G (>42:<36)

Answer 20

• MM
• cirrhosis
• nephrotic syndrome
• SLE

Question 21

What exceptional liver disease gives AST>ALT

Answer 21

AST 2x> ALT
1. alcoholic liver disease 
2. CA/met liver 
AST not 2X> ALT
2.5 NASH progressed to cirrhosis

Question 22

Etiology of acute hepatitis

Answer 22

• hepatitic virus
• drugs
• alcoholic
• obesity
• autoimmune
• metabolic
• nonhepatitic virus

Question 23

Serological markers for HCV

Answer 23

anti-HCV

HCV RNA

Question 24

Etiology of chronic hepatitis

Answer 24

• HBV, HCV, HDV
• drugs
• alcoholic
• NASH
• autoimmune

Question 25

what is Gilbert's syndrome

Answer 25

reduction in hepatic bilirubin glucuronyl transferace activity

Question 26

isolated bilirubinemia what to investigate next

Answer 26

MCV Hb for hemoglobinopathy G6PD for g6pd deficiency Reticulocyte count for hemolysis

Question 27

which autoantibody is associated with PBC

Answer 27

AMA - antimitochondrial antibodies

Question 28

Reasons for HBV chronicity in neonates

Answer 28

Host factors - failure of host to recognize infected hepatocytes cuz antigen is covered by maternal antiHBc Viral factors - excessive production of HBsAg --> modulation of immune signalling pathways - HBx proteins inhibit degradation of viral protein --> reduce antigen presentation - polymerase protein suppress immunity - precore/HBeAg downregulates immunity

Question 29

HBsAg + AntiHBs - AntiHBc +

Answer 29

``` acute infection (IgM anti-HBc +) chronic carriers (IgM anti-HBc -) ```

Question 30

HBsAg + AntiHBs - AntiHBc -

Answer 30

very early phase of incubation period of acute infection

Question 31

HBsAg - AntiHBs + AntiHBc -

Answer 31

past infection | post vaccination

Question 32

HBsAg - AntiHBs - AntiHBc +

Answer 32

acute infection (IgM antiHBc +) past infection occult infection

Question 33

HBsAg - AntiHBs + AntiHBc +

Answer 33

Past infection | occult infection