GI Flashcards
Pattern of Liver Enzyme Elevation
Hepatocellular (ALT, AST)
1000’s: Toxins/Drugs (acetaminophen)
Viral (acute Hep A, B, D, or E)
Vascular: Shock, Budd Chiari
Acute stone w/ in 24 hours
Autoimmune hepatitis
Wilson’s (rare)
100’s: Viral (Hep B, C), CMV, EBV
Alcoholic Hepatitis AST > ALT
<100’s: Autoimmune (Celiac), NASH
Hemochromatosis, Wilson’s, A1AT
Cholestatic (ALP, GGT)
Obtain U/S / MRCP
Extrahepatic (biliary duct dilatation):
- Painful - Stones
- Painless - Strictures (PSC), benign obstruction
(IgG4/AIP, AIDS cholangiopathy), malignant
obstruction
Intrahepatic (no duct dilatation):
Drugs (antibiotics, TPN, estrogens, MTX), PBC,
infections, cholestasis of pregnancy, infiltrative
disease
Workup:
- U/S, CT, MRCP, EUS (for stones)
- ERCP NOT for diagnosis, generally only for
therapeutic intervention
- Liver biopsy
Hepatitis A- diagnosis and treatment
- Self-limited infection
- Fecal-oral transmission
- Diagnosis: Anti-HAV IgM
- Treatment is supportive, transplant for fulminant hepatitis
- You can immunize against it
– Who? - Travelers to Hep A Endemic countries, chronic liver disease, MSM, PWID,
recurrent plasma derived clotting factors, zoo-keepers or vets handling non-
human primates
- Post exposure prophylaxis: Household contacts of Hep A infected
individuals, co-workers and clients of infected food handlers, contacts in
childcare or JK/SK
Acute Hepatitis B- diagnosis and treatment
- Diagnosis
– Hepatitis B surface antigen (HBsAg) and core IgM are positive - Natural history
– <5% of adults progress to chronic HBV
– <1% of adults develop liver failure - Treatment
– Treatment is mainly supportive
– Consider antiviral therapy (knowing they may become surface Ag negative and
not require this long term)
– Ensure household and sexual contacts are immune and provide hepatitis B
vaccine if they are not immune - No need for Hep B Immunoglobulin per CDC for household contacts.
- Sexual contacts and those with percutaneous exposure to high risk source are
recommended for Hep B immunoglobulin within 48h ideally if their immune status is
unknown (or low titre)
Following Chronic Hep B
Baseline work-up for Hep B sAg+
* Physical exam
* ALT, CBC, Cr, HBV DNA, HBe serology, fibroscan
* HIV, Hep D in high risk groups (PWID, from endemic area)
Follow-up for Hep B sAg+
* ALT, HBV DNA q 6-12mos, and repeat fibroscan if persistent elevated ALT and HBV DNA
* US (not AFP) every 6 mos for HCC surveillance if:
– All cirrhotics
– Asian M > 40, Asian F > 50
– African > 20
– Family History HCC (in first degree relatives)
– All HIV co-infected starting age 40
Chronic Hep B: Who and Why to treat?
Why treat?
– Prevent cirrhosis
– Prevent HCC
- Goals of treatment
– Suppress viral replication
(decrease HBV DNA level)
– eAg seroconvert
(eAg+/eAb- à eAg-/eAb+)
– sAg seroconvert
(sAg+/sAb- à sAg-/sAb+)
Who to treat?
– Cirrhosis
* Liver transplant workup if decompensated (MELD >15)
* If Fibrosis > stage 1, regardless of ALT or HBeAg status, with
HBV DNA>2000, treatment is case by case decision
– Extra-hepatic manifestations
– HBeAg positive, ↑ ALT, HBV DNA ≥ 2,000 IU/ml (CASL)
– HBeAg negative,↑ ALT, HBV DNA ≥ 2,000 IU/ml
– Pregnancy
* End 2nd/ Start of 3rd trimester + high DNA levels (HBV DNA
>200,000 IU/ml i.e. 5 logs, 2x105) - treat to prevent fetal transmission [tenofovir]
* Baby should also get HBIG + HBV vaccine after birth
- Do not treat
– Immune-tolerant phase or inactive CHB phase (normal ALT)
– Acute infection is generally managed supportively
Treatment of Chronic HBV
Nucleotide Analogues
(tenofovir, entecavir, lamivudine)
*Pros
– Tenofovir/Entecavir very high barrier to
resistance, considered 1st line
– Potent viral suppression
– Well tolerated
* Cons
– Many years of therapy, and can be life
long (especially in eAg negative disease)
– (Getting less) expensive
– Unlikely to convert to seroconvert sAg
Peg-Interferon
*Pros
– Finite therapy (typically 48w)
– Generally more durable response
* Cons
– Side effects (lots)
– Only specific patients benefit
* Low DNA, high ALT
* Non cirrhotic HBeAg+ CHB (CASL2018,
though practically not used anymore)
– Cannot use in decompensated cirrhosis
Hepatitis C- diagnosis and work-up
Diagnosis -
Prior exposure (and immune cleared, or cured by therapy) = Anti-HCV
Chronic Hepatitis =Anti-HCV HCV RNA
Work-up at diagnosis:
* HCV Genotype testing, HCV RNA level, HIV, HBV
* Liver enzymes, liver function testing
* Abdominal ultrasound
* Fibrosis assessment, prognostication:
– TE/FibroScan, FibroTest, AST: Platelet ratio index (APRI), or biopsy
Extrahepatic manifestations of hepatitis C:
o Autoimmune: Autoimmune thyroid disease, myasthenia gravis, Sjogren’s
o Renal: MPGN > membranous glomerulopathy
o Derm: Porphyria cutanea tarda, leukocytoclastic vasculitis
o Heme: lymphoma (NHL), autoimmune hemolytic anemia, ITP, Cryoglobulinemia
o Other: Insulin resistance / Diabetes mellitus
Approach to HCV Treatment
1) Treat ALL patients with chronic hep C EXCEPT those with short life expectancy due to comorbidities
2) Check HCV RNA (and genotype, especially if cirrhosis), check for co-infections (Hep B, HIV)
3) Fibrosis Assessment
– Can use APRI score/ FIB-4 score to exclude clinically significant fibrosis. If > F2 fibrosis à proceed to fibroscan.
– Fibroscan > 12.5 kPa = cirrhosis.
– Ultrasound is insensitive for cirrhosis. Only needed IF cirrhotic, to exclude HCC.
– If cirrhosis, consider transplant assessment (MELD ≥ 15).
4) If simple HCV (no cirrhosis, co-infection), choose one of 2 pan-genotypic regimens:
– Sofosbuvir/ Velpatasvir (Epclusa; 1 pill once daily x 12 wks) or Glecaprevir/ Pibrentasvir (Maviret; 3 pills once daily x 8 wks)
5) Check viral load 12-weeks post treatment completion. If negative, the patient is likely CURED
(termed SVR12, sustained virological response)
Alcohol-associated Hepatitis- definition and tx
- Acute onset hepa//s associated with ongoing alcohol intake (within 8 wks)
- AST > 50, AST/ALT > 1.5-2, and both values < 400, Tbili > 51
- Clinical diagnosis; Biopsy rarely needed (consider if AST/ALT > 400, other Dx suspected)
- Treatment
– Assess eligibility for steroids: Severe AH i.e. Maddrey Discriminant Funcaon≥ 32 (or MELD >20)
or presence of encephalopathy à Prednisolone 40mg PO daily (⬆28d mortality; max benefit
at MELD 25-39) - If Lille score at 4 or 7 days < 0.45 à continue pred x 28d then taper; if ≥ 0.45 à stop; consider early
liver transplantation (no longer requirement for minimum period of abstinence; case-by-case)
– Assess for contraindications to steroids: Uncontrolled infection, uncontrolled GI bleed, AKI
– EtOH cessation and nutrition (high calorie, high protein diet) are vital
– NAC can be considered in addition to steroids – “may improve 30 d survival in severe AH”
– NO role for pentoxifylline in addition to steroids per ACG/AASLD; trend toward benefit in HRS
– No mortality benefit for prophylactaic antibiotics in Alc hep (Louvet et al. JAMA. 2023)
Metabolic-Associated Fatty Liver Fast Facts
NEW terminology faiy liver disease:
* MASLD (NAFLD): Faiy liver with no
hepatocellular injury
* MASH (NASH): + hepatocellular injury
* Met-ALD: MASLD + increased EtOH intake
MASLD Diagnosis - 1) evidence of steatosis,
2) rule out 2° causes (i.e. EtOH)
– MASH can only by diagnosed definiatively on Bx
– Associated with T2DM (most imp RF), ↑lipids,
HTN, obesity, metabolic syndrome, OSA
– Most common cause of death in MASLD is ♥
– Many cases of cryptogenic cirrhosis are likely
“burned out” MASLD
Screen for clinically significant fibrosis:
– T2DM, medically comorbid obesity, 1st degree relative
with MASH cirrhosis, pts with alcohol use
– FIB-4 score for everyone à if > 1.3 à fibroscan
– Treatment
* Weight loss (diet + moderate intensity exercise)
≥ 3-5% ↓ to improve steatosis, 7-10% to improve fibrosis
* Identify + manage CV risk factors
– Statins are safe in MASLD/MASH, including
compensated cirrhosis
* Pharmacotherapy
– Semaglutide for MASH + T2DM/ obesity
* Bariatric surgery if obese
Approach to Cirrhosis: Causes
Determine etiology
– (1) Viral (2) Fatty liver [EtOH, NASH], (3) Autoimmune/ cholestatic
[AIH, PBC, PSC], (4) Genetic [Wilson, HH, A1AT], (5) Chronic biliary
disease, (6) Vascular [R CHF, Budd Chiari]
– Labs, abdominal imaging (+ doppler), and consider biopsy if
indeterminate cause
* Assess severity
– Child-Pugh score – predicts perioperative mortality for open
abdominal surgery (based on old data, likely overestimates risk):
– CP A (score 5-6) – 10%
– CP B (score 7-9) – 30%
– CP C (score 10-15) – 80%
– MELD ≥ 15 – refer for liver transplant assessment
* 6 mo of EtOH abstinence no longer a rule in Ontario (case by case)
Approach to Cirrhosis:
Complications + Counseling
Assess for complications:
– Varices à EGD at diagnosis, then interval based on findings
– Ascites/SBP à Paracentesis at diagnosis, any inpatient presentation, and if concern for SBP
– Hepatic encephalopathy à History/ exam
– Hepato-renal syndrome, Hep-pulmonary Syndrome/porto-pulmonary hypertension à History/exam/labs
– HCC à Abdominal U/S at diagnosis and q6mo
– Screen for FRAILTY, MALNUTRITION in clinic (new – ACG 2021 Guideline on Frailty, Sarcopenia and
Malnutrition in Cirrhosis)
* Counseling:
– Abstinence from alcohol, adequate nutrition, weight loss for NAFLD
– Limit acetaminophen to ≤ 2g/day
– Avoid sedatives, NSAIDs, ACEI/ARBs
– HAV, HBV, COVID 19, TdAP, Pneumococcal, flu vaccinations (+zoster if age >50, MMR and Varicella where
applicable)
– Refer to multidisciplinary team if frailty, sarcopenia or malnutrition (ACG 2021 Guidelines)
– Refer to palliative care team if decompensated cirrhosis at any point in journey (AASLD 2022 Guidance
statement -improves symptoms, quality of life, caregiver stress)
Approach to Varices
Primary prophylaxis (never bled)
– Screen every patient at diagnosis of cirrhosis or at time of decompensation
– Patients receive: NSBB OR EVL
– Detailed algorithm on next slide
* Secondary prophylaxis (after bleed)
– Patients receive: NSBB AND EVL
NSBB: non selective beta blocker ex. nadolol, propranolol; OR carvedilol | titrate to HR 55-60 and
maintain SBP>90
EVL: endoscopic variceal ligation
(see table in notes)
Ascites- etiology and management
Etiology
– SAAG >11 = ‘transudative’ (e.g., portal HTN)
– SAAG < 11 = ‘exudative’ (e.g., malignancy, pancreatitis, infection (TB), nephrotic syndrome)
* For ascites related to portal HTN
– Initial management
* Treat underlying liver disease (stop alcohol, treat HCV, etc.)
* Salt restriction (< 2 g or 88 mmol/day)
– Water restriction not necessary unless [Na] < 125
* Diuretics (start with Spironolactone 100mg and Lasix 40mg daily, titrate as needed – monitor for :
hypotension, AKI, electrolyte imbalance)
– Failing medical therapy
* Serial therapeutic paracentesis; give albumin 6-8 g/L of fluid removed for taps > 4L
* TIPS if no contraindications (encephalopathy, HCC)
– Liver transplant
10mmol/day of non-urinary Na loss; therefore:
1) For patients not on diuretics, do 24-hour urine Na collection
* 24-hr urine Na <78 mmol - COMPLIANT w diet
* 24-hr urine Na >78 mmol -NON-COMPLIANT
2) Start diuretics if ongoing ascites or unable to comply
3) For patients on diuretics, do 24-hour urine Na collection
* 24-hr uNa <78 mmol -DIURETIC-RESISTANT at current doses à increase diuretic
dose until limited by AKI, electrolyte abN, BP, etc.
* 24-hr uNa >78 mmol AND patient not losing weight -NON-COMPLIANT with Na
restriction - reinforce Na restriction
* 24-hr uNa >78 mmol AND weight loss à patient is adherent to sodium restriction
and diuretic sensitive -stay the course
Spontaneous Bacterial Peritonitis Diagnosis
Perform diagnostic paracentesis in every patient with new ascites AND in every
cirrhotic with ascites who presents to hospital
- SBP classically presents with abdominal pain and fever (can also present with
encephalopathy, hypotension, AKI, or worsening liver function) - Diagnosis of SBP
– Neutrophils in ascitic fluid > 250 cells/mm3 OR culture-positive ascitic fluid - culture-negative ascites still requires complete course of treatment
– Rule out secondary cause of peritonitis (e.g., bowel perforation or recent
surgery)
Spontaneous Bacterial Peritonitis- treatment
Treatment of confirmed SBP
– Ceftriaxone (or Fluoroquinolone if Pen allergic) x 5 days
– HRS prophylaxis - Day 1: Albumin 1.5g/kg; Day 3: Albumin 1 g/kg
* In practice almost everyone gets albumin, but guidelines suggest only if Cr > 88,
BUN > 10.7, or bili > 68
* Post SBP: lifelong prophylaxis with Norfloxacin, Septra DS, or Cipro.
Indications for SBP prophylaxis
1) Patients who have previously had SBP -Indefinite SBP prophylaxis
2) Patients with cirrhosis who present with upper or lower GI bleeding (don’t need to
have ascites) à SBP prophylaxis x 7 days
3) Cirrhotic with ascitic fluid protein is <15 g/L and at least one of:
- Impaired renal function (Cr ≥ 106, BUN ≥ 8.9, Na ≤ 130)
- Impaired liver function (Child-Pugh ≥ 9 and Bili ≥ 51 umol/L)
Hereditary Hemochromatosis (HH) definition
ACG Clinical Guideline: Hereditary Hemochromatosis (2019)
* Autosomal recessive disorder causing ↑ intestinal absorption of iron à iron overload
* More common in Northern European descent;
* Most HH is due to mutation of HFE gene at C282Y, H63D, or S65C
– Type 1A hemochromatosis: C282Y homozygous = confirms diagnosis of HH
– Type 1B hemochromatosis: C282Y/H63D heterozygous = less likely (but possible) to
have iron overload
– Genotypes that do not lead to clinically significant iron overload = C282Y/ wildtype,
H63D/ wildtype, H63D homozygote, S65C mutation (type 1C hemochromatosis)
Hereditary Hemochromatosis Clinical Manifestations
- Iron deposition in end-organs:
– Liver: Cirrhosis, elevated liver enzymes
– Skin: ‘Bronze’ hyperpigmentation
– Endocrine: Hypopituitarism (impotence,
amenorrhea), diabetes (islet cell destruction).
– MSK: Arthropathy (2nd/3rd MCP ‘hooked
osteophytes’) - Fatigue
- Increased risk of infection: Listeria monocytogenes,
Yersinia enterocolitica, E. Coli, Vibrio vulnificus. - DDx Iron Overload (secondary iron overload)
– Dyserythropoeisis (sickle cell, thalassemia)
– Chronic transfusions
– Other chronic liver diseases: - MASLD *RC favorite
- Alcohol-related liver disease
- Hep C
Hereditary Hemochromatosis Treatment
Who + when to treat:
– C282Y homozygotes if ferritin > 300 (men) or > 200 (women) AND Tsat > 45%
– C282Y/H63D heterozygotes/ other à Evaluate for other causes of iron overload/ liver dz + consider
MRI/ Bx to estimate hepatic iron concentration (HIC) à Treat other causes 1st, then, if high HIC à treat
* Treatment:
– 1st-line = phlebotomy targeting ferritin 50 – 100
– 2nd- line (when patient refractory to phlebotomy e.g. anemia, high output CHF) = chelation (i.e.
desferoxamine, deferiprone, deferasirox)
* Risks of retinal/auditory toxicity (desferoxamine), agranulocytosis (deferiprone), liver/renal toxicity (deferasirox).
– No need to limit red meat/dietary iron if undergoing phlebotomy
– Avoid consuming vitamin C supplements (↑iron absorption)
– Avoid uncooked seafood (Listeria, Yersinia, and Vibrio ♥ Fe)
– Liver transplantation for decompensated cirrhosis/focal HCC
* HCC screening: Only if cirrhosis. ACG recommends against screening if fibrosis ≤ stage 3.
* Other Heterozygotes: Monitor iron indices annually + assess for organ damage, no treatment needed
Celiac Disease- diagnosis
Symptoms & Signs:
– Diarrhea/ steatorrhea, abdo pain, bloadng, weight loss, anemia, osteoporosis, enamel defects, elevated
transaminases (mild), inferdlity
– Vitamin + mineral deficiencies – A, D, E, B12, Fe, Ca
– Dermadds herpedformis
* Diagnosis:
– And-TTG IgA & quandtadve immunoglobulins (r/o ↓ IgA) +/- and-deamidated gliadin pepdde [DGP] IgG (if ↓
IgA) +/- and-endomysial andbody [EMA]
– Upper endoscopy with small-bowel biopsy – Marsh Classificadon [High risk, posidve serology]
Celiac Disease tx
Treatment: Lifelong gluten-free diet
* Follow-up – Ensure adherence
– Diet history
– ↓ antibody titres +/- improvement of histology
– Follow-up serology 6 and 12 months post
diagnosis, then annually*
* Patients with persistent symptoms despite
negative serology should undergo repeat biopsy
to determine healing*
HLA DQ2/DQ8 Testing
– Should NOT be routinely ordered (poor PPV)
– Consider if…
* Equivocal histology in seronegative patients
* Evaluation in patients on a gluten-free diet where testing can be falsely negative
* Discordant serology and histology
* Suspicion of refractory Celiac or when Diagnosis in question
* Patients with Down’s syndrome
* Patients with a history diagnosis of Celiac (especially as very young children before
introduction of TTG-IgA testing)
