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Gastroenterology and Hepatology Gastroparesis Diagnosis Gastroparesis is characterized by delayed gastric emptying with recurrent nausea, early satiety, bloating, and weight loss. Causes include: . systemic sclerosis . diabetes mellitus o hypothyroidism . anticholinergicagents ' opioids A viral cause is suggested by rapid onset of gastroparesis after a presumed viral infection. Testing In patients with acute symptoms, upper endoscopy is the initial study to rule out pyloric channel obstruction caused by PUD. Patients with negative findings on upper endoscopy should undergo gastric scintigraphy, wireless motility capsule, or gastric emptying carbon breath testing. DOil'T BE TRICKED o Patients with diabetes mellitus should have a blood glucose level <275 mg/dl during testing because marked hyperglycemia can acutely impair gastric emptying. Treatment Specific dietary recommendations include small low fat meals consumed four to five times per day. Use IV erythromycin for acute gastroparesis and metoclopramide for chronic gastroparesis. Dystonia and parkinsonian-like tardive dyskinesia are serious complications of metoclopramide; the drug must be stopped at the flrst sign of these disorders. TESTYOURSETF A 64-year old woman with a 2O-year history of type 2 diabetes mellitus has a 3 year history of postprandial nausea. ANSWER: For diagnosis, choose diabetic gastroparesis. For management, select endoscopy as the initial diagnostic test. Complications of Gastric Surgery Diagnosis For complications of bariatric surgery see the General Internal Medicine chapter. Early dumping syndrome occurs within 30 minutes of eating. o palpitations, flushing or pallor, diaphoresis, lightheadedness, hypotension, and fatigue . diarrhea, nausea, abdominal bloating, cramping, and borborygmus 88

Gastroenterology and Hepatology Late dumping syndrome occurs 1 to 3 hours after meals. o reactive hypoglycemia . decreased concentration, faintness, and altered consciousness Acute Pancreatitis Diagnosis The major causes of acute pancreatitis are: . gallstone biliary obstruction and alcohol (common) . endoscopic retrograde cholangiopancreatography (ERCP) o sulfonamides, estrogens, didanosine, valproic acid, thiazide diuretics, 6 MP/azathioprine, pentamidine, and furosemide . hypertriglyceridemia (>1000 mg/dl) . hypercalcemia Diagnosis of acute pancreatitis requires at least two of the following criteria: . acute onset of upper abdominal pain . serum amylase or lipase increased >3x ULN (lipase is more specific and sensitive than amylase) . findings suggesting pancreatitis on cross sectional imaging (ultrasonography, CT, MRI) Elevated hematocrit and BUN or the presence of SIRS predicts a poor outcome. Pancreatic pseudocysts are the most common complication of acute pancreatitis. Repeated episodes ofacute pancreatitis may result in chronic pancreatitis. Testing All patients with acute pancreatitis require abdominal ultrasonography to evaluate the biliary tract for obstruction. CT of the abdomen is indicated only if the pancreatitis is severe, it Iasts longer than 48 hours, or complications are suspected. DOil'T BE TRICKED . Uncomplicated pancreatitis is not typically associated with rebound abdominal tenderness, absent bowel sounds, high fever, or melena. When these findings are present, consider abscess, pseudocyst, or necrotizing pancreatitis. . Mildly increased amylase values can also be caused by kidney disease, intestinal ischemia, appendicitis, and parotitis Treatment In addition to vigorous IV hydration and pain relief: . oral leeding when nausea, vomiting, and abdominal pain resolve . enteral jejunal feedings within 72 hours if oral feeding not tolerated o antibiotics for cholangitis, intbcted pancreatic necrosis, and infected pseudocysts o cholecystectomy before discharge for uncomplicated gallstone pancreatitis . ERCP within 24 hours of presentation for ascending cholangitis or biliary obstruction . surgical consultation for pancreatic necrosis 89

Gastroenterology and Hepatology DOil'T BE TRICKED . Fluid resuscitation (250-5oo ml/h) is most beneficial in the flrst 12-24 hours and may be detrimental after this therapeutic window. . Do not withhold oral feeding on the basis of persistent elevations in pancreatic enzyme levels. r Pancreatic pseudocysts do not require drainage unless they cause signiflcant symptoms or are infected, regardless ofsize. TESTYOURSETF A 71 year-old woman is admitted to the hospital with gallstone pancreatitis. On the sixth day, she has increased pain, fever, and leukocytosis. A CT scan ofthe abdomen with contrast shows hypodense, nonenhancing areas involving 50% ofthe pancreas. ANSWER: For diagnosis, choose pancreatic necrosis. For management, select surgical consultation. Chronic Pancreatitis Diagnosis Alcohol use disorder is a common cause. Clinical presentation and diagnosis: o history of abdominal pain, recurrent attacks of pancreatitis, weight loss o pancreatic calcifications on imaging . exocrine pancreatic insuffi ciency (steatorrhea, osteoporosis) . exocrine pancreatic insuffi ciency (diabetes) Testing Pancreatic-protocol abdominal CT is the most sensitive imaging test to document pancreatic calcifications. If calcifications are absent, MRI, MRCB or endoscopic ultrasonography can detect abnormalities of the main and branch pan- creatic ducts. Young adults with chronic pancreatitis require sweat chloride testing for CF. Disease onset in older patients without risk factors requires exclusion of autoimmune pancreatitis (AIP) and pancreatic cancer. DOI{'T BE TRICKED . Normal amylase and lipase levels do not rule out chronic pancreatitis. . Pancreatic biopsy and endoscopic retrograde cholangiopancreatography are not indicated in the diagnosis ofchronic pancreatitis Treatment Treatment of chronic pancreatitis is directed at controlling pain (in the stepwise approach used for chronic pain) and treating diabetes mellitus and malabsorption. Administer pancreatic enzymes as initial therapy for malabsorption. If enzyme supple- ments do not control diarrhea, begin antidiarrheal agents. DO['T BE TRICKED . Avoid opioids for the treatment of chronic pancreatitis. 90

Gastroenterology and Hepatology Chronic Diarrhea Diagnosis Chronic diarrhea is defined as lasting at least 4 weeks. Except for Giardia lamblict, inf'ectious causes of chmnic diarrhea are uncommon in immunocompetent adults. Osmotic diarrhea is most commonly caused by lactase deficiency. It is associated with eating, improves with fasting, and is not nocfurnal. Secretory diarrhea is characterized by large-volume, watery nocturnal bowel movements and is unchanged by fasting (see als<r Celiac Disease). Testing Select colonoscopy for most patients with chronic diarrhea; biopsies of the colonic mucosa should be performed to assess for microscopic colitis. Additional testing is based on pretest probability of disease. . Blood or an elevated fecal calprotectin level supports IBD. . Stool or urine laxative screen supports laxative abuse. . A reduced fecal elastase level supports chronic pancreatitis. o A positive ) hour stool collection lbr fecal fat confirms steatorrhea. 7 The four most common disorders causing steatorrhea are: . celiac disease . SIBO . short bowel syndrome o pancreatic insufficiency Stool electrolytes (sodium and potassium) can be measured in liquid stool to calculate the fecal osmotic gap, which helps to diagnose osmotic diarrhea. The osmotic gap is calculated as 290 - (2 x [Na + K]).

The four most common disorders causing steatorrhea are: . celiac disease . SIBO . short bowel syndrome o pancreatic insufficiency Stool electrolytes (sodium and potassium) can be measured in liquid stool to calculate the fecal osmotic gap, which helps to diagnose osmotic diarrhea. The osmotic gap is calculated as 290 - (2 x [Na + K]). o An osmotic gap >100 mOsm/kg HrO indicates osmotic diarrhea. . A gap <50 mOsm/kg HrO indicates secretory diarrhea. STUAY TABLE: Differential Diagnosis of Chronic Diarrhea lf you see this... Diagnose or do this... Bloating, abdominal discomfort relieved by a bowel movement, IBS; testfor celiac disease no weight loss or alarm features Diarrhea mainly in women aged 45-60 years, nocturnal diarrhea, Microscopic colitis; stop NSAIDs/PPls; biopsy needed to confirm normal colonoscopy diag nosis Diarrhea with dairy products Lactose intolerance; dietary exclusion or hydrogen breath test Use of artificial sweeteners or fructose Carbohydrate intolerance; dietary exclusion or hydrogen breath test Nocturnal diarrhea and diabetes mellitus or SSc SIBO; hydrogen breath test or empiric antibiotic trial Coexistent pulmonary diseases and/or recurre nt Gi a rdi a infection CVID and selective lgA deficiency; measure immunoglobulins; consider CF Somatization or other psychiatric syndromes, history of laxative Self-induced diarrhea; obtain tests for stool osmolality, electrolytes, use magnesium, and laxative screen Severe secretory diarrhea and flushing Carcinoid syndrome; obtain 24-hour urinary excretion of 5-HIAA Diarrhea, pain, bleeding, positive fecal calprotectin IBD 92

Gastroenterology and Hepatology DOil'T BE TRICKED: . Don't forget other causes of diarrhea such as sorbitol (added as a sweetener to gum, candy) and medications, including PPIs, magnesium-containing antacids, metformin, colchicine, and antibiotics. r Infection with G.lamblia should be considered in patients with exposure to young children or potentially contaminated water (lakes and streams). TESTYOURSETF A S5-year-old woman who takes NSAIDs daily has watery diarrhea without weight loss. Colonoscopy is grossly normal. ANSWER: For diagnosis, select microscopic colitis; biopsy confirms the diagnosis. Microscopic Colitis Diagnosis Microscopic colitis is characterized by chronic diarrhea, sometimes accompanied by mild abdominal pain and weight loss, most commonly in women aged 45 to 60 years, and is associated with other autoimmune conditions, particularly celiac disease. Testing Colonoscopy with biopsies is required for diagnosis. The colonic mucosa appears normal on endoscopy. Treatment Discontinue potentially causative medications (NSAIDs, SSRIs, PPIs). Select symptom management with antidiarrheal agents such as loperamide or bismuth subsalicylate. Otherwise, budesonide has the best documented efficacy. DO]I'T BETRICKED . Unlike patients with IBD, patients with microscopic colitis are not at increased risk for colon cancer Celiac Disease Diagnosis Celiac disease occurs secondary to ingestion of wheat gluten or related rye and barley proteins in genetically predisposed per- sons. Potential findings are: . chronic diarrhea or steatorrhea e bloating, weight loss, and abdominal pain o dermatitis herpetiformis o elevated aminotransferase levels o iron deficiency anemia . fat-soluble vitamin deficiencies . osteoporosis 93

Gastroenterology and Hepatology Celiac disease is associated with: o type 1 diabetes mellitus . auloimmune thyroid disease . microscopic colitis . small bowel lymphoma Testing Diagnostic tests include an IgA anti tTG antibody assay with small bowel biopsy for those with a positive antibody assay. An association between celiac disease and IgA deficiency may lead to false negative IgA based tests. In patients with IgA deficiency. assays for IgG anti tTG or IgG deamidated gliadin peptides are necessary. Measure bone mineral density in all patients with newly diagnosed celiac disease Treatment After diagnosis, select a gluten free diet for treatment of celiac disease or dermatitis. The eflectiveness ol'diet therapy is deter mined by remeasuring IgA anti-tTG antibody titers or repeating small bowel biopsies. Nonadherence is the most common reason for failure of a gluten-free diet. Adherent patients with recurrent malabsorption should be evaluated for other conditions, including microscopic colitis and intestinal lymphoma. Dapsone may be added initially to hasten dermatitis herpetiformis symptom resolution. Before using dapsone, check for G6PD deflciency. DON'T BE TRICKED . Celiac disease is often misdiagnosed as IBS. . Empiric treatment with a gluten free diet before serologic testing may result in false-negative serologic test results. TESTYOURSELF A S4-year-old woman has a 4 month history of diarrhea and weight loss. Laboratory studies show hypocalcemia, microcytic anemia. and an increased PT. ANSWER: For diagnosis, choose celiac disease. For management, order an IgA anti tTG antibody assay and, if positive, follow with a small bowel biopsy. f' I / Dermatitis Herpetiformis: Dermatitis herpetilormis is characterized by pruritic pa pu lovesicles over the exte rnal su rface of the extrem ities a nd on the tru nk; test for celiac disease. 94

Gastroenterology and Hepatology STUDY TABLE: MedicalTreatment of lnflammatory Bowel Disease (Continued) DiseaseActivity UlcerativeColitis Crohn Disease Severe Oral or intravenous glucocorticoidsb Oral or intravenous glucocorticoidsb Cyclosporineb Biologic agents (infliximab, adalimumab, certolizumab, vedolizumab, natalizumab, ustekinumab)u Biologic agents (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab)' Tofacitinib" 'Renrission and maintenance. LRenrission. ' Maintenance, glucocorticoid-sparing l'he level of thiopurine methyltransfbrase should be checked before starting azathioprine or 6-MP; enzyme deficiency leads to increased levels of azathioprine and 6 M B so these should not be used or dosages should be adjusted. Fol low-up Surveil Iance Beginning 8 years after diagnosis, surveillance colonoscopy fbr colon cancer should be perfbrmed every I to 2 years for patients with ulcerative pancolitis or Crohn disease involving most of'the colon. If dysplasia is found, proctocolectomy is required. DOil'? BE TRICKED . Before initiating an anti-TNF agent, all patients should be evaluated for TB and hepatitis B and C virus infections. Chronic Constipation Diagnosis Diagr.rosis of'chronic constipation requires >3 months of symptoms. Medications, particularly opioids, are the most common cause of secondary constipation. Pyoderma Gangrenosum: A nonhealing ulcer, often occurring on the lower Colonoscopy should be performed fbr alarm features suggesting extremities, may be seen in association with lBD. The ulcer shown has a purulent colon cancer or in patients aged >50 years without previous base and ragged, edematous borders. colonoscopy. Treatment Chronic constipation can be approached in a stepped fashion.

Medications, particularly opioids, are the most common cause of secondary constipation. Pyoderma Gangrenosum: A nonhealing ulcer, often occurring on the lower Colonoscopy should be performed fbr alarm features suggesting extremities, may be seen in association with lBD. The ulcer shown has a purulent colon cancer or in patients aged >50 years without previous base and ragged, edematous borders. colonoscopy. Treatment Chronic constipation can be approached in a stepped fashion. . Eliminate implicated medications, if'possible. o lncrease physical activity and dietary fiber. . Add soluble fibers, such as psyllium and methylcellulose. . Add surfactants, such as docusate sodium or docusate calcium (appropriate fbr very mild, intermittent constipation). r Add osn.rotic laxatives, such as magnesium hydroxide, lactul<_rse, sorbitol, and PEG 3350 (pEG is superior). o Add stimulant laxatives, such as anthraquinone. senna, and the diphenylmethanes (fastest,acting agents). lf chronic constipation does not respond to initial stepped approach, prosecretory agents (lubiprostone and linaclotide) can be usecl. 96

Gastroenterology and Hepatology DOil'T BE TRICKED . Chronic senna use can lead to benign pigmentation of the colon, known as melanosis coli. lrritable Bowel Syndrome Diagnosis Diagnosis requires recurrent abdominal pain at least 1 day per week for 3 months, as Melanosis toli: Melanosis coli is an abnormal brown or black pigmentation of the colonic mucosa and is well as at least two of the following: frequently found in patients with long-term stimulant laxative use. o defecation related pain . change in stool frequency . change in stool consistency IBS can be further subtyped to include: o predominant constipation (lBS C) o predominant diarrhea (IBS-D) . mixed bowel habits (lBS M) In patients with IBS D, test for celiac disease and giardiasis, and obtain fecal calprotectin to differentiate from IBD. DON'T BE TRICKED o In the absence of alarm symptoms, CBC, serum chemistry studies, TSH, and abdominal imaging are unnecessary. o Screening colonoscopy should be pursued only in patients who otherwise meet criteria for colon cancer screening. . Patients with severe or refractory symptoms require diagnostic colonoscopy. Treatment Management of IBS focuses on controlling symptoms rather than on cure. For all patients: . avoidance ofgluten (even in absence ofceliac disease); dairy products; and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) . dicyclomine and peppermint oil for abdominal pain and global symptoms For IBS-C: o polyethylene glycol (PEG) . lubiprostone, linaclotide, and plecanatide if refractory to PEG ForlBS D . loperamide . tricyclic antidepressants . rifaximin, eluxadoline, and alosetron for refractory symptoms DOil'T BETRICKED . Alosetron should not be used as first line therapy for IBS D because of the risk of ischemic colitis. 97

Gastroenterology and Hepatology Cholestatic liver diseases primarily cause elevated serum bilirubin and alkaline phosphatase values with proportionally lesser elevations of aminotransferase levels. Overproduction (hemolysis) or impaired uptake (e.g., Gilbert syndrome) of bilirubin is characterized by >80% indirect (uncon jugated) bilirubin, whereas hepatoc,le dysfunction or impaired bile flow (obstruction) is characterizedby >2O% direct (conju gated)bilirubin. DON'T BE TRICKED o Extensive testing is not required to establish the diagnosis of Gilbert syndrome; veriry normal aminotransferase levels and the absence of hemolysis. Hepatitis A Prevention Hepatitis A vaccine is indicated for travelers to endemic areas, persons using injection drugs, men who have sex with men, patients with chronic liver disease, patients with HIV infection, homeless persons, and persons working in settings of exposure. Nonimmunized persons recently exposed to HAV should receive the HAV vaccine within 2 weeks of exposure. Immune globulin administration may be considered in addition to vaccination for patients aged >40 years. Diagnosis HAV is transmitted through the fecal-oral route. HAV is associated with abrupt onset of fatigue, anorexia, malaise, nausea, vomiting, and jaundice. Laboratory findings include elevated serum aminotransferase levels, usually >1000 U/L. Patients with unexplained acute hepatitis or acute liver failure should be tested for IgM anti-HAV. Hepatitis B Prevention HBV vaccination decreases the incidence and prevalence of HBV and results in flewer cases of HCC in endemic areas. In previously unvaccinated persons, hepatitis B vaccine plus HBIG is indicated for postexposure prophylaxis after needle stick injury and for sexual and household contacts of patients with HBV. Diagnosis HBV is transmitted by exposure to the blood or body fluids of an infected person, including through injection drug use, sexual contact with an infected person, or transmission by an infected mother to her infant during delivery. Symptoms of acute hepatitis B are similar to those of acute hepatitis A. Persons may have subclinical acute infection. Characteristic findings are increases in serum aminotransferase (AST/ALT) levels; acute liver failure may occur. Chronic HBV infection includes several stages, diagnosed by the immune response, but not all patients go through each stage. 100

Gastroenterology and Hepatology STUDY TABLE: lnterpretation of Hepatitis B Serology Test Results lnterpretation HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe HBV DNA (U/mt) ALT lmmunized + Normal Acute infection + +(lsM) + + I ncreased Resolved infection + +(lgG) Normal Chronic HBV infection lmmune tolerant + +(lgG) + >1 million Normal or mildly elevated lmmune active + + (lsG) + >2000 HBeAg negative; I ncreased chronic HBV >20,000 HBeAg positive (intermittent or infection persistent) lnactive chronic + +(lgG) + <2000 (when measured Normal HBV infection every 3-4 months for 1 year) Data from Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 201 8 hepatitis B guidance. Hepatology. 20 1 8;67 1 560'1 599. IPMID: 29405329] doi:1 0.1 002/hep.29800 Treatment Treatment is recommended for those with:

lmmunized + Normal Acute infection + +(lsM) + + I ncreased Resolved infection + +(lgG) Normal Chronic HBV infection lmmune tolerant + +(lgG) + >1 million Normal or mildly elevated lmmune active + + (lsG) + >2000 HBeAg negative; I ncreased chronic HBV >20,000 HBeAg positive (intermittent or infection persistent) lnactive chronic + +(lgG) + <2000 (when measured Normal HBV infection every 3-4 months for 1 year) Data from Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 201 8 hepatitis B guidance. Hepatology. 20 1 8;67 1 560'1 599. IPMID: 29405329] doi:1 0.1 002/hep.29800 Treatment Treatment is recommended for those with: . acute liver failure or cirrhosis o infection in the immune active phase . infection in the reactivation phase . immunosuppression or planned immunosuppression Treatment usually consists of entecavir or tenofovir.

Data from Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 201 8 hepatitis B guidance. Hepatology. 20 1 8;67 1 560'1 599. IPMID: 29405329] doi:1 0.1 002/hep.29800 Treatment Treatment is recommended for those with: . acute liver failure or cirrhosis o infection in the immune active phase . infection in the reactivation phase . immunosuppression or planned immunosuppression Treatment usually consists of entecavir or tenofovir. In patients coinfected with HIV and who have not yet been treated for either disease, emtricitabine tenofovir is typically used as part ofART. Fol Iow-u p Su rveil lance Surveillance for HCC is recommended in persons with HBV who are at high risk. Surveillance for HCC is recommended even in the absence of cirrhosis in persons with HBV who are at high risk: . those with cirrhosis . Asian men aged >40 years and Asian women aged >50 years o persons from sub Saharan Africa and aged >20 years o those with a family history of HCC TESTYOURSELF A S5-year-old woman has a 6-month history of fatigue and malaise. The serum ALI is 109 U/L. HBsAg, HBeAg, and HBV DNA are positive, and anti-HBV is negative. Hepatitis B DNA is >20,000 U/ml-. ANSWER: For diagnosis, choose immune active chronic hepatitis B. For treatment, select entecavir or tenofovir. 101

Gastroenterology and Hepatology TESilYOURSELF A 46-year-old man has fever and RUQ abdominal pain. He drinks six cans of beer daily. Physical examination discloses ascites. Serum AST is 260 U/L and ALT is 80 U/L. The ascitic fluid leukocyte count is <100/pL. ANSWER: For diagnosis, choose alcoholic hepatitis. Nonalcoholic Fatty Liver Disease Diagnosis NAFLD is the most common cause of abnormal liver test results. Most patients have insulin resistance, obesity, hypertriglyceri- demia, and type 2 diabetes mellitus. Approximately 2Oo/o of patients with NAFLD have nonalcoholic steatohepatitis (NASH), characterized by hepatic steatosis, inflammation, and often fibrosis. A presumptive diagnosis of NAFLD can be made in a patient with . mildly elevated aminotransferase levels . risk factors for NAFLD (diabetes, obesity, and hyperlipidemia) . hyperechoic pattern on ultrasonography or low-density parenchyma on CT Transient elastography is obtained to assess for significant hepatic fibrosis. Liver biopsy is indicated when the diagnosis is in doubt or the presence of hepatic fibrosis cannot otherwise be determined. Treatment Treatment for NAFLD consists of controlling diabetes, obesity, and hyperlipidemia. DOil'T BE TRICKED . No drugs are approved for the primary treatment of NAFLD. r Patients with fatty liver disease and elevated aminotransferase levels can be treated with statin therapy TESTYOURSETF A 38 year-old woman with type 2 diabetes mellitus develops elevated aminotransferase levels. She has obesity. She does not use alcohol excessively. Serum AST is 134 U/L and ALI is 147 U/L. Abdominal ultrasonography shows increased echogeniciSz of the liver. ANSWER: For diagnosis, choose NAFLD. Primary Biliary Cholangitis Diagnosis Primary biliary cholangitis is a chronic progressive autoimmune cholestatic liver disease that occurs predominantly in women aged 40 to 60 years. Characteristic findings are pruritus, fatigue, weight loss, hyperpigmentation, and/or complications of portal hypertension. 104

Gastroenterology and Hepatology Diagnosis of PBC does not require a biopsy if: . alkaline phosphatase level >1.5x ULN o positive antimitochondrial antibody titer, or positive sp100 or gp210 if antimitochondrial antibody is negative In patients with negative antibody results and strong suspicion for PBC, liver biopsy is necessary. Elastography may be used for fibrosis staging. Patients with PBC may have fat-soluble vitamin deficiencies and osteoporosis or osteomalacia. Testing PBC is associated with autoimmune thyroid disease; TSH should be checked yearly DEXA scanning is recommended every 2 years. Men with PBC and patients with PBC and cirrhosis should be screened for hepatocellular carcinoma. Treatment Ursodeoxycholic acid is the primary therapeutic agent. Primary Sclerosing Cholangitis Diagnosis PSC is a chronic cholestatic liver disease of unknown cause characterized by progressive bile duct destruction and biliary cirrhosis. About 85% of patients have IBD (most often ulcerative colitis). Characteristic findings are: o pruritus or jaundice o elevated serum alkaline phosphatase level . elevated total bilirubin level . modestly elevated AST and ALT levels Testing MRCP establishes the diagnosis (look for the "string of beads" pattern). Follow-up Surueillance Patients with PSC are at risk fbr developing cholangiocarcinoma as well as gallbladder carcinoma and colon cancer (when associ- ated with IBD). Screen for colon cancer with colonoscopy every 1-2 years beginning at diagnosis ofPSC, regardless ofpatient age or duration or extent ofthe IBD. Annual MRCP and carbohydrate 19 9 level measurement are rec- ommended for cholangiocarcinoma surveillance. Primary Sderosing Cholangitis: The diagnosis of PSC is established by demon' Patients with cirrhosis require screening for HCC with ultra- stration of characteristic multifocal stricturing and dilation of intrahepatic and/or extrahepatic bile ducts on cholangiography ("string of beads"). sonography every 6 months. 105

Gastroenterology and Hepatology Liver transplantation is the definitive treatment for patients with end stage or decompensated liver disease. DO]I'T BE TRICKED . Stop ACE inhibitors, ARBs, and NSAIDs in patients with ascites. r Blood transfusion to hemoglobin >7.0 g/dl leads to increased portal pressures and risk of further bleeding. r Antimicrobial prophylaxis should be administered during variceal bleeding even if ascites is absent. . Do not select prophylactic protein restriction to prevent hepatic encephalopathy. o Do not select neomycin to treat hepatic encephalopathy because of the significant adverse effects of this drug. TESTYOURSELF A S5-year-old man with alcoholic cirrhosis is admitted to the hospital with fever and abdominal pain. Paracentesis is performed. The ascitic fluid granuloclte count is 650/pL and serum creatinine is 1.6 mg/dl. ANSWER: For diagnosis, choose spontaneous bacterial peritonitis. For management, begin empiric IV cefotaxime and albumin. Do not wait for results of Gram stain or cultures before beginning therapy. Acute Liver lnjury and Acute Liver Failure Diagnosis In acute liver injury, a sudden increase in serum AST and ALT Ievels occurs. Acute liver failure refers to acute liver injury complicated by encephalopathy and coagulopathy in patients without previous cirrhosis. The most common identifiable causes of acute liver injury are acetaminophen hepatotoxicity, idiosyncratic drug reactions, and HBV infection. Other causes include acute HAV infection, hepatic ischemia, herpes infection, mushroom poisoning, and Wilson disease. See also Liver Disease Associated with Pregnancy. Drug induced liver injury is most commonly caused by acetaminophen, antibiotics (particularly amoxicillin-clavulanate), and antiepileptic medications (phenytoin and valproate).

The most common identifiable causes of acute liver injury are acetaminophen hepatotoxicity, idiosyncratic drug reactions, and HBV infection. Other causes include acute HAV infection, hepatic ischemia, herpes infection, mushroom poisoning, and Wilson disease. See also Liver Disease Associated with Pregnancy. Drug induced liver injury is most commonly caused by acetaminophen, antibiotics (particularly amoxicillin-clavulanate), and antiepileptic medications (phenytoin and valproate). STUDY TABLE: Differential Diagnosis of Acute Liver Failure lf you see this... Look for this.. And choose this.. Sudden elevation of serum AST and ALT Acetaminophen overdose, the most Measure serum acetaminophen level and levels up to 20x common cause of acute liver failure use nomogram to determine whether N-acetylcysteine is indicated. Usually caused by acetaminophen ingestion >4 g but can occur with lower doses in patients with alcoholism Outbreaks of acute liver failure associated Acute HAV infection Order serologic studies for HAV with foods such as raspberries and scallions Acute elevation of ASTto >1 000 U/Lwhile Episode of acute hypotension with Review hospital course. hospitalized associated liver hypoperfusion Acute elevation of liver enzymes and Wilson disease Measure serum copper and ceruloplasmin hemolysis in a young patient, Kayser- levels and urine copper excretion. Fleischer rings, history of psychiatric disorders, and/or athetoid movements Herpes (simplex or zoster) in{ection AST and ALT >5000 U/L in Treat with acyclovir immunocompromised patient or during pregnancy. Often associated with encephalitis. Rash is not always present. 108

Gastroenterology and Hepatology Gallstones, Acute Cholecystitis, and Cholangitis Diagnosis Ultrasonography is the initial imaging modality. Dilation of the cystic or biliary duct indicates an obstructing stone. Biliary colic is characterized by the episodic onset ofacute, severe, epigastric or RUQ pain lasting 30 minutes to 6 hours and often accom panied by nausea and vomiting. Fever, leukocytosis, and elevated liver enzymes indicate acute cholecystitis or obstruction of the common bile duct. STUDY TABLE: Biliary Disease Syndromes and Mimics lf you see this.. Diagnose this... Epigastric or RUQ pain, fever, bilirubin <4 mg/dL, normal or minimally elevated AST or ALT, Acute cholecystitis leukocytosis Sonogram shows thickened gallbladder wall and the presence of pericholecystic fluid. Biliary colic or pancreatitis and no gallstones or bile duct dilation on imaging studies Bi I iary crysta ls (sludge) RUO pain, fever, jau ndice, or these find ings plus shock a nd menta I status changes; biliru bin Acute cholangitis >4 mg/dL; AST and ALT >1 000 U/L Critically ill, febrile, or septic patient Acute acalculous cholecystitis No gallstones on sonogram, but findings otherwise compatible with acute cholecystitis RUO pain, pelvic adnexal tenderness, leukocytosis, cervical smear showing gonococci Fitz-Hugh-Curtis syndrome (gonococcal or chlamydial perihepatitis) lmpacted gallstone in cystic duct, jaundice, and dilated common hepatic duct caused by Mirizzi syndrome extrinsic compression Biliary colic or cholecystitis with small-bowel obstruction and air in biliary tree Cholecystoenteric fistula (gallstone ileus)

RUO pain, fever, jau ndice, or these find ings plus shock a nd menta I status changes; biliru bin Acute cholangitis >4 mg/dL; AST and ALT >1 000 U/L Critically ill, febrile, or septic patient Acute acalculous cholecystitis No gallstones on sonogram, but findings otherwise compatible with acute cholecystitis RUO pain, pelvic adnexal tenderness, leukocytosis, cervical smear showing gonococci Fitz-Hugh-Curtis syndrome (gonococcal or chlamydial perihepatitis) lmpacted gallstone in cystic duct, jaundice, and dilated common hepatic duct caused by Mirizzi syndrome extrinsic compression Biliary colic or cholecystitis with small-bowel obstruction and air in biliary tree Cholecystoenteric fistula (gallstone ileus) Treatment STUDY TABLE: Treatment for Biliary Colic, Cholecystitis, and Acute Cholangitis Diagnosis Treatment Biliary colic Elective cholecystectomy if gallstones are demonstrated on imaging Acute cholecystitis B-lactam/B-lactamase inhibitor or a third-generation cephalosporin plus metronidazole Surgery before hospital discharge Acute cholangitis Antibiotic therapy same as for acute cholecystitis ERCP removal of common bile duct stones DOil'T BE TRICKED . Surgery is generally not indicated for asymptomatic gallstones TESTYOURSETF A 72 year-old woman is evaluated in the ICU for new-onset fever. She had been stable fbllowing treatment for urosepsis until now. Temperature is 38.2 'C (100.8 "F) and blood pressure is 90 I 62 mm Hg. RUQ tenderness is present. Ultrasound shows a distended gallbladder with wall thickening and pericholecystic fluid but no gallstones or dilated bile ducts. ANSWER: For diagnosis, choose acalculous cholecystitis. 110

Gastroenterology and Hepatology Upper GI Bleeding Diagnosis Major causes: PUD, esophagogastric varices, and Mallory-Weiss tear. Helicobacter pylori infection and NSAID use are the most common causes of nonvariceal UGI bleeding. Characteristic findings are hematemesis, melena, or (infrequently) bright red blood per rectum. STUDY TABLE: Differential Diagnosis of Upper Gl Bleeding lf you see this.. Diagnose this... Dyspepsia, H. pylori infection, NSAID use, anticoagulation, severe medical illness Peptic ulcer disease Stigmata of chronic liver disease, evidence of portal hypertension or risk factors for cirrhosis (alcohol Variceal bleeding use, viral hepatitis) History of heavy alcohol use and retching before hematemesis, hematemesis following weightlifting, Mallory-Weiss tear young woman with bulimia NSAID use, heavy alcohol intake, severe medical illness; usually small'volume or occult bleeding Gastroduodena I erosions DOil'T BE TRICKED . Do not order a barium x-ray, because this will interfere with subsequent upper endoscopy or other studies. Treatment Risk stratification tools guide decisions regarding upper endoscopy, hospital admission, and discharge home. The Glasgow Blatchford score (range 0-23) is particularly useful when the score is 0, which has a nearly 100% negative predictive value for severe GI bleeding and the need for hospital-based intervention. Pre-endoscopic management:

Treatment Risk stratification tools guide decisions regarding upper endoscopy, hospital admission, and discharge home. The Glasgow Blatchford score (range 0-23) is particularly useful when the score is 0, which has a nearly 100% negative predictive value for severe GI bleeding and the need for hospital-based intervention. Pre-endoscopic management: o insertion of two large caliber intravenous catheters r . IV crystalloids targeting HR <100/min, SBP >100 mm Hg, and no orthostasis . blood transfusion for hemodynamic instability or to a target hemoglobin Ievel of 7 g/dl o PPI therapy (stop if no ulcer found on upper endoscopy) o vitamin K or 4f-PCC for significantly elevated INR o activated 4f-PCC or the appropriate agent (idarucizumab or andexanet alfa) for DOACs o octreotide and antibiotics before upper endoscopy for suspected variceal bleeding . aspirin discontinuation (permanent) if being used for primary prevention, continue if possible when used for secondary prevention o dual antiplatelet therapy for recent ACS or stent is discussed with cardiologist; continue aspirin alone if P2Yu inhibitor must be stopped o antibiotic therapy for 7 days in patients with cirrhosis and UGI bleeding Upper endoscopy evaluation and treatment: o upper endoscopy witlrlin 24 hours; within 12 hours for suspected variceal bleed or rapid bleeding . Iow-risk ulcers are clean based or have a nonprotuberant pigmented spot; treat low risk ulcers with oral PPI, begin food, early hospital discharge (t2 24 hours) . high-risk ulcers have active arterial spurting or a nonbleeding visible vessel; treat high risk ulcers endoscopically (hemo clips, thermal therapy, or injection therapy) and continuous IV PPI infusion for 72 hours . repeat endoscopic therapy for repeat or continued bleeding 111