Performance of Transient Elastography for the Staging of Liver Fibrosis in Patients with Chronic Hepatitis B: A Meta-Analysis

Background

Transient elastography (TE), a non-invasive tool that measures liver stiffness, has been evaluated in meta-analyses for effectiveness in assessing liver fibrosis in European populations with chronic hepatitis C (CHC). However, these data cannot be extrapolated to populations in Asian countries, where chronic hepatitis B (CHB) is more prevalent. In this study, we performed a meta-analysis to assess the overall performance of TE for assessing liver fibrosis in patients with CHB.

Methods

Studies from the literature and international conference abstracts which enrolled only patients with CHB or performed a subgroup analysis of such patients were enrolled. Combined effects were calculated using area under the receiver operating characteristic curves (AUROC) and diagnostic accuracy values of each study.

Result

A total of 18 studies comprising 2,772 patients were analyzed. The mean AUROCs for the diagnosis of significant fibrosis (F2), severe fibrosis (F3), and cirrhosis (F4) were 0.859 (95% confidence interval [CI], 0.857–0.860), 0.887 (95% CI, 0.886–0.887), and 0.929 (95% CI, 0.928–0.929), respectively. The estimated cutoff for F2 was 7.9 (range, 6.1–11.8) kPa, with a sensitivity of 74.3% and specificity of 78.3%. For F3, the cutoff value was determined to be 8.8 (range, 8.1–9.7) kPa, with a sensitivity of 74.0% and specificity of 63.8%. The cutoff value for F4 was 11.7 (range, 7.3–17.5) kPa, with a sensitivity of 84.6% and specificity of 81.5%.

Conclusion

TE can be performed with good diagnostic accuracy for quantifying liver fibrosis in patients with CHB.     

The Performance of Enhanced Liver Fibrosis (ELF) Test for the Staging of Liver Fibrosis: A Meta-Analysis

Background

The enhanced liver fibrosis test (ELF) has been shown to accurately predict significant liver fibrosis in several liver diseases.

Aims

To perform a meta-analysis to assess the performance of the ELF test for the assessment of liver fibrosis.

Study

Electronic and manual searches were performed to identify studies of the ELF test. After methodological quality assessment and data extraction, pooled estimates of the sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and summary receiver operating characteristics (sROC) were assessed systematically. The extent of heterogeneity and reasons for it were assessed.

Results

Nine studies were identified for analysis. The pooled sensitivity, specificity, positive LR, negative LR, and DOR values of ELF test, for assessment of significant liver fibrosis, were 83% (95% CI = 0.80–0.86), 73% (95% CI = 0.69–0.77), 4.00 (95% CI = 2.50–6.39), 0.24 (95% CI = 0.17–0.34), and 16.10 (95% CI = 8.27–31.34), respectively; and, for evaluation of severe liver fibrosis, were 78% (95% CI = 0.74–0.81), 76% (95% CI = 0.73–0.78), 4.39 (95% CI = 2.76–6.97), 0.27 (95% CI = 0.16–0.46), and 16.01 (95% CI: 7.15–35.82), respectively; and, for estimation of cirrhosis, were 80% (95% CI = 0.75–0.85), 71% (95% CI = 0.68–0.74), 3.13 (95% CI = 2.01–4.87), 0.29 (95% CI = 0.19–0.44), and 14.09 (95% CI: 5.43–36.59), respectively.

Conclusions

The ELF test shows good performance and considerable diagnostic value for the prediction of histological fibrosis stage.     

Coffee Consumption Decreases Risks for Hepatic Fibrosis and Cirrhosis: A Meta-Analysis

Background and Aim

Previous studies have demonstrated that coffee consumption may be inversely correlated with hepatic fibrosis and cirrhosis. However, the reported results have been inconsistent. To summarize previous evidences quantitatively, a meta-analysis was performed.

Methods

The Medline, Web of Science, and Embase databases (from inception to June 2015) were searched to identify relevant trials that evaluated the effects of coffee consumption on hepatic fibrosis or cirrhosis. Odds ratios (ORs) of advanced hepatic fibrosis or cirrhosis for low or moderate, high, and any coffee consumption versus no consumption were pooled. Two cups per day was used as the cut-off level between low or moderate and high consumption.

Results

Sixteen studies were included, involving 3034 coffee consumers and 132076 people who do not consume coffee. The pooled results of the meta-analysis indicated that coffee consumers were less likely to develop cirrhosis compared with those who do not consume coffee, with a summary OR of 0.61 (95%CI: 0.45–0.84). For low or moderate coffee consumption versus no consumption, the pooled OR of hepatic cirrhosis was 0.66 (95%CI: 0.47–0.92). High coffee consumption could also significantly reduce the risk for hepatic cirrhosis when compared with no coffee consumption (OR = 0.53, 95%CI: 0.42–0.68). The effect of coffee consumption on hepatic fibrosis was summarized as well. The pooled OR of advanced hepatic fibrosis for coffee consumption versus no consumption was 0.73 (95%CI: 0.58–0.92). The protective effect of coffee on hepatic fibrosis and cirrhosis was also identified in subgroup meta-analyses of patients with alcoholic liver disease and chronic hepatitis C virus (HCV) infection.

Conclusion

Coffee consumption can significantly reduce the risk for hepatic fibrosis and cirrhosis.     

The Diagnostic Value of the FIB-4 Index for Staging Hepatitis B-Related Fibrosis: A Meta-Analysis

Background

Liver fibrosis stage is an important factor in determining prognosis and need for treatment in patients infected with hepatitis B virus (HBV). Liver biopsies are typically used to assess liver fibrosis; however, noninvasive alternatives such as the FIB-4 index have also been developed.

Aims

To quantify the accuracy of the FIB-4 index in the diagnosis of HBV related fibrosis and cirrhosis.

Methods

A meta-analysis of studies comparing the diagnostic accuracy of the FIB-4 index vs. liver biopsy in HBV-infected patients was performed using studies retrieved from the following databases: PubMed, Ovid, EMBASE, the Cochrane Library, the Chinese National Knowledge Infrastructure and the Chinese Biology Medicine disc. A hierarchical summary receiver operating curves model and bivariate model were used to produce summary receiver operating characteristic curves and pooled estimates of sensitivity and specificity. The heterogeneity was explored with meta-regression analysis. Publication bias was detected using Egger’s test and the trim and fill method.

Results

12 studies (N = 1,908) and 10 studies (N = 2,105) were included in the meta-analysis for significant fibrosis and cirrhosis, respectively. For significant fibrosis, the area under the hierarchical summary receiver operating curve (AUHSROC) was 0.78 (95% CI = 0.74–0.81). The recommended cutoff value was between 1.45 and 1.62, and the AUHSROC, summary sensitivity and specificity were 0.78 (95% CI = 0.74–0.81), 0.65 (95% CI = 0.56–0.73) and 0.77 (95% CI = 0.7–0.83), respectively. For cirrhosis, the AUHSROC was 0.89 (95% CI = 0.85–0.91). The recommended cutoff value was between 2.9 and 3.6, and the AUHSROC, summary sensitivity and specificity were 0.96 (95% CI = 0.92–1.00), 0.42 (95% CI = 0.36–0.48) and 0.96 (95% CI = 0.95–0.97), respectively. No publication bias was detected.

Conclusions

The FIB-4 index is valuable for detecting significant fibrosis and cirrhosis in HBV-infected patients, but has suboptimal accuracy in excluding fibrosis and cirrhosis.     

Biopsy-Controlled Liver Fibrosis Staging Using the Enhanced Liver Fibrosis (ELF) Score Compared to Transient Elastography

Background and Aims

Chronic liver diseases are characterized by inflammatory and fibrotic liver injuries that often result in liver cirrhosis with its associated complications such as portal hypertension and hepatocellular carcinoma. Liver biopsy still represents the reference standard for fibrosis staging, although transient elastography is increasingly used for non-invasive monitoring of fibrosis progression. However, this method is not generally available and is associated with technical limitations emphasizing the need for serological biomarkers staging of liver fibrosis. The enhanced liver fibrosis (ELF) score was shown to accurately predict significant liver fibrosis in different liver diseases, although extracellular matrix components detected by this score may not only mirror the extent of liver fibrosis but also inflammatory processes.

Methods

In this prospective biopsy-controlled study we evaluated the utility of the ELF score in comparison to transient elastography to predict different stages of fibrosis in 102 patients with chronic liver diseases.

Results

Both techniques revealed similar area under receiver operating characteristic curve values for prediction of advanced fibrosis stages. Compared to transient elastography, the ELF score showed a broader overlap between low and moderate fibrosis stages and a stronger correlation with inflammatory liver injury.

Conclusions

Both the ELF score as well as transient elastography allowed for high quality fibrosis staging. However, the ELF score was less discriminative in low and moderate fibrosis stages and appeared more strongly influenced by inflammatory liver injury. This should be considered when making clinical interpretations on the basis of ELF score values.     

Non-Invasive Evaluation of Hepatic Fibrosis: The Diagnostic Performance of Magnetic Resonance Elastography in Patients with Viral Hepatitis B or C

Purpose

To compare the accuracy of magnetic resonance elastography (MRE) with that of aspartate aminotransferase-to-platelet ratio index (APRI) for estimating the stage of hepatic fibrosis in patients with chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection.

Materials and Methods

We retrospectively enrolled 160 patients with chronic hepatitis and 25 healthy living liver donors. Fibrosis stage (METAVIR, F0 to F4) was determined histopathologically for all patients. APRI was recorded at the time of histopathologic examination and liver stiffness values were measured on MRE quantitative stiffness maps. The cutoff values, sensitivity, and specificity of MRE and APRI for each fibrosis stage were determined using receiver operating characteristic (ROC) analysis.

Results

MRE had a significantly greater area under the ROC curve than APRI score for discriminating among METAVIR stages F2-F4. Using a cutoff value of 2.80 kPa, MRE had a sensitivity of 94.4% and a specificity of 97.8% for detecting significant fibrosis (≥F2). There were no significant differences in fibrosis stage between patients with HBV and those with HCV infection. For ≥F2, the cutoffs were 2.47 kPa (100% sensitivity), 2.80 kP (maximum sum of sensitivity and specificity), and 3.70 kPa (100% specificity).

Conclusions

MRE is a more accurate modality than APRI for detecting significant fibrosis in patients with chronic HBV or HCV infection. Antiviral treatment should be considered in patients with liver stiffness values ≥ 2.8 kPa.     

Pirfenidone for Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. In the last decades pirfenidone an anti-inflammatory and anti-fibrotic agent has shown benefit in inhibit collagen production and has also demonstrated benefit in decline progression in IPF in physiological outcomes as Forced vital capacity (FVC), in clinical outcomes such as progression free survival (PFS) and a benefit in mortality but no in clinically relevant outcomes as exacerbations or worsening of IPF. Methods: We conducted a systematic review to evaluate the effectiveness of physiological and clinical outcomes of pirfenidone compared to placebo in IPF. We performed a search with no language restriction. Two researchers performed literature search, quality assessment, data extraction and analysis. And was performed a summary of findings table following the GRADE approach. Results: We included 5 RCTs (Randomized controlled trials) in analysis. The meta-analysis resulted in a decrease in all cause-mortality (RR 0.52 IC 0.32–0.88) and IPF related mortality (RR 0.32 IC 0.14–0.75); other outcomes evaluated were worsening of IPF (RR 0.64 IC 0.50–0.83) and acute exacerbation (RR: 0.72 IC 0.30–1.66 respectively). Also there was a decrease in progression free survival (PFS) (RR 0.83 IC 0.74–0.92) compared to placebo. Conclusions: We observed significant differences in physiologic and clinically relevant outcomes such as reduction in all-cause mortality, IPF related mortality, worsening and exacerbation of IPF and PFS. So pirfenidone treatment should be considered not only for its benefits in pulmonary function tests but also by its clinically relevant outcomes.     

Adverse Events of Pirfenidone for the Treatment of Pulmonary Fibrosis: A Meta-Analysis of Randomized Controlled Trials

Background

Pirfenidone (PFD) is a novel antifibrotic agent approved for patients with pulmonary fibrosis. However, there are concerns regarding toxicity of the drug. In this meta-analysis, we analyzed the adverse events (AEs) of PFD for the treatment of pulmonary fibrosis.

Methods

We performed a systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for trials published between January 1999 and October 2011. Data extracted from literature were analyzed with Review manager 5.0.24.

Results

The results of six randomized controlled trials (1073 participants) revealed that the number of individuals who discontinued PFD therapy was significantly higher than patients receiving placebo. The PFD group had a significantly higher rate of gastrointestinal (nausea, dyspepsia, diarrhea, and anorexia), neurological (dizziness and fatigue), and dermatological (photosensitivity and rash) AEs compared to the placebo group.

Conclusions

PFD used for the treatment of pulmonary fibrosis is not so safe or well-tolerated. Notably, gastrointestinal, neurological and dermatological adverse effects were more common in patients receiving PFD therapy, and therefore appropriate precaution is needed.     

Comparative Effectiveness of Hepatic Artery Based Therapies for Unresectable Colorectal Liver Metastases: A Meta-Analysis

BackgroundPatients with unresectable Colorectal Liver Metastases (CRLM) are increasingly being managed using Hepatic Artery Based Therapies (HAT), including Hepatic Arterial Infusion (HAI), Radioembolization (RE), and Transcatheter Arterial Chemoembolization (TACE). Limited data is available on the comparative effectiveness of these options. We hypothesized that outcomes in terms of survival and toxicity were equivalent across the three strategies.MethodsA meta-analysis was performed using a prospectively registered search strategy at PROSPERO (CRD42013003861) that utilized studies from PubMed (2003–2013). Primary outcome was median overall survival (OS). Secondary outcomes were treatment toxicity, tumor response, and conversion of the tumor to resectable. Additional covariates included prior or concurrent systemic therapy.ResultsOf 491 studies screened, 90 were selected for analyses—52 (n = 3,000 patients) HAI, 24 (n = 1,268) RE, 14 (n = 1,038) TACE. The median OS (95% CI) for patients receiving HAT in the first-line were RE 29.4 vs. HAI 21.4 vs. TACE 15.2 months (p = 0.97, 0.69 respectively). For patients failing at least one line of prior systemic therapy, the survival outcomes were TACE 21.3 (20.6–22.4) months vs. HAI 13.2 (12.2–14.2) months vs. RE 10.7 (9.5–12.0). Grade 3–4 toxicity for HAT alone was 40% in the HAI group, 19% in the RE group, and 18% in the TACE groups, which was increased with the addition of systemic chemotherapy. Level 1 evidence was available in 5 studies for HAI, 2 studies for RE and 1 for TACE.ConclusionHAI, RE, and TACE are equally effective in patients with unresectable CRLM with marginal differences in survival.     

Utility of Real-Time Shear Wave Elastography in the Assessment of Testicular Torsion

Real-time shear-wave elastography (SWE) is a newly developed method which can obtain the stiffness of tissues and organs based on tracking of shear wave propagation through a structure. Several studies have demonstrated its potential in the differentiation between diseased and normal tissue in clinical practices, however the applicability to testicular disease has not been well elucidated. We investigated the feasibility and reproducibility of SWE in the detection of testicular torsion. This prospective study comprised 15 patients with complete testicular torsion. Results obtained from SWE along with conventional gray-scale and color Doppler sonography and post-operative pathology were compared. The results revealed that (i) the size of injured testis was increased and the twisted testis parenchyma was heterogeneous. The blood flow signals in injured testis were barely visible or absent; (ii) The Young’s modulus, including Emean, Emax, Emin and SD values in the border area of torsional testis were higher than those of normal testis (Emean, 78.07±9.01kPa vs 22.0±5.10kPa; Emax,94.07±6.53kPa vs 27.87±5.78kPa; Emin, 60.73±7.84 kPa vs 18.90±4.39kPa; SD, 7.67±0.60 kPa vs 2.30±0.36 kPa, [P<0.05]); The Emax and SD values in the central area of the torsional testis were higher than the corresponding area of the normal testis (Emax, 8.23±0.30 kPa vs 3.97±0.95kPa; SD, 1.5±0.26kPa vs 0.67±0.35kPa,[P<0.05]) and Emin values was lower than those of normal testicles(0.93±0.51kPa vs 1.6±0.36kPa; [P<0.05]); (iii) The Young''s modulus measurement between two physicians showed good agreement. The pathological findings were accordance with SWE measurement. SWE is a non-invasive, convenient and high reproducible method and may serve as an important alternative tool in the diagnosis and monitoring the progression of the acute scrotums, in additional to conventional Doppler sonography.     

肝纤维化动物模型探讨

目的 寻找肝纤维化最佳模型.方法 将Wistar大鼠随机分成血清组、四氯化碳皮下注射组、四氯化碳腹腔注射组,每组30只,各组分别给予猪血清腹腔注射、40%四氯化碳皮下和腹腔注射造模(每周2次),观察造模过程中大鼠死亡情况以及4周及6周各组大鼠肝纤维化的程度.结果 3种方法都能成功制备肝纤维化模型.从动物死亡情况来看,四氯化碳腹腔注射组死亡率明显高于前两组;血清组死亡率最低,但与四氯化碳皮下注射组比较无显著差异;从模型形成时间来看,血清组造模时间较长,明显高于其他两组,四氯化碳皮下注射组与四氯化碳腹腔注射组在模型形成时间上无明显差异.结论 四氯化碳皮下注射组制备肝纤维化模型动物死亡率较低,肝纤维化形成时间较短,是一种制作肝纤维化模型较好的方法.     

壳聚糖介导CrmA基因治疗小鼠肝纤维化的研究

目的:探讨壳聚糖介导的CrmA对小鼠肝纤维化的治疗效果,以期为肝纤维化的基因治疗提供实验基础。方法:清洁级的75只雄性小鼠随机分为正常组、模型组、壳聚糖介导的CrmA组、壳聚糖介导的空载体组、壳聚糖组,每组15只。应用30%四氯化碳橄榄油溶液3 ml/kg腹腔注射制备肝纤维化小鼠模型。治疗8周后,眼眶取血,检测血清的肝功能指标,并取肝组织做HE染色,观察各组小鼠肝脏的病理形态,Real Time PCR检测肝组织IL-1β、α-SMA、TGF-β1、TIMP-1表达量。结果:与模型组小鼠相比,壳聚糖介导的CrmA组小鼠的肝纤维化程度减轻,ALT、AST显著降低(P0.01),肝组织IL-1β、α-SMA、TIMP1、TGF-β1的表达明显减少(P0.05),而模型组、壳聚糖介导的空载体组和壳聚糖组均无显著性差异。结论:壳聚糖介导的CrmA能有效减轻肝纤维化小鼠的肝脏损伤和纤维化程度,为基因治疗肝纤维化提供了一种潜在的新思路和方法。     

壳聚糖介导CrmA基因治疗小鼠肝纤维化的研究

目的：探讨壳聚糖介导的CrmA对小鼠肝纤维化的治疗效果,以期为肝纤维化的基因治疗提供实验基础。方法：清洁级的75只雄性小鼠随机分为正常组、模型组、壳聚糖介导的CrmA组、壳聚糖介导的空载体组、壳聚糖组,每组15只。应用30％四氯化碳橄榄油溶液3ml／kg腹腔注射制备肝纤维化小鼠模型。治疗8周后,眼眶取血,检测血清的肝功能指标,并取肝组织做HE染色,观察各组小鼠肝脏的病理形态,Real TimePCR检测肝组织IL-1β、α-SMA、TGF—β1、TIMP-1表达量。结果：与模型组小鼠相比,壳聚糖介导的CrmA组小鼠的肝纤维化程度减轻,ALT、AST显著降低（P〈0．01）,肝组织IL-1β、α-SMA、TIMP1、TGF-β1的表达明显减少（P〈0．05）,而模型组、壳聚糖介导的空载体组和壳聚糖组均无显著性差异。结论：壳聚糖介导的CrmA能有效减轻肝纤维化小鼠的肝脏损伤和纤维化程度,为基因治疗肝纤维化提供了一种潜在的新思路和方法。     

Angiopoietin-2 Serum Levels Improve Noninvasive Fibrosis Staging in Chronic Hepatitis C: A Fibrogenic-Angiogenic Link

Aims

Accurate liver fibrosis staging is crucial for the management of chronic hepatitis C (CHC). The invasiveness and cost burden of liver biopsy have driven the search for new noninvasive biomarkers of fibrosis. Based on the link between serum angiopoietin-1 and 2 levels and CHC progression, we aimed to determine the value of these angiogenic factors as noninvasive biomarkers of liver fibrosis.

Methods

Serum levels of angiopoietin-1 and -2 were measured by ELISA in 108 CHC patients who underwent pretreatment liver biopsy. The correlation between angiopoietins and clinical and demographic variables with liver fibrosis was analyzed by univariate regression. Significant factors were then subjected to multivariate analysis, from which we constructed a novel noninvasive liver fibrosis index (AngioScore), whose performance was validated in an independent series of 71 CHC patients. The accuracy of this model was compared with other documented fibrosis algorithms by De Long test.

Results

Angiopoietins correlated significantly with hepatic fibrosis; however, only angiopoietin-2 was retained in the final model, which also included age, platelets, AST, INR, and GGT. The model was validated and behaved considerably better than other fibrosis indices in discriminating all, significant, moderate and severe liver fibrosis (0.886, 0.920, 0.923). Using clinically relevant cutoffs, we classified CHC patients by discarding significant fibrosis and diagnosing moderate and severe fibrosis with greater accuracy, sensitivity, and specificity.

Conclusions

Our novel noninvasive liver fibrosis model, based on serum angiopoietin-2 levels, outperforms other indices and should help substantially in managing CHC and monitoring long-term follow-up prognosis.     

肝纤维化的实验动物模型

本文讨论了建立肝纤维化动物模型的技术与存在的问题,以大鼠为主要动物讨论了目前常用的几种造模方法、每种造模方法的致病机理、造模途径、效果,同时比较了不同造模方法的优缺点及各自的用途,提出了肝纤维化动物模型领域的研究方向。     

Viscoelastic Parameters for Quantifying Liver Fibrosis: Three-Dimensional Multifrequency MR Elastography Study on Thin Liver Rat Slices

Objective

To assess in a high-resolution model of thin liver rat slices which viscoelastic parameter at three-dimensional multifrequency MR elastography has the best diagnostic performance for quantifying liver fibrosis.

Materials and Methods

The study was approved by the ethics committee for animal care of our institution. Eight normal rats and 42 rats with carbon tetrachloride induced liver fibrosis were used in the study. The rats were sacrificed, their livers were resected and three-dimensional MR elastography of 5±2 mm liver slices was performed at 7T with mechanical frequencies of 500, 600 and 700 Hz. The complex shear, storage and loss moduli, and the coefficient of the frequency power law were calculated. At histopathology, fibrosis and inflammation were assessed with METAVIR score, fibrosis was further quantified with morphometry. The diagnostic value of the viscoelastic parameters for assessing fibrosis severity was evaluated with simple and multiple linear regressions, receiver operating characteristic analysis and Obuchowski measures.

Results

At simple regression, the shear, storage and loss moduli were associated with the severity of fibrosis. At multiple regression, the storage modulus at 600 Hz was the only parameter associated with fibrosis severity (r = 0.86, p<0.0001). This parameter had an Obuchowski measure of 0.89+/−0.03. This measure was significantly larger than that of the loss modulus (0.78+/−0.04, p = 0.028), but not than that of the complex shear modulus (0.88+/−0.03, p = 0.84).

Conclusion

Our high resolution, three-dimensional multifrequency MR elastography study of thin liver slices shows that the storage modulus is the viscoelastic parameter that has the best association with the severity of liver fibrosis. However, its diagnostic performance does not differ significantly from that of the complex shear modulus.     

Radiofrequency Ablation versus Hepatic Resection for Small Hepatocellular Carcinomas: A Meta-Analysis of Randomized and Nonrandomized Controlled Trials

Objectives

To evaluate the efficacy and safety of radiofrequency ablation (RFA) versus hepatic resection (HR) for early hepatocellular carcinoma (HCC) meeting the Milan criteria.

Methods

A meta-analysis was conducted, and PubMed, Web of Science, the Cochrane Library, CBM, CNKI and VIP databases were systematically searched through November 2012 for randomized and nonrandomized controlled trials (RCTs and NRCTs). The Cochrane Collaboration''s tool and modified MINORS score were applied to assess the quality of RCTs and NRCTs, respectively. The GRADE approach was employed to evaluate the strength of evidence.

Results

Three RCTs and twenty-five NRCTs were included. Among 11,873 patients involved, 6,094 patients were treated with RFA, and 5,779 with HR. The pooled results of RCTs demonstrated no significant difference between groups for 1- and 3-year overall survival (OS), recurrence-free survival (RFS) and disease-free survival (DFS) (p>0.05). The 5-year OS (Relative Risk, RR 0.72, 95% CI 0.60 to 0.88) and RFS (RR 0.56, 95% CI 0.40 to 0.78) were lower with RFA than with HR. The 3- and 5-year recurrences with RFA were higher than with HR (RR 1.48, 95% CI 1.14 to 1.94, and RR 1.52, 95% CI 1.18 to 1.97, respectively), but 1-year recurrence and in-hospital mortality showed no significant differences between groups (p>0.05). The complication rate (RR 0.18, 95% CI 0.06 to 0.53) was lower and hospital stays (Mean difference -8.77, 95% CI −10.36 to −7.18) were shorter with RFA than with HR. The pooled results of NRCTs showed that the RFA group had lower 1-, 3- and 5-year OS, RFS and DFS, and higher recurrence than the HR group (p<0.05). But for patients with very early stage HCC, RFA was comparable to HR for OS and recurrence.

Conclusion

The effectiveness of RFA is comparable to HR, with fewer complications but higher recurrence, especially for very early HCC patients.