Pyogenic liver abscess

Pyogenic liver abscess; introduction, clinical features, investigation and management along with some special cases .

1. Pratap Sagar Tiwari, MD, DM Resident, Hepatology , NAMS, Bir Hospital, Nepal Pyogenic Liver Abscess

2. Contents Background: Intra-abdominal abscess Introduction: Liver abscess Pyogenic liver abscess: risk factors and causes Clinical features Lab Investigations Imaging Management Pyogenic liver abscess vs Amoebic Liver abscess

3. BACKGROUND: INTRA-ABDOMINAL ABSCESS INTRA-PERITONEAL ABSCESS LIVER ABSCESS VISCERAL ABSCESS RETRO-PREITONEAL ABSCESS Altemeier W.A, Culbertson W.R, Fullen W.D. Intra-abdominal Abscesses. The American Journal of Surgery. January 1973Volume 125, Issue 1, Pages 70–79 Pic Source: https://www.memorangapp.com/flashcards/49387/Anatomy+of+the+Abdomen/

4. Extranote The peritoneum is a continuous membrane which lines the abdominal cavity and covers the abdominal organs (or viscera).It acts to support the viscera, and provides a pathway for blood vessels and lymph. The peritoneum consists of two layers which are continuous with each other; the parietal peritoneum and the visceral peritoneum . They both consist of a layer of simple squamous epithelial cells, called mesothelium. Parietal Peritoneum: The parietal peritoneum lines the internal surface of the abdominopelvic wall. It is derived from somatic mesoderm in the embryo. It receives the same somatic nerve supply as the region of the abdominal wall that it lines, therefore pain from the parietal peritoneum is well localised and it is sensitive to pressure, pain, laceration and temperature. Visceral Peritoneum: The visceral peritoneum invaginates to cover the majority of the abdominal viscera. It is derived from splanchnic mesoderm in the embryo. The visceral peritoneum has the same nerve supply as the viscera it invests. Unlike the parietal peritoneum, pain from the visceral peritoneum is poorly localised and is only sensitive to stretch and chemical irritation. Pain from the visceral peritoneum is referred to areas of skin (dermatomes) which are supplied by the same sensory ganglia and spinal cord segments as the nerve fibres innervating the viscera. Peritoneal Cavity : The peritoneal cavity is a potential space between the parietal and visceral peritoneum. It contains a small amount of lubricating fluid. Retroperitoneal Organs : These organs are only covered in peritoneum on their anterior surface. They can be subdivided into two groups: Primarily retroperitoneal organs develop and remain outside of the parietal peritoneum. The oesophagus , rectum and kidneys are all primarily retroperitoneal Secondarily retroperitoneal organs were initially intraperitoneal, suspended by mesentery. Through the course of embryogenesis they became retroperitoneal, with their mesentery fusing with the posterior abdominal wall. Thus, peritoneum only covers the anterior surface. Examples of secondarily retroperitoneal organs include is the ascending and descending colon.

5. Extranote : Retroperitoneal organs S = Suprarenal (adrenal) Glands A = Aorta/IVC D =Duodenum (except the duodenal cap- first 2cm) P = Pancreas (except the tail) U = Ureters C = Colon (ascending and descending parts) K = Kidneys E = (O)esophagus R = Rectum

6. Altemeier W.A, Culbertson W.R, Fullen W.D. Intra-abdominal Abscesses. The American Journal of Surgery. January 1973Volume 125, Issue 1, P 70–79

7. Extranotes Intraperitoneal abscesses were considered to be areas of localized peritonitis which developed within the peritoneal envelope and in which the infection continued to progress but was walled off by an inflammatory barrier . This barrier included the omentum , the involved parietal and visceral peritoneum, and the contiguous viscera. Retroperitoneal abscesses were considered as localized areas of infection which occurred in the retroperitoneal space. The retroperitoneal area was defined as the potential space between the peritoneum and the transversalis fascia lining the posterior aspect of the abdominal cavity, extending from the parietes laterally at the lateral edge of the quadratus lumborum muscle to the pelvic brim inferiorly and the diaphragm superiorly. It included an anterior retroperitoneal space and a posterior space, the latter being further divided into the two lateral fossas or perinephric spaces. Both spaces extended across the midline. The lateral fossa on each side was further divided by the renal fascia which separated into an anterior and posterior layer, surrounding the kidneys and passing medially in front of and behind the great vessels. The renal fascial compartment was noted to be open inferiorly but closed. Visceral abscesses formed the third major category of intra-abdominal abscess. These abscesses developed within the confines of one of the abdominal viscera, such as the liver, pancreas, kidney, and gallbladder.

8. Introduction: Liver Abscess A liver abscess is a space-occupying suppurative lesion in the liver resulting from the invasion of microorganisms entering directly from an injury, through the blood vessels, or through the bile ducts . (Schiff) The three major forms of liver abscess, classified by etiology , are as follows: Pyogenic abscess , which is most often polymicrobial , accounts for 80% of hepatic abscess cases in the US. Amebic abscess due to Entamoeba histolytica accounts for 10% of cases [1] Fungal abscess , most often due to Candida species, accounts for fewer than 10% of cases. Othman N, Mohamed Z, Yahya MM, Leow VM, Lim BH, Noordin R. Entamoeba histolytica antigenic protein detected in pus aspirates from patients with amoebic liver abscess. Exp Parasitol . 2013 Aug. 134 (4):504-10.

9. Pyogenic Liver Abscess There are four major ways in which pyogenic organisms invade the liver. First, they may travel though the portal vein from regions drained by it. Suppurative appendicitis, complicated by pyelophlebitis , is one of the most frequent causes. Ulceration of the stomach or bowel and disease of the rectum , spleen and pancreas frequently cause HA. Second , blood borne infections may be transmitted though hepatic artery. Osteomyelitis, acute infections of upper respiratory tract or pyemia from any source may be the cause. Third there may be direct extension from a contiguous infection . Subphrenic abscess, empyema, nephritic or perinephric abscess are less frequently the causes. Lastly trauma may be the cause. There may be a penetrating injury or subcutaneous injury to the liver.

10. Introduction: Liver Abscess Source Biliary Source multiple and of small size and involve both lobes of the liver Septic emboli from the PV solitary and tend to be more common in the right lobe of the liver Contiguous source solitary and localized to one lobe only Amebic liver abscesses tend to be solitary and large. Most commonly, they are located in the right lobe of the liver . ( The right lobe receives a major part of the venous drainage from the cecum and ascending colon, which are the parts of the bowel most commonly affected by amebiasis . ) Abscesses located in the dome of the liver or complicated by a bronchopleural fistula are typically amebic in origin. Approximately 60% are solitary and they are mainly located in the RT lobe as a result of the streaming pattern of PBF, secondary to the fact that the right lobe is supplied predominantly by the SMV and because most of the hepatic volume is in the RT lobe. Note: Approximately 75% of PLA are located in the right lobe of the liver. ( Suchy / Zakim ) and 25 % in the left lobe and the caudate in approximately 5%. ( Zakim )

11. Pyogenic Liver abscess In the past, most cases of PLA were a consequence of appendicitis complicated by pylephlebitis (portal vein inflammation) in a young pt. This presentation is uncommon today as a result of earlier diagnosis and effective antibiotic therapy. Note: About half of the cases now are cryptogenic or occur in older men. 60 % ( Zakim / boyer ) Predisposing conditions include previous biliary surgery or interventional endoscopy. Note: Benign or malignant biliary tract disease, diverticulitis , and Crohn disease are the mc predisposing factors. (Schiff)

12. Risk factors for development of HA Diabetes mellitus Immunocompromised state Liver Cirrhosis Use of PPI Advanced age Male Gender DM is a predisposing factor for HA that is well documented in the literature. [1,2,3] Studies have found DM as a concomitant disease in 29.3–44.3 % of pts with HA .[1,3] Diabetic pts are also more likely to present with multiple abscesses .[3] There are several pathophysiologic features of DM that contribute to higher infection risk.[2,4] For instance, hyperglycemia is known to alter neutrophil metabolism .[5] Diabetics also have been shown to have impaired PMN chemotaxis and phagocytosis ,[2,4]which weakens their immune defense against infections and leaves them more susceptible to abscess formation. Lee KT, Wong SR, Sheen PC. Pyogenic liver abscess: an audit of 10 years’ experience and analysis of risk factors. Dig Surg. 2001;18:459–465. discussion 465-466. Jeong SW, Jang JY, Lee TH, Kim HG, Hong SW, Park SH, et al. Cryptogenic pyogenic liver abscess as the herald of colon cancer. J Gastroenterol Hepatol . 2012;27:248–255. Tian LT, Yao K, Zhang XY, Zhang ZD, Liang YJ, Yin DL, et al. Liver abscesses in adult patients with and without diabetes mellitus: an analysis of the clinical characteristics, features of the causative pathogens, outcomes and predictors of fatality: a report based on a large population, retrospective study in China. Clin Microbiol Infect. 2012;18:E314–E330. Eltawansy SA, Merchant C, Atluri P, Dwivedi S. Multi-organ failure secondary to a Clostridium perfringens liver abscess following a self-limited episode of acute gastroenteritis. Am J Case Rep. 2015;16:182–186 . Weng SW, Liu JW, Chen WJ, Wang PW. Recurrent Klebsiella pneumonia liver abscess in a diabetic patient followed by Streptococcus bovis endocarditis- Occult colon tumor plays an important role. Jpn J Infect Dis. 2005;58:70–72 . Huang CJ , Pitt HA , Lipsett PA et al . Pyogenic hepatic abscess. Changing trends over 42 years . Ann. Surg. 1996 ; 223 : 600 – 607 . Yang CC , Chen CY , Lin XZ et al . Pyogenic liver abscess in Taiwan: emphasis on gas - forming liver abscess in diabetics . Am. J. Gastroenterol . 1993 ; 88 : 1911 – 1915 . DM is present in up to 40% of cases and is more commonly a/w abscesses due to Klebsiella pneumoniae [6,7] .

13. Risk factors for development of HA Diabetes mellitus Immunocompromised state Liver Cirrhosis Use of PPI Advanced age Male Gender Like diabetics, pts with liver cirrhosis have an ↑ risk of HA due to their immune-compromised state .[1] Cirrhotics are 15.4 times more likely to develop HA than the general population .[1,2] Other conditions and treatments may compromise the immune system and render it inadequate to counteract pathogens. These include various immunodeficiencies , chemotherapy, solid malignancies, immunosuppression therapy after organ transplant ,[3] as well as splenectomy ,[4] all of which have been a/with an ↑ risk of HA. Kumar D, Ramanathan S, Al Faki A, Nepal P. Faecolith migrating from the appendix to produce liver abscess after subhepatic laparoscopic appendectomy. Trop Doct . 2015;45:241–244. Mølle I, Thulstrup AM, Vilstrup H, Sørensen HT. Increased risk and case fatality rate of pyogenic liver abscess in patients with liver cirrhosis: a nationwide study in Denmark. Gut. 2001;48:260–263. Eltawansy SA, Merchant C, Atluri P, Dwivedi S. Multi-organ failure secondary to a Clostridium perfringens liver abscess following a self-limited episode of acute gastroenteritis. Am J Case Rep. 2015;16:182–186. Lai SW, Lai HC, Lin CL, Liao KF. Splenectomy correlates with increased risk of pyogenic liver abscess: a nationwide cohort study in Taiwan. J Epidemiol . 2015;25:561–566.

14. Risk factors for development of HA Diabetes mellitus Immunocompromised state Liver Cirrhosis Use of PPI Advanced age Male Gender The use of PPI medications has also been found to increase the risk of HA formation .[1] This is presumably because PPI medications ↑ the gastric pH , which decreases the natural gastric defense against bacteria.[1] In a large case-control study, Wang et al . demonstrated a dose-response relationship between HA formation and dose of PPI over a 90 day period .[1] Although this was a large study, encompassing 10 years of data, it was conducted exclusively in Taiwan, where the incidence of HA in general is high. Additionally, control subjects were not matched for comorbidities or indication for PPI use. Both of these factors may have had some influence on their findings. Wang YP, Liu CJ, Chen TJ, Lin YT, Fung CP. Proton pump inhibitor use significantly increases the risk of cryptogenic liver abscess: a population-based study. Aliment Pharmacol Ther . 2015;41:1175–1181.

15. Risk factors for development of HA Diabetes mellitus Immunocompromised state Liver Cirrhosis Use of PPI Advanced age Male Gender Most cases of HA present at advanced age . One study reported a mean age > 57 years .[1] This finding suggests that older individuals are more susceptible to bacterial infection and thus abscess formation .[2] However, more research is needed to clarify the mechanism of this association. In a 10-year audit of experience with HA from 1989 to 1999, Lee et al . found the ratio of males to females presenting with HA was about 2 to 1 .[3] This was confirmed by Pang et al .[4] and Lin et al .[ 5] Tian LT, Yao K, Zhang XY, Zhang ZD, Liang YJ, Yin DL, et al. Liver abscesses in adult patients with and without diabetes mellitus: an analysis of the clinical characteristics, features of the causative pathogens, outcomes and predictors of fatality: a report based on a large population, retrospective study in China. Clin Microbiol Infect. 2012;18:E314–E330. Weng SW, Liu JW, Chen WJ, Wang PW. Recurrent Klebsiella pneumonia liver abscess in a diabetic patient followed by Streptococcus bovis endocarditis- Occult colon tumor plays an important role. Jpn J Infect Dis. 2005;58:70–72. Lee KT, Wong SR, Sheen PC. Pyogenic liver abscess: an audit of 10 years’ experience and analysis of risk factors. Dig Surg. 2001;18:459–465. Pang TC, Fung T, Samra J, Hugh TJ, Smith RC. Pyogenic liver abscess: An audit of 10 years’ experience. World J Gastroenterol . 2011;17:1622–1630. Lin AC, Yeh DY, Hsu YH, Wu CC, Chang H, Jang TN, et al. Diagnosis of pyogenic liver abscess by abdominal ultrasonography in the emergency department. Emerg Med J. 2009;26:273–275.

16. Pathogenesis Infections of the biliary tract: (e.g., cholangitis, cholecystitis ) are the MC identifiable source of PLA. Infection may spread to the liver from the bile duct, along a penetrating vessel , or from an adjacent septic focus (including pylephlebitis ). Portal pyaemia may follow pelvic or GI infection , resulting in portal pylephlebitis or septic emboli . It can follow appendicitis, empyema of the gallbladder , diverticulitis, regional enteritis [ 1] , Yersinia ileitis [2 ] , perforated gastric or colonic ulcers leading to peritonitis, leaking anastomoses, pancreatitis [3 ] or infected haemorrhoids , IBD , or rarely from bacterial endocarditis. 1 Vakil N , Hayne G , Sharma A et al . Liver abscess in Crohn ’ s disease . Am. J. Gastroenterol . 1994 ; 89 : 1090 – 1095 . 2 Khanna R , Levendoglu H . Liver abscess due to Yersinia enterocolitica : case report and review of the literature . Dig. Dis. Sci . 1989 ; 34 : 636 – 639 . 3 Ammann R , M ü nch R , Largiad è r F et al . Pancreatic and hepatic abscesses: a late complication in 10 patients with chronic pancreatitis . Gastroenterology 1992 ; 103 : 560 – 565 .

17. Post Procedures : As a late complication of endoscopic sphincterotomy for bile duct stones or within 3-6 wks of a surgical biliary-intestinal anastomosis . Injury to the hepatic arterial system may lead to PLA. This can follow cholecystectomy . In liver transplant pts , abscesses may develop 2 weeks postoperatively a/with technical complications , particularly hepatic arterial thrombosis. Abscesses may follow local treatment of liver tumours by transhepatic chemoembolization or percutaneous tumour injections [1] . Others 1 De Baere T , Roche A , Amenabar JM et al . Liver abscess formation after local treatment of liver tumours . Hepatology 1996 ; 23 : 1436 – 1440 .

18. Microbiology Gram- tive Aerobic Bacteria 50-70% Gram+tive Aerobic Bacteria 25% Escherichia coli Klebsiella pneumoniae Enterobacter spp. Pseudomonas spp. Citrobacter spp. Morganella spp. Proteus spp. Salmonella spp. Serratia marcescens * Yersinia spp.* Burkholderia pseudomallei * Capnocytophaga canimorsus * Pasteurella multocida * Achromobacter xylosoxidans Enterococcus spp. Streptococcus pyogenes Staphylococcus aureus Streptococcus milleri group Listeria monocytogenes * Bacillus cereus Anaerobic Bacteria 40-50% Bacteroides spp. Fusobacterium spp. Streptococcus spp. Peptostreptococcus spp. Peptococcus spp. Prevotella spp.* Clostridium spp.* Actinomyces spp.* Others Candida spp. Mycobacterium tuberculosis Sleisenger

19. Clinical Features Pre antibiotic era Spiking fevers Pain RUQ Shock Acute presentation Present Context Low grade fever Anorexia Weight loss Dull pain abdomen Sub-Acute presentation Only 10% of pts will have the “characteristic” symptom triad of fever, jaundice, and right upper quadrant (RUQ) tenderness . ( Zakim /Boyer) When an abscess is situated near the dome of the liver, pain may be referred to the rt shoulder , or a cough resulting from diaphragmatic irritation or atelectasis may be present. In 1928 penicillin , the first true antibiotic, was discovered by Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital in London

20. Symptoms Associated with PLA Zakim and Boyer

21. Physical Examination Fever PHTN may follow recovery if the PV has been thrombosed. Ascites is rare In the absence of cholangitis, jaundice is present only late in the course of the illness. Splenomegaly is unusual, except with a chronic abscess. Hepatomegaly Liver tenderness Note: Jaundice predicts a complicated clinical course but has no impact on mortality. (Schiff)

22. Physical Signs Associated with PLA Zakim and Boyer

23. Microbiology studies Microbiology studies are the gold standard in establishing the DX of PLA. Direct cultures of blood & aspirated fluid are useful for identification of the organism and determination of antibiotic susceptibility and should be sent for both aerobic and anaerobic culture. Blood culture specimens will identify the causative organism in at least 50% of cases .[1] but this should not delay the initiation of antibiotics. Organisms in culture - negative pus may be identifiable using PCR . Chemaly R, Hall G, Keys T, et al. Microbiology of liver abscesses and the predictive value of abscess Gram stain and associated blood cultures. Diagn Microbiol Infect Dis 2003; 46:245-8. Positive culture data in 5% to 10% of pts . Zakim / boyer Aspirated material is positive on culture in 70 – 90%. Sherlock

24. Laboratory Findings Associated with PLA Zakim and Boyer In summary, laboratory studies may suggest liver abnormalities but are neither SN nor SP for DX of PLA.

25. Chest x-rays/ Abd X ray A chest radiograph may be abnormal in 50% to 80% of pts with PLA .( Zakim /Boyer) Right-lower-lobe atelectasis, right pleural effusion, and an elevated right hemi-diaphragm may be clues to the presence of a liver abscess. Perforation of a PLA into the thoracic cavity may result in empyema . In plain abdominal films, air can be seen in the abscess cavities in 10% to 20% of cases. However, these features are not sensitive for the diagnosis of PLA.

26. Ultrasonography Ultrasound is the screening test of choice . Abscesses as small as 1 cm in diameter can be detected . US is inexpensive and can guide needle aspiration of the abscess. Features identified on US can be highly variable and nonspecific , ranging from hypoechoic to hyperechoic lesions with a varying degree of internal echoes and debris. However, in most cases, HA are usually less echogenic than the surrounding liver tissue on ultrasound. CEUS shows wall enhancement during arterial phase and progressive washout during portal or late phases . The liquefied necrotic area does not enhance. Sensitivity :65%-95 %, with higher detection rates in pts with larger lesions. ( Zakim ) Note: In pts with K. pneumoniae abscesses, the lesion may appear solid and mimic a hepatic tumour . Limitations are a lack of sensitivity for microabscesses and singular lesions high in the dome of the liver.

27. USG PLA (A) Initial US showing debris inside the abscess cavity. (B) Liquefied pus inside the abscess . (SCHIFF)

28. USG US of a PLA shows a low - density lesion containing echogenic material which is pus and necrotic tissue. Acoustic enhancement beyond the lesion is characteristic. (Sherlock)

29. CEUS: HA Arterial Phase: An increased echogenicity of the liver parenchyma during arterial phase. The aspect suggests liver congestion and represents an indirect sign that supports the diagnosis of a HA. Portal-venous phase: A decrease of liver echogenicity is noted while the infected collection is emphasized. Ref: Contrast-Enhanced Ultrasonography (CEUS) of Liver Masses — Principles, Clinical Applications, Drawbacks. By R. Badea and Simona Ioaniţescu https://www.intechopen.com/books/liver-tumors-epidemiology-diagnosis-prevention-and-treatment/contrast-enhanced-ultrasonography-ceus-of-liver-masses-principles-clinical-applications-drawbacks

30. CT SCANS CT scans can detect collections as small as 0.5 cm in diameter .(Schiff) CT is also accurate, with a SN approaching 100%. CT permits precise localization of an abscess , assessment of its relationship to adjacent structures , and detection of gas in the abscess , which is a/with increased mortality . The appearance of LA is variable . In general, they appear as peripherally enhancing, centrally hypoattenuating lesions . [1] Occasionally they appear solid or contain gas (which is seen in ~20% of cases [2]). The gas may be in form of bubbles or air-fluid levels .[3] Segmental , wedge-shaped or circumferential perfusion abnormalities, with early enhancement, may be seen .[1,3] 1. Skucas J. Advanced imaging of the abdomen. Springer Verlag . (2006) . 2. Lee TY, Wan YL, Tsai CC. Gas-containing liver abscess: radiological findings and clinical significance. Abdom Imaging. 1994;19 (1): 47-52. 3. Bächler P, Baladron MJ, Menias C et-al. Multimodality Imaging of Liver Infections: Differential Diagnosis and Potential Pitfalls. Radiographics . 2016;36 (4): 1001-23 ..

31. CT Scan: HA   The " double target sign " is a characteristic imaging feature of hepatic abscess demonstrated on CECT scans, in which a central low attenuation lesion (fluid filled) is surrounded by a high attenuation inner rim and a low attenuation outer ring .[1] The inner ring (abscess membrane) demonstrates early contrast enhancement which persists on delayed images, in contrast to the outer rim ( oedema of the liver parenchyma) which only enhances on delayed phase .[1]   The " cluster sign " is a feature of PLA.[2] It is an aggregation of multiple low attenuation liver lesions in a localised area to form a solitary larger abscess cavity.  1. Bächler P, Baladron MJ, Menias C et-al. Multimodality Imaging of Liver Infections: Differential Diagnosis and Potential Pitfalls. Radiographics . 2016;36 (4): 1001-23. 2 . Jeffrey RB, Tolentino CS, Chang FC et-al. CT of small pyogenic hepatic abscesses: the cluster sign. AJR Am J Roentgenol . 1988;151 (3): 487-9

32. CT SCANS: PLA PLA in the RL showing a hypointense rim which is secondary to peripheral inflammation . Ref: SCHIFF CT scan shows a low attenuation defect in the right lobe of the liver. Note gas in bile ducts ( arrow). Ref: Sherlock.

33. CT Scan: PLA: Cluster sign (a)Arterial phase CECT shows a hypoattenuating lesion consisting of smaller aggregating cystic lesions, known as the “ cluster” sign. (b) Portal venous phase CT depicts enhancement of the irregular septa within the abscess. Source: https ://radiologykey.com/focal-hepatic-infections/

34. CT Scan of PLA Coronal CT image in portal venous phase depicts multiple round low-attenuating lesions in both hepatic lobes. The cluster sign is also noted in some of the larger lesions Source: https ://radiologykey.com/focal-hepatic-infections/

35. General Approach Suspicious? USG/CT Send blood & Aspirate Culture Send Serum IgG/IgM Elisa for Entamoeba Start Empirical Antibiotics Adjust antibiotics as per C & S

36. Modalities of Management Management with Antibiotics Aspiration : percutaneous needle aspiration Drainage: CT or US-guided percutaneous drainage (with or without catheter placement) Surgical drainage Drainage by endoscopic retrograde cholangiopancreatography (ERCP)

37. Antibiotics Regime Empiric broad-spectrum parenteral antibiotics should be administered pending abscess gram stain and culture results. Regardless of the initial empiric regimen, the therapeutic regimen should be revisited once culture and susceptibility results are available. Recovery of more than one organism should suggest polymicrobial infection including anaerobes , even if no anaerobes are isolated in culture . In such circumstances, anaerobic coverage should be continued.

38. Empirical Antibiotic Regime Antibiotic therapy choices involve combining broad spectrum antibiotics: Third-generation cephalosporin plus clindamycin or metronidazole. Broad spectrum penicillin plus aminoglycosides. Second-generation cephalosporin plus aminoglycosides. Schiff Treatment should be started immediately after specimens have been obtained for culture without waiting for definitive results .

39. Empiric antibiotic therapy Regimen Dose First choice Monotherapy with a beta-lactam inhibitor: Piperacillin- tazobactam Ticarcillin-clavulanate 3.375 or 4.5 g IV every six hours 3.1 g IV every four hours Combination 3RD gen cephalosporin PLUS metronidazole: Ceftriaxone plus 1 g IV every 24 hours Metronidazole 500 mg IV every eight hours Alternative empiric regimens Combination fluoroquinolone PLUS metronidazole: Ciprofloxacin or 400 mg IV every 12 hours Levofloxacin plus 500 or 750 mg IV once daily Metronidazole 500 mg IV every eight hours Uptodate21.6

40. Duration of therapy This is typically determined by the extent of infection and the pt's clinical response to initial MX . Pts with abscess( es ) that are difficult to drain or slow to resolve on follow-up imaging usually require longer courses of therapy. Useful clinical indicators to follow are T, WBC and S CRP. Radiological abnormalities resolve much more slowly than clinical and biochemical markers. Among 102 pyogenic liver abscess patients in Nepal, the mean time to US resolution of abscesses <10 cm was 16 wks ; mean time to resolution for abscesses >10 cm was 22 wks [ 1]. When there is good response parenteral therapy for 2–3 weeks followed by oral antibiotics for 4–6 weeks is recommended . (Schiff/ zakim ) K C S, Sharma D. Long-term follow-up of pyogenic liver abscess by ultrasound. Eur J Radiol 2009; [ Epub ahead of print ].

41. Drainage: single abscesses with a diameter ≤5 cm For single abscesses with a diameter ≤5 cm , either percutaneous catheter drainage or needle aspiration is acceptable [1,2,3,4]. Drainage catheters should remain in place until drainage is minimal (usually up to 7 days). Repeat needle aspiration may be required in up to half of cases if a catheter is not left in situ [1,2]. Rajak CL, Gupta S, Jain S, et al. Percutaneous treatment of liver abscesses: needle aspiration versus catheter drainage. AJR Am J Roentgenol 1998; 170:1035. Ch Yu S, Hg Lo R, Kan PS, Metreweli C. Pyogenic liver abscess: treatment with needle aspiration. Clin Radiol 1997; 52:912. Yu SC, Ho SS, Lau WY, et al. Treatment of pyogenic liver abscess: prospective randomized comparison of catheter drainage and needle aspiration. Hepatology 2004; 39:932. Zerem E, Hadzic A. Sonographically guided percutaneous catheter drainage versus needle aspiration in the management of pyogenic liver abscess. AJR Am J Roentgenol 2007; 189:W138. Calvo-Romero JM, Lima-Rodriguez EM. Favourable outcome of multiple pyogenic liver abscesses with conservative treatment. Scand J infect Dis 2005;37:141–57. Bergert H, Kersting S, Pyrc J, et al. Therapeutic options in the treatment of pyogenic liver abscess. Ultraschall Med 2004;25:356–62. For a solitary abscess < 5 cm in diameter, confirmed by aspirate and with available antimicrobial sensitivity, resolution can be achieved with antibiotics alone [5,6].

42. Drainage: single abscesses with diameter >5 cm For percutaneous management of single abscesses with diameter >5 cm , catheter drainage is preferred over needle aspiration . These principles were illustrated in a trial of 60 pts with PLA treated with antibiotics and percutaneous drainage via catheter or needle aspiration [ 1]. Among pts with an abscess diameter >5 cm, RX was successful in 100 % of pts treated with catheter drainage compared with 50 % of pts with needle aspiration . Successful outcomes were observed for all pts with abscess ≤5 cm, regardless of drainage modality. For single abscesses with diameter >5 cm, some favor surgical intervention over percutaneous drainage [2,3]. The efficacy of this approach was suggested in a retrospective study of 80 pts with abscess >5 cm managed with percutaneous or surgical drainage; there was no difference in mortality, morbidity, duration of fever or complication rates . However, the rate of treatment failure was lower with surgical drainage (7 versus 28 %). Zerem E, Hadzic A. Sonographically guided percutaneous catheter drainage versus needle aspiration in the management of pyogenic liver abscess. AJR Am J Roentgenol 2007; 189:W138. Tan YM, Chung AY, Chow PK, et al. An appraisal of surgical and percutaneous drainage for pyogenic liver abscesses larger than 5 cm. Ann Surg 2005; 241:485. Bertel , CK, van Heerden , JA, Sheedy, PF. Treatment of pyogenic hepatic abscesses: Surgical vs percutaneous drainage. Arch Surg 1986; 121:554.

43. Multiple Abscess With multiple abscesses, only the largest abscess may need to be aspirated ; smaller lesions often resolve with antibiotic treatment alone, but rarely, each lesion may need drainage . Multiple or loculated abscesses may be successfully managed by percutaneous drainage ; this was illustrated in a retrospective study of pts with PLA[1]. Successful percutaneous drainage was achieved in the setting of multiple abscesses (22 of 24 pts) and multiloculated abscesses (51 of 54 patients) [1]. Liu CH, Gervais DA, Hahn PF, et al. Percutaneous hepatic abscess drainage: do multiple abscesses or multiloculated abscesses preclude drainage or affect outcome? J Vasc Interv Radiol 2009; 20:1059.

44. Endoscopic drainage Biliary decompression is essential when a hepatic abscess is associated with biliary tract obstruction or communication and may be accomplished through the endoscopic or transhepatic route. In patients with stones or strictures of the bile duct and abscess formation in continuity with the biliary system , endoscopic therapy provides biliary drainage, promoting abscess drainage [1]. Dull JS, Topa L, Balgha V, Pap A. Non-surgical treatment of biliary liver abscesses: efficacy of endoscopic drainage and local antibiotic lavage with nasobiliary catheter. Gastrointest Endosc 2000;51(1): 55–9.

45. Surgical Drainage Surgical drainage is also appropriate in the following circumstances: Multiple abscesses Loculated abscesses Abscesses with viscous contents obstructing the drainage catheter Underlying disease requiring primary surgical management Inadequate response to percutaneous drainage within seven days

46. Surgery Surgical therapy is necessary for multiple macroscopic or multiloculated abscesses, or those in the left lobe, after percutaneous drainage failure . Surgical drainage may be required in the presence of ascites or renal failure , when there is evidence of clinical deterioration, persistent jaundice , or concomitant steroid therapy , or when abscesses are not accessible to radiologic manipulation, and in the case of a ruptured abscess [1,2]. Bergert H, Kersting S, Pyrc J, et al. Therapeutic options in the treatment of pyogenic liver abscess. Ultraschall Med 2004;25:356–62. Tan YM, Chung AY, Chow PK, et al. An appraisal of surgical and percutaneous drainage for pyogenic liver abscess larger than 5 cm. Ann Surg 2005;241:485–90.

47. Successful hepatectomy for hepatic abscess with chronic granulomatous disease: a case report Background: CGD, a rare inherited disorder, is characterized by impaired ability of phagocytic cells to kill certain bacteria and fungi. Although HA is a common manifestation of CGD, its optimal MX in these pts is unknown. Case presentation: An adolescent pt with previously diagnosed CGD presented to the ped department with fever. Blood tests showed high concentrations of inflammatory markers. A CT scan showed a multilocular mass measuring 52 mm × 34 mm in hepatic segment 4 (S4). Blood cultures were negative. Despite administration of antibiotics and γ -globulin, his fever and high concentrations of inflammatory markers persisted and the mass did not change on CT scan images. Because the medications had proved ineffective and percutaneous drainage would have been difficult because of the honeycombing in the abscess, hepatic S4a + S5 anatomic resection and cholecystectomy was performed . Culture of the excised specimen was negative. The pt’s postoperative course was uneventful. On day 62, CT showed no abscess around the resection stump. On day 81, he was transferred to undergo BMT. Conclusions: Surgical treatment for hepatic abscess can be effective when medical treatment has failed. Ryo Muranushi et al. Successful hepatectomy for hepatic abscess with chronic granulomatous disease: a case report. Surg Case Rep. 2017 Dec; 3: 57.

48. Inflammatory pseudotumor of the liver Inflammatory pseudotumor of the liver (also called plasma cell granuloma ) is a rare, benign lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The cause is unknown. Affected persons (typically young men ) often have a history of recent infection, but a causative infectious agent is rarely isolated from the lesion. Additional associated disorders include chronic inflammatory and autoimmune disorders , particularly ascending cholangitis and PSC, as well as DM, Sjögren’s syndrome, gout, IBD, HIV infection, EBV infection, and acute myeloblastic leukemia . CT: In most reported cases, the they appear as hypo-attenuating masses with a variable degree of hepatic enhancement

49. Inflammatory pseudotumor of the liver Patients typically present with intermittent fever, abdominal discomfort, vomiting, diarrhea, weight loss, and malaise and have hepatomegaly, RUQ tenderness, and jaundice on physical examination. Portal hypertension may develop. Lab findings also are similar to those associated with liver abscess, including polyclonal hyperglobulinemia in 50% of cases, and imaging studies generally are interpreted as showing a tumor or an abscess . Treatment generally has been by surgical resection of the lesion , although some patients may recover spontaneously or after treatment with antibiotics or glucocorticoids, once the diagnosis is made on the basis of needle biopsy findings.

50. Prognosis When left untreated, PLA is a/with a mortality of 100%. With early diagnosis, appropriate drainage, and long-term antibiotic therapy, the prognosis has improved markedly[1] ; mortality is now in the range of 15-20 %.[2,3]   Poor prognostic factors are as follows: Age older than 70 years Multiple abscesses Polymicrobial infection Presence of associated malignancy or immunosuppressive disease[4,5] Evidence of sepsis [2,4,6,7,8] Chu KM, Fan ST, Lai EC, et al. Pyogenic liver abscess. An audit of experience over the past decade. Arch Surg. 1996 Feb. 131(2):148-52. Gyorffy EJ, Frey CF, Silva J Jr, McGahan J. Pyogenic liver abscess. Diagnostic and therapeutic strategies. Ann Surg. 1987 Dec. 206(6):699-705. Hashimoto L, Hermann R, Grundfest-Broniatowski S. Pyogenic hepatic abscess: results of current management. Am Surg. 1995 May. 61(5):407-11. Seeto RK, Rockey DC. Pyogenic liver abscess. Changes in etiology, management, and outcome. Medicine (Baltimore). 1996 Mar. 75(2):99-113. Branum GD, Tyson GS, Branum MA, Meyers WC. Hepatic abscess. Changes in etiology, diagnosis, and management. Ann Surg. 1990 Dec. 212(6):655-62. Bowers ED, Robison DJ, Doberneck RC. Pyogenic liver abscess. World J Surg. 1990 Jan-Feb. 14(1):128-32. Chou FF, Sheen-Chen SM, Chen YS, et al. Prognostic factors for pyogenic abscess of the liver. J Am Coll Surg. 1994 Dec. 179(6):727-32. Wang W, Lee WJ, Wei PL, et al. Laparoscopic drainage of pyogenic liver abscesses. Surg Today. 2004. 34(4):323-5.

51. Complications of pyogenic liver abscess Pleural or pericardial effusion Empyema Portal vein thrombosis =24 % [1] Hepatic Vein thrombosis= 22 % [1] Splenic vein thrombosis Rupture into the pericardium, thoracic and abdominal fistula formation, and sepsis. Metastatic septic endophthalmitis occurs in as many as 10% of diabetic patients with a liver abscess caused by Klebsiella pneumoniae . Syed MA, Kim TK, Jang HJ. Portal and hepatic vein thrombosis in liver abscess: CT findings. European journal of radiology. 61 (3): 513-9.

52. OBJECTIVES : To study the differences between the clinical presentation and complications of amoebic and PLA . To correlate the diagnostic significance of Entamoeba Indirect Haemagglutination test (E.IHA) in establishing the diagnosis of ALA. PARTICIPANTS : 52pts aged 13-70 years admitted in Medical Unit and diagnosed to have LA. INTERVENTIONS: Group A comprised of pts clinically diagnosed to have ALA and received Metronidazole 500mg iv x 8 hrly for atleast 10 d or more if pt developed complications. Group B comprised of pts diagnosed to have PLA and received Cefotaxime 1g iv x 8 hrly for the same duration or more if complicated (antibiotic reviewed in accordance with C&S). MAIN OUTCOME MEASURES: Differences in the clinical presentation, complications and diagnostic parameters between the two groups of pts . RESULTS: It was not possible to differentiate between amoebic and PLA on clinical grounds, routine investigations and imaging techniques. Aspiration of pus, especially if the abscess was multiple, was most helpful in differentiating the two types of abscesses . Serological test of E.IHA was highly specific and sensitive for ALA. CONCLUSION: Majority of LA in Karachi are due to E. Histolytica . PLA though less frequent, must be excluded by pus aspiration and C&S . E.IHA is a good rapid method of discriminating between the two types of abscesses.

53. Features distinguishing amoebic from PLA: a review of 577 adult cases. S. Lodhi , A. R. Sarwari , M. Muzammil , A. Salam and R. A. Smego Distinguishing amoebic from PLA is crucial because their RX and prognoses differ . We retrospectively reviewed the medical records of 577 adults with LA in order to identify clinical, laboratory, and radiographic factors useful in differentiating these microbial aetiologies . Presumptive diagnoses of amoebic ( n:471 ; 82%) vs. pyogenic ( n:106 ; 18%) abscess were based upon amoebic serology, microbiological culture results, and response to therapy. Pts with ALA were more likely to be young males with a tender, solitary, right lobe abscess (P<0.012 ). Pts with PLA more likely to be>50 years old , with a history of DM and jaundice, with pulmonary findings, multiple abscesses, amoebic serology titres <1:256 IU, and lower levels of S albumin (P < 0.04). Study analysis confirmed that age >50 years, pulmonary findings on examination, multiple abscesses, and amebic serology titres <1:256 IU were predictive of PLA.

54. Evaluated the c/f of 96 cases of ALA and 48 of PLA . Most pts with ALA were young Hispanic males. Those with PLA were older. Symptoms tended to be acute and localized to the RUQ in ALA . In PLA , symptoms were often nonspecific and chronic in nature . Increased leukocyte count occurred more frequently in PLA , as did markedly abnormal values of the S albumin, direct bilirubin, LDH and AST. Sonography detected all cases of ALA and missed the lesions in 2 of 39 pts with PLA.

55. Abscess cultures yielded pathogens in 90% of cases of PLA , while blood cultures were positive in 50%. 5 of 20 pts with positive blood cultures had additional organisms isolated from the abscess that required adjustment of antibiotics for optimal coverage. We believe that all PLA should be aspirated to guide antibiotic therapy . In ALA , the Dx was usually based on clinical and sonographic findings, aspiration being performed in only 14% of cases . 98% of pts were treated with amebicidal agents alone , and all responded to therapy. Therapeutic needle aspiration was rarely necessary. In PLA , prolonged fever was common during medical therapy . Even in those eventually cured without surgery, the median time to defervescence was 8 days . Though 19 pts underwent surgical drainage , only 2 clearly did not benefit from medical Rx, having high fevers after >2 weeks on a regimen of appropriate antibiotics. Surgery is often performed prematurely because physicians expect fever to resolve quickly, but persistent fever of <2 weeks' duration should not constitute an indication for surgical drainage. 7 pts with PLA died.

56. Diagnostic differences betn amoebic and PLA Schiff ALA are usually solitary and present in Rt lobe near the diaphragm.

57. End of slides