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GI Board Review – Part II Intestines, Liver, and Biliary Tract March 5, 2013.

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Presentation on theme: "GI Board Review – Part II Intestines, Liver, and Biliary Tract March 5, 2013."— Presentation transcript:

1 GI Board Review – Part II Intestines, Liver, and Biliary Tract March 5, 2013

2 Intestines

3 A 32-year-old man is evaluated in the emergency department for a 5-day history of worsening crampy abdominal pain and eight to ten loose bowel movements a day. The patient has a 5-year history of ulcerative colitis treated with azathioprine and topical mesalamine; before this episode, he had one or two bowel movements of well-formed stool a day. The patient had sinusitis recently, which resolved with antibiotic therapy. He has otherwise been healthy and has not traveled recently, had contact with sick persons, or been noncompliant with medication. On exam, temp 38.3 °C, BP 130/76 mm Hg, he is orthostatic. The abdomen is diffusely tender without rebound or guarding. Laboratory studies reveal hemoglobin 12.3 g/dL (123 g/L), leukocyte count of 28,000/µL (28 × 10 9 /L) with 15% band forms. Intravenous fluids are started and stool studies are obtained. Which of the following is the most appropriate next step in the management of this patient? 1.Increase dosage of azathioprine 2.Start oral vancomycin 3.Start oral mesalamine 4.Small-bowel radiographic series

4 55yo male with 1 month history of increasing flatulence and loose stools – BMs occurring 2-3x daily. Denies weight loss, fever, or other symptoms. PMHx: DM2 (A1c 7%), HTN. Meds: statin, ASA, glyburide, enalapril, Ca supplement. Has been trying to lose weight via exercise, diet, and using sugar-free snacks. Exam is normal. Stool cultures show no growth of pathogens. An empiric trial of which of the following is most appropriate at this time? 1.Discontinuation of sugar-free snacks 2.Discontinuation of calcium supplements 3.Substitute Metformin for glyburide 4.Add acarbose to current regimen 5.Initiate 2-week course of Cipro

5 Diarrhea Acute (<4 weeks) – Typically infectious etiology Chronic (>4 weeks) – Infectious/Inflammatory IBD, C diff, Giardia, etc – Secretory Carcinoid, Glucagonoma, VIPoma, etc – Osmotic +/- malabsorption (steatorrhea) Celiac disease, Carb intolerance, Pancreatic insufficiency, small bowel bacterial overgrowth, bile salt deficiency, etc

6 Chronic Diarrhea - Workup Chronic diarrheaCheck stool culture, Cdiff, fecal leuks Infectious/Inflammatory cause Check offending meds Laxative screen Lactose test Stop culprit med/supplement Improves with NPO? Stool Osmolar gap? Yes Osmotic diarrhea Does NOT improve with NPO Osmolar gap <50 Secretory diarrhea Stool Osm Gap: 290 – 2(Na+K) Quant fecal fat >10-24g/24h? Improves with NPO Osmolar gap >125 Fat Malabsoroption present

7 A 68-year-old man with a history of osteoporosis and alcoholism is evaluated in the emergency department for a 7-month history of diarrhea during which he has noted an increased volume of stool and decreased consistency. He has had intermittent abdominal pain but not severe enough to prevent him from eating or drinking. He is not taking any medications. On physical examination, he is afebrile; the blood pressure is 108/72 mm Hg, the pulse rate is 80/min, and the respiration rate is 16/min. The abdomen is soft with mild periumbilical tenderness but no distention AST 155, ALT 88, Alk phos 96, Bili 1.1, Lipase 70, INR 1.4 CT abdomen shows calcifications but no mass. Quantitative fecal fat 26g/24h. Which of the following is the most appropriate management for this patient? 1.Fiber 2.Cholestyramine 3.Loperamide 4.Pancreatic enzymes

8 Fat Absorption Gold Standard Dx: Quant fecal fat >10-24g/24h Remember: ADEK Deficiencies

9 Fat Malabsorption – Few specifics Celiac Disease – Suspect if signs of ADEK deficiency + iron deficiency – Dx: gold standard – duodenal biopsy (villous atrophy) Antitissue transglutaminase Ab (anti-tTG) – IgA is preferred over IgG (unless patient also with IgA deficiency) – still need to confirm with bx Antiendomysial IgA/IgG – more expensive – Tx: gluten avoidance Small Intestine Bacterial Overgrowth – Flatulence, bloating, diarrhea – RFs: dysmotility syndromes (i.e. DM2), hypochlorhydria, elderly – *Megaloblastic anemia: B12 deficiency + ELEVATED folate (due to bacterial production) – Low carb, high fat diet (to minimize substrate for bacteria) + empiric Abx trial x10-14d (tetracycline, augmentin, rifaximin)

10 55 yo male evaluated for a 4-month history of frequent and urgent defecation with loose and bloody stool, mild abdominal cramping, and fatigue. Has 8 BMs daily and often wakes at night with symptoms; before this episode he had one bowel movement a day with well-formed stool. He does not have fever, nausea, or vomiting, but he has lost 3 kg (7 lb). He has mild joint pain in his knees and ankles that also began 4 months ago. On physical examination, there is mild lower abdominal tenderness without rebound or guarding; there are no palpable abdominal masses. Examination of the rectum shows gross blood. Labs reveal microcytic anemia. Fecal leukocytes are present, but stool analysis is negative for infection. Colonoscopy shows continuous erythema, friability, and loss of vascular pattern from the rectum to the splenic flexure; the rest of the colon and terminal ileum is normal. Histology shows cryptitis, crypt abscesses, and crypt architecture distortion. Which of the following is the most likely diagnosis? 1.Crohn colitis 2.Infectious colitis 3.Ischemic colitis 4.Microscopic colitis 5.Ulcerative colitis

11 A 45-year-old woman is evaluated for a 2-week history of right leg and flank pain and a slight limp. The patient was diagnosed with Crohn disease at age 20 years. She had an elective ileocolic resection with a primary anastomosis when her disease proved to be refractory to corticosteroid therapy. She has since been pain-free but has required intermittent courses of antibiotics and mesalamine for diarrheal flares of disease. She has had routine colonoscopic examinations with biopsy specimens revealing non-necrotizing granulomas in the colon and neo-terminal ileum. Her most recent colonoscopy was 5 years ago. She is otherwise healthy and takes no medication. On physical examination, the temperature is 38.0 °C, BP 120/80 mm Hg, HR 90/min; there is right-sided abdominal tenderness and restricted painful extension of the right hip; otherwise, the range of motion of the hip is normal and without pain. She has an abnormal gait, favoring her right leg. Which of the following is the most likely diagnosis? 1.Avascular necrosis of the hip 2.Crohn disease-related arthritis 3.Osteoporosis-related fracture of the femoral neck 4.Psoas muscle abscess

12 IBD Crohn’s Disease Mouth to anus – skip lesions Transmural involvement with granulomas Large volume diarrhea, steatorrhea, +/- bloody diarrhea, abd pain Fistulae, Strictures, abscesses Differentiate colonic vs small intestine involvement Ulcerative Colitis Extends proximally from anal verge Mucosal involvement with crypt abscesses Bloody diarrhea, tenesmus, constipation, abd pain Diagnosis: exclude infectious diarrhea **Colonoscopy with biopsy Serum antibodies (only assists with diagnosis): p-ANCA: 66% of UC and 20% of Crohn’s ASCA: 5% of UC and 50% of Crohn’s

13 IBD Extraintestinal Manifestations Musculoskeletal – Arthritis (nondestructive, large joint) – Osteopenia/Osteoporosis – Ankylosing spondylitis & Sacroilitis Eye – Uveitis, scleritis, episcleritis Skin – Erythema Nodosum – Pyoderma Gangrenosum Hepatobiliary – PSC – and thus increased cholangiocarcinoma – Fatty liver – Autoimmune liver disease Heme – Arterial and venous VTE – AIHA Pulm – Serositis Colon Cancer Risk Crohn’s – increased risk if colon involved UC – very increased risk – **Start screening 8-10 years after diagnosis – **Rescreen 1-2 years after initial colonoscopy – If dysplasia seen – total proctocolectomy

14 A 35-year-old woman is evaluated for symptomatic ulcerative colitis. One year ago, she was diagnosed with pan-ulcerative colitis and responded well to initial and maintenance therapy with balsalazide. However, 2 months ago she developed urgent bloody diarrhea several times a day and lower abdominal cramping; prednisone, 40 mg/d, alleviated her acute symptoms, but her symptoms have returned with prednisone tapering. The patient is otherwise healthy, and her medications are balsalazide, 750 mg three times a day, prednisone, 15 mg/d, and calcium with vitamin D. On physical examination, vital signs and other findings are normal. Laboratory studies reveal hemoglobin 11.4 g/dL (114 g/L) and plasma glucose 140 mg/dL (7.77 mmol/L). Stool analysis for Clostridium difficile toxin A and B is negative. Which of the following is the most appropriate next step in the treatment of this patient? 1.Add olsalazine 2.Add budesonide 3.Add metronidazole 4.Increase prednisone dosage to 40 mg/d and add 6-mercaptopurine

15 IBD – Treatment Like chemo: induction of remission, then maintenance therapy Surgery Cyclosporine/Inflixi mab Azathioprine/6-MP Prednisone 5-ASA Surgery Infliximab/ Adalimumab Azathioprine/6-MP/MTX Prednisone/Budesonide 5-ASA + Abx (only if colonic disease ) Crohn’s UC

16 A 42-year-old woman is evaluated for a 20-year history of constipation. She has approximately one or two bowel movements a week consisting of lumpy or hard stool. She strains at defecation and has a sense of incomplete evacuation after a bowel movement. She does not have bloody stool, abdominal pain or discomfort, weight loss, or diarrhea. She is otherwise healthy, and her only medication is an occasional over-the-counter laxative or stool softener. On physical examination, vital signs are normal. The anorectal tone is normal, and on rectal examination, the patient is able to expel the examiner’s finger when asked to mimic a bowel movement. Laboratory studies are normal. Radiopaque marker study shows delayed transit time through the right colon. Which of the following is the most likely diagnosis? 1.Chronic intestinal pseudo-obstruction 2.Constipation-predominant irritable bowel syndrome 3.Pelvic floor dysfunction 4.Colonic inertia

17 A 47-year-old woman is evaluated in the emergency department for 3 days of abdominal pain, distention, and constipation. She has had nausea and vomited once. No BM for the past 3 days. She has had similar symptoms in the past. PMHx of systemic sclerosis. No abdominal surgeries. Meds include nifedipine for Raynaud’s and PPI for GERD On exam, vital signs are wnl. The abdomen is distended with hypoactive bowel sounds and tympany. There is no succussion splash. There are no abdominal masses or organomegaly. Labs wnl. Plain radiograph of the abdomen shows dilated loops of small bowel. After bowel decompression with a nasogastric tube and bowel rest, upper and lower gastrointestinal radiographic series shows no obstructive lesions. Which of the following is the most likely diagnosis? 1.Chronic intestinal pseudo-obstruction 2.Colonic inertia 3.Gastroparesis 4.Small-bowel obstruction

18 Dysmotility Syndromes Major categories: 1.Constipation 2.Ileus vs Pseudo-obstruction (Ogilvie’s) Can be acute or chronic Etiologies: post-operative, neurologic or CT disorders, DM, hypothyroidism, electrolyte disturbance, meds (esp narcs, CCBs), sepsis Acute tx: NG/rectal tube, stop offending meds, replace lytes, prokinetic agents, neostigmine (if severe) vs colonic decompression (last resort) 3.Diabetic dysmotility (gastroparesis, anorectal dysfunction, and decreased intestinal motility) Due to autonomic dysfunction -> can lead to bacterial overgrowth Cause cause both diarrhea and constipation Tx: loperamide +/- clonidine for diarrhea; abx for bact overgrowth 4.IBS Diarrhea predom vs constipation predom vs mixed (but always a combination) Associations: depression, anxiety, sexual abuse, phobias, somatization Dx – clinical and based on Rhome III criteria and absence of alarm features Tx – symptomatic – bulking agents, loperamide, antispasmodics, TCAs, etc

19 Constipation Workup Rule out secondary causes Rule out IBS (if suspected) Functional Constipation Dyssynergic Pelvic Floor Dysfunction (Outlet Delay) Slow Transit (Colonic Inertia) Good anorectal manometry ++Finger poop test Normal defecography Slow Transit Marker Study Poor anorectal manometry Negative Finger poop test Abnormal defecography Normal Transit Marker Study

20 A 74-year-old man is evaluated in the hospital for severe diffuse abdominal pain. He was hospitalized 5 days ago for chest pain and was found to be in rapid atrial fibrillation and a myocardial infarction was diagnosed. He underwent cardiac catheterization and double stent placement after which he has had intermittent hypotension and has remained in atrial fibrillation with a controlled ventricular rate. At the bedside the patient is sweating, nauseated, and holding his abdomen. He cannot respond to questions. His wife says that he has never had any gastrointestinal problems, but that he has not had a bowel movement since he entered the hospital. His medications are heparin, metoprolol, simvastatin, clopidogrel, and aspirin. On exam, temp is 38.0 °C, BP 102/60 mm Hg, HR 94/min, and RR 25/min. There is mild, diffuse abdominal tenderness to palpation without rebound or guarding. Radiograph of abdomen shows no evidence of perforation or obstruction. Which of the following would be the most appropriate management for this patient? 1.CT arteriography 2.Colonoscopy 3.Intravenous famotidine 4.Lactulose

21 A 75-year-old woman is evaluated in the emergency department for the acute onset of passage of bright red blood per rectum. This morning she had crampy abdominal pain and had two episodes of diarrhea after which she passed bright red blood. The patient has a history of hypertension and coronary artery disease, and her medications are aspirin, ramipril, metoprolol, and simvastatin. She is otherwise healthy and has not traveled recently or taken antibiotics. She had a colonoscopy 6 months ago, which was normal. On exam, the patient is not in acute distress; temp is 36.8 °C, BP 130/80 mm Hg, HR 70/min, and RR 14/min. The abdomen is soft with tenderness in the left lower quadrant without rebound or guarding. Rectal examination shows the presence of bright red blood. CT scan of the abdomen and pelvis shows segmental thickening in the sigmoid colon. Which of the following is the most likely diagnosis? 1.Crohn disease 2.Cytomegalovirus colitis 3.Irritable bowel syndrome 4.Ischemic colitis 5.Peptic ulcer disease

22 Intestinal Ischemia Mesenteric Ischemia \ = Ischemic Colitis Acute: sudden abd pain out of proportion to exam; appear VERY ILL Mild abdominal pain ++Bloody diarrhea

23 Intestinal Ischemia Acute Mesenteric Ischemia (small bowel) – Chronic (Intestinal Angina) – in pts with vascular disease Postprandial abd pain, fear of eating, wt loss Dx: MRA or CTA; Tx: perc antioplasty/stent – Acute – typically has precipitating cause Etiologies: – SMA embolus (50%) – usually due to Afib – SMA thrombis – progression of chronic ischemia; also after abd trauma or infection – Nonocclusive (25%) – physiologic vasoconstriction in response to shock – Acute mesenteric vein thrombosis – younger patients with hypercoag states Dx: Angiography; Tx: IVF, Abx, surgery Ischemic Colitis (watershed areas of colon) – 90% in patients >60yo – Occurs if colonic hypoperfusion Usually L-side (supplied by IMA) If R-sided involvement, likely also will see mesenteric ischemia (b/c SMA supplies proximal colon and mesentery) – Dx: Colonoscopy; Tx: IVF + Abx

24 A 34-year-old man is evaluated as a new patient. He is asymptomatic and has no significant medical history, but he is concerned about his risk for colon cancer. His 59- year-old mother had two adenomatous polyps detected at the age of 52 years. She has had surveillance colonoscopy every 3 years since then and has had two additional polyps detected. His father has no history of colon polyps, and there is no family history of colorectal cancer. On physical examination, vital signs are normal; BMI is 21.5; the rest of the physical examination is normal. Laboratory results are all within normal limits. Which of the following is the most appropriate screening strategy for this patient? 1.Colonoscopy at age 40 years 2.Colonoscopy at age 42 years 3.Colonoscopy at age 50 years 4.Fecal occult blood testing at age 40 years 5.Fecal occult blood testing at age 50 years

25 Colon Cancer Screening: – When? If no FHx: 50yo (unless AA, then 45yo) If 1 st degree relative with colon CA or adenomatous polyp at age <60: start age 40 or 10 yrs younger than affected individual – How? Colonoscopy q10 yrs if normal Flex sig q5 yrs if normal Annual FOBT Other: double contrast barium enema, CT colonography (only if cannot due other methods) Hereditary Syndromes: – FAP (Auto dominant; APC gene) – 100% Risk Start screening age 10 -> total colectomy once polyposis develops -> then start looking for duodenal CA – HNPCC (Auto dominant; MLH1 or MLH2 gene) Family hx of Colon, Ovarian, Endometrial CA amongst others – Gardner Syndrome (FAP variant) – often associated with osteomas – Peutz-Jeghers – Juvenile Polyposis Syndrome

26 A 74-year-old man is evaluated for a 2-month history of recurrent melena. He has had recurrent 2 - or 3-day periods of black, tarry stool followed by normal stool for the next week. His most recent black stool was yesterday. During this time, he has developed anemia and required transfusions of a total of eight units of blood. He has not had chest pain, abdominal pain, nausea or vomiting, or bleeding. The patient’s medical history includes hypertension and mild chronic obstructive pulmonary disease. His exam (including vital signs) is benign except for rectal examination which reveals black, tarry stool that is positive for occult blood. Laboratory studies reveal hemoglobin of 8.6 g/dL (86 g/L) with a mean corpuscular volume of 80 fL. EGD on two occasions and a colonoscopy fail to identify a bleeding source. Which of the following is the most appropriate next step in the evaluation of this patient? 1.CT angiography 2.Double-balloon enteroscopy 3.Intraoperative endoscopy 4.Small-bowel barium examination 5.Wireless capsule endoscopy

27 GI Bleeding Upper GI bleed (Variceal vs non-variceal) Lower GI bleed Obscure GI bleed – recurrent blood loss without identified source despite investigation with EGD/colonoscopy – DDX based on age: <20: Peutz-Jeghers, Meckel’s diverticulum, Hemangioma, congenital AVM, dieulafoy 20-60: Crohn’s, radiation/NSAIDs, cameron erosion, meckel’s, GAVE, dieulafoy, tumor >60: amyloid, AVMs, malignancy, all in group – Dx: Repeat EGD/Colonoscopy Capsule endoscopy – ***test of choice following negative scopes Double-balloon enteroscopy – if suspect small bowel lesion but negative capsule study; can also be used to treat small bowel lesions found during capsule Push enteroscopy – often used to treat prox small bowel lesions found on capsule Angiography – if brisk, overt bleeding; can also use to treat Tagged RBC scan – can detect bleeding at a slower rate than angiography, but still need lesion to be actively bleeding to detect it

28 Hepatobiliary

29 Acute Liver Injury (Acute onset of elevated transaminases and coagulopathy in patient with no known underlying liver disease) Acute Liver Injury Biliary abnormality Viral hepatitis Autoimmune disease Alcoholic Hepatitis Metabolic Disease HemodynamicDrug-Induced Fatty Liver of Pregnancy Fulminant Liver Failure (ALI + encephalopathic)

30 A 55-year-old man is hospitalized for a 2-week history of jaundice and altered mental status. The patient has a 10-year history of alcohol dependence and has failed several attempts to stop drinking. His family reports that he had been drinking heavily every day until about 3 weeks ago. On physical examination, the patient is confused and lethargic; the temperature is 38.0 °C (100.0 °F), the blood pressure is 90/60 mm Hg, the pulse rate is 120/min, and the respiration rate is 30/min. The BMI is 24. Examination reveals scleral icterus. There is no guarding on palpation of the abdomen. The liver edge is tender and easily palpable 3 cm below the right costal margin. There is no ascites, edema, or evidence of bleeding. WBC 17000, Plt , INR 4.0, Bili 37.0, AST 98, ALT 50, Alk phos 230, Albumin 2.0. Ultrasound shows enlarged, fatty liver with no nodules, ascites, pericholecystic fluid, or bile duct dilatation. Blood and urine cultures are negative. In addition to enteral nutrition, which of the following is the most appropriate management for this patient? 1.Ceftriaxone 2.Methylprednisolone 3.Fresh frozen plasma 4.Liver transplantation

31 Alcoholic Hepatitis Often presents with leukocytosis, jaundice, hepatomegaly, and RUQ pain **need to rule out infection Discriminant Function (DF) DF = 4.6 (PT – control PT) + bili – If >32, patient has 50% mortality in 30 days Candidates for steroids (typically after liver biopsy) Consider pentoxifylline (trental) to prevent hepatorenal syndrome

32 A 25-year-old woman is brought to the emergency department by her husband for yellowing of the eyes and increasing confusion and somnolence. The patient is 30 weeks’ pregnant and just returned from visiting her parents in Africa. She has been previously healthy and takes only prenatal vitamins. Previously a social drinker, she stopped consuming alcohol entirely at the onset of her pregnancy. On physical examination, the temperature is 37.2 °C (99.0 °F), the blood pressure is 90/40 mm Hg, the pulse rate is 100/min, and the respiration rate is 12/min; the BMI is 20. Examination reveals a gravid uterus and asterixis Hgb 14, WBC 15000, Plt 450k, INR 4.7 Bili 12.0 (direct 9.0), AST 3000, ALT 2870, Alk phos 400, Albumin 2.3 Hep A IgM negative, Hep B surface Ag negative, Hep B viral PCR negative, Hep C virus Ab negative, ANA negative, anti-smooth muscle Ab negative, AMA negative, alcohol negative, HSV PCR negative Which of the following is most likely cause of this patient’s fulminant hepatic failure? 1.Acute autoimmune hepatitis 2.Acute alcoholic hepatitis 3.HELLP syndrome 4.Hepatitis E virus infection

33 A 20-year-old woman is evaluated in the emergency department for a 2-week history of malaise, fatigue, and mild jaundice. The patient has no significant medical history, but she uses injection drugs. She drinks alcohol socially. On physical examination, the temperature is 37.8 °C (100.0 °F), the blood pressure is 128/70 mm Hg, the pulse rate is 100/min, and the respiration rate is 16/min. Examination reveals slight scleral icterus, needle puncture marks in the antecubital fossae, and hepatomegaly; there is no splenomegaly, cutaneous angiomata, ascites, or asterixis Bili 4.6, AST 580, ALT 750, Alk phos 145, Albumin 4.2, Hep B surface Ag negative, Hep B core Ab negative, Hep C virus Ab negative, Hep A antibody negative, drug and alcohol screen negative. Ultrasound shows hepatomegaly. In addition to screening for HIV infection, which of the following is the most appropriate next diagnostic test? 1.Hepatitis B virus DNA 2.Hepatitis C virus RNA 3.Liver biopsy 4.MRI of the liver

34 Viral Hepatitis Acute infection: fatigue, malaise, abd symptoms, jaundice HepA – Transmitted fecal/oral route – Dx: Hep A IgM (stays + for 6 mo) – Vaccinate if: traveling to endemic area, IVDU, MSM, chronic liver disease HepB – Transmitted blood/body fluid contact or perinatal – Dx: serologies (see next slide) – Vaccinate all! HepC – Most common bloodborne infection in the US – Dx: HepC virus RNA (active infection), anti-HCV (past exposure) Anti-HCV can be falsely + in rheum disease -> can check HCV RIBA to confirm viral clearance if anti-HCV is positive and HCV RNA negative HepD – Depends on HbsAg for its replication – RF: IVDU – Can present as acute hepatitis in HepB pt (coinfection) or exacerbation of preexisting chronic hepatitis (superinfection) HepE – RF: underdeveloped countries; fecal-oral transmission – Severe disease seen in PREGNANT folk

35 Hep B HbsAgHbsAbAnti Hbc (IgM) Anti Hbc (IgG) HbeAgHbeAbHbDNA Acute Chronic, nonreplicative Chronic, replicative Immune, prior infxn Vaccinated Acute HepB infection typically resolves in 6 months -> if persistent HbsAg after 6 months, then considered chronic HepB infection Window period: time between clearance of HbsAg and development of HbsAb – during this time, only Anti-Hbc present Virus VERY active Have disease; Not yet immune Host immune Exposed (acutely) Exposed (remotely)

36 Viral Hepatitis Hep B Active Infection Chronic (5%) Nonreplicative Replicative (25%) Cleared HepC Active HepC Chronic (80%) Cirrhosis (20-25%) HCC (5%/year) Cleared (20%) 15-40% of chronic HepB develop Cirrhosis or HCC (do NOT need cirrhosis prior to HCC) US and alpha-fetoprotein q6-12 mo in all pts with chronic HepB Need Cirrhosis prior to HCC in HepC Only need to screen for HCC in those with known cirrhosis

37 Hep B – Which stage of infection? Window Period Acute infection Vaccinated Immune, prior infection Chronic nonreplicative Chronic replicative HbsAg HbsAb antiHbC HbeAg

38 A 38-year-old woman is evaluated for elevated results of liver chemistry tests detected in an evaluation for new-onset fatigue, joint pains, and jaundice. The patient recently started a job in a hospital and received a hepatitis B vaccination. She has a history of hypothyroidism, and her only medication is levothyroxine. She has never used illicit drugs and does not drink alcohol. Her mother has rheumatoid arthritis. On physical examination, the patient is afebrile; the blood pressure is 130/75 mm Hg, the pulse rate is 80/min, and the respiration rate is 14/min. The BMI is 26. There is scleral icterus; the rest of the examination is normal WBC 3400, Bili 6.0, Direct bili 3.6, AST 890, ALT 765, Alk phos 100, ANA 1:40, Anti-smooth muscle Ab 1:640, AMA negative. Viral serologic tests negative. Abdominal ultrasound shows normal gallbladder. Which of the folloiwng is the most likely diagnosis? 1.Acute cholecystitis 2.Autoimmune hepatitis 3.Drug-induced liver injury 4.Primary biliary cirrhosis 5.Primary sclerosing cholangitis

39 Autoimmune hepatitis More common in women; most are asymptomatic; often seen with other autoimmune history Elevated bili, AST/ALT; Alk Phos near normal AutoAbs: ANA, SMA, anti-LKM1 Dx: biopsy showing lymphocytic & plasmacytic periportal infiltrate Tx: consider if 5-fold increase in transaminases with acute inflammation on bx – Prednisone +/- azathioprine until remission

40 A 57-year-old man is evaluated for elevated LFTs detected on evaluation for fatigue. The patient has a history of osteoarthritis, Dm1, and hypertension. The patient does not use illicit drugs, alcohol, or tobacco; he has never had a blood transfusion. His mother died of heart failure and a maternal aunt died of cirrhosis of unknown cause. Exam is benign and there are no stigmata of chronic liver disease Hgb 14, Glc 145, Bili 1.2, AST 75, ALT 88, Alk phos 120, Albumin 4.2, Ferritin 1267, Transferrin saturation 75% Viral hepatitis serologies negative; ANA, anti-smooth muscle, and AMA negative Which of the following is the most appropriate next step in the management for this patient? 1.Deferoxamine therapy 2.Genetic testing for mutations of the HFE gene 3.MRI abdomen 4.phlebotomy

41 Metabolic Liver Disease Non-alcoholic fatty liver disease 1.Nonalcoholic steatohepatitis (NASH) Obese, dyslipidemia, DM2 Tx: RF modification 2.Steatosis (fatty degeneration) Wilson Disease (autosomal recessive) – Genetic defect causing copper transport abnormality thus Cu accumulates in body – Liver, neuro, psych, ophtho, BM – Dx: biopsy, decreased ceruloplasmin, increased urinary copper – Tx: chelators (penicillamine and trientene) or agents to decrease absorption (zinc) Hereditary Hemochromatosis (HFE gene mutation) – Iron overload (high ferritin) – liver, heart, pancreas, pituitary (bronze diabetes) – Dx: 1) fasting transferrin saturation >50% in females or >60% in males 2) genetic screening for HFE gene mutation 3) liver biopsy to determine degree of fibrosis – Tx: phlebotomy Alpha-1 Antitrypsin Deficiency – Accumulation of abnormal variant A1AT in body – lung, liver, skin Seen as PAS+ inclusions on liver biopsy – Increased risk of HCC and cirrhosis – Tx: transplant if decompensated disease

42 A 55-year-old woman is evaluated for a 4-month history of progressive fatigue and pruritus. She is otherwise healthy and takes no medications. On physical examination, vital signs are normal; BMI is 25. Examination reveals mild hepatomegaly and excoriations of the skin. There is no jaundice, rash, or skin eruption Bili 1.5, AST 60, ALT 75, Alk Phos 470, Albumin 4.0, Hep C Ab negative, Hep B sAg negative Ultrasonography of the abdomen is normal with no bile duct dilatation. Which of the following is the most appropriate next step in the diagnosis of this patient? 1.A1AT phenotype 2.Liver biopsy 3.Measurement of serum AMA 4.SPEP

43 Cholestatic Liver Disease fatigue, pruritis, jaundice, cholestatic LFT pattern, ADEK deficiency Primary Biliary Cirrhosis – Autoimmune inflammation of ducts -> blocks bile -> destroys liver cells -> cirrhosis – “Cirrhosis” = think liver (thus only intrahepatic ducts affected) – Dx: +AMA, elevated IgM – Tx: Ursodeoxycholic Acid (esp if early stage) to decrease bile production Primary Sclerosing Cholangitis – Duct inflammation -> fibrosis – 80% have ulcerative colitis – 10% develop cholangiocarcinoma – “Cholangitis” = biliary system (thus all ducts - both intra and extrahepatic - involved) – Dx: ERCP – multifocal strictures Large bile duct obstruction Drug induced cholestasis Infiltrative disease (i.e. sarcoidosis)

44 A 57-year-old woman is evaluated for a 1-month history of increased abdominal girth. The patient has a 15-year history of alcohol abuse, drinking a bottle of wine a day. She also has type 2 diabetes mellitus, hypertension, and hyperlipidemia, and her medications are metformin, hydrochlorothiazide, propranolol, simvastatin, and aspirin. On physical examination, the temperature is 37.1 °C (98.8 °F), the blood pressure is 90/50 mm Hg, the pulse rate is 99/min, and the respiration rate is 13/min; the BMI is 21. Examination reveals scleral icterus; bulging flanks; a small umbilical hernia; caput medusae; spider angiomata of the face, arms, and chest; and mild asterixis. There is no abdominal tenderness WBC 5200, Plt 65000, INR 2.2, Bili 3.4, AST 120, ALT 65, Alk phos 196, Albumin 2.7, Creat 2.7, Urinalysis normal. Blood cultures negative. Which of the following is the most appropriate management for this patient? 1.Diagnostic paracentesis 2.Cefotaxime and albumin 3.Furosemide and spironolactone 4.Transjugular intrahepatic portosystemic shunt

45 A 57-year-old woman is evaluated in the intensive care unit for rapidly progressive renal failure requiring dialysis. The patient had been hospitalized for advanced liver disease due to Hep C including mental status changes secondary to encephalopathy. She has ascites. The patient has no history of renal insufficiency and has not received antibiotics, intravenous contrast agents, or other nephrotoxic agents. Her medications are lactulose, nadolol, midodrine, octreotide, and albumin. She does not drink alcohol. On physical examination, the temperature is 36.6 °C (97.8 °F), the blood pressure is 110/70 mm Hg, the pulse rate is 97/min, and the respiration rate is 12/min; the BMI is 22 Creat 5.4, BUN 120, Urine sodium <5, urinalysis negative. Renal ultrasound shows normal size kidneys and no obstruction. Which of the following is the most appropriate management for this patient? 1.Add lisionpril 2.Kidney and liver transplantation 3.Kidney transplantation 4.Liver transplantation 5.Peritoneovenous shunt

46 Complications of Cirrhosis Portal Hypertension – Varices All cirrhotics need screening – place on bblocker if they are present If bleed: to ICU, PPx Abx, Octreotide (splanchnic constrictor), EGD for band ligation – Ascites (SAAG >1.1) – treat with low na diet and diuretics SBP (ANC >250 or + cultures) – Tx 3 rd gen ceph x 5 days Diuretic resistant ascites – need occ LVP Hepatorenal Syndrome – Result of splanchnic vasodilation and thus activation of renin-angiotensin system thus renal vasoconstriction – Dx of exclusion; Urine Na <10 in absence of intrinsic renal injury – Type 1 – acute progression (2 wk mortality 80%); Type 2 – more indolent, usually in setting of diuretic resistant ascites, better prognosis – Tx: systemic vasoconstrictor (midodrine) + splanchnic vasoconstrictor (octreotide) + albumin + liver transplant Hepatopulmonary Syndrome – Hypoxemia due to intrapulmonary shunt – Dx with Echo and bubble study – Tx: liver transplant Encephalopathy – Due to elevated glutamine in brain 2/2 elevated ammonia -> brain edema – Precipitants: bleed, dehydration, electrolyte abnorm, over-diuresis, SBP, renal failure, TIPS – Tx: Lactulose (to decrease gut ammonia), Rifaximine HCC – No need to biopsy (could seed the tumor) – Dx: imaging + elevated alpha-fetoprotein – Local ablative therapy (if 2 or less tumors all <3cm in size): RFA, Perc EtOH ablation, TACE – Resection if: one tumor <5cm or 3 or less tumors all <3cm

47 A 65-year-old man is evaluated in the emergency department for fever and abdominal pain. The patient has a history of diverticulitis, and his latest flare 2 months ago was treated as an outpatient with antibiotics. While improved, he still has residual pain in the left lower quadrant. He has no other significant medical history and has not traveled recently. On physical examination, the temperature is 38.8 °C (101.8 °F), the blood pressure is 120/85 mm Hg, the pulse rate is 100/min, and the respiration rate is 18/min; the BMI is 25. There is right upper quadrant abdominal pain with normal bowel sounds and no peritoneal signs, scleral icterus, or ascites. Hgb 14.2 WBC 17,000 with 15% bands Plt 320,000 INR 1.0 Total Bili 1.6 Direct bili 0.6 AST 97 ALT 86 Alk phos 220 CT scan of abdomen/pelvis shows mass with fluid level consistent with a hepatic abscess. Abx are started. Which of the following is the most appropriate next step in the management of this patient? 1.ERCP 2.Lobectomy 3.MRI with gadolinium 4.Perc drainage of the hepatic lesion

48 Liver abscess & cysts Hepatic Abscess (consider in workup of FUO) – Pyogenic (E.coli, anaerobes, Klebsiella) Often from direct seeding of intraabd process of hematogenous spread Need Abx and PERC DRAINAGE – Amebic (Entamoeba histolytica - recent travel to Mexico or South America; HIV also risk factor) Treat with Flagyl if E. histolytica; NO DRAINAGE REQUIRED Hepatic cysts – usually asymptomatic; only resect if large and causing symptoms Cystadenomas (thicker irregular walls) – can undergo malignant transformation, need resected Focal Nodular Hyperplasia – benign; central scar; don’t need to stop OCPs as it is not hormone responsive Hepatic Adenomas – rare malignant potential; are hormone responsive so need to stop OCPs; high risk of bleeding esp in pregnancy so resect prior to pregnancy

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