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AIDS Research and Treatment 2022Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the... (Review)
Review
BACKGROUND
Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the mortality of HIV but increased coagulopathies. HIV-related thrombocytopenia, prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), and high D-dimer level commonly manifested in patients with HIV. Thus, this study is aimed to compare coagulation parameters of HAART-treated and HAART-naïve HIV-infected patients with HIV-seronegative controls.
METHODS
A systematic literature search was conducted using the databases PubMed/MEDLINE, Embase, Web of Science, and Google Scholar of studies published until July 2021. The primary outcome of interest was determining the pooled mean difference of coagulation parameters between HIV-infected patients and seronegative controls. The Joana Briggs Institute (JBI) critical appraisal tool was used for quality appraisal. Statistical analyses were performed using Stata11.0 software. The statistical results were expressed as the effect measured by standardized mean difference (SMD) with their related 95% confidence interval (CI).
RESULTS
A total of 7,498 participants (1,144 HAART-naïve patients and 2,270 HAART-treated HIV-infected patients and 3,584 HIV-seronegative controls) from 18 studies were included. HIV-infected patients (both on HAART and HAART-naive) exhibited significantly higher levels of PT than HIV-seronegative controls (SMD = 0.66; 95% CI: 0.53-0.80 and SMD = 1.13; 95% CI: 0.60-2.0, respectively). The value of APTT was significantly higher in patients with HIV on HAART than in seronegative controls. However, the values of PLT count, APTT, and fibrinogen level were significantly higher in seronegative controls. Besides, the level of fibrinogen was significantly higher in HAART-treated than treatment-naïve patients (SMD = 0.32; 95%CI: 0.08, 0.57). Moreover, the level of APTT and PT had no statistical difference between HAART and HAART-naïve HIV-infected patients.
CONCLUSIONS
This study identified that HIV-infected patients are more likely to develop coagulation abnormalities than HIV-seronegative controls. Therefore, coagulation parameters should be assessed regularly to prevent and monitor coagulation disorders in HIV-infected patients.
PubMed: 35492260
DOI: 10.1155/2022/6782595 -
Scars, Burns & Healing 2017Dynamic monitoring of coagulation is important to predict both haemorrhagic and thrombotic complications and to guide blood product administration. Reducing blood loss... (Review)
Review
INTRODUCTION
Dynamic monitoring of coagulation is important to predict both haemorrhagic and thrombotic complications and to guide blood product administration. Reducing blood loss and tailoring blood product administration may improve patient outcome and reduce mortality associated with transfusion. The current literature lacks a systematic, critical appraisal of current best evidence on which clinical decisions may be based.
OBJECTIVES
Establishing the role of different coagulation markers in burn patients, diagnosing coagulopathy, tailoring blood product administration and indicating prognosis.
METHODS
Literature during 2004-2017 from the Cochrane Library, PubMed, Scopus, Medline and Embase was reviewed. Eligibility criteria included randomised controlled trials, systematic reviews, multi-/single-centre study and meta-analyses. Keywords searched were 'burns', 'blood coagulation disorders', 'rotem', 'blood coagulation' and 'thromboelastography'. The PRISMA flow system was used for stratification and the CASP framework for appraisal of the studies retrieved.
RESULTS
In total, 13 articles were included after inclusion/exclusion criteria had been applied to the initial 79 studies retrieved. Hypercoagulation increases in proportion to the severity of thermal injury. Whole blood testing, using thrombelastography (TEG) and rotation thromboelastometry (ROTEM), was superior to standard plasma based tests, including prothrombin time (PT) and activated partial thromboplastin time (APTT) at detecting burn-related coagulopathies.
CONCLUSIONS
Routine laboratory markers such as PT/APTT are poor indicators of coagulation status in burns patients. Viscoelastic tests, such as TEG and ROTEM, are efficient, fast and have a potential use in the management of burn patients; however, strong evidence is lacking. This review highlights the need for more randomised controlled trials, to guide future practice.
PubMed: 29799542
DOI: 10.1177/2059513117728201 -
Phytotherapy Research : PTR Jul 2023Medicinal plants with minimal side effects, low cost, and liver-protective effects can be a suitable treatment option for cirrhosis. Therefore, this systematic review... (Review)
Review
Medicinal plants with minimal side effects, low cost, and liver-protective effects can be a suitable treatment option for cirrhosis. Therefore, this systematic review aimed to determine the effectiveness of herbal medicines on cirrhosis, a life-threatening liver disease. PubMed, Scopus, Web of Science, and Google Scholar were systematically searched for clinical trials that investigated the effect of medicinal plants on cirrhosis. This review includes 11 clinical trials, of which eight studies including 613 patients assessed the effect of silymarin on cirrhosis. Three of six studies showed the beneficial effects of silymarin on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Two studies including 118 patients investigated the effect of curcumin on cirrhosis, one showing improvement in quality of life and the other showing improvements in alkaline phosphatase (ALP), bilirubin, prothrombin time (PT), and the international normalized ratio (INR). An article including four patients investigated the effect of ginseng on cirrhosis; two patients reported improvement in the Child-Pugh score, and ascites decreased in two. All studies included here reported no or negligible side effects. Results showed that medicinal plants including silymarin, curcumin, and ginseng have beneficial effects on cirrhosis. However, due to the limited number of studies, further high-quality studies are warranted.
Topics: Humans; Plants, Medicinal; Curcumin; Quality of Life; Liver Cirrhosis; Silymarin
PubMed: 37218361
DOI: 10.1002/ptr.7816 -
Journal of Clinical Laboratory Analysis Jul 2022Hypercoagulability in lung cancer patients is associated with a high incidence of mortality and morbidity in the world. Therefore, this meta-analysis aimed to explore... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypercoagulability in lung cancer patients is associated with a high incidence of mortality and morbidity in the world. Therefore, this meta-analysis aimed to explore the correlation of the basic coagulation abnormalities in lung cancer patients compared with the control.
METHOD
PubMed, Scopus, and other sources were employed to identify eligible studies. The outcome variable was expressed using mean ± standard deviation (SD). Heterogeneity among studies and publication bias were evaluated. The quality of included studies was also assessed based on Newcastle-Ottawa Scale checklist.
RESULT
Finally, through a total of eight studies, prolonged prothrombin time (PT; standard mean difference [SMD]: 1.29; 95% CI: 0.47-2.11), plasma D-dimer value (SMD 3.10; 95% CI 2.08-4.12), fibrinogen (SMD 2.18; 95% CI:1.30-3.06), and platelet (PLT) count (SMD 1.00; 95% CI 0.84-1.16) were significantly higher in lung cancer patients when compared with the control group. The single-arm meta-analysis also showed that compared with control, lung cancer patients had high pooled PT 13.7 (95% CI:12.2-15.58) versus 11.79 (95% CI = 10.56-13.02), high D-dimer 275.99 (95% CI:172.9-11735.9) versus 0.2 (95% CI:0.20-0.37), high plasma fibrinogen 5.50 (95% CI:4.21-6.79) versus 2.5 (95% CI:2.04-2.91), and high PLT count 342.3 (95% CI:236.1-448.5) versus 206.6 (95% CI:176.4-236.7).
CONCLUSION
In conclusion, almost all the coagulation abnormalities were closely associated with lung cancer, and hence coagulation indexes provide an urgent clue for early diagnosis and timely management.
Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Lung Neoplasms
PubMed: 35719003
DOI: 10.1002/jcla.24550 -
The British Journal of Surgery Dec 2013Vascular clamping reduces blood loss during liver resection but leads to ischaemia-reperfusion injury. Ischaemic preconditioning (IP) may reduce this. This study aimed... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Vascular clamping reduces blood loss during liver resection but leads to ischaemia-reperfusion injury. Ischaemic preconditioning (IP) may reduce this. This study aimed to evaluate IP in liver resection under clamping.
METHODS
This was a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating IP in adults undergoing liver resection under either continuous clamping (CC) or intermittent clamping (IC). Primary outcomes were mortality, liver failure and morbidity. Secondary outcomes included duration of operation, blood loss, length of hospital stay, length of intensive therapy unit stay, transfusion requirements, prothrombin time, and bilirubin and aminotransferase levels. Weighted mean differences were calculated for continuous data, and pooled odds ratios (ORs) for dichotomous data. Results were produced with a random-effects model with 95 per cent confidence intervals (c.i.).
RESULTS
A total of 2960 records were identified and 11 RCTs included 669 patients (IP 331, control 338). No significant difference in mortality (6 RCTs; IP 186, control 190; OR 1·36, 95 per cent c.i. 0·13 to 13·68; P = 0·80) or morbidity (6 RCTs; IP 186, control 190; OR 0·58, 0·31 to 1·07; P = 0·08) was found for IP plus CC versus CC. Nor was there a significant difference in mortality (4 RCTs; IP 122, control 121; OR 1·33, 0·24 to 7·32; P = 0·74) or morbidity (4 RCTs; IP 122, control 121; OR 0·87, 0·52 to 1·47; P = 0·61) for IP plus (CC or IC) versus IC. No significant differences were found for secondary outcome measures.
CONCLUSION
This meta-analysis failed to find a significant benefit of IP in liver resection.
Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Blood Loss, Surgical; Blood Transfusion; Constriction; Hepatectomy; Humans; Ischemic Preconditioning; Length of Stay; Liver Failure; Operative Time; Postoperative Complications; Prothrombin Time; Randomized Controlled Trials as Topic; Reperfusion Injury; Treatment Outcome
PubMed: 24227353
DOI: 10.1002/bjs.9277 -
Journal of Neurotrauma Jul 2016The association between coagulopathy and either isolated traumatic brain injury (TBI) or progressive hemorrhagic injury (PHI) remains controversial. The aims of this... (Meta-Analysis)
Meta-Analysis Review
The association between coagulopathy and either isolated traumatic brain injury (TBI) or progressive hemorrhagic injury (PHI) remains controversial. The aims of this study were to evaluate whether isolated TBI induces pronounced coagulopathy, in comparison with non-TBI or TBI in conjunction with other injuries (TBI + other injuries), and to examine whether there is any evidence of a relationship between coagulopathy and PHI in patients who have experienced TBI. The MEDLINE(®) and Embase databases, and the Cochrane Central Register of Controlled Trials (Central), were trawled for relevant studies. Searches covered the period from the inception of each of the databases to June 2015, and were conducted using appropriate combinations of terms and key words based on medical subject headings (MeSH). Studies were included if they compared isolated TBI with a similar severity of injury to other body regions, or compared PHI with non-PHI, with regard to coagulation tests and the prevalence of coagulopathy. We extracted the means and standard deviations (SD) of coagulation test levels, as well as their ranges or the percentage of abnormal coagulation tests, in both cases and controls. A total of 19 studies were included in our systematic review and meta-analysis. Only the mean fibrinogen (FIB) in isolated TBI was found to be significantly higher than in TBI + other injuries (pooled mean difference [MD] 32.09; 95% confidence interval [CI] 4.92-59.25; p = 0.02); in contrast, it was also significantly higher than in non-TBI (pooled MD 15.44; 95% CI 0.28-30.59; p = 0.05). We identified 15 studies that compared coagulopathy between a PHI group and a non-PHI group. The PHI group had a lower platelet count (PLT) value (pooled MD -19.21; 95% CI: -26.99 to -11.44, p < 0.001) and a higher international normalized ratio (INR) value (pooled MD 0.07; 95% CI: 0.02-0.13, p = 0.006) than the non-PHI group, but no differences were observed in the mean activated partial thromboplastin time (APTT) and prothrombin time (PT) between the PHI and non-PHI patients. In addition, PHI was significantly associated with a higher percentage of INR >1.2 (pooled OR 3.49 [95% CI 1.97-6.20], p < 0.001), PLT <100 × 109/L (pooled OR 4.74 [95% CI 2.44-9.20], p < 0.001), and coagulopathy (pooled OR 2.52; 95% CI 1.88- 3.38; p < 0.001), compared with non-PHI. The current clinical evidence does not indicate that the prevalence of coagulopathy in TBI is significantly higher than in injuries of similar severity to other areas of the body, or in multiple injuries with TBI. With respect to the association between coagulopathy and PHI, the occurrence of coagulopathy, INR, and PLT was significantly associated with PHI, but APTT and PT were not found to be associated with PHI. In the future, high quality research will be required to further characterize the effects of coagulopathy on TBI and subsequent PHI.
Topics: Blood Coagulation Disorders; Brain Injuries, Traumatic; Humans; Intracranial Hemorrhage, Traumatic
PubMed: 26850305
DOI: 10.1089/neu.2015.4205 -
PLoS Neglected Tropical Diseases 2013The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.
METHODS AND FINDINGS
PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies.
CONCLUSIONS
The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.
Topics: Animals; Asia, Southeastern; Dengue Virus; Humans; Incidence; Risk Factors; Serotyping; Severe Dengue
PubMed: 24086778
DOI: 10.1371/journal.pntd.0002412 -
The Cochrane Database of Systematic... Mar 2014Treatment of haemorrhagic shock involves maintaining blood pressure and tissue perfusion until bleeding is controlled. Different resuscitation strategies have been used... (Review)
Review
BACKGROUND
Treatment of haemorrhagic shock involves maintaining blood pressure and tissue perfusion until bleeding is controlled. Different resuscitation strategies have been used to maintain the blood pressure in trauma patients until bleeding is controlled. However, while maintaining blood pressure may prevent shock, it may worsen bleeding.
OBJECTIVES
To examine the effect on mortality and coagulation times of two intravenous fluid administration strategies in the management of haemorrhagic hypovolaemia, early compared to delayed administration and larger compared to smaller volume of fluid administered.
SEARCH METHODS
We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), ISI Web of Science (SCI-Expanded and CPCI-S) and clinical trials registries. We checked reference lists of identified articles and contacted authors and experts in the field. The most recent search was run on 5 February 2014.
SELECTION CRITERIA
Randomised trials of the timing and volume of intravenous fluid administration in trauma patients with bleeding. Trials in which different types of intravenous fluid were compared were excluded.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed trial quality.
MAIN RESULTS
Six trials involving a total of 2128 people were included in this review. We did not combine the results quantitatively because the interventions and patient populations were so diverse. Early versus delayed fluid administration Three trials reported mortality and two reported coagulation data.In the first trial (n = 598) the relative risk (RR) for death with early fluid administration was 1.26 (95% confidence interval (CI) 1.00 to 1.58). The weighted mean differences (WMD) for prothrombin time and partial thromboplastin time were 2.7 (95% CI 0.9 to 4.5) and 4.3 (95% CI 1.74 to 6.9) seconds, respectively.In the second trial (n = 50) the RR for death with early blood transfusion was 5.4 (95% CI 0.3 to 107.1). The WMD for partial thromboplastin time was 7.0 (95% CI 6.0 to 8.0) seconds. In the third trial (n = 1309) the RR for death with early fluid administration was 1.06 (95% CI 0.77 to 1.47). Larger versus smaller volume of fluid administration Three trials reported mortality and one reported coagulation data.In the first trial (n = 36) the RR for death with a larger volume of fluid resuscitation was 0.80 (95% CI 0.28 to 22.29). Prothrombin time and partial thromboplastin time were 14.8 and 47.3 seconds in those who received a larger volume of fluid, as compared to 13.9 and 35.1 seconds in the comparison group.In the second trial (n = 110) the RR for death with a high systolic blood pressure resuscitation target (100 mm Hg) maintained with a larger volume of fluid as compared to a low systolic blood pressure resuscitation target (70 mm Hg) maintained with a smaller volume of fluid was 1.00 (95% CI 0.26 to 3.81). In the third trial (n = 25) there were no deaths.
AUTHORS' CONCLUSIONS
We found no evidence from randomised controlled trials for or against early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy.
Topics: Hemorrhage; Humans; Hypovolemia; Infusions, Intravenous; Plasma Substitutes; Randomized Controlled Trials as Topic; Time Factors; Wounds and Injuries
PubMed: 24599652
DOI: 10.1002/14651858.CD002245.pub2 -
The Cochrane Database of Systematic... Jul 2015Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of bleeding. The purpose of this review is to assess the risk of mortality for patients undergoing cardiovascular surgery who receive FFP.
OBJECTIVES
To evaluate the risk to benefit ratio of FFP transfusion in cardiovascular surgery for the treatment of bleeding patients or for prophylaxis against bleeding.
SEARCH METHODS
We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE (OvidSP, 1946 to 21 April 2015), EMBASE (OvidSP, 1974 to 21 April 2015), PubMed (e-publications only: searched 21 April 2015), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 21 April 2015). We also searched the references of all identified trials and relevant review articles. We did not limit the searches by language or publication status.
SELECTION CRITERIA
We included randomised controlled trials in patients undergoing major cardiac or vascular surgery who were allocated to a FFP group or a comparator (no plasma or an active comparator, either clinical plasma (any type) or a plasma-derived blood product). We included participants of any age (neonates, children and adults). We excluded studies of plasmapheresis and plasma exchange.
DATA COLLECTION AND ANALYSIS
Two authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two authors assessed risk of bias in the included studies and extracted data independently. We took care to note whether FFP was used therapeutically or prophylactically within each trial.
MAIN RESULTS
We included 15 trials, with a total of 755 participants for analysis in the review. Fourteen trials compared prophylactic use of FFP against no FFP. One study compared therapeutic use of two types of plasma. The timing of intervention varied, including FFP transfusion at the time of heparin neutralisation and stopping cardiopulmonary bypass (CPB) (seven trials), with CPB priming (four trials), after anaesthesia induction (one trial) and postoperatively (two trials). Twelve trials excluded patients having emergency surgery and nine excluded patients with coagulopathies.Overall the trials were small, with only four reporting an a priori sample size calculation. No trial was powered to determine changes in mortality as a primary outcome. There was either high risk of bias, or unclear risk, in the majority of trials included in this review.There was no difference in the number of deaths between the intervention arms in the six trials (with 287 patients) reporting mortality (very low quality evidence). There was also no difference in blood loss in the first 24 hours for neonatal/paediatric patients (four trials with 138 patients; low quality evidence): mean difference (MD) -1.46 ml/kg (95% confidence interval (CI) -4.7 to 1.78 ml/kg); or adult patients (one trial with 120 patients): MD -12.00 ml (95% CI -101.16 to 77.16 ml).Transfusion with FFP was inferior to control for preventing patients receiving any red cell transfusion: Peto odds ratio (OR) 2.57 (95% CI 1.30 to 5.08; moderate quality evidence). There was a difference in prothrombin time within two hours of FFP transfusion in eight trials (with 210 patients; moderate quality evidence) favouring the FFP arm: MD -0.71 seconds (95% CI -1.28 to -0.13 seconds). There was no difference in the risk of returning to theatre for reoperation (eight trials with 398 patients; moderate quality evidence): Peto OR 0.81 (95% CI 0.26 to 2.57). Only one included study reported adverse events as an outcome and reported no significant adverse events following FFP transfusion.
AUTHORS' CONCLUSIONS
This review has found no evidence to support the prophylactic administration of FFP to patients without coagulopathy undergoing elective cardiac surgery. There was insufficient evidence about treatment of patients with coagulopathies or those who are undergoing emergency surgery. There were no reported adverse events attributable to FFP transfusion, although there was a significant increase in the number of patients requiring red cell transfusion who were randomised to FFP. Variability in outcome reporting between trials precluded meta-analysis for many outcomes across all trials, and there was evidence of a high risk of bias in most of the studies. Further adequately powered studies of FFP, or comparable pro-haemostatic agents, are required to assess whether larger reductions in prothrombin time translate into clinical benefits. Overall the evidence from randomised controlled trials for the safety and efficacy of prophylactic transfusion of FFP for cardiac surgery is insufficient.
Topics: Adult; Blood Loss, Surgical; Cardiovascular Surgical Procedures; Child; Elective Surgical Procedures; Erythrocyte Transfusion; Hemostasis, Surgical; Humans; Infant, Newborn; Plasma; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 26171897
DOI: 10.1002/14651858.CD007614.pub2 -
The Cochrane Database of Systematic... May 2010Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review from 2005 showed that methotrexate seemed to significantly increase mortality in patients with primary biliary cirrhosis. Since that last review version, follow-up data of the included trials have been published.
OBJECTIVES
To assess the beneficial and harmful effects of methotrexate for patients with primary biliary cirrhosis.
SEARCH STRATEGY
Randomised clinical trials were identified by searching The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, and EMBASE (from their inception until September 2009). Reference lists were also read through. Authors of trials were contacted.
SELECTION CRITERIA
We searched to include randomised clinical trials comparing methotrexate with placebo, no intervention, or another drug irrespective of blinding, language, year of publication, or publication status.
DATA COLLECTION AND ANALYSIS
Our primary outcomes were mortality, and mortality or liver transplantation combined. Dichotomous outcomes were reported as relative risks (RR) and hazard ratios (HR) if applicable. Continuous outcomes were reported as mean differences (MD).
MAIN RESULTS
Five trials were included. Four trials with 370 patients compared methotrexate with placebo or no intervention (three trials added an equal dose of ursodeoxycholic acid to the intervention groups). The bias risk of these trials was high. We did not find statistically significant effects of methotrexate on mortality (RR 1.32, 95% CI 0.66 to 2.64), mortality or liver transplantation combined, pruritus, fatigue, liver complications, liver biochemistry, liver histology, or adverse events. The pruritus score (MD - 0.17, 95% CI - 0.25 to - 0.09) was significantly lower in patients receiving methotrexate. The prothrombin time was significantly worsened in patients receiving methotrexate (MD 1.60 s, 95% CI 1.18 to 2.02). One trial with 85 patients compared methotrexate with colchicine. The trial had low risk of bias. Methotrexate, when compared to colchicine, did not significantly effect mortality, fatigue, liver biopsy, or adverse events. Methotrexate significantly benefited pruritus score (MD - 0.68, 95% CI - 1.11 to - 0.25), serum alkaline phosphatases (MD - 0.41 U/l, 95% CI - 0.70 to - 0.12), and plasma immunoglobulin M (MD - 0.47 mg/dl, 95% CI - 0.74 to - 0.20) compared with colchicine. Other outcomes showed no statistical difference.
AUTHORS' CONCLUSIONS
Methotrexate had no statistically significant effect on mortality in patients with primary biliary cirrhosis nor the need for liver transplantation. Although methotrexate may benefit other outcomes (pruritus score, serum alkaline phosphatase, immunoglobulin M levels), there is no sufficient evidence to support methotrexate for patients with primary biliary cirrhosis.
Topics: Colchicine; Folic Acid Antagonists; Humans; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Liver Transplantation; Methotrexate; Pruritus; Randomized Controlled Trials as Topic
PubMed: 20464729
DOI: 10.1002/14651858.CD004385.pub3