Image-guided percutaneous procedure plus metronidazole versus metronidazole alone for uncomplicated amoebic liver abscess

  • Review
  • Intervention

Authors

  • Norberto C Chavez-Tapia,

    Corresponding author
    1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Department of Gastroenterology, Mexico City, Distrito Federal, Mexico
    • Norberto C Chavez-Tapia, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #5, Mexico City, Distrito Federal, 14000, Mexico. khavez@gmail.com.

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  • Jorge Hernandez-Calleros,

    1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Department of Gastroenterology, Mexico City, Distrito Federal, Mexico
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  • Felix I Tellez-Avila,

    1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Department of Gastroenterology, Mexico City, Distrito Federal, Mexico
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  • Aldo Torre,

    1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Department of Gastroenterology, Mexico City, Distrito Federal, Mexico
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  • Misael Uribe

    1. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Department of Gastroenterology, Mexico City, Distrito Federal, Mexico
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Abstract

Background

Metronidazole is the standard of care for uncomplicated amoebic liver abscesses (considering that complicated liver abscesses are those localized in left lobe, multiple, and/or pyogenic abscesses). However, a subset of patients with amoebic liver abscesses remain symptomatic, with a significant risk of rupture of the abscess into the peritoneum. The role of image-guided percutaneous therapeutic aspiration in these patients remains controversial.

Objectives

To assess the beneficial and harmful effects of image-guided percutaneous procedure plus metronidazole versus metronidazole alone in patients with uncomplicated amoebic liver abscess.

Search methods

We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2007), MEDLINE (1966 to November 2007), EMBASE (1988 to September 2007), and Science Citation Index Expanded (1945 to September 2007).

Selection criteria

Randomised or quasi-randomised trials comparing an image-guided percutaneous procedure plus metronidazole versus metronidazole alone in patients with uncomplicated amoebic liver abscess.

Data collection and analysis

Inclusion criteria, trial quality assessment, and data extraction were done in duplicate. We calculated relative risks (RR) and mean differences, and checked for heterogeneity by visual inspection of forest plots and chi-squared and I2 tests.

Main results

Seven low quality randomised trials were included. All studies included a total of 310 patients, but due to selective outcome reporting bias, less patients could be included in our analyses. Pooled analysis of three homogenous trials showed that needle aspiration did not significantly increase the proportion of patients with fever resolution (RR 0.60, 95% confidence interval (CI) 0.22 to 1.61). Sensitivity analysis according to trial quality preserved these findings. Trials that evaluated resolution of abdominal pain, days to resolution of fever, pain, resolution of abscess cavities, reduction in liver size, and duration of hospitalisation were heterogeneous. The benefits in the number of days to resolution of pain (MD -1.59, 95%CI -2.73 to -0.42), number of days to resolution of abdominal tenderness (MD -1.70, 95%CI -2.86 to -0.54), and duration of hospitalisation (MD -1.31, 95%CI -2.05 to -0.57) were observed in the needle aspiration group only.

Authors' conclusions

Therapeutic aspiration in addition to metronidazole to hasten clinical or radiologic resolution of uncomplicated amoebic liver abscesses cannot be supported or refuted by the present evidence. The trials lack methodological rigour and adequate sample size to conclude on the presence of effectiveness of adjunctive image-guided aspiration plus metronidazole versus metronidazole alone. Further randomised trials are necessary.

摘要

背景

影像引導經皮穿刺抽吸合併metronidazole對照metronidazole單一治療無併發症阿米巴肝膿腫

metronidazole是治療無併發症阿米巴肝膿腫的標準(認為發生在肝左葉的複雜肝腫膿,多發性腫膿和化膿性膿腫)。 但是,少量的阿米巴肝膿腫病人會有症狀,膿腫突然爆裂至腹膜的風險特別高。人們對於影像導航用於經皮穿刺抽吸治療膿腫病人的作用還存有爭議。

目標

評估影像引導經皮穿刺抽吸合併metronidazole對照metronidazole單一治療無併發症阿米巴肝膿腫的利弊。

搜尋策略

我們搜尋Cochrane HepatoBiliary Group Controlled Trials Register, Cochrane Library(第2期, 2007)的Cochrane Central Register of Controlled Trials, MEDLINE (1966 年−2007年9月), EMBASE (1988年−2007年9月)和Science Citation Index Expanded (1945年 2007年9月)。

選擇標準

影像引導經皮穿刺抽吸合併metronidazole對照metronidazole單一治療無併發症阿米巴肝膿腫的隨機或半隨機試驗。

資料收集與分析

文獻回顧者負責收錄標準,試驗品質評估,資料提取,製作成2份。 我們評估相對風險 (relative risks ,RR) 平均差,透過目測森林圖及卡方和I2檢定,我們檢查試驗的異質性。

主要結論

共包括7個品質低的隨機試驗。研究共包括310 位病人,但是由於選擇結果存在偏誤,我們的分析僅包括了較少的病人。合併3個同性質的試驗之後,結果顯示穿刺術沒有顯著增加有發熱緩解的病人比例(RR 0.60, 95%CI 0.22 1.61)。 依據試驗品質、敏感性分析保存這些發現結果。 評估腹痛緩解、發熱緩解天數、膿腫腔緩解、肝臟大小的縮小和住院日的試驗具異質性。只有穿刺抽吸組觀察了在疼痛緩解天數(MD −1.59, 95%CI −2.73  0.42),腹部壓痛緩解天數(MD −1.70, 95%CI −2.86  0.54)和住院日(MD −1.31, 95%CI −2.05  0.57)上的效益。

作者結論

另外,目前證據不能支持或反對抽吸治療合併metronidazole能夠在臨床或應用放射學方面,促進無併發症阿米巴肝膿腫的緩解。試驗缺乏嚴謹方法論和適當的樣本大小 決定輔助影像引導抽吸法合併metronidazole對照metronidazole單一治療的有效性。需要深入的隨機試驗。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

經皮穿刺抽吸似乎不能幫助無併發症阿米巴肝膿腫的病人: 阿米巴病 (由單細胞阿米巴原蟲引起的疾病) 仍然是世界各個國家一大重要的臨床問題,4百萬−5百萬的人受到該疾病的影響。死亡率顯著,大約每年死亡案例達到40,000 110,000起。實際上,阿米巴病死亡是唯一第2種由於原生寄生蟲致死的瘧疾。阿米巴病引起的最常見併發症是讓肝臟內部充滿了膿腫塊(肝臟膿腫)。metronidazole是使用管腔劑之後治療阿米巴肝膿腫的一種方案消除無症狀載體的狀態。治癒率達到95%,發熱,疼痛和厭食在72 96小時內消失。本次文獻回顧比較標準治療和更激進的替代療法,透過影像引導經皮穿刺抽吸排泄膿腫塊(穿透皮膚實施)。共包括7個品質低的隨機試驗。7個研究共包括310位病人但是由於選擇結果存在偏見,我們的分析包括較少的病人。合併3個同性質的試驗之後, 穿刺抽吸術顯著增加有發熱緩解的病人比例。從疼痛和壓痛緩解時間可以觀察到這種有益療效。發現經皮穿刺抽吸合併metronidazole對照metronidazole單一治療無併發症阿米巴肝膿腫的過程中,在促進臨床和放射緩解方面,沒有顯示額外有益的療效。 但是,這種結論是建立在研究方法有缺陷,樣本大小不足的基礎上得到的,需要在大規模,設計良好的隨機試驗中確認。

Plain language summary

Percutaneous needle aspiration does not seem to help patients with uncomplicated amoebic liver abscesses

Amoebiasis (disease caused by the protozoan Entameoba histolytica) remains an important clinical problem in countries around the world, with 40 to 50 million people affected. Mortality rates are significant, with 40,000 to 110,000 deaths each year. In fact, amoebiasis mortality is second only to malaria as cause of death from protozoan parasites. The most common complication of amoebiasis is the formation of a pus-filled mass inside the liver (liver abscess). Metronidazole is the drug of choice for treatment of amoebic liver abscesses followed by a luminal agent to eradicate the asymptomatic carrier state. Cure rates are 95% with disappearance of fever, pain, and anorexia within 72 to 96 hours. This review compares the standard treatment with a more invasive alternative, where pus-filled mass is drained by image-guided percutaneous procedure (performed through the skin). Seven low quality randomised trials were included. All the seven studies included a total of 310 patients, but due to selective outcome reporting bias, less patients could be included in our analyses. Pooled analysis of three homogenous trials showed that needle aspiration did not significantly increase the proportion of patients with fever resolution. Benefits could be observed in resolution time of pain and tenderness. No additional benefit has been found with percutaneous needle aspiration plus metronidazole versus metronidazole alone for uncomplicated amoebic liver abscesses in hastening clinical and radiologic resolution. However, this conclusion is based on trials with methodological flaws and with insufficient sample sizes, and requires further confirmation in larger well-designed, randomised trials.

Background

Epidemiology
Amoebiasis remains an important clinical problem in countries around the world, with 40 to 50 million people affected. Mortality rates are significant, with 40,000 to 110,000 deaths each year. In fact, amoebiasis mortality is second only to malaria as cause of death from protozoan parasites (Hughes 2000; Stanley 2003). Amoebiasis is prevalent in countries where public health and personal hygiene are sub-optimal (Hughes 2000; Stanley 2003). Increasing travelling, immigration of individuals from endemic areas, growth of the homosexual population, and increasing immunosuppression are factors contributing to the increased risk for amoebiasis worldwide (Hughes 2000). Endemic areas are the Indian subcontinent, Southeast Asia, Africa, and South and Central America (Reed 1992).

Pathogenesis
Ingestion of Entamoeba (E) histolytica cysts through food or water contaminated by human faeces causes amoebiasis. Asymptomatic colonisation of the gastrointestinal tract is common, but some patients develop invasive disease of the colon (Hughes 2000; Stanley 2003). The amoebae can breach the colonic mucosal barrier and travel through the portal circulation to the liver. E histolytica blocks intrahepatic portal venules, and proteolytic enzymes digest the parenchymal cells forming a liquefied central area of necrosis, this causes amoebic liver abscesses.

Amoebic liver abscess is the most common extraintestinal manifestation of E. histolytica infection. All age groups are affected, but it is 10 times more common in the 20 to 40-year old age group (Ruiz-Palacios 1997; Petri 1999) and 12 times more common in men than women. If left untreated, amoebic liver abscesses can be fatal, with death from sepsis. With early diagnosis and treatment with metronidazole alone, mortality has dropped to less than 1% (Ravdin 1995).

Diagnosis
Ultrasound and computed tomography scans are non-invasive, equally sensitive imaging modalities for the detection of amoebic liver abscesses (Hughes 2000; Stanley 2003), but they cannot specifically differentiate amoebic from pyogenic abscess. Serum antibody detection is an important confirmatory test in the case of amoebic liver abscesses. Serologic tests are about 90% sensitive for amoebic liver abscess, with important limitations within the first week of the disease, and complementary serological assays must be performed (Petri 1999).

Treatment
Metronidazole is the drug of choice for treatment of amoebic liver abscesses followed by a luminal agent to eradicate the asymptomatic carrier state (Hughes 2000). Cure rates are 95% with disappearance of fever, pain, and anorexia within 72 to 96 hours (Ravdin 1995; Reed 1998). Most abscesses heal from the periphery usually in four weeks after initiating therapy. Mean time to complete radiologic resolution is three to nine months with greater than 50% reduction in liver size within a week (Hughes 2000).

However, approximately 10% to 15% of patients remain symptomatic despite of proper drug treatment. In recent years, imaging-guided percutaneous treatment with needle aspiration or catheter drainage has replaced surgical intervention as the procedure of choice for therapeutically reducing abscess size (Tandon 1997). Simple needle aspiration is less invasive, less expensive, allows for aspiration of multiple abscesses in the same session, and avoids problems related to follow-up catheter care (Giorgio 1995; Tandon 1997). Therapeutic aspiration is the standard of care in complicated liver abscesses, which include those with high risk of abscess rupture; left lobe liver abscesses, because of increased frequency of peritoneal leak or rupture into the pericardium; no response to drug therapy within five to seven days; bacterial co-infection, and uncertainty in diagnosis (Haque 2003; Stanley 2003).

It is important in clinical practice to identify subgroups of patients with amoebic liver abscesses who will benefit from ultrasound- or computed tomography-guided therapeutic aspiration. Spontaneous rupture of the abscess into the peritoneum can occur in 2% to 7% of patients (Ravdin 1995), and mortality rates ranged from 2% to 18% (Sharma 1996). Prediction of rupture is difficult in a setting without a high index of suspicion or without ultrasound monitoring to ascertain changes in the thickness between the skin surface, the liver capsule, and the cavity margin. Existing evidence, however, on the role of image-guided percutaneous therapy is conflicting. Clinical trials are small with debatable results and we have been unable to identify systematic reviews or meta-analyses on this topic. If needle aspiration hastens response to amoebicidal drugs and clinical recovery, this can potentially improve the quality of life, shorten hospital stay, and possibly reduce health care costs especially in developing countries.

Objectives

To determine the beneficial and harmful effects of image-guided percutaneous procedure plus metronidazole compared with metronidazole alone in patients with uncomplicated amoebic liver abscess.

Methods

Criteria for considering studies for this review

Types of studies

All randomised clinical trials were included in the review regardless of language, blinding, and publication status. In case there were too few randomised clinical trials, quasi-randomised clinical trials were considered for inclusion in an exploratory analysis to assess adverse events.

Types of participants

Adult patients admitted to the hospital with a clinical diagnosis of uncomplicated amoebic liver abscesses confirmed by a positive serologic result for E histolytica either by enzyme-linked immunosorbent assay (ELISA) or indirect hemagglutination assay (IHA), and with characteristic radiologic features on diagnostic imaging (computed tomography scan or ultrasound) confirming liver abscesses.

The trials that included patients with pyogenic abscesses, impending rupture, and/or other findings suggestive of complicated liver abscess, were not considered in this review.

Types of interventions

Image-guided percutaneous procedure, either needle aspiration or catheter drainage, plus metronidazole versus metronidazole in a similar dosage and duration alone.

Any collateral interventions if used equally in all intervention groups were allowed.

Types of outcome measures

Primary outcomes

  1. Mortality.

  2. Proportion of patients without resolution of abscess size on image follow-up.

  3. Clinical improvement or response to treatment as follows:

Lack of resolution of fever expressed as:

  • proportion of patients remaining febrile;

  • days to resolution of fever;

Lack of resolution of pain expressed as:

  • proportion of patients without resolution of pain;

  • days to resolution of pain;

Lack of resolution of abdominal tenderness expressed as:

  • proportion of patients without resolution of tenderness;

  • days to resolution of tenderness;

  • proportion of patients without reduction in liver size.

Secondary outcomes
4. Duration of hospitalisation.
5. Adverse events. Occurrence of complications, that is, rupture of abscess cavity and number of patients requiring surgical intervention.

Search methods for identification of studies

We searched the following databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (Gluud 2008), The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2007), MEDLINE (1950 to November 2007), EMBASE (1980 to September 2007) and Science Citation Index Expanded (1945 to September 2007) (Royle 2003). The search strategies are displayed in Appendix 1. We reviewed the reference lists of the retrieved articles for potentially relevant studies, including review articles on the topic. We contacted the corresponding authors of relevant studies identified from the initial search and experts in the field for any information on unpublished articles.

Data collection and analysis

Study selection
Two authors (NC, JH) independently reviewed the search output for potentially relevant trials for inclusion. Two authors (NC, JH) assessed the trials for potential inclusion. We excluded studies that do not meet the inclusion criteria and stated the reason in the 'Characteristics of excluded studies'. Disagreements were settled by discussion with a third co-author (FT). Each trial was assessed for possible multiple publications from the same data set to ensure that each trial is included only once in the review. We contacted the authors of the studies to obtain or verify missing information in the trial.

Assessment of bias risk by components of methodological quality
Two authors (NC, JH) independently assessed the bias risk by the following components of methodological quality of included studies (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008):

Generation of the allocation sequence

  • Adequate, if the allocation sequence was generated by a computer or random number table. Drawing of lots, tossing of a coin, shuffling of cards, or throwing dice were also considered as adequate if a person who was not otherwise involved in the recruitment of participants performed the procedure.

  • Unclear, if the trial was described as randomised, but the method used for the allocation sequence generation was not described.

  • Inadequate, if a system involving dates, names, or admittance numbers were used for the allocation of patients.

Allocation concealment

  • Adequate, if the allocation of patients involved a central independent unit, on-site locked computer, identically appearing numbered drug bottles or containers prepared by an independent pharmacist or investigator, or sealed envelopes.

  • Unclear, if the trial was described as randomised, but the method used to conceal the allocation was not described.

  • Inadequate, if the allocation sequence was known to the investigators who assigned participants or if the study was quasi-randomised.

Blinding

  • Adequate, if the trial was described as double blind and the method of blinding involved identical placebo or active drugs. Due to the use of image-guided aspiration or catheter drainage as an intervention, we are well aware that it may be very difficult to properly blind such trials.

  • Unclear, if the trial was described as double blind, but the method of blinding was not described.

  • Not performed, if the trial was not double blind.

Follow-up

  • Adequate, if the numbers and reasons for dropouts and withdrawals in all intervention groups were described or if it was specified that there were no dropouts or withdrawals.

  • Unclear, if the report gave the impression that there had been no dropouts or withdrawals, but this was not specifically stated.

  • Inadequate, if the number or reasons for dropouts and withdrawals were not described.

Furthermore, we registered whether or not the randomised clinical trials used 'intention-to-treat' analysis (Gluud 2001) and sample size calculation.

Any disagreement was resolved by discussion and settled by a third author (FT). We contacted the trial author for clarification as necessary.

Data extraction
Two authors (NC, JH) independently extracted data for each of the outcomes from each relevant study using a pre-designed data extraction form. We extracted the following information on study characteristics: population studied, interventions performed, and outcomes evaluated. These include trial setting, criteria for inclusion and exclusion of participants, details on interventions performed including dose of medications, duration of treatment, and co-interventions. Outcome measures to be extracted included mortality, symptom resolution, radiologic resolution of abscess cavity, and length of hospital stay. We also extracted adverse events reported such as occurrence of complications, non-responders, and those needing surgical intervention.

Data analysis
Data were entered in Review Manager Version 5.0 (RevMan 2008) by one author (NC) and checked by two other authors (JH, FT). Continuous outcomes were expressed as mean differences with 95% confidence intervals while dichotomous outcomes were expressed as relative risks with a 95% CI. For each outcome we extracted the number of participants assigned to each group and whenever possible extracted data to allow for an intention-to-treat analysis. If the number randomised and the numbers analysed were inconsistent, we reported this as the percentage lost to follow-up. For binary outcomes, the number of participants experiencing the event in each group was recorded. For continuous outcomes, the arithmetic means and standard deviations for each group were extracted. Any disagreement was resolved by discussion with reference to the trial report and resolution by a co-author (FT). For outcomes for which data were not reported or were reported in a different format, we contacted the authors for clarification. We checked for heterogeneity among trials by visual inspection of the forest plots and by using the chi-squared and I2 tests for heterogeneity (Higgins 2008), using a P-value less than 0.10 as the cut-off level for statistically significant heterogeneity. When heterogeneity was detected, potential sources of heterogeneity according to intervention, participants, trial setting, and trial quality were explored. We conducted subgroup analyses according to study quality and subgroup analysis according to type of percutaneous procedure where sufficient data were available. We analysed data by both the fixed-effect model analysis and random-effects model analysis, but we only reported the former in the text if the outcome of both analyses were the same. Outcomes were analysed as reported in the trial, that is, either per protocol or as intention-to-treat analysis.

Results

Description of studies

A total of 124 studies were retrieved from the broad search strategies used. After the elimination of editorials, reviews, and repeated reports, seven trials met the inclusion criteria, and 31 studies were excluded from inclusion in this review. The 31 excluded studies with details on why they failed to meet the inclusion criteria are outlined in the table of 'Characteristics of excluded studies'. Details of the seven included trials are outlined in the table of 'Characteristics of included studies'. All seven trials were published in English. The number of participants per trial ranged from 29 to 52 participants. Unfortunately a detailed description of included participants (eg, anatomical considerations, serological status, and a precise definition of disease status) was not provided and limits the overview of the included population.

Considering the lack of a clear definition of large abscess in the included studies, the magnitude of the abscess was diverse. In the Blessman 2003 et al trial, abscess larger than 10 cm were excluded, but in all other trials no information on the size of the abscess was stated. Additionally, a significant difference on the abscess size among groups was observed in the trial by Sharma 1989 et al, and some information about the size was provided in de la Rey Nel 1989. Most of the trials involved abscess within the range of 6 cm to 8 cm.

Population studied
Six trials were performed in developing countries where amoebic liver abscesses are prevalent and one trial was performed in the United States (Van Allan 1992). All trials involved a total of 310 patients diagnosed with uncomplicated amoebic liver abscess based on clinical, serologic, and radiologic criteria. The mean age ranged from 35 to 46 years, with the majority of trials involving a greater number of males than females.

Description of interventions
Five trials employed ultrasound-guided aspiration of the abscess cavities by needle aspiration (de la Rey Nel 1989; Sharma 1989; Arredondo 1993; Tandon 1997; Blessman 2003) and two trials by insertion of a temporary catheter (Widjaya 1991; Van Allan 1992). In all trials, aspiration or drainage of the abscess cavities were performed until drainage ceased. All trials but two evaluated oral metronidazole in doses ranging from 750 mg to 800 mg three times a day over ten days. de la Rey Nel 1989 et al trial administered the drug for five days and Van Allan 1992 et al trial administered the drug for a period of three weeks. Three trials administered other luminal amoebicidal drugs as co-interventions in addition to metronidazole; that is, dehydroemetine (Arredondo 1993), iodoquinol (Van Allan 1992), and chloroquine (Widjaya 1991).

Outcome assessment
All trials but Widjaya 1991 measured clinical improvement in terms of fever lysis and resolution of abdominal pain as outcomes. Analysis of fever resolution was precluded in two trials due to incomplete reporting (Arredondo 1993; Blessman 2003). Three trials reported clinical improvement as resolution of symptoms on a daily basis (de la Rey Nel 1989) and based on a graded scale measuring severity (Van Allan 1992; Tandon 1997). The latter two trials assessed symptom resolution as a reduction from baseline level. Data from Van Allan 1992; Tandon 1997 were reported as continuous data. One trial reported on fever lysis (Sharma 1989), and one reported resolution of abdominal pain as proportions of patients experiencing symptom resolution (Blessman 2003). Two trials reported the number of days to resolution of abdominal tenderness as an outcome (de la Rey Nel 1989; Tandon 1997), and one trial reported the proportion of patients demonstrating a reduction in liver size (Sharma 1989). One trial evaluated radiologic resolution of the abscess size by serial ultrasonographic monitoring and reported these outcomes as proportions of patients with radiologic resolution of abscess cavities (Sharma 1989). Three trials measured duration of hospitalisation as an outcome (Van Allan 1992; Arredondo 1993; Tandon 1997). Five of the eight trials reported adverse events (de la Rey Nel 1989; Sharma 1989; Widjaya 1991; Van Allan 1992; Arredondo 1993), but the report was incomplete, precluding analysis.

Risk of bias in included studies

The included trials varied in methodological quality, which in general was low (Figure 1; Figure 2). A description of the methodological quality of each of the included trials is given in the table of 'Characteristics of included studies'. All trials failed to report randomisation procedures in sufficient detail (and additional information was not provided). Only one trial was considered to have adequate allocation concealment (Van Allan 1992). Allocation concealment was unclear in five trials (de la Rey Nel 1989; Sharma 1989; Widjaya 1991; Tandon 1997; Blessman 2003). In one trial, the methodological quality was not possible to be clearly determined (Arredondo 1993). Blinding of outcome assessment was unclear in six trials (de la Rey Nel 1989; Sharma 1989; Widjaya 1991; Arredondo 1993; Tandon 1997; Blessman 2003) and not blinded in one trial (Van Allan 1992). All trials reported a per-protocol analysis. Four trials reported number of participants lost to follow-up (de la Rey Nel 1989; Sharma 1989; Widjaya 1991; Blessman 2003), and three trials did not specify whether there was any lost to follow-up (Van Allan 1992; Arredondo 1993; Tandon 1997). It was observed an important heterogeneity in the outcomes reported, which is an important limitation to pool the trials as their result will be highly biased.

Figure 1.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Figure 2.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Effects of interventions

The results of the included trials are described in the table of 'Data and analyses' and are described below.

Mortality
Van Allan 1992 et al reported that there were no deaths. The other six trials did not report any data on deaths.

Proportion of patients remaining febrile
Two trials reported the number of patients remaining febrile as an outcome, with an aggregate sample size of 78 patients (aspiration plus metronidazole = 37, and metronidazole = 41) (Sharma 1989; Van Allan 1992). The study population, methods of intervention, and outcomes measured in these two trials were similar enough in order to combine them in a meta-analysis. No statistical heterogeneity was found with a Chi square = 0.22, df = 1, P = 0.64, I2 = 0%. The relative risk is 0.60 (95% CI 0.22 to 1.61), showing no evidence of a statistical difference between aspiration and no aspiration Figure 3.

Figure 3.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.1 Proportion of patients remaining febrile.

Days to resolution of fever
Two trials with an aggregate sample size of 70 patients (aspiration plus metronidazole = 35, metronidazole = 35) reported this outcome (Van Allan 1992; Tandon 1997). When data from these two trials were pooled, a statistically significant heterogeneity was noted (Chi square = 13.69, df = 1, P = 0.0002, I2 = 92.7%), and no statistical difference was observed Figure 4.

Figure 4.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.2 Days to resolution of fever.

Proportion of patients without resolution of pain
Three trials reported this outcome with an aggregate sample size of 117 patients (metronidazole = 60, aspiration = 57) (Sharma 1989; Van Allan 1992; Blessman 2003). The pooled relative risk showed a tendency towards favouring aspiration 0.66 (95% CI 0.35 to 1.26) in terms of resolution of abdominal pain, although this was not found to be statistically significant. A medium level of heterogeneity was noted with a Chi square = 4.50, df = 2, P = 0.11, I2 = 56% Figure 5.

Figure 5.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.3 Proportion of patients without resolution of pain.

Days to resolution of pain
Two trials (Van Allan 1992; Tandon 1997) with an aggregate sample size of 70 patients (metronidazole = 35, aspiration = 35) reported this outcome. When data from these trials were pooled, a statistically significant heterogeneity was found (Chi square = 10.04, df = 1, P = 0.002 I2 = 90%), and a reduction in the number of days to resolution of pain was observed in the needle aspiration group (MD -1.59, 95% CI -2.73 to -0.42) Figure 6, but with the few trials available, the subgroup analyses was not performed in order to explain the heterogeneity.

Figure 6.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.4 Days to resolution of pain.

Proportion of patients without resolution of abscess size
Two trials monitored resolution of abscess size by serial ultrasonographic monitoring with an aggregate sample size of 70 participants (metronidazole = 37, aspiration = 33) (Sharma 1989; Widjaya 1991). When data for this outcome were pooled, heterogeneity was not noted (Chi square = 0.58, df = 1, P = 0.44, I2 = 0%). The pooled relative risk is of 0.90 (95% CI 0.62 to 1.32), showing no significant difference between needle aspiration and metronidazole alone Figure 7.

Figure 7.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.5 Proportion of patients without resolution of abscess size.

Proportion of patients without resolution of abdominal tenderness
One trial reported this outcome with a relative risk of 0.54 (95% CI 0.19 to 1.56) with a sample size of 39 participants (aspiration plus metronidazole = 20, metronidazole = 19) (Blessman 2003) Figure 8.

Figure 8.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.6 Proportion of patients without resolution of abdominal tenderness.

Days to resolution of abdominal tenderness
Two trials with an aggregate sample size of 81 patients (aspiration plus metronidazole = 39, metronidazole = 42) reported this outcome (de la Rey Nel 1989; Tandon 1997). When data for these two trials were pooled, statistical heterogeneity was found (Chi square = 2.69, df = 1, P = 0.10, I2 = 62.8), and a reduction in the number of days to resolution of abdominal tenderness was observed in the needle aspiration group (MD -1.70, 95% CI -2.86 to -0.54) Figure 9, but with the few trials available, the subgroup analyses was not performed in order to explain the heterogeneity.

Figure 9.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.7 Days to resolution of abdominal tenderness.

Duration of hospitalisation
Three trials reported this outcome with an aggregate sample size of 92 patients (Van Allan 1992; Arredondo 1993; Tandon 1997). The results of Arredondo 1993 and Tandon 1997 were not consistent with the Van Allan 1992 trial, favouring metronidazole treatment alone. When data for these three trials were pooled, a medium level of heterogeneity (Chi square = 11.32, df = 2, P = 0.003, I2 = 82%) was detected, and a reduction in the duration of hospitalisation was observed in the needle aspiration group (MD -1.31, 95% CI -2.05 to -0.57) Figure 10, but with the few trials available, the subgroup analyses was not performed in order to explain the heterogeneity.

Figure 10.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.8 Duration of hospitalisation.

Adverse events
Number of patients requiring surgical intervention and rupture of abscess cavity
Two trials reported adverse events as proportion of non-responders to initial intervention (de la Rey Nel 1989; Arredondo 1993). When data from these two trials were meta-analysed, a statistically significant heterogeneity was noted (Chi square = 7.84, df = 1, P = 0.02, I2 = 82%) and no difference was observed between the groups Figure 11. Only in one trial, five patients underwent surgical intervention (there were no data to which group the patients belonged) (Widjaya 1991). Only one trial reported a single case of abscess rupture in the non-aspirated group (de la Rey Nel 1989). However, reporting in the other trials was incomplete, precluding an analysis for this outcome.

Figure 11.

Forest plot of comparison: 1 Needle aspiration and metronidazole versus metronidazole alone, outcome: 1.9 Proportion of non-responders.

Discussion

The decision to therapeutically decrease abscess size in uncomplicated amoebic liver abscess is an area of controversy and we address this issue in our review. We found no evidence that image-guided needle aspiration provides added benefits in the management of uncomplicated amoebic liver abscess. However, small study populations, inadequate methods to minimize bias, and significant heterogeneity made interpretation of pooled estimates problematic. Most of the trials included in this review were performed in the late 1980s and early 1990s in low-income countries where amoebic liver abscesses are endemic. Evidence shows that the quality of randomised clinical trials affects estimates of intervention efficacy, which is significantly exaggerated in low-quality trials. Kjaergard et al reported the association between trial quality, trial setting, and year of publication (Kjaergard 1999). Most of the trials included in the present review failed to incorporate methodological procedures, which restrict bias. This lack of rigorousness may bias estimates of treatment effect. Inadequate sample size, unclear methods of generation of allocation sequence to ensure adequacy of randomisation, inability to conceal treatment allocation, and lack of blinding allow exaggeration of treatment efficacy when results of these high-risk bias trials are meta-analysed. To minimise bias, adequate methodological approaches in trial design, conduct, and reporting of results when assessing therapy of amoebic liver abscesses are needed to obtain robust conclusions. However, the clinical expertise and knowledge about the intrinsic limitations of statistic inferences must be another important tool to interpret the available information (Guller 2008).

In addition, significant heterogeneity has cast doubt on the robustness of conclusion drawn from these trials. Possible sources for heterogeneity in this review are variability in timing of outcome assessment, variability in definition of outcomes to be assessed, presence of co-interventions, and differences in the general quality of care received as a consequence of trial setting. Trials varied in defining the most relevant clinical outcome, ie, is it symptomatic improvement or is it radiologic resolution. Improvement in symptoms is no doubt important; however, these symptoms have to be clearly defined and timing of assessment must be uniformly evaluated.

Furthermore, it is equally important to study hard clinical outcomes, such as mortality and adverse events related to the treatment intervention, which can greatly influence treatment success. However, other outcomes, albeit more subjective, are more likely to be impacted upon by the experimental therapy, as observed in the analyses on resolution of pain and tenderness. Drug-related adverse events, as well as treatment-related complications as a result of invasive procedures, such as needle aspiration, were not explored in greater detail in the trials included in this review.

This lack of uniformity and inadequate methodological approach in clinical evaluation reflect the lack of standardisation in the therapeutic approach to amoebic liver abscesses. The creation of a diagnostic and therapeutic algorithm for amoebic liver abscesses may contribute to create this much-needed uniformity in therapy and the potential to give rise to well-designed clinical trials in the future.

Authors' conclusions

Implications for practice

This review found no evidence to support or refute aspiration of the abscess cavity plus metronidazole versus metronidazole alone in uncomplicated amoebic liver abscess. Trials were, however, small and lacked methodological rigour for us to be able to conclude that aspiration does or does not benefit patients. Accordingly, our findings are inconclusive to make a definite recommendation on the benefit of adjunctive therapeutic needle aspiration.

Implications for research

Randomised clinical trials with larger sample sizes and adequate randomisation (generation of the allocation sequence as well as allocation concealment) and blinded outcome assessment of outcomes important to patients are urgently needed. Such trials should use uniform measures to assess outcomes.

Strict evaluation of adverse events resulting from different interventions employed in the management of amoebic liver abscesses should be included in future trials. Furthermore, trials ought to be reported according to the recommendations of the CONSORT statement.

Acknowledgements

We recognise the valuable efforts of E Labio, R Destura, MM Alejandria, and MLO Daez who started on the preparation of the review after publishing its protocol (Labio 2004), but due to other obligations could not finalise it and had abandoned it before the external peer reviewing process began. Parts of the text from the abandoned version of the review were kept by the new team of authors, though they too had to undergo modifications and updates during the process of developing the present review.

We thank Kate Whitfield for her assistance in the search strategy and retrieval of full-text journal articles, and Dimitrinka Nikolova and Christian Gluud of The Cochrane Hepato-Biliary Group for ongoing support for this review.

We thank Sandra Garcia-Osogobio (Department of Surgery, Medica Sur Clinic & Foundation) for her criticism and corrections.

We thank the CHBG Editors RL Koretz, USA; U Güller, Canada; BR Davidson, UK for the helpful comments.

Peer Reviewers: A Merens, France; NA Deepak, India.
Contact Editor: C Gluud, Denmark.

Data and analyses

Download statistical data

Comparison 1. Needle aspiration and metronidazole versus metronidazole alone
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Proportion of patients remaining febrile278Risk Ratio (M-H, Fixed, 95% CI)0.60 [0.22, 1.61]
2 Days to resolution of fever270Mean Difference (IV, Random, 95% CI)-0.31 [-3.05, 2.43]
3 Proportion of patients without resolution of pain3117Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.35, 1.26]
4 Days to resolution of pain270Mean Difference (IV, Random, 95% CI)-1.59 [-2.77, -0.42]
5 Proportion of patients without resolution of abscess size270Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.62, 1.32]
6 Proportion of patients without resolution of abdominal tenderness1 Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
7 Days to resolution of abdominal tenderness281Mean Difference (IV, Random, 95% CI)-1.70 [-2.86, -0.54]
8 Duration of hospitalisation392Mean Difference (IV, Fixed, 95% CI)-1.31 [-2.05, -0.57]
9 Proportion of non-responders2110Odds Ratio (M-H, Fixed, 95% CI)0.54 [0.25, 1.19]
Analysis 1.1.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 1 Proportion of patients remaining febrile.

Analysis 1.2.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 2 Days to resolution of fever.

Analysis 1.3.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 3 Proportion of patients without resolution of pain.

Analysis 1.4.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 4 Days to resolution of pain.

Analysis 1.5.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 5 Proportion of patients without resolution of abscess size.

Analysis 1.6.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 6 Proportion of patients without resolution of abdominal tenderness.

Analysis 1.7.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 7 Days to resolution of abdominal tenderness.

Analysis 1.8.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 8 Duration of hospitalisation.

Analysis 1.9.

Comparison 1 Needle aspiration and metronidazole versus metronidazole alone, Outcome 9 Proportion of non-responders.

Appendices

Appendix 1. Search strategies

DatabaseTime of searchSearched Items
The Cochrane Hepato-Biliary Group Controlled Trials RegisterSeptember 2007.(metronidazole OR 'image-guided percutaneous' OR (needle AND (aspiration OR biops*)) OR 'catheter-drain*') and (amoeb* OR ameb*AND (liver OR hepatic) AND abscess*)
Cochrane Central Register of Controlled Trials (CENTRAL) in The
Cochrane Library
Issue 2, 2007.#1 MeSH descriptor Metronidazole explode all trees in MeSH products
#2 MeSH descriptor Biopsy, Needle explode all trees in MeSH products
#3 MeSH descriptor Drainage explode all trees in MeSH products
#4 metronidazole OR image-guided percutaneous OR needle aspiration OR catheter drain* in All Fields in all products
#5 (#1 OR #2 OR #3 OR #4)
#6 MeSH descriptor Liver Abscess, Amebic explode all trees in MeSH products
#7 am*eb* AND (liver OR hepatic) AND abscess* in All Fields in all products
#8 (#6 OR #7)
#9 (#5 AND #8)
MEDLINE1950 to October 2007.#1 explode "Metronidazole"/ all subheadings
#2 explode "Biopsy-Needle"/ all subheadings
#3 explode "Drainage"/ all subheadings
#4 metronidazole or image-guided percutaneous or needle aspiration or catheter drain*
#5 #1 or #2 or #3 or #4
#6 explode "Liver-Abscess-Amebic"/ all subheadings
#7 am*eb* and (liver or hepatic) and abscess*
#8 #6 or #7
#9 #5 and #8
#10 am*eb* AND (liver OR hepatic) AND abscess*
#11 #9 and #10
EMBASE1980 to October 2007.#1 explode "metronidazole"/ all subheadings
#2 explode "needle-biopsy"/ all subheadings
#3 explode "percutaneous-drainage"/ all subheadings
#4 metronidazole or image-guided percutaneous or needle aspiration or catheter drain*
#5 #1 or #2 or #3 or #4
#6 explode "liver-amebiasis"/ all subheadings
#7 am*eb* and (liver or hepatic) and abscess*
#8 #6 or #7
#9 #5 and #8
#10 random* or blind* or placebo* or meta-analysis
#11 #9 and #10
Science Citation Index Expanded (http://portal.isiknowledge.com/portal.cgi?DestApp=WOS&Func=Frame)1945 to October 2007.#1 TS=(metronidazole OR image-guided percutaneous OR needle aspiration OR catheter drain*)
#2 TS=(am*eb* AND (liver OR hepatic) AND abscess*)
#3 #2 AND #1
#4 TS=(random* or blind* or placebo* or meta-analysis)
#5 5 #4 AND #3

What's new

Last assessed as up-to-date: 4 April 2008.

DateEventDescription
10 April 2008AmendedConverted to new review format.

Contributions of authors

Norberto C Chavez-Tapia. Co-ordinating, data collection, designing search strategies, undertaking searches, screening search results, screening retrieved papers against eligibility criteria, extracting data from papers, writing to authors of papers for additional information, data management for the review, entering data into RevMan, analysis of data, writing the review.

Jorge Hernandez-Calleros. Data collection, undertaking searches, screening search results, screening retrieved papers against eligibility criteria, extracting data from papers.

Felix I Tellez-Avila. Data collection, designing search strategies, undertaking searches, screening search results, screening retrieved papers against eligibility criteria, extracting data from papers, analysis of data, writing the review.

Aldo Torre-Delgadillo. Interpretation of data, providing a clinical perspective, and providing general advice on the review.

Misael Uribe. Performing previous work that was the foundation of the current review, providing general advice, and securing funding for the review.

Declarations of interest

None known.

Sources of support

Internal sources

  • None, Not specified.

External sources

  • None, Not specified.

Differences between protocol and review

The protocol of this review was published with a title 'Metronidazole with or without image-guided percutaneous procedure for uncomplicated amoebic liver abscess'. We have modified it into 'Image-guided percutaneous procedure plus metronidazole versus metronidazole alone for uncomplicated amoebic liver abscess' for clearer wording.

In the excluded studies, left lobe abscesses was also considered as an exclusion criteria.

The Science Citation Index Expanded was included in the searching for identification methods.

Data analysis was performed with Review Manager Version 5.0 instead of Review Manager Version 4.2.

Notes

Additional information was requested to all authors by e-mail or conventional mail.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Arredondo 1993

Methods

Randomised trial.

Generation of the allocation sequence: Unclear. No information provided.

Allocation concealment: Unclear. No information provided.

Blinding: Unclear. No information provided.

ITT analysis: No.

Follow-up: No information provided.

Sample size calculation: No information provided.

Participants

Country: Mexico.

Number of participants randomised: 22.

Inclusion criteria: Right upper quadrant abdominal pain, fever, increased white blood counts, and suggesting image by ultrasound.

Exclusion criteria: Pleuropulmonary and pericardial complications, sever liver failure, abdominal guarding, shock or previous medical therapy.

Interventions

Experimental: US guided aspiration plus metronidazole 750 mg TID, and dehydroemetine 1-1.5 mg/kg/day.

Control: Metronidazole 750 mg TID, and dehydroemetine 1 to 1.5 mg/kg/day.

OutcomesFever, white blood count, pain, hospitalisation time.
NotesData obtained from abstract.
The authors were not able to send the complete manuscript, to include all data.
Risk of bias
BiasAuthors' judgementSupport for judgement
Adequate sequence generation?Unclear riskNo information provided.
Allocation concealment?Unclear riskNo information provided.
Blinding?
All outcomes
Unclear riskNo information provided.
Follow-up?Unclear riskNo information provided.

Blessman 2003

Methods

Randomised trial.

Generation of the allocation sequence: Unclear. No information provided.

Allocation concealment: Unclear. No information provided.

Blinding: Unclear. No information provided.

ITT analysis: No information provided.

Follow-up: 28 days after discharge, all patients were re-examined at the end of the follow-up period.

Sample size calculation: No information provided.

Participants

Country: Vietnam

Number of participants randomised: 39.

Inclusion criteria: Abscess with a diameter of 6 cm to 10 cm; abscess localisation in the right liver lobe, except the caudate lobe; age >18 years.

Exclusion criteria: Treatment with amoebicidal drugs before hospital admission, pregnancy, or presence of aerobic or anaerobic bacteria in the abscess fluid.

Interventions

Experimental: Fine needle US guided aspiration plus metronidazole 30 mg/kg TID for 10 days.

Control: Metronidazole 30 mg/kg TID for 10 days.

OutcomesBody temperature, pain and tenderness in right upper abdomen, leucocyte count, erythrocyte sedimentation rate, haemoglobin, and C-reactive protein and abscess volume.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Adequate sequence generation?Unclear riskNo information provided.
Allocation concealment?Unclear riskNo information provided.
Blinding?
All outcomes
Unclear riskNo information provided.
Follow-up?Low risk28 days after discharge, all patients were re-examined at the end of the follow-up period.

de la Rey Nel 1989

Methods

Randomised trial.

Generation of the allocation sequence: Unclear.

Allocation concealment: Unclear. No information provided.

Blinding: No information provided.

ITT analysis: No information provided.

Follow-up: Monthly until complete resolution of the cavity, all patients were re-examined at the end of the follow-up period.

Sample size calculation: No information provided.

Participants

Country: South Africa.

Number of participants randomised: 80.

Inclusion criteria: Liver abscess by ultrasound and positive amoebiasis gel diffusion test.

Exclusion criteria: Refuse to be hospitalised, liver abscess located in the superior half of the left lobule.

Interventions

Experimental: US guided aspiration plus metronidazole 800 mg TID for 5 days.

Control: Metronidazole 800 mg TID for 5 days.

OutcomesBody temperature, tenderness, liver size, and size of abscess cavity.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Adequate sequence generation?Unclear riskNo information provided.
Allocation concealment?Unclear riskNo information provided.
Blinding?
All outcomes
Unclear riskNo information provided.
Follow-up?Low riskMonthly until complete resolution of the cavity, all patients were re-examined at the end of the follow-up period.

Sharma 1989

Methods

Randomised case-control trial.

Generation of the allocation sequence: No information provided.

Allocation concealment: No information provided.

Blinding: Unclear.

ITT analysis: No.

Follow-up: 12 months, all patients were re-examined at the end of the follow-up period.

Sample size calculation: No information provided.

Participants

Country: India.

Number of participants randomised: 39.

Inclusion criteria: Positive serological results for E histolytica (ELISA and indirect hemagglutination), one or more lesions occupying space in the right lobe of the liver with characteristic features of amoebic liver abscess on ultrasound examination.

Exclusion criteria: Abscess in the left lobe, multiple liver abscesses, and impending rupture.

Interventions

Experimental: Needle aspiration plus metronidazole 2.4 g at day for 10 days.

Control: Metronidazole 2.4 g at day for 10 days.

OutcomesAbdominal pain, fever, anorexia, and hepatomegaly.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Adequate sequence generation?Unclear riskNo information provided.
Allocation concealment?Unclear riskNo information provided.
Blinding?
All outcomes
Unclear riskNo information provided.
Follow-up?Low risk12 months, all patients were re-examined at the end of the follow-up period.

Tandon 1997

Methods

Randomised trial.

Generation of the allocation sequence: Unclear. No information provided.

Allocation concealment: Unclear. No information provided.

Blinding: Patient and provider not blinded.

ITT analysis: No information provided.

Follow-up: No information provided.

Sample size calculation: No information provided.

Participants

Country: India.

Number of participants randomised: 29.

Inclusion criteria: uncomplicated, amoebic liver abscess larger than 5 cm.

Exclusion criteria: No information provided.

Interventions

Experimental: Needle aspiration plus metronidazole 800 mg TID for 10 days.

Control: metronidazole alone.

OutcomesResolution of fever, pain, duration of hospital stay.
NotesData obtained from abstract.
The authors were not able to send the complete manuscript, to include all data. Not information about dose in control group was provided.
Risk of bias
BiasAuthors' judgementSupport for judgement
Adequate sequence generation?Unclear riskNo information provided.
Allocation concealment?Unclear riskNo information provided.
Blinding?
All outcomes
High riskPatient and provider not blinded.
Follow-up?Unclear riskNo information provided.

Van Allan 1992

Methods

Randomised trial.

Generation of the allocation sequence: Unclear.

Allocation concealment: Adequate. Using sealed envelopes.

Blinding: No.

ITT analysis: No.

Follow-up: No information provided.

Sample size calculation: No information provided.

Participants

Country: United States.

Number of participants randomised: 41.

Inclusion criteria: Abscess at least 5 cm in diameter (US or CT), and/or abscess less than 5 cm in diameter accompanied by moderate or severe pain, and/or abscess less than 5 cm in diameter accompanied by fever (>102°F).

Exclusion criteria: Inability to obtain informed consent, rupture at the time of diagnosis, contraindication to one or both of the therapeutic regimens, or identification of patients more than 24 hours after initiation of therapy.

Interventions

Experimental: US or CT guided needle aspiration plus metronidazole 750 mg TID +/- iodoquinol for 10 to 14 days.

Control: Metronidazole 750 mg TID +/- iodoquinol for 10 to 14 days.

OutcomesTemperature, pain, tenderness, and length of hospitalisation.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Adequate sequence generation?Unclear riskNo information provided.
Allocation concealment?Low riskUsing a sealed-envelope procedure.
Blinding?
All outcomes
High riskFrom randomisation status could not be obscured from the medical staff.
Follow-up?Unclear riskNo information provided.

Widjaya 1991

  1. a

    ITT = intention to treat
    US = ultrasound
    BID = twice-daily dosage
    TID = thrice-daily dosage
    CT = computed tomography

Methods

Randomised trial.

Generation of the allocation sequence: Unclear.

Allocation concealment: Unclear.

Blinding: Unclear.

ITT analysis: No.

Follow-up: Until resolution of abscesses, all patients were re-examined at the end of the follow-up period.

Sample size calculation: No information provided.

Participants

Country: Indonesia.

Number of participants randomised: 60.

Inclusion criteria: Symptoms and signs, positive indirect hemagglutination test and suggestive ultrasound findings.

Exclusion criteria: No information provided.

Interventions

Experimental: Metronidazole 750 mg TID, and chloroquine (500 mg BID the first day, after 500 mg) for 10 days plus US guided aspiration.

Control: Metronidazole 750 mg TID, and chloroquine (500 mg BID the first day, after 500 mg at day) for 10 days.

OutcomesResolution of abscess.
NotesA clear definition of "resolution of abscess" was not provided.
Risk of bias
BiasAuthors' judgementSupport for judgement
Adequate sequence generation?Unclear riskNo information provided.
Allocation concealment?Unclear riskNo information provided.
Blinding?
All outcomes
Unclear riskNo information provided.
Follow-up?Low risk56 days, until resolution of abscesses, all patients were re-examined at the end of the follow-up period.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Bhatia 1998A randomised trial comparing metronidazole versus secnidazole in 32 patients with amoebic liver abscess. There was no comparison made with percutaneous needle aspiration.
Cervantes 1974A clinical trial evaluating the use of estrogens in the treatment of amoebic liver abscess.
Cohen 1975A randomised trial including 36 patients with amoebic liver abscess comparing metronidazole and chloroquine for the treatment of amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Datta 1974A controlled clinical trial comparing emetine hydrochloride, niridazole, and metronidazole in the treatment of amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Esquivel Lopez 1979This study is non-randomised. Sixty patients with complicated amoebic liver abscesses failing medical therapy received different pharmacologic interventions. No comparison made with percutaneous procedures.
Filice 1992This study is a retrospective observational study of 51 patients with amoebic liver abscess comparing medical therapy with nitroimidazole, open surgical drainage, and percutaneous drainage followed by intralesional nitroimidazole administration.
Freeman 1990This study is quasi randomised, without information about adverse events.
Genadieva 1997A clinical study examining fine needle aspiration biopsy of diffuse liver lesions including non-amoebic hepatic lesions. No comparison was made with medical therapy.
Hatchuel 1975A randomised, double blind trial comparing tinidazole with metronidazole in 14 patients with amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Irusen 1992A prospective cohort study investigating the prevalence and natural history of asymptomatic intestinal colonisation in 50 patients with amoebic liver abscess.
Islam 1978A randomised trial comparing two medical treatment, tinidazole and metronidazole, in 31 patients with hepatic amoebiasis. No comparison was made with percutaneous needle aspiration.
Jain 1990A study of 33 patients with hepatopulmonary amoebiasis which compared the efficacy of dehydroemetine and metronidazole. No comparison was made with percutaneous needle aspiration.
Jayawickrema 1975A randomised trial comparing metronidazole with emetine and chloroquine in the treatment of hepatic amoebiasis. No comparison was made with percutaneous needle aspiration.
Khokhani 1977A randomised trial comparing the efficacy of tinidazole and metronidazole in 20 patients with amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Khokhani 1978A randomised trial of 20 patients with amoebic liver abscess comparing tinidazole and metronidazole. No comparison was made with percutaneous needle aspiration.
Lasserre 1983A randomised double blind trial evaluating the efficacy of single-day treatment with either ornidazole or tinidazole in 72 patients with amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Mogollon 1999Prospective, non-randomised study, in 170 patients, with a high proportion of puncture procedure (n=131). No outcomes were compared.
Morales 1975A randomised, double blind comparison of intravenous metronidazole and intramuscular emetine in acute amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
N'Gbesso 1993Non-randomised study, assessing medical treatment, ultrasound-guided puncture and surgical puncture.
Powell 1965A clinical trial evaluating dehydroemetine in the treatment of amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Powell 1967A randomised trial comparing dehydroemetine and emetine hydrochloride in identical dosage in amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Powell 1974A clinical trial of benzoyl metronidazole suspension in the treatment of amoebic dysentery and amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Rajak 1998A randomised trial including 50 patients with mixed amoebic and pyogenic liver abscesses who received either percutaneous needle aspiration or catheter drainage. No comparison was made to medical treatment alone.
Ramani 1993Prospective non-randomised study, in 200 patients with ultrasound and serologic diagnosis of liver abscess. The 6-months response was not different among groups.
Ruas 1973A comparative study of the effects of a novel anti-amoebic drug (RO 7-020) versus metronidazole in amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Satpathy 1988A randomised trial comparing intravenous metronidazole and intramuscular dehydroemetine in amoebic liver abscess.
Simjee 1985A randomised trial of metronidazole versus tinidazole in 48 patients with amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Singh 1989A randomised trial including 50 patients with drug resistant amoebic liver abscess who received a repeat trial of conservative therapy, needle aspirations, percutaneous catheter drainage, and open surgical drainage.
Soh 1980A randomised trial comparing ornidazole verus tinidazole in patients with amoebic liver abscess. No comparison was made with percutaneous needle aspiration.
Yu 2004A randomised trial comparing continuous catheter drainage and intermittent needle aspiration in 64 patients with pyogenic liver abscesses.
Zafar 2002This study is non-randomised. Forty-six patients with amoebic liver abscess received needle aspiration with antiamebic drug treatment versus drug treatment alone, based on size of the abscess.

Ancillary