Case Discussion <Brief History> A 75-year-old man was admitted to the hospital because of progressive abdominal fullness for 1 month. Four years before admission, the patient had been hospitalized because of tarry stool. A diagnosis of gastric varices with bleeding in addition to alcoholic liver cirrhosis was made at that time. Two years before admission, imaging studies revealed two hypervascular tumors in the right liver lobe, and he received transcatheter arterial embolization (TAE). Diabetes mellitus was noted during the same admission course. Six months before admission, elevated alpha-fetoprotein level and multiple hepatic tumors were noted. The patient hesitated and refused further TAE treatment. One month before admission, he became aware of progressive abdominal fullness. Abdominal sonography showed ascites. He was prescribed with furosemide and spironolactone, but the abdominal fullness didn't improve. There was no history of chills, sweats, headache, a recent stiff neck, cough, dysuria, diarrhea, myalgia, arthralgia or weight loss.  On admission, the temperature was 38.4°C, the pulse was 96, and the respirations were 20. The blood pressure was 140/ 80 mmHg. Physical examination revealed shifting dullness. Mild tenderness with mild rebound tenderness was noted in the whole abdomen. Bowel sounds were hypoactive, and no masses were palpated. The urine was normal. The white cell count was 6440 per cubic millimeter, and neutrophils were 90.7%. Abdominal fullness improved with peritoneocentesis. The white cell count of ascites was 1900 per cubic millimeter, but lymphocyte predominated to 72%. The serum-ascites albumin gradient was 1.4 gram per deciliter. Cefoxitin was given intravenously under the suspicion of spontaneous bacterial peritonitis since the first hospital day. The fever fluctuated in spite of the use of antibiotics, so flomoxef was prescribed in place of cefoxitin since the 4th hospital day. A CT scan of the abdomen revealed thickening of the peritoneum (Fig-3.JPG) and edematous change of the omentum and mesentery. No obvious lymphadenopathy was present. Several tumors of 1.5cm in size were also noted over both lobes of liver with global enhancement in the arterial phase (Fig-1.JPG, Fig-2.JPG ). In spite of the antibiotic treatment, there was still mild fever. Metronidazole was added 10th hospital day, but the fever persisted. Blood and ascites culture for bacteria didn't yield any microorganism. There was also no response to discontinuation of all antibiotics. Because of lymphocyte predominance on repeated ascites examinations, diagnostic laparoscopy was performed on the 26th hospital day. Multiple miliary lesions were noted with little adhesion (Fig-4.JPG). Pathology of the biopsy specimen revealed granulomatous inflammation with patches of caseating necrosis and multiple atypical Langhans giant cells (Fig-5.JPG). Acid-fast stain showed a few acid-fast positive bacilli (Fig-6.JPG ). Mycobacterium tuberculosis was also reported on the 28th hospital day. So the patient was given anti-TB treatment with combination of INH, RIF, EMB and PZA. However, conjugate hyperbilirubinemia developed on the 32nd hospital day. Anti-TB treatment was shifted to EMB and streptomycin. Levofloxacin was added on the 36th hospital day according to the suggestion of the infection specialist. Fever subsided gradually later. Hyperbilirubinemia also improved after the change of anti-TB regimen. <Laboratory Results> 1. CBC and Differential Count: WBC  RBC  Hb  Hct  MCV  Plt  Band  Seg Eos Baso Mono Lym   K/μl M/μl g/dl % fl K/μl % % % % % % 4/14 6.44 3.81 12.4 35.3 92.7 169 0.0 90.7 0.6 0.3 5.4 3.0 5/10 6.22 3.48 11.2 33.3 95.7 148 0.0 86.5 1.0 0.5 7.7 4.3 5/15 5.89 3.63 11.6 33.8 93.1 183 0.0 76.0 2.0 0.0 7.0 12.0 5/24 5.09 3.34 11.1 32.9 98.5 140 0.0 69.0 0.0 0.0 13.0 17.0 2. Biochemistry:   Alb Glo Bil T/D AST  ALT  ALP  gGT  BUN  Cre Na K   g/dl g/dl mg/dl U/l U/l U/l U/l mg/dl mg/dl mmol/l mmol/l 4/14 2.8 3.1 0.81/ 23       14.0 0.7 132 3.58 5/10     1.2/ 44 18 301 160 23.8 0.9 137 4.4 5/15 2.9 3.9 3.2/2.5 69 19 320 185 17.6 0.7 133 4.6 5/27     1.47/0.5 52 29 293 151 13.2 0.9 129 3.3 3. Coagulation:   PT PTT 4/14 13.6/12.0 52.3/38.6 4. Ascites Studies:   Appear. Rivalta RBC WBC L:N:M&H A/G LDH Glu Cytology             g/dl U/l mg/dl   4/17 Y;T + 5000 1900 72:21:7 1.4/1.2 209 201 Negative 4/23 Y;T + 0 1500 95:3:2 1.8/1.5 218 217 Negative 5/01 Y;TT + 0 800 96:4:0 1.19/   170 Negative 5.Hepatology Profiles:   aFP HbsAg Anti-HBs Anti-HCV   ng/ml       4/16 194.47 Negative Weakly Positive Negative 案例分析 此為一個酒精性肝炎併肝硬化及肝腫瘤的病人, 同時患有糖尿病. 腹水在一個月的利尿劑使用後仍持續存在, 接著發生腹痛以及發熱. 在自發性腹膜炎的懷疑之下住院進行抗生素治療. 期間雖然曾經更換過抗生素的處方, 發熱情況仍然持續. 而細菌培養均無結果. 反覆的腹水檢查, 白血球數依然升高, 但係淋巴球為主. 經腹部電腦斷層攝影檢查, 並無明顯的淋巴節病變. 在懷疑結核性腹膜炎的前提下, 病人接受腹腔鏡檢查. 腹腔鏡可見粟粒狀病灶散佈在腹膜上, 切片下亦顯示有肉芽腫性發炎及蘭格罕士氏巨細胞. 油鏡下可以看到少量的抗酸桿菌. 腹水結核菌培養在送檢四週後證實結核桿菌的存在. 病人發熱的情況在抗結核藥物使用後一週回復到正常體溫. 此外, 病人的膽紅素值在四種抗結核藥物使用下竄升三倍, 經更換藥物後逐漸改善. 繼續教育考題 1. (A) Which of the following parameter is diagnostic for SBP (spontaneous bacterial peritonitis)? A Neutrophil count > 300 / mm3 in ascites B GNB (gram-negative bacilli) in blood culture C Serum WBC count > 10000 / mm3 D SAAG (serum-ascites albumin gradient) level < 1.1 g / dl E Cirrhotic liver in abdominal sonography 2. (D) Which of the following statement about SBP is NOT true? A SBP occurs commonly in conjunction with cirrhosis of the liver B Absence of abdominal pain cannot exclude the diagnosis of SBP C Ascitic fluid protein is usually less than 1 g/dl in SBP D Mixed flora including anaerobes is typically isolated E Recurrence rate of SBP in one year is as high as 69% 3. (B) Elevated SAAG (serum-ascites albumin gradient) can occur in the following conditions EXCEPT A Liver cirrhosis B Tuberculous peritonitis without liver cirrhosis C Budd-Chiari syndrome D VOD (venous occlusive disease) E Cardiac ascites 4. (C) Empirical therapy for SBP is NOT appropriate with A Ampicillin plus gentamicin B Oral quinolone C First-generation cephalosporins D Carbapenems E Broad-spectrum penicillin/ beta-lactamase inhibitor combinations 5. (D) There are several tools in differential diagnosis of TB peritonitis EXCEPT A ADA (adenosine deaminase) level of ascites B TB culture of ascites C Laparoscopic examination with biopsy D LDH level of ascites E Acid-fast bacilli in ascites smear 6. (E) The CT findings in favor of peritoneal TB rather than peritoneal carcinoma- tosis include A Presence of mesenteric macrodules B Thin densely enhancing peripheral rim covering omental infiltration C Splenic calcification D Smooth pattern of infiltrated omentum E All of the above 7. (D) Which of the following statements about diagnosis of TB is NOT true? A Ziehl-Neelsen basic fuchsin stain may detect acid-fast bacilli (AFB) B Isolation of TB with L-J medium may take 4 to 8 weeks C Liquid media with radiometric growth detection may shorten the isolation period to 2 to 3 weeks D PPD skin test is still useful in persons having received BCG vaccination E Normal chest radiograph does not rule out the diagnosis of pulmonary TB 8. (C) Which of the following statement of anti-TB drugs is NOT true? A Isoniazid may cause increase in serum transaminase level within the first 10 weeks of treatment B Rifampin can enhance the hepatotoxicity of isoniazid C Ethambutol rarely causes optic neuritis D Pyrazinamide may cause liver injury after more than 1 month of treatment E Streptomycin is nephrotoxic and ototoxic 9. (A) Which of the following items is NOT the risk factor for hepatotoxic reactions to anti-TB drugs? A Age < 35 years old B Living in an area where hepatitis is endemic C History of malnourishment D AIDS or HIV infection E Alcohol-induced liver disease 10. (E) What should be done when hepatotoxic reaction after taking anti-TB drugs developed? A Stop all anti-TB medication B Follow up liver functions within one week C May start modified protocol with "EMB + Streptomycin + Fluoro- quinolone" D Rechallenge with two-combined regimen after liver function recovered E All of the above

答案解說 答案解說: 1. ( A ) The neutrophil count in ascitic fluid is thought to be the single best predictor of SBP. A neutrophil count > 500/mm3 has a sensitivity > 80% and a specificity of 98%, while a neutrophil count > 250/mm3 has a sensitivity of 85% and a specificity of 93%. 2. (D) In SBP, the infection is blood-borne and in 90% monomicrobial. Enteric gram-negative bacilli such as E. coli are most commonly encountered. But in secondary peritonitis, a mixed flora including anaerobes is the rule. 3. (B)The SAAG is a reflection of the portal pressure. The higher the gradient, the higher the pressure. If SAAG is >=3 1.1 g/dl, the patient has portal hypertension with 97% accuracy.  4. (C) In light of the high mortality associated with SBP, third-generation cephalosporins are currently considered the drugs of choice for SBP with a cure rate of at least 85%. They also have superior safety profiles. 5. (D) ADA level of ascites greater than 33 U/liter can be used for differentiating TB peritonitis from cases of cirrhosis and malignancy. (Am J Gastroenterol 1990; 85: 1123-1125) 6. (E) 7. (D ) Positive PPD skin test is obtained when patients have been infected with M. tuberculosis but do not have active disease and when persons have been sensitized by nontuberculous mycobacteria or BCG vaccination. 8. (C)Ethambutol is usually well tolerated. Retrobulbar optic neuritis is the most serious adverse effect. Hyperuricemia occurs but is usually asymptomatic. 9. (A ) Age more than 35 years is a risk for developing hepatotoxic reactions to anti-TB drugs. 10. (E )