Gastroenterology Flashcards
Interpreting Hep B serology, Autoimmune hepatitis
Interpretating Hepatitis B serology
* HbsAg
* Anti-Hbs
- HbSag surface antigen is the first marker to appear and causes the production of anti-HbS
- if HBsAg is present for > 6 months then this implies chronic disease (i.e. Infective)
Anti-HBs implies immunity (either exposure or immunisation). It is negative in chronic disease
previous immunisation: anti-HBs positive, all others negative
Interpretating Hepatitis B serology
- Explain Anti-HBc and what having IgM vs IgG means
Anti-HBc implies previous (or current) infection.
* IgM anti-HBc appears during acute or recent hepatitis B infection and is present for about 6 months.
* IgG anti-HBc persists and positivity indicates past infection or reactivation
Will never appear in a vaccinated individual
Interpreting Hepatitis B serology
What would previous hepatitis B >6 months ago, NOT a carrier?
What would hepatitis B but now a carrier?
- previous hepatitis B (> 6 months ago), not a carrier: anti-HBc positive, HBsAg negative
- previous hepatitis B, now a carrier: anti-HBc positive, HBsAg positive
What is hepatitis B
Transmission
Incubation period
Features
Hepatitis B is a double-stranded DNA hepadnavirus
spread through exposure to infected blood or body fluids, including vertical transmission from mother to child.
The incubation period is 6-20 weeks.
The features of hepatitis B include fever, jaundice and elevated liver transaminases.
Complications of hepatitis B infection
chronic hepatitis (5-10%). ‘Ground-glass’ hepatocytes may be seen on light microscopy
fulminant liver failure (1%)
hepatocellular carcinoma
glomerulonephritis
polyarteritis nodosa
cryoglobulinaemia
National immunisation program Hep B
- children born in the UK are now vaccinated as part of the routine immunisation schedule. This is given at 2, 3 and 4 months of age
How to interpret anti-Hbs levels
When do you test anti-Hbs
- testing for anti-HBs is only recommended for those at risk of occupational exposure (i.e. Healthcare workers) and patients with chronic kidney disease. In these patients anti-HBs levels should be checked 1-4 months after primary immunisation
Management of hepatitis B
- pegylated interferon-alpha used to be the only treatment available. It reduces viral replication in up to 30% of chronic carriers.
- A better response is predicted by being female, < 50 years old, low HBV DNA levels, non-Asian, HIV negative, high degree of inflammation on liver biopsy
- whilst NICE still advocate the use of pegylated interferon firstl-line other antiviral medications are increasingly used with an aim to suppress viral replication (not in a dissimilar way to treating HIV patients)
- examples include tenofovir, entecavir and telbivudine (a synthetic thymidine nucleoside analogue)
Hepatitis C
Incubation period
Features
Incubation period 6-9 weeks
After exposure to the hepatitis C virus only around 30% of patients will develop features such as:
* a transient rise in serum aminotransferases / jaundice
* fatigue
* arthralgia
Hepatitis C
Investigations
Prognosis
Investigations
HCV RNA is the investigation of choice to diagnose acute infection
whilst patients will eventually develop anti-HCV antibodies it should be remembered that patients who spontaneously clear the virus will continue to have anti-HCV antibodies
Outcome
around 15-45% of patients will clear the virus after an acute infection (depending on their age and underlying health) and hence the majority (55-85%) will develop chronic hepatitis C
What is defined as chronic hepatitis C
What are the complications
Chronic hepatitis C may be defined as the persistence of HCV RNA in the blood for 6 months.
Potential complications of chronic hepatitis C
rheumatological problems: arthralgia, arthritis
eye problems: Sjogren’s syndrome
cirrhosis (5-20% of those with chronic disease)
hepatocellular cancer
cryoglobulinaemia: typically type II (mixed monoclonal and polyclonal)
porphyria cutanea tarda (PCT): it is increasingly recognised that PCT may develop in patients with hepatitis C, especially if there are other factors such as alcohol abuse
membranoproliferative glomerulonephritis
Hepatitis C - management
- treatment depends on the viral genotype - this should be tested prior to treatment
- the management of hepatitis C has advanced rapidly in recent years resulting in clearance rates of around 95%. Interferon based treatments are no longer recommended
- the aim of treatment is sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy
- currently a combination of protease inhibitors (e.g. daclatasvir + sofosbuvir or sofosbuvir + simeprevir) with or without ribavirin are used
Ribavirin side effects
ribavirin - side-effects: haemolytic anaemia, cough. Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic
Interferon alpha side effects
interferon alpha - side-effects: flu-like symptoms, depression, fatigue, leukopenia, thrombocytopenia
Define hepatitis D co-infection vs superinfection
How to distinguish between the two
Hepatitis D terminology:
* Co-infection: Hepatitis B and Hepatitis D infection at the same time.
* Superinfection: A hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection.
Diagnosis is made via reverse polymerase chain reaction of hepatitis D RNA. Interferon is currently used as treatment, but with a poor evidence base.
What are causes of hepatomegaly
3 C’s and 3 I’s
C - cirrhosis (early)
C - cancer (craggy)
C - congestion (portal hypertension 2 to RHF or cirrhosis)
I - infection (HBV HCV / CMV / EBV / malaria)
I - immune - (hepatitis / PSC / PBC)
I - infiltration with amyloid / sarcoid / haem malignancy / haemochromatosis
What should you do if abnormal LFT and what is 1st line imaging / other imaging [4]
Liver screen
USS = 1st line to show duct dilatation / mets
MRCP - MRI
ERCP if removing i.e. cholangitis / pancreatitis
What is in a liver screen [8]
Hep B,C,E EBV, CMV, HIV Auto-immune / Ab / Ig Serum copper - for Wilson disease Ferritin and transferrin - Haemochromatosis A1-anti-trypsin Glucose Lipids
How do you investigate hepatomegaly [6]
LFT’s
If abnormal = liver screen
FBC - liver disease cause BM suppression / MCV alcohol
U+E - hepatorenal syndrome / malnourishment
CLotting / albumin
CRP
Imaging
What is 1st line imaging
USS to show mets / stone / cirrhosis
What is hepatorenal syndrome
HRS is a form of functional renal failure without renal pathology that occurs in 10% of patients with advanced cirrhosis or acute liver failure
Arterial renal circulation disturbanced causing increased vascular resistance causing renal vasoconstriction
Type 1
Type 2
distinguished by chronicity - type 1 is acute occurring within 1-2 weeks while type 2 is a more chronic picture
What are causes of splenomegaly [7]
Infection - Lyme’s, meningitis, sepsis, Glandular fever, TB
DIC
Malignancy - lyphhoma / leukaemia / myeloma
Sjogren / SLE / RA / vasculitis/ Sarcoid
Portal hypertension
IE, Rheumatic fever
Amyloid
What are causes of massive splenomegaly [4]
Malaria
CML
Myelofibrosis
Leishmaniasis
What is important in history of splenomegaly [7]
Fever - infection / TB / malignancy / sarcoid
Lymphadenopathy - glandular / malignancy
Ascites - portal / malignancy
Arthritis / vasculitis/ RA / sjogre / SLE / lyme
Weight loss - malignancy / TB
Purpura - meningitis / DIC /sepsis
Murmur - IE / rheumatic
What can cause abdominal distension 5 F’s
Flatus Fat Fluid Faeces Fetus
What are differential of ascites? [6]
Malignancy Infection - TB Decreased albumin CCF Pancreatitis / cancer Portal hypertension - cirrhosis / IVC / portal vein thrombosis
How do you investigate differentials for ascites [7]
FBC + film U+E, LFT, CRP Ca tumour marker - Ca19-19 (pancreas) TB USS CT, MRI
What are RF for jaundice [7]
BBV - Blood transfusion, IVDA, Piercing / tattoo, STI, Foreign travel
Alcohol
FH
Drugs
What causes mass in RIF [8]
Appendicitis Caecal cancer Crohn's disease Intussception TB Kidney malformation / transplant Undescended testis
What can obstructive jaundice be further classified into [2]
Calcular
Malignant
Calcular causes of obstructive jaundice features [4]
F>M
Biliary colic
No weight loss
Fluctuates
Malignant causes of obstructive jaundice features [4]
M>F
Painless
Weight loss
Progressive
Ascitic fluid investigations, biochemistry [7]
Tap: MC&S and AFB, cytology, albumin, LDH, glucose, protein
Ascitic fluid investigations: SAAG
What does it mean if SAAG >1.1g/dL and what does it mean if <1.1 [4]
Serum ascites albumin gradient (SAAG): serum albumin – ascites albumin
o SAAG >1.1g/dL: portal HTN (transudates)
o SAAG <1.1g/dL: other causes (peritoneal or visceral neoplasia, inflammation (pancreatitis), nephrotic syndrome, TB peritonitis) (exudates)
Management of ascites [4]
daily weights (aim for <0.5kg/d) & restrict Na intake fluid restriction (<1.5L/d) therapeutic paracentesis (with 100mL 20% albumin per L drained to reduce post paracentesis circulatory dysfunction) TIPSS transjugular intrahepatic portosystemic shunt
Spontaneous bacterial peritonitis
Ax [4]
Symptoms [3]
Ix [2]
Ax: ascites becomes infected with E. coli, Klebsiella or strep
Sy/Si: ascites, abdo pain, fever
Ix: paracentesis (neutrophil count >250 cells/uL and MC&S tends to show E. coli)
Spontaneous bacterial peritonitis
Mx
Cx
Prevention
Mx: IV CEFOTAXIME
Cx: hepatorenal syndrome 30%
Pre: prophylactic CIPROFLOXACIN if ascites and protein <15g/L
What is PBC
Chronic autoimmune granulomatous attack on bile duct INSIDE liver
Leads to cholestasis
Cirrhosis / portal hypertension
What causes PBC
Autoimmune
Genetic
Environment
M rule
- Middle age
- IgM
- Anti mitochondrial Ab
What are the symptoms of PBC
None Incidental raised ALP Fatigue *Tiredness & Pruritus = classic Jaundice RUQ pain Bone and joint pain Dry eyes and mouth Hyperpigmentation HSM Clubbing Xanthesomata
Who is at risk of PBC
Women Smoking Autoimmune Pregnancy UTI Nail polish FH
What is associated with PBC
Sjogren
Systemic sclerosis
RA
Thyroid
How do you Dx PBC
Initial investigations
Blood - raised ALP, GGT
AMA + IGM = Dx
Increased bilirubin, INR, decreased platelet
Increased TSH?
Other imaging
USS to exclude extra-hepatic
Liver biopsy / cholangiogram not usually needed unless AMA negative which it can be in 10%
How do you treat PBC
UDCA - doesnt cure but halts progression
Fat soluble vitamins
Bone protection like bisphosphonates
Treat dry eyes
Treat pruritus - cholestryalmine, plasma exchange
Liver transplant if severe
How do you monitor PBC
Regular LFT
USS and AFP 6 monthly
What are the complications of PBC
Cirrhosis Decompensated liver Vitamin deficiency due to fat malabsorption - ADEK -Osteomalacia -OSteoporosis -Coagulopathy HCC
What is PSC
Chronic autoimmune inflammation and scarring of intra and extra hepatic ducts
Cholestasis
What causes PSC
Unknown
80% = UC
Who is at risk of PSC
Male
Young adult
pANCA
ANA +ve
AMA -ve
Autoimmue hepatitis
UC > Crohns
HIV
What are the symptoms of PSC
Fatigue CHolestasis = jaundice / pruritus Abdo pain RUQ Fever Ascending cholangitis if advanced Cirrhosis Hepatic failure
How do you Dx PSC
Bloods - LFT / ANCA / IgG
USS - look for other cause e.g. gall stone
MRCP = diagnostic, beaded appearance
ERCP if going to do invasive Rx
Liver biopsyy / cholangiogram not usually needed
How do you treat PSC
URODEOXYCHOLIC ACID Treat itch - rifampicin Liver transplant = main stay Endoscopic treatment of bile duct / stent Ax if infection
When do you transplant
Chronic and poor QOL
Carcinoma
Genetic
MELD score
What do you give before transplant
Anti-rejection
Immunosuppresion
Steroid
Ax
What are the complications of PSC
Cirrhosis
Intrahepatic obstruction
Cholangiocarcinoma
What is advised in patients with PSC
Annual colonoscopy especially if UC
What is cholangiocarcinoma
mucin-producing adenocarcinomas arising from the biliary tract with features of cholangiocyte differentiation
grouped by site of origin: intrahepatic, perihilar or peripheral
90% adenocarcinoma
Extrahepatic 80%
What are the symptoms of cholangiocarcinoma
Obstructive painless jaundice - gradual onset
Weight loss
Pruritus
Signs
Mass in RUQ
LN (peri-umbilical) + Virchow
Ascites
Hypercalcaemia
Hypophosphate
Bloods
Ca-125, CEA, Ca 19-9
What tumour markers are elevated
Ca-125 - ovarian
Ca19-19 - pancreas
CEA - bowel
What are the RF for cholangiocarcinoma
Age
Liver fluke
Choledochal cysts
Chronic liver inflammation
How do you Dx cholangiocarcinoma
Raised bilirubin and ALP Coag and INR may be affected USS = 1st line may show dilatation EUS Staging = CT / MRI / MRCP
How do you treat cholangiocarcinoma
Surgery = only option but only 30% operable
Adjuvant chemo / RT
What is palliative Rx for cholangiocarcinoma
Surgical bypass
ECRP / PTC to stent
Chemo or RT
What are post-op complications
Liver failure
Bile leak
Bleeding
What is Ddx
Stone
Cholecystitis
Benign stricture
What is ampulla cancer
Cancer of ampulla
Adenocarcinoma
Rx = endoscopic excision or pancreaticoduodectomy
