PYOGENIC LIVER ABSCESS: DIAGNOSTIC AND THERAPEUTIC MANAGEMENT

ABSTRACT Background: The pyogenic liver abscess has an incidence of 1.1/1,000 habitants. Mortality can reach 100%. The use of less invasive procedures diminish morbidity and hospital stay. Aim: Identify risk factors in patients who underwent percutaneous drainage guided by ultrasound as treatment. Method: Were analyzed 10 patients submitted to the method. Epidemiological characteristics, laboratory markers and imaging exams (ultrasound and CT) were evaluated. Results: The majority of the patients were men with mean age of 50 years old. Liver disease, alcoholism and biliary tract disease were the most common prodromes. Abdominal pain (90%), fever (70%) and jaundice (40%) were the most common clinical manifestations. Mortality of 20% was observed in this series. Hypoalbuminemia and days of hospitalization had a statistically significant positive association with death. Conclusion: The pyogenic liver abscess has subacute evolution which makes the diagnosis difficult. Image exams have high sensitivity in diagnosis, particularly computed tomography. Percutaneous drainage associated with antibiotic therapy is safe and effective therapeutic resource.


INTRODUCTION
P yogenic hepatic abscess is caused by the development of intra-hepatic pus collection, secondary to a local inflammatory reaction by bacteria infection in the hepatic parenchyma 9,16 . It has an incidence varying from 1,1-2,3 for each 100.000 habitants 3 . The main symptoms are abdominal pain -mainly in the right hypochondrium -fever and hepatomegaly. It has a subacute evolution with symptoms varying between 3-120 days 8 .
The etiology can vary according to region. In Central Europe prevails biliary causes, followed by cryptogenic abscess by Staphylococcus aureus, Streptococcus and E. coli. In Southeast Asia, the most prevalent microorganism is Klebsiella pneumoniae. Such differences in the microbiological spectrum have implications in risk and course factors of the disease 3 . Pang et al. 14 found a higher proportion of cryptogenic causes, followed by biliary and portal (appendicitis, diverticulitis). Also, verified association between microbiology and etiology. E. coli is associated with biliary diseases; Klebsiela with cryptogenic and Streptococcus milleri with portal causes.
It is a very harmful disease, always fatal without treatment. Mortality can vary between 5,6-80% 10,13 . A series published in 1938, showed mortality of 60-80% 9 . An expressive downfall on the mortality rate, to 13-18%, was possible because of the effective use of antibiotics after 1980 11 . Another decrease was seen in studies with the use of CT scan and ultrasound. The mortality in studies during and after 1990, remained between 4-10% 15 . The development of interventional radiology, with percutaneous drainage guided by image and minimal invasive surgery, on recent decades, are contributing for the increase of patient's survival 11 .
The treatment to be instituted must consider the cause, the service's experience and the access to diagnostic means and treatment. Antibiotics, interventional radiology, and surgical therapy can be used, combined or as a single therapy. However, the combination of interventional radiology (aspiration or drainage) with antibiotics has shown better results in hospitalization, morbidity, mortality and complications 5,13 .
The aim of this study was to identify risk factors of pyogenic liver abscess treated by percutaneous drainage guided by ultrasound.

METHOD
This is a prospective study in which all patients included were treated in Hospital Geral do Grajaú, São Paulo, SP, Brazil for pyogenic hepatic abscess. Ten patients were included in the period between April and September 2015.
The diagnosis of pyogenic hepatic abscess was confirmed based on clinical characteristics, laboratorial and image exams (ultrasound and tomography). Basic demographic characteristics, prodromes, signs and symptoms, exam results, interventions, complications and outcomes were registered in a standardized protocol.
Fever was defined as a temperature measured in the first 24 h bigger than 37,5 o C. All other vital signs were defined by the first set of available observations after presentation. Tachycardia was defined as a cardiac rhythm higher or equal 100 beats per minute, and hypotension as a systolic blood pressure below 90 mmHg. For blood test results, the first available test, in the first 48 h was used for reference. Laboratorial tests reference values were defined by the local laboratory normal values. The abscess size was defined as the largest found diameter. In case of multiple abscesses, was considered the largest abscess diameter. The etiology was a presumptive diagnosis, based on previous treatment history, in the first approach and thorough examination by the team.
The patients with pyogenic abscess suspicion were submitted to large spectrum antibiotics therapy. As protocol instituted by the Hospital Infection Control Commission based on the local bacterial flora, quinolone (ciprofloxacin), associated with a nitroimidazole (metronidazole) were used. The antibiotics were kept in use for 4-6 weeks.
The intervention defined in this study was the percutaneous drainage guided by ultrasound, with maintenance of drainage in situ, applied in a surgical environment, with sedation and local anesthesia. It was used a Pigtail drain with free drainage.

Statistical analysis
Was realized using Epi Info 7. The categorical variables in each group were compared with the chi-square (if 20% or more of the expected frequencies were below 5), as appropriated. The continuous variables were compared using the independent t-student sample test, p=<0.05 was considered statistically significant.

RESULTS
There was men predominance (70%) with an average age of 50 years old, with peak incidence around 54 years. Half the patients had positive medical history for liver disease. Alcoholism and biliary disease were the most frequent conditions associated (40%). Other diseases were Crohn's and dysentery (Figure 1).
Clinical analysis results in admission are shown in Table 2 with inflammatory alterations (leucocytes and C-reactive protein); 40% had serum levels of urea and creatinine elevated; almost 90% had alterations in hepatic enzymes and hyperbilirubinemia; 90% had altered canalicular enzymes and 75% increased INR.  All patients were submitted to ultrasound and tomography and 50% had multiple abscesses with average diameter of 12.54 cm (4-18). Right hepatic lobe was compromised in 90% of the cases and segments VI, VII e VIII in 75% (Table 3).

DISCUSSION
Men predominated. Data found in this study is in consonance with others 6,10,14 . On the present series hepatic abscess was more common in adults with 50 years old, 10 years earlier in relation to literature. The age difference between deaths and good outcome had no statistic significance (p=0.6690). Meddings et al. 10 in a population based study found patients between 18-84 years old, with 42.9% prevalence between 65-85. Pang et al. 14 found an average of 64 years and Küster -Filho et al. 8 average of 30.8 years. In more recent studies, it can be observed a higher preponderance on the elderly.
The clinical presentation show unspecific signals and symptoms. Abdominal pain, jaundice, fever, inappetence and weight loss were the most common. These data are also the ones found in the literature 9,14 . This strengthens the fact that hepatic abscess diagnosis is made with high clinical suspicion, given the low prevalence and unspecific symptoms. It can explain the average of 8.2 days for diagnosis, what suggest subacute evolution 14 .
The main cause found in this study was portal, secondary to abdominal cavity contamination. Such results differ from the literature showing preponderance of biliary causes in 44% of patients 8 or, as Pang et al. 14 , cryptogenic causes in 34% 14 .
The most common microorganism isolated was Escherichia coli, similar to Küster-Filho et al. 8 and Meddings 10 papers, despite of etiology. In Brazilian study 8 biliary causes were more common, but in Americans portal causes 10 prevailed. Asian series showed a great proportion of patients with Klebsiella associated with cryptogenic etiology 4 , mainly in diabetic group 9 .
The abdominal ultrasound had 40% sensibility to diagnose abscesses while abdominal CT scan had 90%. Abscesses were located, in majority, in the right hepatic lobe as single abscesses measuring 12.54 cm. Küster-Filho et al. 8 found preponderance of multiple abscesses, in the right lobe, measuring 7.33 cm in average.
Antibiotics associated with puncture and drainage have found better results in reference of morbidity and mortality, compared to antibiotic therapy and puncture or open surgery 5,8,14 . Yu-Long et al. 16 in a systematic revision with meta-analysis of five RCT comparing puncture and drainage concluded that drainage was superior in success rate (p=0.04), clinical improvement (p=0.0001) and reduction in days to reduce the abscess size in 50% (p<0.00001).
This study showed mortality of 20% , high when compared to Pang et al. 14 (6.3%) and a historic Australian series (8%) 1 , but explained by the enrollment of bad cases, one patient with Chron's disease presented generalized peritonitis and multiples enterocutaneous fistulae and another had bronchial aspiration. In the USA this rate is around 5.6%, decreasing from prior 6-19% 10 .
Hospital stay showed association with death, with an average of 48 days in the death group (p=0.0153), while in good outcome it was in average 21.63, not surpassing 34 days. The culture was positive in 70% of the patients and the most prevailed microorganism isolated was Escherichia coli in 50%, followed by multiresistent beta-lactamase extendedspectrum (ESBL MR) in 25%. Figure 2 shows the etiology.

CONCLUSION
The pyogenic liver abscess has subacute evolution which makes the diagnosis more difficult. Image exams have high sensitivity, particularly computed tomography. Percutaneous drainage associated with antibiotic therapy is safe and effective therapeutic resource.