Gastroenterology 2025 PDF

Gastroenterology Sunday, December 1st, 2024 Dr. Navneet Natt www.internalmedicinereview.ca © Internal Medicine Review 2025  Overview Disorders of the Liver...

Gastroenterology Sunday, December 1st, 2024 Dr. Navneet Natt www.internalmedicinereview.ca © Internal Medicine Review 2025  Overview Disorders of the Liver Disorders of the Esophagus – Approach to elevated liver enzymes – Barrett’s – Viral Hepatitis – Dysphagia – Alcoholic Hepatitis Achalasia, EoE – Fatty Liver – Cirrhosis Disorders of the Pancreas – Hemochromatosis – Acute Pancreatitis Disorders of the Intestines – Chronic pancreatitis – Celiac Disease – Autoimmune Pancreatitis – Inflammatory Bowel Disease – GI Bleeding COVID19 and GI – H. pylori BONUS SLIDES: GI Potpourri 2  BONUS Read on own Acronyms Used in this Talk BCS Budd Chiari Syndrome CP Score Child-Pugh Score CTX Ceftriaxone EUS Endoscopic ultrasound GIB Gastrointestinal Bleed (Upper or Lower) HCC Hepatocellular Carcinoma IFN Interferon MASH Metabolic Dysfunction Associated Steatohepatitis PPI Proton Pump Inhibitor (ex lansoprazole) RCE Rational Clinical Examination SBP Spontaneous Bacterial Peritonitis TE Transient Elastography TIPS Transjugular intrahepatic portosystemic shunt TPN Total parenteral nutrition 3  BONUS Read on own Guidelines CAG Guidelines: https://www.cag-acg.org/publications/guideline-library CASL Guidelines: https://hepatology.ca/publications/guidelines/ AASLD Guidelines: https://www.aasld.org/publications/practice-guidelines-0 ACG Guidelines: https://gi.org/clinical-guidelines/clinical-guidelines-sortable- list/?sort=datedesc AGA Guidelines: https://gastro.org/clinical-guidance/ 4  Question 1: Liver – NEW 2025 A 42 year-old male with alcohol use disorder presents to the ED with new onset jaundice, ascites, and fever of 39.2 degrees Celsius. His last drink was 6 weeks ago. He does not use any other drugs or medications. His labs demonstrate the following: total bilirubin 128, AST 368, ALT 162, ALP 224. His MELD score is 32 and Maddrey Discriminant Function score is 44. What is the next best step? A. Start prednisolone 40mg daily for severe alcohol hepatitis and calculate a Lille score at day 4 to determine response to corticosteroids B. Send off blood and urine cultures, complete diagnostic paracentesis to r/o SBP, and consider broad-spectrum antibiotics while awaiting results C. Order transjugular liver biopsy for confirmation of histologic diagnosis D. Start IV N-Acetylcysteine for severe AH 5  Pattern of Liver Enzyme Elevation Hepatocellular (ALT, AST) Cholestatic (ALP, GGT) *Obtain US / MRCP* 1000’s: Toxins/Drugs (acetaminophen, cocaine – associated with ischemic injury) Extrahepatic (biliary duct dilatation): Viral (Acute Hep A, B, D, or E) - Painful à Stones Vascular: Shock, Budd Chiari - Painless à Strictures (PSC), Benign obstruction Acute stone w/ in 24 hours (IgG4/AIP, AIDS cholangiopathy), malignant Autoimmune hepatitis obstruction Wilson’s (rare) Intrahepatic (no duct dilatation): Drugs (antibiotics, TPN, estrogens, MTX), PBC, infections, 100’s: Viral (Hep B, C, CMV, EBV), Congestive cholestasis of pregnancy, infiltrative disease (e.g. Hepatopathy, Alcohol Hepatitis AST > ALT sarcoidosis), congestive hepatopathy MPGN, aplastic anemia 2018 CASL-AMMI HBV Guidelines: https://hepatology.ca/publications/guidelines/current-guidelines/ AASLD Guidelines for Treatment of Chronic Hepatitis B (Hepatology. 2016 Jan;63(1):261-83.) 10  Following Chronic Hepatitis B – CASL 2018 Who to screen for Hep B Baseline work-up for Hep B sAg+ CASL 2018 Physical exam (look for stigmata CLD & extrahepatic manifestations of HBV) (HBsAg, HBsAb. HBcAb) ALT, CBC, Cr, HBV DNA, HBe serology, HIV, HCV 1. Born in HBV endemic area Hep D in high-risk groups (PWID, hemodialysis, MSM, from endemic area) 2. Household contacts of Non-invasive fibrosis testing (Fibroscan or APRI [AST-to-platelet ratio index] in HBV carriers resource limited setting as per WHO 2024*) 3. HBV+ sexual partner 4. IVDU Follow-up for Hep B sAg+ 5. Incarcerated 6. CKD needing dialysis ALT & HBV DNA q 6-12mos 7. Elevated liver enzymes or Repeat fibroscan if persistent elevated ALT and HBV DNA signs of liver disease US + AFP (AASLD 2023*) every 6 mos for HCC surveillance if: 8. All pregnant women – Cirrhosis 9. Patients needing – Asian M > 40, Asian F > 50 immunosuppression e.g. biologics, chemotherapy – African > 20 – Family History HCC in first degree relatives) – All HIV co-infected starting age 40 2018 CASL-AMMI HBV Guidelines: https://hepatology.ca/publications/guidelines/current-guidelines/ 2024 WHO Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection: https://www.who.int/publications/i/item/9789240090903 11  Chronic Hepatitis B: Who to treat Goals of treatment: 1. Prevent cirrhosis, 2. Prevent HCC (which can develop w/out cirrhosis) CASL 2018 INDICATIONS TO TREAT WHO 2024 INDICATIONS TO TREAT 1. Cirrhosis 1. Evidence of >F2 fibrosis regardless of ALT or Liver transplant workup if MELD >15 HBV DNA levels 2. Extrahepatic manifestations of HBV 2. Extrahepatic manifestations of HBV 3. HBV DNA > 2000 IU/mL + ↑ ALT 3. HBV DNA > 2000 IU/mL + ↑ ALT ALT elevation defined as persistent ALT elevation above ULN x 3-6 months in CASL 2018 ALT elevation defined as persistent ALT elevation Regardless of HBeAg status pos. or neg. above ULN similar to CASL 4. Pregnancy: HBV DNA > 200 000 IU/mL in late 4. Pregnancy: HBV DNA > 200 000 IU/mL or HBeAg 2nd/early 3rd trimester (24-32 weeks GA) positive in 2nd trimester Goal of treatment is to prevent fetal transmission Recommendation is also for tenofovir (TDF) Preferred tx = tenofovir (TDF) Baby should also get HBIG + HBV vaccine within 12h WHO also recommends treatment for CHB in those with: 1. Co-infections (HIV, Hep C, Hep D); 2. Family hx of liver cancer or cirrhosis; 3. of birth and complete primary vaccination series Comorbidities such as MASLD or Diabetes; 4. Immune suppression (e.g. Breastfeeding is not contraindicated transplant) Since these are not in Canadian guidelines, go with CASL indications to treat for an MCQ question! For indications 1-4, can cite CASL or WHO for an oral exam. 12  Treatment of Chronic HBV Nucleotide Analogues Pegylated-Interferon. Rarely used Tenofovir (TDF or TAF) + Entecavir (ETV) >> Lamivudine Pros – Finite therapy x 48 weeks Pros – Generally more durable response – Tenofovir & ETV considered 1st line; very high barrier to resistance Cons Also recommended as 1st line Tx in WHO 2024 Generally, prefer TAF given less renal and bone A/E but $$ – ++ Side effects Tenofovir disoproxil fumarate (TDF) has best evidence in pregnancy – Only specific patients benefit – Potent viral suppression – Low DNA, high ALT – Well-tolerated – Non cirrhotic HBeAg+ CHB (CASL 2018, though practically Cons not used anymore) – Usually life-long therapy (especially in eAg negative disease) – Cannot use in decompensated – Unlikely to seroconvert sAg cirrhosis – (Getting less) expensive Lamivudine is cheaper but high rate of resistance – Adverse Effects: Renal insufficiency (Fanconi syndrome with TDF – check Cr and Ph periodically) Osteomalacia / osteoporosis Lactic acidosis (rare) 13  Hepatitis C Diagnosis Anti-HCV HCV RNA Who to screen for Hep C? (CASL 2018) Prior exposure & cleared ✔ - (spontaneously resolved or cured by 1. One-time population-based testing for anyone therapy) born between 1945-1975 Chronic Hepatitis ✔ ✔ 2. Risk-based Screening: History of past or current IVDU Natural History of Hepatitis C: Received blood products before 1992 in Canada Acute infection (15-30% spontaneously resolve) à Chronic Born or lived in area w/ Hep C prevalence >3% Hepatitis à Cirrhosis à Decompensation à HCC (N. and subsaharan Africa; Middle East; Central, East, and South Asia; Eastern Europe; Australia) Born to Hep C + mother Work-up at diagnosis: Current or previous incarceration HCV RNA level, HCV Genotype Testing HIV co-infection Liver enzymes, liver function tests, Cr Sexual contact with HCV+ partner Test for co-infections: HIV, HBV (HBsAg, anti-HBs, anti-HBc) Elevated ALT Baseline Abdominal US in everyone Receiving hemodialysis Fibrosis Staging to exclude cirrhosis Annual re-testing of HCV RNA recommended for individuals – TE/FibroScan, FibroTest, AST: Platelet ratio index (APRI), or with ongoing high-risk exposures e.g. HIV+, MSM, IVDU biopsy as normal US does not exclude cirrhosis! Recommendations on Hepatitis C Screening in Adults: 2018 Guideline Update CASL (CMAJ 2018 Jun 4;190(22):E677-E687. doi: 10.1503/cmaj.170453.) 14  MCQ on Hepatitis C Factors which increase risk of cirrhosis o Older age, male sex, HIV/HBV co-infection, obesity/DM/fatty liver, alcohol abuse Factors which increase risk of HCC o Cirrhosis or co-existing liver disease which may accelerate fibrosis 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 15  Approach to HCV Treatment HCV RNA, HCV Genotype Treatment-Naive Choose from 1 of 2 pan-genotypic direct acting ALT, AST, ALP, Bili, INR, Albumin anti-viral (DAA) agents*: Creatinine, BhCG, HIV, Hep B panel No cirrhosis or compensated Child Sofosbuvir/ Velpatasvir (Epclusa 1 pill once daily x 12 wks) Pugh A cirrhosis Fibrosis staging for cirrhosis or Glecaprevir/ Pibrentasvir (Maviret 3 pills once daily x 8wk) - Prev treated for HCV *Treat ALL patients with chronic hep C EXCEPT - eGFR 15 -Review tx adherence/ -USq6mo if cirrhosis for If listed, Tx usually deferred drug-drug interactions HCC screening till post-transplant to avoid -Resistance testing -Consider annual HCV MELD purgatory -Refer to hep for salvage RNA if ongoing high-risk regimens (e.g. Vosevi) exposures for relapse Recommendations on Hepatitis C Screening in Adults: 2018 Guideline Update CASL (CMAJ 2018 Jun 4;190(22):E677-E687. doi: 10.1503/cmaj.170453.) Hepatitis C Guidance 2019: AASLD/IDSA (Hepatology. 2020 Feb;71(2):686-721. doi: 10.1002/hep.31060.) 16  Alcohol-Associated Hepatitis (AH) Clinical Diagnosis for Probable AH: Liver biopsy rarely needed. – Acute onset jaundice within 60 days of heavy alcohol use (>40g/day women & Consider if 1. ALT, AST > 400, >60g/day men for >6 months); other causes of liver disease/jaundice excluded 2. Jaundice > 3 months, 3. >1 – AST > 50, AST/ALT > 1.5-2, and both values < 400, Tbili > 51 clinical criteria not met, 4. Other dx suspected Prognostication – Severe AH: Maddrey Discriminant Function (MDF) ≥ 32 or MELD > 20 – Infection associated. w/ 3x increased risk of mortality (order septic screen: blood cx, urine cx, CXR, para to r/o SBP) Treatment – EtOH cessation NO role for the following – Enteral nutrition (target = 35 kcal/kg/d and 1.2–1.5 g/kg/d of protein, consider thiamine & zinc supplement) therapies: -Pentoxifylline – Prednisolone 40mg daily x 28 days for severe AH or presence of encephalopathy -G-CSF IV methylprednisolone 32mg daily is alternative for those unable to take PO meds -Prophylactic antibiotics If 4 or 7-day Lille score < 0.45 à pred x 28d then taper; if ≥ 0.45 à stop pred; consider early transplant (no longer need minimum period of abstinence; case-by-case) vs. palliative care C/I to steroids: Uncontrolled infection, uncontrolled GI bleed, AKI 2024 ACG Guideline: https://journals.lww.com/ajg/fulltext/2024/01000/acg_clini – IV N-Acetylcysteine (NAC) cal_guideline__alcohol_associated_liver.13.aspx 2019 AASLD Guidelines: https://www.aasld.org/practice- Recommended by ACG 2024 as adjunct to steroids (improved 30d survival) guidelines/alcohol-associated-liver-disease, 17 Metabolic-Dysfunction Associated Steatotic Liver Disease – NEW 2023 terminology for fatty liver disease: MASLD (NAFLD): Fatty liver with no hepatocellular injury MASH (NASH): + hepatocellular injury Met-ALD: MASLD + increased EtOH intake (20-30g/day females or 30-60g/day men) – MASLD Diagnosis à 1) Evidence of steatosis and 2) Rule out 2° causes (i.e. EtOH, drugs – steroids, methotrexate, amiodarone, estrogens) – MASH can only be diagnosed definitively on Bx – Associated with T2DM (most important risk factor), ↑lipids, HTN, obesity, metabolic syndrome, OSA, and endocrine disorders (PCOS, hypogonadism, hypothyroidism) – Most common cause of death in MASLD is CARDIAC – Most cryptogenic cirrhosis likely “burned out” MASLD 2023 AASLD Guidelines: https://www.aasld.org/practice-guidelines/clinical-assessment-and-management-nonalcoholic-fatty-liver-disease New terminology 2023: https://journals.lww.com/hep/fulltext/9900/a_multi_society_delphi_consensus_statement_on_new.488.aspx 18 Metabolic-Dysfunction Associated Steatotic Liver Disease – Who to screen for clinically significant fibrosis (>F2 fibrosis): T2DM, obesity w/ metabolic complications, 1st degree relative with MASH cirrhosis, pts with alcohol use Screen with FIB-4 score for everyone à if > 1.3, refer for fibroscan. If F2) – Coffee (>3 cups/day reduced risk of advanced fibrosis) Pharmacotherapy – Semaglutide for MASH + T2DM/ obesity – Also studied: (1) pioglitazone for Bx-proven MASH + T2DM, but risk of edema, CHF, (2) vitamin E 800 IU daily for Bx-proven MASH w/o T2DM, but may increase risk of adverse CV outcomes Bariatric surgery if BMI>35 – Increased post-op mortality w/ decompensated cirrhosis or clinically significant portal hypertension 2023 AASLD Guidelines: https://www.aasld.org/practice-guidelines/clinical-assessment-and-management-nonalcoholic-fatty-liver-disease 19 New terminology 2023: https://journals.lww.com/hep/fulltext/9900/a_multi_society_delphi_consensus_statement_on_new.488.aspx  Approach to Cirrhosis: Causes Determine etiology – (1) Viral (2) Steatotic liver disease [EtOH, MASH], (3) Autoimmune/ Child Pugh Score cholestatic [AIH, PBC, PSC], (4) Genetic [Wilson, HH, A1AT], (5) *Don’t memorize, but helpful to have a Chronic biliary disease, (6) Vascular [R CHF, Budd Chiari] sense of ‘A’ vs ‘C’! – Labs, abdominal imaging (+ doppler), and consider biopsy if Ascites indeterminate cause Absent (1), slight (2), moderate (3) Assess severity Bilirubin – Child-Pugh score – predicts perioperative mortality for open 51.3 (3) abdominal surgery (based on old data, likely overestimates risk): – CP A (score 5-6) – 10% Coagulopathy (INR) – CP B (score 7-9) – 30% < 1.7 (1), 1.7 – 2.2 (2), > 2.2 (3) – CP C (score 10-15) – 80% Albumin – MELD ≥ 15 – refer for liver transplant assessment >35 (1), 28 – 35(2), < 28 (3) 6 mo of EtOH abstinence no longer a rule in Ontario (case by case) – For perioperative liver-related mortality, can use the Mayo clinic Encephalopathy surgical risk score or the VOCAL-Penn score (both online, more None (1), grade 1-2 (2), grade 3-4 (3) refined + current than the Child-Pugh score; but know CP for exam) 20 Approach to Cirrhosis: Complications + Counseling Assess for complications – signs of “Decompensated” cirrhosis: – Varices à EGD at diagnosis (if Fibroscan not available) or time of decompensation, 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 + AFP at diagnosis and q6mo thereafter Counselling: – Complete abstinence from alcohol, adequate nutrition, weight loss for MASLD – Limit acetaminophen to ≤ 2g/day – Avoid sedatives, NSAIDs, ACEI/ARBs – HAV, HBV, COVID 19, TdAP, Pneumococcal, flu vaccinations (+zoster if age >50, MMR & Varicella where applicable) – Refer to multidisciplinary team if frailty, sarcopenia or malnutrition (AASLD 2021) – Inquire about sexual activity, contraception, and pregnancy planning in reproductive-aged patients (AASLD 2021 Reproductive Health & Liver Disease Guideline) Estrogen-containing contraception and menopause hormonal therapy should be avoided in decompensated cirrhosis, Budd-Chiari, or hepatocellular adenoma – Refer to palliative care team if decompensated cirrhosis at any point in journey (AASLD 2022 Guidance statement à improves symptoms, quality of life, caregiver stress) Screen for FRAILTY & MALNUTRITION (AASLD 2021 Guideline on Frailty, Sarcopenia and Malnutrition in Cirrhosis) 21  Clinically Significant Portal Hypertension (CSPH) is a Risk Factor for Varices in Compensated Cirrhosis CSPH = Hepatic venous pressure gradient (HVPG) ≥ 10 mmHg ↑ risk of hepatic decompensation Can be assessed invasively at time of transjugular liver biopsy or non-invasively (preferred) based on platelet count & liver stiffness measurement (LSM) on transient elastography (TE aka Fibroscan) defined as: LSM > 25kpa or LSM > 20 kpa + Plt < 150 or LSM 15-19.9 kpa + Plt < 110 If TE is not available, other surrogate markers of CSPH include: 1. presence of portosystemic collaterals or hepatofugal flow on imaging, 2. evidence of varices on imaging, or 3. clinical decompensation 1st line TREATMENT = Non-Selective Beta Blocker (NSBB reduces risk of future decompensation) No indication for assessing LSM once pt has developed decompensated cirrhosis (they already have CSPH!) Perform EGD at time of decompensation If high-risk varices identified, treat with NSBB or endoscopic variceal ligation (NSBB > EVL) 22  Clinically Significant Portal Hypertension (CSPH) is a Risk Factor for Varices in Compensated Cirrhosis Compensated No CSPH Cirrhosis CSPH - LSM150 - LSM > 25kpa or LSM > 20kpa + Plt 25kpa or LSM > 20kpa + Plt 25kpa or varices; no need for (carvedilol preferred) to NSBB EGD LSM > 20 kpa + Plt < 150 EGD or NSBB NSBB = 1st line Tx for CSPH to prevent future - Monitor LSM + plt q1y Intolerant to decompensation for CSPH à if or C/I to NSBB develops, start NSBB No indication for assessing LSM once pt has EGD surveillance to developed decompensated cirrhosis (they already detect varices *High-risk varices: - q2y if ongoing liver injury mod-large size, red wale have CSPH!) - q3y if no ongoing injury marks, or Child-Pugh C Perform EGD if patient is not already on NSBB If high-risk varices identified, administer primary *High risk varices Low-med risk varices prophylaxis as per previous slide (NSBB > EVL) identified identified EVL EGD q1-2y Once eradicated q2-4wks until depending on if EGD q6-12mo varices obliterated ongoing liver injury 24 Management of Varices in Decompensated Cirrhosis Primary prophylaxis = no prior acute EVL: Endoscopic Variceal Ligation (aka variceal banding) variceal hemorrhage (AVH) Requires serial EGD w/ banding q2-4 weeks to eradicate – Patients receive: EVL OR NSBB varices and then ongoing surveillance q6-12months AASLD 2023 preferentially recommends NSBB over NSBB: Non-Selective Beta Blocker EVL, reserving EVL for those who cannot tolerate Carvedilol preferred over nadolol and propranolol NSBB or have contraindications (AASLD 2023) Carvedilol starting dose = 3.125mg BID and titrate up to Secondary prophylaxis = after AVH maintain sBP >90 (no HR target) Nadolol & Propranolol: titrate to HR 55-60 and maintain – Patients receive: EVL (within 12h of bleed) AND SBP>90 NSBB* Contraindications to NSBB (AASLD 2023) *Exception: In rare cases, patients may undergo pre- 2nd/3rd degree AV Block (no PPM) emptive TIPS as 1st line therapy for AVH. If so, no need Sick sinus syndrome for secondary prophylaxis with NSBB Bradycardia (HR 25 matosis Refractory Ascites Cirrhosis Post-sinusoidal causes Assess adherence to diuretics & *SAAG: Na+ restriction (see next slide) -CHF [serum albumin] – Large volume paracentesis -Constrictive pericarditis – Give albumin 6-8 g/L of fluid removed -Budd Chiari [albumin in ascitic fluid] for taps > 5L TIPS if no contraindications (encephalopathy, HCC, pulm. HTN, R. HF) AASLD 2021 guideline: Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Liver transplant Syndrome. https://journals.lww.com/hep/fulltext/2024/05000/aasld_practice_guidance_on_risk_stratification_and.22.aspx 26  Ascites management Patients with ascites should be Na restricted (1 as surrogate for 24h 24-hr urine Na 78 mmol, but 24-hr urine Na >78 mmol à NON-COMPLIANT gold standard (eg on exam) remains 24h urine Na 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 AND patient not losing weight à NON-COMPLIANT with Na restriction à reinforce Na restriction 24-hr uNa >78 mmol AND weight loss à patient is adherent to sodium restriction and diuretic sensitive à stay the course AASLD 2021 guideline: Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome. https://journals.lww.com/hep/fulltext/2024/05000/aasld_practice_guidance_on_risk_stratification_and.22.aspx 27  Spontaneous Bacterial Peritonitis 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, recent surgery, intraabdominal abscess) AASLD 2021 guideline: Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome. https://journals.lww.com/hep/fulltext/2024/05000/aasld_practice_guidance_on_risk_stratification_and.22.aspx 28  Spontaneous Bacterial Peritonitis Treatment of confirmed SBP – Ceftriaxone (or Fluoroquinolone if CTX allergic) x 5 days – HRS prophylaxis à Day 1: Albumin 1.5g/kg; Day 3: Albumin 1 g/kg In practice everyone gets albumin, but guidelines suggest greatest benefit if Cr > 88, BUN > 10.7, or bili > 68 Post SBP: lifelong prophylaxis with Norfloxacin, Septra DS, or Cipro – NSBB should be temporarily held in patients with SBP + hypotension or AKI Indications for SBP prophylaxis 1) Patients who have previously had SBP à indefinite SBP prophylaxis 2) Patients with cirrhosis who present with any upper or lower GI bleeding (don’t need to have ascites, doesn’t need to be a variceal bleed) à SBP prophylaxis x 5 days - AASLD 2023: “Antimicrobial therapy can be discontinued once bleeding is controlled and in absence of an active infection” 3) Cirrhotic with ascitic fluid protein is 18 years old (Guideline suggests for offspring of affected individual to screen their other parent w HFE testing; avoids testing all offspring if other parent negative.) As per Choosing Wisely Canada: TS ≥ 45% AND elevated SF. USE THIS Tsat < 45% AND ferritin < 300 (M)/ 200 (F) ACG 2019 rules out HH with good NPV 97%! HH Algorithm Ferritin >1000 should suspect end-organ damage Ferritin > 300 (M), >200 (F) 32  HH 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 33  Question 1: Liver A 42 year-old male with alcohol use disorder presents to the ED with new onset jaundice, ascites, and fever of 39.2 degrees Celsius. His last drink was 6 weeks ago. He does not use any other drugs or medications. His labs demonstrate the following: total bilirubin 128, AST 368, ALT 162, ALP 224. His MELD score is 32 and Maddrey Discriminant Function score is 44. What is the next best step? A. Start prednisolone 40mg daily for severe alcohol hepatitis and calculate a Lille score at day 4 to determine response to corticosteroids – while this patient meets cut-off for severe AH, the fever is concerning for infection which is a relative C/I to steroids. Note: Day 4 Lille is now an accepted alternative to Day 7 Lille as per ACG 2024 B. Send off blood and urine cultures, complete diagnostic paracentesis to r/o SBP, and consider broad-spectrum antibiotics while awaiting results – the safer option in this case; there is no urgency to starting steroids which have questionable benefit in very severe AH. In the trials, mean time to initiating prednisolone was 6 days - aka we have time to work-up the patient for possible sepsis and other causes of liver dysfunction C. Order transjugular liver biopsy for confirmation of histologic diagnosis – AH can be diagnosed clinically and does not usually require liver bx unless suspecting alternate dx that may alter management (e.g. AIH) D. Start IV N-Acetylcysteine for severe AH – NAC studied as adjunct to steroids in severe AH, no benefit to NAC monotherapy in studies 34  Celiac Disease Celiac disease is an immune-mediated enteropathy due to gluten hypersensitivity Risk Factors: – Northern European descent, family history (1st degree relative), T1DM, AI disease, Down Syndrome (6x risk), Turner’s syndrome, IgA deficiency Symptoms & Signs: – Diarrhea/ steatorrhea, abdo pain, bloating, weight loss, anemia, osteoporosis, enamel defects, elevated transaminases (mild), infertility – Vitamin & mineral deficiencies: A, D, E, B12, Fe, Ca – Dermatitis herpetiformis rash seen in 25% of pt with celiac Tx = Gluten Free Diet (GFD), Dapsone (after r/o G6PD deficiency) Grouped, pruritic papules and vesicles on extensor surfaces Diagnosis: – Serology: Anti-TTG IgA & IgA level (to r/o IgA deficiency) +/- Anti-Deamidated Gliadin Peptide [DGP] IgG if ↓ IgA (anti-endomysial Ab [EMA] mentioned in guideline as high specificity but not widely available, and used moreso as confirmatory testing in kids) – Histology: Upper endoscopy with duodenal biopsies (histologic changes as per Marsh Classification) EGD indicated if 1. symptomatic 2. elevated TTG-IgA 3. high pre-test suspicion of celiac >5% (even if negative serology) ACG 2023 Celiac Disease: https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx?context=FeaturedArticles&collectionId=2 AGA 2019 guidelines: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.gastrojournal.org/article/S0016-5085(18)35408-8/pdf 35  Who to screen for Celiac Disease: ACG 2023 Symptoms, signs, or laboratory evidence suggestive of malabsorption – Chronic diarrhea with weight loss – Steatorrhea – Abdominal pain +/- bloating – Irritable Bowel Syndrome à ACG 2021 IBS Guidelines recommend celiac serology in initial evaluation of suspected IBS + diarrhea Type 1 Diabetes Mellitus + suggestive signs/symptoms or undergoing EGD for another reason Individual with 1st degree relative who has celiac who has compatible signs/symptoms/biochemical abnormalities – Also consider testing in asymptomatic individuals with 1st degree relative CD Elevated liver enzymes Also consider testing in: ACG 2023 recommends against mass Chronic iron deficiency anemia / unexplained anemia population level screening of asymptomatic individuals but rather a Premature osteoporosis / metabolic bone disease case-finding strategy to ↑ detection of Amenorrhea/infertility CD in those groups most at risk Unexplained weight loss / growth failure No consensus about which symptoms, laboratory abnormalities, and/or associated Down & Turner Syndrome diseases require evaluation for CD Dermatitis herpetiformis (>90% have underlying CD) 36  Simplified Diagnostic Algorithm for Celiac Disease *Histologic findings CD: Adult patient with signs/symptoms of What if my patient has IgA deficiency? Consider Anti-DGP IgG or TTG-IgG as - Intraepithelial Celiac Disease (CD) alternative serologic testing lymphocytes OR - Villous Atrophy Asymptomatic adult at risk for CD - Crypt Hyperplasia (assuming patient is eating gluten) Graded according to Low to medium pre-test High pre-test probability Marsh Classification (Beyond scope of IM probability of CD of CD (>5%) exam) Serology (-) TTG-IgA + IgA TTG-IgA + IgA Histology normal and No CD EGD Negative Positive Discordant serology High negative Confirm dx w/ Serology (+) & histology predictive value; EGD & duodenal Histology Abnormal rules out CD biopsy Potential CD Abnormal Histology* Confirmed CD R/O other enteropathy 37 ACG 2023 Celiac Disease: https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx?context=FeaturedArticles&collectionId=2  What if my patient is on a Gluten-Free Diet (GFD)? About HLA DQ2/DQ8 HLA DQ2/DQ8 POSITIVE in almost all patients with Celiac disease. NEGATIVE test rules out Celiac disease (negative predictive value = 100%) Negative Positive Sensitivity – 100% Specificity – 57% Gluten Challenge 3g gluten ≈ 2 slices bread No CD 3g gluten daily If not well tolerated, can When to order: x 8 weeks do shorter trial of 2 weeks - Patient is on GFD - Equivocal histology in seronegative patients or 8 weeks discordant serology and histology - Suspicion of refractory celiac TTG-IgA + IgA - Patients with Down’s syndrome - Patients with remote history of Celiac dx (especially as young children before introduction of TTG-IgA ) Positive Negative Compatible histology based on Marsh Classification Confirm dx w/ What is the pre- Low to medium CD EGD & duodenal test probability of No CD biopsy* having CD? High 38 ACG 2023 Celiac Disease: https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx?context=FeaturedArticles&collectionId=2  Celiac Disease Treatment: Lifelong gluten-free diet (GFD) Gluten Containing Follow-up: Foods – ‘BROW’ – Ensure adherence to GFD Barley Diet history à consider dietitian consult Rye F/U serology at 6 & 12 months then annually to ensure ↓ antibody titres Repeat EGD to assess for mucosal healing Oats *often contaminated – Monitor for complications Nutritional deficiencies and anemia (Fe, folate, Vit D, B12) Wheat Osteopenia/osteoporosis (BMD at dx and then per guidelines) Elevated liver enzymes Dermatitis herpetiformis Enteropathy-associated T cell lymphoma (EATL) – Consider refractory celiac disease and progression to EATL if a celiac patient stops responding to GFD à repeat EGD ACG 2023 Celiac Dx and Mgmt guidelines: https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx?context=FeaturedArticles&collectionId=2 AGA 2019 guidelines: https://www.gastrojournal.org/article/S0016-5085(18)35408-8/pdf 39  Question 2: IBD – NEW 2025 A 32M with ileocolonic Crohn’s Disease since age 16 presents to the ED with a four- day history of worsening abdominal pain, nausea, vomiting, and rectal bleeding. He has been stable on Ustekinumab 90mg SC q8wks for the past 3 years, with new intermittent abdominal pain for the last 8 weeks. On examination his vitals are: HR 112, 100/54, T38.3, RR12. His abdomen is tender on deep palpation to the RLQ. BW demonstrates the following: Hgb 107, WBC 13.4, Plt 504, CRP 128. Which of the following is NOT part of your initial management? a) Start IV fluids, consider NG tube placement if concerns of bowel obstruction b) Order CT abdomen to assess for intra-abdominal abscess c) Administer stat dose of IV methylprednisolone 60mg and continue daily d) Order stool cultures, c difficile assay, and O&P e) Start enoxaparin 40mg SC daily for thromboprophylaxis 40  Crohn’s Disease Inflammatory bowel disease characterised by transmural inflammation that can affect anywhere in the GI tract from ‘gum to bum’ associated w/ development of abscesses, fistulas, and strictures Common disease locations: – Small bowel - terminal ileal involvement is most common – Ileocolonic – Colonic – Mouth + upper GI tract Clinical Manifestations: – Abdominal pain, diarrhea*, weight loss, fever, perianal symptoms (abscess, drainage from fistula) Patients with stricturing CD, may present with obstructive symptoms (obstipation rather than diarrhea)* – ↑ CRP, anemia, ↓ Albumin, ↓ Fe, ↓ B12, ↑ fecal calprotectin Diagnosis: – Ileocolonoscopy & biopsy Patchy inflammation, skip lesions, aphthous ulcers, cobble-stone mucosa Rectal involvement + circumferential continuous inflammation less common in CD vs UC – Small bowel imaging (CT/MR enterography, capsule endoscopy) +/- EGD if suspecting upper GI crohn’s – No role for serology in diagnosis of IBD (e.g. ANCA/ ASCA) Roda et al. Crohn’s Disease. Nature Reviews. April 2020. 41  Crohn’s Treatment Options Thiopurines take ~8-12 Induction Maintenance weeks to have effect – Mild – Mild Refer for TPMT testing to Budesonide (Entocort, Cortiment) Thiopurine (AZP, 6-MP) identify those with low enzyme activity and at risk – Moderate to Severe – Moderate to Severe for adverse effects Budesonide MTX Prednisone/methylprednisolone Thiopurine (AZP, 6-MP) Methotrexate (MTX) Anti-TNF – Infliximab, Adalimumab Anti-TNF – Infliximab (Remicade), Anti-integrin – Vedolizumab Adalimumab (Humira) Anti-IL-12/23 – Ustekinumab Anti-Integrin – Vedolizumab (Entyvio) Anti-IL 23 – Risankizumab (Skyrizi) – NEW! Anti-IL12/23 – Ustekinumab (Stelara) JAKi – Upadacitinib (Rinvoq) – NEW! Anti-IL 23 – Risankizumab (Skyrizi) – NEW! JAKi – Upadacitinib (Rinvoq) – NEW! 42  General Patterns in CD Treatment – 5-ASAs are NOT effective for Crohn’s ileitis, fistulizing or moderate-severe disease. Sulfasalazine can be considered for mild colonic Crohn’s disease but rarely used with expansion of biologics; occasionally used for concurrent treatment of enteropathic arthritis – Fistulas à Anti-TNF have the most evidence (IFX > ADA) followed by other biologics Consider combination of Anti-TNF with thiopurine or methotrexate for fistulizing CD – Perianal disease (abscesses or fistulae) à Anti-TNF +/- thiopurine +/- Abx if concern for infection Do not use antibiotics alone to induce or maintain remission – Upadacitinib NOT Tofacitinib is approved for CD (tofacitinib only approved for UC) – Once remission achieved, generally continue the agent that induced remission (except steroids) – Indications for surgery in Crohn’s disease: Intestinal obstruction, refractory/ fulminant disease, high- grade dysplasia/ cancer, severe perianal disease/ fistulas/ abscess, perforation. Alternative therapies CAG Recommends against: Probiotics, Marijuana, Dietary modification, Omega fatty acids. 43  Crohn’s Disease Complications If a Crohn’s patient has pain + fever à CT abdomen to look for abscess! – Abscess: Drain (IR or I+D or surgery) and antibiotics (Cipro/Flagyl or CTX/flagyl) à Biologic – Fistula: Characterize perianal fistulae w/ MRI pelvis (or endoscopic US) + EUA (exam under anesthesia) Anti-TNF (+/- thiopurine) preferred to induce a symptomatic response and maintain remission Other options: vedolizumab, ustekinumab, or surgery – Stricture: ‘Cold’ stricture: – Fibrostenotic disease, no active inflammation on imaging or endoscopy AGA 2021: https://gastro.org/clinical- – Conservative mgmt. (i.e. bowel rest, NG tube), endoscopic dilation or surgery guidance/medical- ’Hot’ stricture management-of-moderate- to-severe-luminal-and- – Active inflammation (may be overlying area of fibrosis/ cold stricture) perianal-fistulizing-crohns- – Steroid bridge to maintenance therapy (biologics) disease/ 44  Ulcerative Colitis Immune-mediated condition of the colon often associated with rectal inflammation, extending proximally to involve the adjacent colon in a continuous manner. Disease Location: – Proctitis – within 18 cm from the anal verge – Left-sided colitis – sigmoid to splenic flexure – Extensive/pancolitis – beyond the splenic flexure Truelove & Witts Criteria for Severe UC: Clinical Manifestations: 1. Bowel movements ≥ 6 – ‘Proctitis’ – small volume + frequent BMs w/ blood, tenesmus, urgency, crampy abdominal pain 2. Visible blood in stool – Fever, fatigue, weight loss 3. Pyrexia T ≥ 37.8C* – Inflammatory markers: Anemia, ↓ Albumin, ↑ ESR/CRP, 4. Pulse > 90bpm* ↑ fecal calprotectin 5. Anemia Hgb ≤ 105* Diagnosis: 6. ESR (or CRP) >30* – Ileocolonoscopy + biopsies Severe UC when criteria for frequency Continuous inflammation from rectum proximally of bowel movement and ≥1 features of Granular, friable mucosa systemic upset (*) are satisfied. Bx – i.e. crypt abscesses, lamina propria cellularity 45  Ulcerative Colitis Treatment Options Induction Maintenance – Mild – Mild 5ASA PO (extensive), PR (proctitis) (suppository < 5ASA PO, PR 18cm, enema – to splenic flexure) – Moderate to Severe Budesonide Thiopurine (AZP, 6-MP) – Moderate to Severe Anti-TNF – Infliximab, Adalimumab, Budesonide Golimumab Prednisone/methylpred Anti-Integrin – Vedolizumab Anti-TNF – Infliximab, Adalimumab, Golimumab Anti-IL-12/23 – Ustekinumab Anti-Integrin – Vedolizumab Anti-IL23 – Mirikizumab (approved 2023) Anti-IL-12/23 – Ustekinumab JAK-inhibitor – Tofacitinib, Upadacitinib Anti-IL 23 – Mirikizumab (NEW!) (approved 2023) JAK-inhibitor – Tofacitinib, Upadacitinib (NEW!) Sphingosine 1-phosphate receptor modulator “Small – Ozanimod, etrasimod (approved 2024) Sphingosine 1-Phosphate Receptor Modulator – molecules”, Ozanimod (approved 2022), Etrasimod (NEW!) oral agents 46  IBD – General Principles Work-up prior to starting advanced therapies (biologic or small molecule): – HBV, HCV – TB skin test; If BCG vaccinated à CXR and/ or IGRA IBD is associated with ↑ risk of – Strongyloides serology if high pretest probability (see next slide) colorectal cancer – TPMT testing if considering combination therapy with AZA/6MP *See Med Onc – BHCG à JAKi and S1PR modulators C/I in pregnancy lecture for more – VZV titres for JAKi à vaccinate with Shingrix if not immune details – Lipid profile for JAKi – Baseline ECG +/- ophthalmology assessment (if risk factors for retinal disease) for S1PR modulators Treatment targets – Clinical (symptoms, steroid free) remission – Biochemical (normalization of CRP and fecal calprotectin) remission, and – Endoscopic (mucosal healing) remission 47  Screening: Serology +/- Stool O&P Strongyloides Screening BONUS Read on own Clinical Risk factor for disseminated Strongyloides HTLV-1 infxn No known defects in cell Epidemiologic Risk category for Pred ≥20mg/d ≥ 2wks mediated immunity. Strongyloides exposure/infxn Immunomodulatory agent (chemo, TNFa, biologics) Hematologic Malignancy Birth/residence/longterm travel in SE Asia, HIGH Moderate Oceania, Sub-Saharan Africa, S. America, Caribbean Birth/residence/longterm travel in Moderate Low Mediterranean countries, middle east, N Africa, Indian sub-continent, Asia Birth/residence/longterm travel in Australia, Overall VERY LOW risk North America or Western Europe [Florida, Kentucky, Virginia may be higher risk. Indigenous Australians higher risk] Travel = (6mos cumulative or more) w contact of skin with sand or soil, esp if exposure to rural/beach areas Note: CCRIH recommends screening all refugees from SE Asia and Africa on entry to Canada. In the GI LECTURE we are talking about screening patients before immunomodulating therapy ** Boggild AK, CCDR 42(1);2016. 48  Inpatient IBD IBD flares commonly overlap with infection 1. Rule out C. diff/ other infection if worsening diarrhea (even if no recent antibiotics) 2. Rule out abscess in a Crohn’s patient with fever and abdominal/perianal pain Use appropriate imaging (CT abdo, MR pelvis, EUS, etc.) 3. Withhold immunosuppression until (1+2) are addressed. If the patient looks septic, cover with antibiotics 4. CMV colitis can co-exist with IBD and requires colonic biopsies to diagnose (CMV blood PCR is not enough; look for “owl-eye inclusion bodies” on pathology and CMV+ immunohistochem off biopsy) Don’t stop DVT prophylaxis even if patient having bloody diarrhea – Risk of thrombosis > risk of life-threatening hemorrhage in hospitalized IBD patients with acute flare Bile-salt diarrhea – Occurs with ileitis or after ileal resection – ALWAYS assess for and treat active IBD (CT imaging, CRP, Fcal, colonoscopy) before treating for bile salt diarrhea Treatment = cholestyramine (bile acid sequestrant) 49  Inpatient IBD Work-up: – Labs – CBC, lytes, extended lytes, Cr, AST/ALT/ALP, bilirubin, INR, albumin, ESR/CRP – Stool tests – Stool C&S, Stool O&P, C. diff toxin, +/- fecal calprotectin – Imaging – AXR, +/- CT abdomen, +/- CT/MR enterography (i.e. small bowel imaging) – Endoscopy – for diagnosis, to assess disease severity, rule out mimics (ischemia, CMV), can send aspirates for micro Management: – IV fluids, bowel rest, VTE prophylaxis – Minimize narcotics, NSAIDS – Start IV steroids once infection is ruled out – If minimal response after ~ 72h IV steroids à Infliximab – Consider general surgical consultation for treatment refractory colitis, toxic megacolon, perianal/intra-abdominal abscess, complex fistulizing Crohn’s 50  Acute Severe UC (ASUC) Management IFX used as rescue therapy in most centres across Canada *Radiographic megacolon (TC diameter >6cm) + Indications for colectomy: Toxic megacolon* At least 3 of colonic perforation, severe refractory hemorrhage, Fever (>38 deg C) refractory to medical therapy HR >120 In biologic era, rates of colectomy for ASUC have declined Neutrophils >10.5 Anemia + Multidisciplinary care with early surgical involvement At least 1 of is important Dehydration Altered sensorium Electrolyte disturbances Hypotension 51  Question 2: IBD – NEW 2024 A 32M with ileocolonic Crohn’s Disease since age 16 presents to the ED with a four-day history of worsening abdominal pain, nausea, vomiting, and rectal bleeding. He has been stable on Ustekinumab 90mg SC q8wks for the past 3 years, with new intermittent abdominal pain for the last 8 weeks. On examination his vitals are: HR 112, 100/54, T38.3, RR12. His abdomen is tender on deep palpation to the RLQ. BW demonstrates the following: Hgb 107, WBC 13.4, Plt 504, CRP 128. Which of the following is NOT part of your initial management? a) Start IV fluids, consider NG tube placement if concerns of bowel obstruction – YES! This patient has tachycardia, fever, and soft BP with features of SIRS. Fluid resuscitation should be a part of initial management. In a CD patient with obstructive symptoms (i.e. nausea/vomiting), bowel obstruction secondary to stricturing CD should be part of your differential and can be investigated with plain film X-ray or CT. If bowel obstruction is confirmed manage medically (NPO, NG for decompression) and consult general surgery b) Order CT abdomen to assess for intra-abdominal abscess – YES! Always r/o abscess in CD patient w/ fever and abdominal pain c) Administer stat dose of IV methylprednisolone 60mg and continue daily – While this patient is likely having an IBD flare and will need steroid induction treatment, the pain, fever, and labwork is concerning for an infection which needs to be ruled out prior to starting high dose steroids. d) Order stool cultures, c difficile assay, and O&P – YES! C diff colitis is more common in patients with IBD and can both mimic IBD flare and precipitate de novo flare. Always order stool studies on IBD inpatient with worsening symptoms e) Start Lovenox 40mg SC daily for thromboprophylaxis – YES! IBD patients are at higher risk of VTE. Always order DVT prophylaxis even if having rectal bleeding / anemia 52  Question 3 – NEW 2025 A 56yo male is brought to the ED by EMS with frank hematemesis. He has a history of an NSTEMI with previous PCI to the LAD 2 years ago. He also has T2DM, hypertension, dyslipidemia and is on ASA, metformin, empagliflozin, bisoprolol, candesartan, and rosuvastatin. He has been adherent to all of his medications. His vitals on presentation are: HR 124, BP 88/56, O2 95%, T 36.8, RR 16. He is lethargic and confused but does rouse to verbal commands. His initial bloodwork shows: Hgb 62, MCV 103, WBC 8.2, Plt 118. Which of the following is not part of your initial management? a) Administer 1g tranexamic acid b) Cross match, group & screen, and transfuse packed red blood cells c) Start IV pantoprazole, octreotide, and ceftriaxone d) Consult ICU for consideration of airway protection and admission to monitored bed 53  Upper GI Bleeding UGIB Variceal Non-Variceal IV PPI * IV octreotide IV PPI IV antibiotics (if cirrhosis) Use *IV PPI even if you Endoscopy within suspect variceal etiology – 12-24 hours you don’t know until you scope and PUD is always Endoscopy possible! within 12 hours Ongoing PPI Assess depending on medications, H. lesion pylori status 54  UGIB Pre-endoscopy (**POSSIBLE ORAL SCENARIO**) – ABC’s, monitoring, O2, 2-large bore IV’s, fluids (ABC-MOIF) – [Apply Glasgow-Blatchford score to identify low-risk patients that can be discharged with outpatient follow up] – CBC, urea, Cr, cross and type, INR/PTT, Liver enzyme and function tests – Transfuse Hb > 70; consider higher target (>80) if symptomatic/ active cardiac ischemia, or unstable Plts > 50 if actively bleeding/unstable Tranexamic Acid does not reduce – Reverse anticoagulation mortality in UGI Bleed based on See slide on antithrombotic mgmt. in GI bleed HALT-IT Trial (Lancet 2020) – do – PPI therapy (IV bolus + infusion or BID dosing) not use routinely! 55  UGIB in Patient with Cirrhosis UGIB (variceal or not) + Cirrhosis (or suspected non-cirrhotic portal HTN) 1. Restrictive transfusion strategy (target 70-90 g/dL) No FFP 2. IV vasoactive drug (octreotide, somatostatin, terlipressin [not yet in Canada] or vasopressin) as soon as variceal bleed is suspected; continue x 2-5 days post-endoscopy if variceal bleed 3. IV PPI until varices ruled out 4. Endoscopy within 12h of presentation 5. Antibiotic prophylaxis is indicated for any GI bleed in a patient with cirrhosis Ceftriaxone 1g/24h x 5 days Pre-emptive TIPS can be considered in high-risk patients (Child Pugh C cirrhosis or Child Pugh B 8-9 with active bleeding at time of EGD) within For refractory variceal bleed à rescue TIPS 72h of AVH. Diaz-Soto MP, Garcia-Tsao G. Therap Adv Gastroenterol. 2022;15:17562848221101712 Following variceal bleed + EVL: For exam: prioritize ABCs, medical Tx with abx/PPI/vasoactive therapy, and GI consult for EGD within 12h for suspected variceal bleed! – Initiate NSBB when vasoactive drugs stopped NSBB not required if pt had a TIPS placed; TIPS is rescue if bleed despite NSBB+EVL Diaz-Soto MP, Garcia-Tsao G. Therap Adv Gastroenterol. 2022;15:17562848221101712. 56 AASLD guideline: Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management (Hepatology. 2017 Jan;65(1):310-335)  Non-variceal UGIB Endoscopic management – Erythromycin 250 mg IV suggested 30 min before endoscopy – Endoscopy should be performed within 24 hours (or within 12 hours in high-risk patients, including suspected variceal bleeds) – Endoscopic therapy only for high-risk ulcers (Forest IA, IB, IIA ulcers) If ongoing/ re-bleeding: repeat EGD, consider IR embolization or surgical management Consider radiation for tumor bleeds Barkun et al. Management of Nonvariceal Upper Gastrointestinal ACG Guideline: Upper Gastrointestinal and Ulcer Bleeding. Bleeding: Guidelines Recommendations from the International Am J Gastroenterol. 2021 May 1;116(5):899-917. doi: Consensus Group. Annals of Internal Medicine. Dec. 2019. 10.14309/ajg.0000000000001245. 57  Non-variceal UGIB Post-endoscopy – High-risk ulcers à IV PPI BID or PPI infusion x 72 hours, then oral PPI BID for at least the first 2 weeks after endoscopy – Low-risk ulcers à Oral PPI (no guidelines; typically BID x 2-4 weeks then stop) – Restart anti-platelets and anticoagulation as soon as possible (see ACG-CAG guidelines next slide) Restarting OAC and/or antiplatelets not associated with increased GI bleed risk but IS associated with a reduction in all cause mortality (Witt DM Hematology ASH education Program 2016:620). Timing – variable decision incorporating patient factors and endoscopic findings (Forrest class) Consider risk factors – Test all patients with PUD or gastritis for H. pylori – can biopsy at time of EGD or check serology Treat with quadruple therapy if positive After treatment and confirmation of eradication, PPI therapy can be stopped – Stop all unnecessary NSAIDs, stop ASA for primary prophylaxis – For CV patients requiring ongoing ASA and/or Plavix, consider indefinite PPI prophylaxis – Indefinite PPI if unclear cause of PUD (conditional recommendation) ACG Guideline: Upper Gastrointestinal and Ulcer Bleeding. Am J Gastroenterol. 2021 May 1;116(5):899-917. doi: 10.14309/ajg.0000000000001245. CAG Guideline: Intl. Consensus on Mgt of Patients with NVUGIB (Ann Intern Med. 2010 Jan 19;152(2):101-13) 58  Anti-thrombotic management (Joint ACG-CAG Guideline April 2022) Acute GI Bleeding – All guidance “suggest” due to low level of evidence à use your clinical judgement! i) Patient stable, “hospitalized or under observation for GI Bleed [upper or lower]” ASA 81-325 mg for 2o cardiovascular prevention à Suggest no interruption; if interrupted à re-start on the day that hemostasis is endoscopically confirmed. Anticoagulation reversal? – Warfarin à Suggest AGAINST vitamin K and FFP use. No recommendation for/ against PCC. Do not routinely give Vitamin K unless low dose to correct supratherapeutic INR – DOAC à Suggest AGAINST reversal with PCC/ idarucizumab/ andaxnet alpha ii) Life threatening hemorrhage, “major clinically overt or apparent bleeding, resulting in hypovolemic shock, or severe hypotension requiring pressors or surgery”, ↓Hgb >50, transfusion ≥5u PRBC, or causing death” – Warfarin à PCC “could be considered” (or in patients in whom massive transfusion is undesirable) Uncertain re use of vitamin K – see above, conditional recommendation to not use if INR in target range and intervention planned – DOAC à selective use of PCC (for anti-Xa DOAC) or idarucizumab (for Dabigatran) for those who took DOAC within 24h who have life threatening bleed “may be appropriate” – No Platelet transfusions to reverse effect of antiplatelet! ACG-CAG Guideline April 2022: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period https://journals.lww.com/ajg/Fulltext/2022/04000/American_College_of_Gastroenterology_Canadian.16.aspx  BONUS Read on own Anti-thrombotic management peri-procedure (Joint ACG-CAG Guideline April 2022) Anti-thrombotic management in the elective endoscopy setting*: ASA 81-325 mg for 2o preventionà Suggest no interruption DAPT à Suggest interrupting only the P2Y12 inhibitor; Re-start 0-7d post-endoscopy (no consensus) P2Y12 monotherapy à No consensus for or against interruption*, or when to restart DOACs à Suggest interruption⌃; Re-start 0-7d post-endoscopy (no consensus) Warfarin à Suggest no interruption#, and if interrupted à Suggest no need to bridge *Individualize risk of thrombosis versus bleeding in setting of high risk endoscopic procedures: (eg) high risk examples: >1cm polypectomy, ERCP w sphincterotomy, PEG/PEJ tube, ampullary resection, treatment of varices incl band ligation … ⌃ In line w thrombosis Canada – see Periop Medicine Lecture In an Oral scenario “I will liaise with my GI/Gen Surg colleague and their heme/cardio”… # Based on a single observational study, ACG-CAG Guideline April 2022: Management of Anticoagulants and Antiplatelets During Acute depends on what you’re expecting to Gastrointestinal Bleeding and the Periendoscopic Period find on endoscopy https://journals.lww.com/ajg/Fulltext/2022/04000/American_College_of_Gastroenterology_Canadian.16.aspx  Question 3 A 56yo male is brought to the ED by EMS with frank hematemesis. He has a history of an NSTEMI with previous PCI to the LAD 2 years ago. He also has T2DM, hypertension, dyslipidemia and is on ASA, metformin, empagliflozin, bisoprolol, candesartan, and rosuvastatin. He has been adherent to all of his medications. His vitals on presentation are: HR 124, BP 88/56, O2 95%, T 36.8, RR 16. He is lethargic and confused but does respond to verbal commands. His initial bloodwork shows: Hgb 62, MCV 103, WBC 8.2, Plt 118. Which of the following is not part of your initial management? a) Administer 1g tranexamic acid – not recommended for management of UGIB as per HALT-IT Trial b) Cross match, group & screen, and transfuse pRBC - YES! Hgb3 tx testing for H. pylori to ACG 2024 lists this as both 1st line tx option (conditional recommendation based on low improve test accuracy! quality of evidence) and 2nd line In those with tx failure Confirm eradication in all treated patients – Urea breath test, stool antigen test, or repeat gastric biopsy 64  Management of GERD – ACG 2022 Guideline DIAGNOSIS OF GERD GERD is a clinical dx based on Management of GERD (in absence of red flag* symptoms) classic esophageal symptoms of – Non pharm mgmt. = weight loss, avoid trigger foods, quit smoking, elevate HOB, etc) heartburn & regurgitation – Trial PPI once daily 30-60min before a meal x 8 weeks responsive to PPI - do not need Symptoms improve? à Try to wean PPI, if unable: maintain lowest dose PPI Symptoms refractory? à Ensure optimization of PPI therapyà Sx refractory despite EGD or pH monitoring in this case! optimizationà EGD off PPI, if normal à reflux monitoring à if negative, discontinue PPI, consider other causes In those with atypical presentation, – Consider sucralfate in pregnancy, H2R blocker at night for nocturnal symptoms red flags*, or refractory symptoms: – Recommend AGAINST prokinetics, sucralfate, baclofen, routine H2RA in PPI non-responders EGD à look for erosive esophagitis or long-segment Extra-esophageal symptoms (cough, asthma, laryngitis, dental erosions) Barretts (specific for GERD), r/o – R/O non-GI causes (e.g. PFTs, referral to resp/ENT/dentist) other causes of symptoms – Mainstay of dx = 24h pH monitor 24h pH reflux monitoring – Consider BID PPI x 8-12 weeks if pt also has typical GERD symptoms; failing this à EGD off PPI Recommend against barium Anti-Reflux Surgery studies or manometry to establish – Candidates: objective evidence of GERD (based on EGD or pH monitor), normal manometry, dx of GERD persistent bothersome GERD symptoms, large hiatal hernia, severe reflux esophagitis – Options: Nissen fundoplication, Magnetic Sphincter Augmentation, Roux-en-Y bypass if obese Endoscopic options: Transesophageal incisionless fundoplication if not willing to have surgery *Red flags = dysphagia, wt loss, GI bleeding, anemia à EGD ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. The American Journal of Gastroenterology 117(1):p 27-56, January 2022. 65  Barrett’s Esophagus Diagnosis: – Metaplasia of normal squamous epithelium to salmon-colored columnar epithelium ≥ 1 cm proximal to the gastroesophageal junction. – Biopsy confirmation of columnar intestinal metaplasia, +/- goblet cells. Malignant potential: – 30 fold ↑ risk of esophageal adenocarcinoma vs average population – Low overall annual risk (0.1% – 3%) – Dysplastic > Non-dysplastic; long segment > short segment ( 50 ACG Guideline: Diagnosis and Management of Barrett’s 3. Male gender Esophagus (Am J Gastroenterol 2022; 117 (4): 559-587). 4. Tobacco use NEW! AGA Clinical Practice Guideline on Endoscopic 5. Central obesity Eradication Therapy of Barrett's Esophagus and Related 6. Caucasian Neoplasia. Gastroenterology. 2024 Jun;166(6):1020-1055 7. Family history of Barrett’s esophagus/ esophageal adenocarcinoma Alcohol is not known to ↑ risk of Barrett’s or esophageal adenocarcinoma! Only SCC 66  Screening for Barrett’s Esophagus ACG April 2022 Guidelines (strength of recommendation: conditional; quality of evidence: very low): Single screening endoscopy (or capsule + biomarker) for patients with chronic GERD (weekly symptoms for >5years) and ≥ 3 risk factors for Barrett’s including: – Age > 50 – Male – Caucasian – Obesity – Tobacco smoking – 1st degree relative with Barrett’s or esophageal adenocarcinoma. Canadian Task Force 2020: “We recommend not screening adults (≥ 18 years) with chronic GERD for esophageal adenocarcinoma or precursor conditions (Barrett esophagus or dysplasia) (strong recommendation; very low-certainty evidence” Go with this for your exam, considering ACG was a conditional recommendation re screening ACG Guideline: Diagnosis and Management of Barrett’s Esophagus (Am J Gastroenterol 2022; 117 (4): 559-587). 67  Management of Barrett’s Esophagus (ACG 2022 & NEW AGA 2024 Guidelines) IF suspecting BE (i.e. >1cm salmon-coloured mucosa seen extending from GE AGA 2024 recommends the following junction), obtain ≥8 biopsies (Seattle protocol): in all patients with bx confirmed BE:. Tobacco cessation 1. NO METAPLASIA à Repeat EGD w/ biopsy in 1-2 yrs to R/A area Weight loss if overweight 2. INTESTINAL METAPLASIA à Confirms BE; assess if there is any dysplasia Optimize reflux control - Non-Dysplastic BE (NDBE) ACG says once daily PPI adequate EGD q3y if long-segment BE (>3cm) & no role for BID PPI unless EGD q5y if short-segment BE ( 50 yo, odynophagia, vomiting, bleeding, weight loss 70  Approach to Dysphagia Step 2: Imaging and/or Endoscopy – Oropharyngeal à Video fluoroscopy swallowing study – Esophageal Alarm symptoms? à Endoscopy – Weight loss – Anemia – Vomiting No alarm symptoms and age < 50, Sx GERD à Trial of PPI x 4 weeks Key Concepts from CAG 2018 Guideline – EGD is recommended > barium swallow for investigation of esophageal dysphagia. *Can biopsy for EoE on endoscopy! – High resolution esophageal manometry is recommended > barium swallow for investigation of esophageal motility disorders 71  Achalasia Esophageal motility disorder defined by incomplete relaxation of lower esophageal sphincter (LES) and ineffective esophageal peristalsis Signs & Symptoms: Okwara C, Cangemi D. – Progressive solid and liquid dysphagia Achalasia with – Regurgitation + reflux symptoms Megaesophagus. N Engl J Med 2015; – Chest pain 373:e30 – Weight loss DOI: 10.1056/NEJMic – Symptoms refractory to PPI therapy 1502835. Epidemiology: – M=F – Age 30 – 60 years – All ethnicities Complications: – Megaesophagus > 6cm – Sigmoid esophagus – Esophageal squamous cell carcinoma >>>> adenoCA *NB* - Esophageal involvement from chagas is indistinguishable from achalasia on endoscopy! It is diagnosed via serology. Biopsies are not helpful! Treatment is the same. 72  Achalasia Diagnosis: – Step 1 – EGD Rule out pseudoachalasia & obstruction – Pseudoachalasia should be suspected in older patients with short duration progressive symptoms, usually caused by infiltrating tumours at the GE junction or cardia that mimic achalasia by affecting LES function or paraneoplastic phenomenon ‘Puckered’ GE junction seen w/ achalasia Dilated, fluid filled esophagus as disease progresses – Step 2 - High resolution manometry +/- barium swallow Manometry – Gold standard test for achalasia – Measures pressures and peristaltic waveform throughout esophagus Barium swallow: Dilated – Impaired relaxation of LES and abnormal peristalsis are diagnostic – ID’s multiple subtypes of achalasia (Updated Chicago Classification v4.0, 2021) – esophagus, narrow GEJ with Don’t need to know for IM exam!! “bird-beak” appearance, poor Barium Swallow – ‘Bird’s beak esophagus’ barium emptying 73  Achalasia ACG Guideline (2020) Diagnosis and Management of Achalasia Poor surgical candidates due to comorbidities – Endoscopic Botox Injection – 1st line *NB – Achalasia ↑ risk of – Smooth muscle relaxants – CCB, nitrates esophageal SCC. Poor esophageal Ex. Nifedipine 10-30mg SL TID, ISDN 5mg SL TID emptying à stasis of food/liquid *Least effective therapy à inflammation à dysplasia à malignancy. Good surgical candidates – Pneumatic dilatation However, current guidelines do st 1 line option not recommend routine Risk of tear/perforation endoscopic surveillance for SCC. – Laparoscopic Heller Myotomy 1st line option Often performed with fundoplication (anti-reflux surgery) – Peroral endoscopic myotomy (POEM) 1st line option (especially type 3 achalasia) Often complicated by GERD – patients need lifelong acid suppression – Esophagectomy For patients with megaesophagus, sigmoid esophagus, failure of above treatments 74  Eosinophilic Esophagitis (EoE) Immune-mediated disease characterized by esophageal symptoms and eosinophilic infiltration (>15 eos/hpf) of the esophageal mucosa in absence of secondary causes of eosinophilia**. Risk factors: – M > F (3:1). Peak incidence at 30-44 yo. – History of atopy (asthma, eczema, allergic rhinitis), food allergies, autoimmune disease Clinical presentation: Intermittent solid food dysphagia, food bolus obstruction Endoscopic findings: ‘Trachealization’ of the esophagus (‘Feline Esophagus’), linear furrows, white exudates/ papules, ‘Crate-paper’ esophagus, strictures Treatment goal = Symptomatic and histologic improvement – Non-pharmacologic Rx: 6 food elimination diet (eggs, soy, cow’s milk, wheat, tree nuts, seafood). New evidence that animal milk elimination equivalent to 6 food elimination. **Secondary causes of – Pharmacologic Rx: esophageal eosinophilia: GERD, achalasia, connective 1st line: PPI, topical steroids (orodispersible budesonide [Jorveza] > swallowed fluticasone/budesonide) tissue diseases, Crohn’s hypermobility syndromes, 2nd line: Prednisone, Dupilumab (anti-IL 4/IL13) – may be considered as 1st line tx in select pill esophagitis, pemphigus, patients with concomitant atopic dermatitis or asthma hyperIgE syndrome, GVHD – Endoscopic dilation for symptomatic strictures CMAJ Review: Diagnosis and management of eosinophilic esophagitis. 2024 Feb 4;196(4):E121-E128. AGA 2020 guideline: https://gastro.org/clinical-guidance/management-of-eosinophilic-esophagitis-eoe/ 75  Question 4 – NEW A 62-year-old female from Brazil is seen in the urgent medicine clinic for a three-month history of progressive dysphagia to solids and liquids as well as intermittent chest pain. She has had 40 lbs of unintentional weight loss over the last 3 months. She does not endorse any GI bleeding or constitutional symptoms. Her current BMI is 17.5. She has a 50-pack year smoking history and continues to smoke 1 pack of cigarettes per day but is otherwise healthy. Which of the following would not be part of your initial work-up? a) Serology for chagas disease – While chagas can mimic achalasia which would