Evaluation of quality and quantity of randomized controlled trials in hepatobiliary surgery: A scoping/mapping review.

AIM: To evaluate the quantity and quality of randomized controlled trials (RCTs) in hepatobiliary surgery and for identifying gaps in current evidences. METHODS: A systematic search was conducted in MEDLINE (via PubMed), Web of Science, and Cochrane Controlled Register of Trials (CENTRAL) for RCTs of hepatobiliary surgery published from inception until the end of 2023. The quality of each study was assessed using the Cochrane risk-of-bias (RoB) tool. The associations between risk of bias and the region and publication date were also assessed. Evidence mapping was performed to identify research gaps in the field. RESULTS: The study included 1187 records. The number and proportion of published randomized controlled trials (RCTs) in hepatobiliary surgery increased over time, from 13 RCTs (.0005% of publications) in 1970-1979 to 201 RCTs (.003% of publications) in 2020-2023. There was a significant increase in the number of studies with a low risk of bias in RoB domains (p < .01). The proportion of RCTs with low risk of bias improved significantly after the introduction of CONSORT guidelines (p < .001). The evidence mapping revealed a significant research focus on major and minor hepatectomy and cholecystectomy. However, gaps were identified in liver cyst surgery and hepatobiliary vascular surgery. Additionally, there are gaps in the field of perioperative management and nutrition intervention. CONCLUSION: The quantity and quality of RCTs in hepatobiliary surgery have increased over time, but there is still room for improvement. We have identified gaps in current research that can be addressed in future studies.

Promising Results of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Perihilar Cholangiocarcinoma in a Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients with phCC in a systematic review as well as a pooled data analysis. METHODS: MEDLINE and Web of Science databases were systematically searched for relevant literature up to December 2023. All studies reporting ALPPS in the management of phCC were included. A single-arm meta-analysis of proportions was carried out to estimate the overall rate of outcomes. RESULTS: After obtaining 207 articles from the primary search, data of 18 studies containing 112 phCC patients were included in our systematic review. Rates of major morbidity and mortality were calculated to be 43% and 22%, respectively. The meta-analysis revealed a PHLF rate of 23%. One-year disease-free survival was 65% and one-year overall survival was 69%. CONCLUSIONS: ALPPS provides a good chance of cure for patients with phCC in comparison to alternative treatment options, but at the expense of debatable morbidity and mortality. With refinement of the surgical technique and better perioperative patient management, the results of ALPPS in patients with phCC were improved.

Risk factors and management of biliary leakage after Endocystectomy for hepatic cystic echinococcosis.

BACKGROUND: Endocystectomy is a conservative surgical approach to managing cystic echinococcosis. Bile leakage is the main complication of this technique. The aim of this study was to evaluate the factors associated with bile leakage and to assess the outcomes and cost efficiency of strategies used to treat bile leakage. METHODOLOGY/PRINCIPAL FINDINGS: Patients who underwent endocystectomy between 2005 and 2020 were included. The preoperative characteristics, intra- and postoperative outcomes, hospital costs, and cost efficiency (the Diagnosis-Related Group reimbursement minus the overall cost) were evaluated prospectively. A total of eighty patients with 142 cysts were included. Postoperative complications occurred in 17 patients (21%), including 11 patients with bile leakage (type A: 1, type B: 6 and type C: 4 patients, total 13%). Bile leakage was more frequent in patients with preoperative MRI signs of cysto-biliary fistulas or intraoperative visible cysto-biliary fistulas (p = 0.03 and p = 0.04, respectively) and in patients with cysts larger than 8 cm (p = 0.03). Patients with bile leakage who underwent reoperation (type C) had significantly shorter hospital stays (9 vs. 16 days, p<0.01) and better cost efficiency than those who received radiologic or endocscopic interventions (€2,072 vs. -€2,097 p = 0.01). No mortality was observed, and recurrence was seen in two patients. CONCLUSIONS/SIGNIFICANCE: Endocystectomy is a safe and efficient technique. Preoperative and intraoperative cysto-biliary fistulas and a cyst diameter larger than 8 cm are correlated to postoperative bile leakage. Early operative management of bile leakage reduces hospital stay and improves cost efficiency compared with radiologic or endoscopic treatments.

Association of perioperative use of statins, metformin, and aspirin with recurrence after curative liver resection in patients with hepatocellular carcinoma: A propensity score matching analysis.

BACKGROUND: Statins, metformin, and aspirin have been reported to reduce the incidence of hepatocellular carcinoma (HCC). However, the effect of their perioperative use on survival outcomes of HCC patients following curative liver resection still remains unclear. METHOD: Three hundred and fifty three patients with a first diagnosis of HCC who underwent curative liver resection were included. Propensity score matching analysis with a users: nonusers ratio of 1:2 were performed for each of the medications (statins, metformin, and aspirin). Overall survival (OS) and recurrence-free survival (RFS) were evaluated and multivariable Cox proportional hazard analysis was performed. RESULTS: Sixty two patients received statins, 48 patients used metformin, and 53 patients received aspirin for ≥90 days before surgery. None of the medications improved OS. RFS of statin users was significantly longer than that of nonusers (p = 0.021) in the matched cohort. Users of hydrophilic statins, but not lipophilic ones had a significantly longer RFS than nonusers. Multivariable analysis showed that statin use significantly improved RFS (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.17-0.97, p = 0.044). No difference was seen in RFS between metformin users and nonusers. Among patients with diabetes, RFS was nonsignificantly longer in metformin users than in non-metformin users (84.1% vs. 60.85%, p = 0.069) in the matched cohort. No difference in postoperative RFS was seen between aspirin users and nonusers. CONCLUSION: Preoperative use of statins in patients with HCC can increase RFS after curative liver resection, but metformin and aspirin were not associated with improved survival. Randomized controlled trials are needed to confirm the findings of the present study.

Comparison of the modified piggyback with standard piggyback and conventional orthotopic liver transplantation techniques: a network meta-analysis.

BACKGROUND: In conventional orthotopic liver transplantation (OLT), the recipient's retrohepatic inferior vena cava (IVC) is completely clamped and replaced with the donor IVC. The piggyback technique has been used to preserve venous return, either via an end-to-side or standard piggyback (SPB), or via a side-to-side or modified piggyback (MPB) anastomosis, using a venous cuff from the recipient hepatic veins with partially clamping and preserves the recipient's inferior vena cava. However, whether these piggyback techniques improve the efficacy of OLT is unclear. To address the low quality of the available evidence, we performed a meta-analysis to compare the efficacy of conventional, MPB, and SPB techniques. METHODS: Literature was searched in Medline and Web of Science databases for relevant articles published until 2021 without any time restriction. A Bayesian network meta-analysis was performed to compare the intra- and postoperative outcomes of conventional OLT, MPB, and SPB techniques. RESULTS: Forty studies were included, comprising 10,238 patients. MPB and SPB had significantly shorter operation times and fewer transfusions of red blood cell and fresh frozen plasma than conventional techniques. However, there were no differences between MPB and SPB in operation time and blood product transfusion. There were also no differences in primary non-function, retransplantation, portal vein thrombosis, acute kidney injury, renal dysfunction, venous outflow complications, length of hospital and intensive care unit stay, 90-day mortality rate, and graft survival between the three techniques. CONCLUSION: MBP and SBP techniques reduce the operation time and need for blood transfusion compared with conventional OLT, but postoperative outcomes are similar. This indicates that all techniques can be implemented based on the experience and policy of the transplant center.

Declined Organs for Liver Transplantation: A Right Decision or a Missed Opportunity for Patients with Hepatocellular Carcinoma?

BACKGROUND: Liver transplantation is the only promising treatment for end-stage liver disease and patients with hepatocellular carcinoma. However, too many organs are rejected for transplantation. METHODS: We analyzed the factors involved in organ allocation in our transplant center and reviewed all livers that were declined for transplantation. Reasons for declining organs for transplantation were categorized as major extended donor criteria (maEDC), size mismatch and vascular problems, medical reasons and risk of disease transmission, and other reasons. The fate of the declined organs was analyzed. RESULTS: 1086 declined organs were offered 1200 times. A total of 31% of the livers were declined because of maEDC, 35.5% because of size mismatch and vascular problems, 15.8% because of medical reasons and risk of disease transmission, and 20.7% because of other reasons. A total of 40% of the declined organs were allocated and transplanted. A total of 50% of the organs were completely discarded, and significantly more of these grafts had maEDC than grafts that were eventually allocated (37.5% vs. 17.7%, p < 0.001). CONCLUSION: Most organs were declined because of poor organ quality. Donor-recipient matching at time of allocation and organ preservation must be improved by allocating maEDC grafts using individualized algorithms that avoid high-risk donor-recipient combinations and unnecessary organ declination.

Bariatric surgery in patients with obesity and end-stage renal disease.

BACKGROUND: Bariatric surgery has been suggested as a treatment for obesity and end-stage renal disease (ESRD). Although the number of bariatric surgeries in patients with ESRD is increasing, its safety and effectiveness in these patients are still controversial and the surgical method of choice in these patients is under debate. OBJECTIVES: To compare the outcomes of bariatric surgery between patients with and without ESRD and to assess different methods of bariatric surgery in patients with ESRD. SETTING: Meta-analysis. METHODS: A comprehensive search was conducted in Web of Science and Medline (via Pubmed) until May 2022. Tow meta-analyses were performed: A) to compare bariatric surgery outcomes among patients with and without ESRD, and B) to compare outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in patients with ESRD. Using a random-effect model, odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were computed for surgical and weight loss outcomes. RESULTS: Of 5895 articles, 6 studies were included in meta-analysis A and 8 studies in meta-analysis B. The risk of bias was moderate to serious among studies. Major postoperative complications (OR = 2.82; 95% CI = 1.66-4.77; P = .0001), reoperation (OR = 2.66; 95% CI = 1.99-3.56; P < .00001), readmission (OR = 2.37; 95% CI = 1.55-3.64; P < .0001), and in-hospital/90-d mortality (OR = 4.03; 95% CI = 1.80-9.03; P = .0007) were higher in patients with ESRD. Patients with ESRD also had a longer hospital stay (MD = 1.23; 95% CI = .32-2.14; P = .008). Bleeding, leakage, and total weight loss were comparable among groups. SG showed a 10% lower rate of overall complications and significantly shorter hospital stay than RYGB did. The quality of evidence was very low for the outcomes CONCLUSIONS: Bariatric surgery in patients with ESRD seems to have higher rates of major complications and perioperative mortality than in patients without ESRD, but a comparable rate of overall complications. SG has fewer postoperative complications and could be the method of choice in these patients. These findings should be interpreted cautiously in light of the moderate to high risk of bias in most included studies.

Outcomes of Robot-Assisted Surgery in Rectal Cancer Compared with Open and Laparoscopic Surgery.

With increasing trends for the adoption of robotic surgery, many centers are considering changing their practices from open or laparoscopic to robot-assisted surgery for rectal cancer. We compared the outcomes of robot-assisted rectal resection with those of open and laparoscopic surgery. We searched Medline, Web of Science, and CENTRAL databases until October 2022. All randomized controlled trials (RCTs) and prospective studies comparing robotic surgery with open or laparoscopic rectal resection were included. Fifteen RCTs and 11 prospective studies involving 6922 patients were included. The meta-analysis revealed that robotic surgery has lower blood loss, less surgical site infection, shorter hospital stays, and higher negative resection margins than open resection. Robotic surgery also has lower conversion rates, lower blood loss, lower rates of reoperation, and higher negative circumferential margins than laparoscopic surgery. Robotic surgery had longer operation times and higher costs than open and laparoscopic surgery. There were no differences in other complications, mortality, and survival between robotic surgery and the open or laparoscopic approach. However, heterogeneity between studies was moderate to high in some analyses. The robotic approach can be the method of choice for centers planning to change from open to minimally invasive rectal surgery. The higher costs of robotic surgery should be considered as a substitute for laparoscopic surgery (PROSPERO: CRD42022381468).

Prognostic Value of Red Blood Cell Distribution Width (RDW) in the Recurrence of Hepatocellular Carcinoma Following Curative Resection.

Purpose: Although surgery is associated with an acceptable cure rate, tumor recurrence is still a challenging issue in hepatocellular carcinoma (HCC) patients. Red blood cell distribution width (RDW) is considered an inflammatory marker for predicting overall mortality in a wide spectrum of malignancies. In the current study, the prognostic role of pre- and postoperative RDW in HCC recurrence after liver resection (LRx) is investigated. Patients and Methods: In 395 patients, RDW levels were evaluated preoperatively as well as six and twelve months after curative LRx. The RDW cutoff values were determined using receiver operating characteristic curves (ROCs) according to the recurrence-free survival (RFS). Survival analyses were performed using the Kaplan-Meier, and differences were compared using the Log rank test. Results: The RFS was significantly higher among patients with low RDW at the 6th month and 12th month, postoperatively (P < 0.001 and P = 0.028). RDW levels of higher than 16.15% at the 6th (HR: 2.047, P <0.001) and higher than 15.85% at 12th (HR: 3.105, P < 0.002) months after liver resection were independent predictors of RFS. Conclusion: Postoperative RDW values seem to be predictive of tumor recurrence in HCC patients. RDW levels at the 6th and 12th months postoperatively were independent predictors of recurrence after LRx.

Outcomes of bariatric surgery in patients with obesity and compensated liver cirrhosis.

BACKGROUND: Obesity is a major health burden worldwide and is associated with nonalcoholic fatty liver disease, which can lead to cirrhosis. Bariatric surgery is increasingly being used to treat obesity, and the number of patients with obesity and cirrhosis undergoing bariatric surgery is also rising. However, the safety and feasibility of bariatric surgery in patients with obesity and cirrhosis are controversial. OBJECTIVES: In this meta-analysis, we compared postoperative complications, mortality, and weight loss between patients with and without cirrhosis undergoing bariatric surgery. SETTING: An electronic search of Medline, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). METHODS: Patient morbidity and mortality odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were assessed. Intraoperative and overall complications, length of hospital stay, in-hospital mortality, long-term mortality, and total weight loss were recorded. RESULTS: The literature search yielded 2977 articles. Eight studies were included in the analysis. Meta-analysis showed that the overall complications (OR: 2.1; 95% CI: 1.47-3.00; P < .0001), postoperative bleeding (OR: 2.22; 95% CI: 1.95-2.54; P < .00001), length of hospital stay (MD: .68; 95% CI: .14-1.19; P = .01), and in-hospital/90-day mortality (OR: 3.59; 95% CI: 2.84-4.54; P < .00001) were significantly higher in patients with compensated cirrhosis than in patients without cirrhosis. Intraoperative complications, operation time, major complications, and long-term mortality were similar between the groups. Total weight loss was also not significantly different between the groups. CONCLUSION: Bariatric surgery can be considered only in highly selected patients with obesity and compensated cirrhosis.

Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: a network meta-analysis.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) are selected for transplantation if they have a low tumour burden and low risk of recurrence. The morphometric Milan criteria have been the cornerstone for patient selection, but dynamic morphological and biological tumour characteristics surfaced as an encouraging tool to refine the selection of patients with HCC and to support the expansion of the Milan criteria. The outcomes of the most prevalent models that select patients with HCC for liver transplantation were analysed in this study, which aimed to identify the selection model that offered the best recurrence-free and overall survival after transplantation. METHODS: Studies that compared Milan, University of California San Francisco (UCSF), up-to-seven (UPTS), alpha-fetoprotein (AFP), and MetroTicket 2.0 (MT2) models were included. One-year, 3-year, and 5-year recurrence-free and overall survival rates of patients selected for transplantation using different models were analysed. RESULTS: A total of 60 850 adult patients with HCC selected for liver transplantation using Milan, UCSF, UPTS, AFP, or MT2 criteria were included. Patients selected for transplantation using the MT2 model had the highest 1-, 3-, and 5-year recurrence-free survival. In addition, patients selected for transplantation using MT2 criteria had the best 1- and 3-year overall survival, whereas patients selected for transplantation using the Milan criteria had the best 5-year overall survival rates. CONCLUSION: The MT2 model offered the best post-transplant outcomes in patients with HCC, highlighting the importance of considering tumour morphology and biology when selecting patients with HCC for liver transplantation.

Efficacy of Technical Modifications to the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure: A Systematic Review and Meta-Analysis.

To compare the outcomes of modified-Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) techniques with those of conventional-ALPPS. Background: ALPPS is an established technique for treating advanced liver tumors. Methods: PubMed, Web of Science, and Cochrane databases were searched. The outcomes were assessed by single-arm and 2-arm analyses. Results: Seventeen studies containing 335 modified-ALPPS patients were included in single-arm meta-analysis. The estimated blood loss was 267 ± 29 mL (95% confidence interval [CI], 210-324 mL) during the first and 662 ± 51 mL (95% CI, 562-762 mL) during the second stage. The operation time was 166 ± 18 minutes (95% CI, 131-202 minutes) during the first and 225 ± 19 minutes (95% CI, 188-263 minutes) during the second stage. The major morbidity rate was 14% (95% CI, 9%-22%) after the first stage. The future liver remnant hypertrophy rate was 65.2% ± 5% (95% CI, 55%-75%) and the interstage interval was 16 ± 1 days (95% CI, 14-17 days). The dropout rate was 9% (95% CI, 5%-15%). The overall complication rate was 46% (95% CI, 37%-56%) and the major complication rate was 20% (95% CI, 14%-26%). The postoperative mortality rate was 7% (95% CI, 4%-11%). Seven studies containing 215 patients were included in comparative analysis. The hypertrophy rate was not different between 2 methods (mean difference [MD], -5.01; 95% CI, -19.16 to 9.14; P = 0.49). The interstage interval was shorter for partial-ALPPS (MD, 9.43; 95% CI, 3.29-15.58; P = 0.003). The overall complication rate (odds ratio [OR], 10.10; 95% CI, 2.11-48.35; P = 0.004) and mortality rate (OR, 3.74; 95% CI, 1.36-10.26; P = 0.01) were higher in the conventional-ALPPS. Conclusions: The hypertrophy rate in partial-ALPPS was similar to conventional-ALPPS. This shows that minimizing the first stage of the operation does not affect hypertrophy. Moreover, the postoperative overall morbidity and mortality rates were lower following partial-ALPPS.

Prognostic role of the Donor Risk Index, the Eurotransplant Donor Risk Index, and the Balance of Risk score on graft loss after liver transplantation.

This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.

Considering extended right lobe grafts as major extended donor criteria in liver transplantation is justified.

The outcomes of split-liver transplantation are controversial. This study compared outcomes and morbidity after extended right lobe liver transplantation (ERLT) and whole liver transplantation (WLT) in adults. MEDLINE and Web of Science databases were searched systematically and unrestrictedly for studies on ERLT and its impact on graft and patient survival, and postoperative complications. Graft loss and patient mortality odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Vascular and biliary complications, primary nonfunction, 3-month, 1-, and 3-year graft and patient survival, and retransplantation after ERLT and WLT were analyzed. The literature search yielded 10 594 articles. After exclusion, 22 studies (n = 75 799 adult transplant patients) were included in the analysis. ERLT was associated with lower 3-month (OR = 1.43, 95% CI = 1.09-1.89, P = 0.01), 1-year (OR = 1.46, 95% CI = 1.08-1.97, P = 0.01), and 3-year (OR = 1.37, 95% CI = 1.01-1.84, P = 0.04) graft survival. WL grafts were less associated with retransplantation (OR = 0.57; 95% CI = 0.41-0.80; P < 0.01), vascular complications (OR = 0.53, 95% CI = 0.38-0.74, P < 0.01) and biliary complications (OR = 0.67; 95% CI = 0.47-0.95; P = 0.03). Considering ERLT as major Extended Donor Criteria is justified because ERL grafts are associated with vasculobiliary complications and the need for retransplantation, and have a negative influence on graft survival.

Safety and Efficacy of Repeated Bone Marrow Mononuclear Cell Therapy in Patients with Critical Limb Ischemia in a Pilot Randomized Controlled Trial.

BACKGROUND: Critical limb ischemia is a manifestation of peripheral arterial disease characterized by insufficient arterial blood flow for maintaining tissue viability in the lower extremities. Therapeutic angiogenesis is used for peripheral arterial disease patients who are not candidates for surgical revascularization or radiological intervention. There is accumulating evidence for the beneficial impact of autologous bone marrow mononuclear cell transplantation for treatment of critical limb ischemia in humans. This study aims to investigate the safety and efficacy of repeated bone marrow mononuclear cell injections in comparison with a single bone marrow mononuclear cell injection in critical limb ischemia patients. METHODS: Patients with critical limb ischemia (n = 22) were randomized (http://clinicaltrials.gov/ct2 show/NCT01480414) to receive either a single (n = 11) or four (n = 11) intramuscular injections of bone marrow mononuclear cells as a cell therapy product. RESULTS: There were no reported adverse events during the 24-week follow-up period after cell delivery. Efficacy assessment indicated that after cell injections, there was significant improvement in Ankle-Brachial Index, Visual Analog Scale, pain-free walking distance, and Wagner stage as well as reduction in ulcer size. There was no significant difference between the two groups in terms of clinical parameters. However, by the 24th week the pain-free walking distance improved significantly in the group who received four injections of cells. CONCLUSION: Favorable clinical outcomes strongly indicate the long-term benefit of bone marrow mononuclear cell transplantation, either as one or several injections, for retrieval from critical limb ischemia. Repeated cell injections have shown increased improvement of pain-free walking distance in patients. These findings warrant further exploration in later-phase clinical trials with repeated injections.

Safety and Efficacy of Adding Ribavirin to Interferon or Peginterferon in Treatment of Hepatitis C Infection in Patients With Thalassemia: A Systematic Review on Randomized Controlled Trials.

CONTEXT: Hepatitis C virus (HCV) infection is a major cause of liver-morbidity and mortality among patients with thalassemia. Peginterferon plus ribavirin is currently the recommended therapy for hepatitis C infection in patients do not have thalassemia, but using ribavirin in patients with thalassemia is restricted due to its hemolytic effect. To evaluate the efficacy and safety of adding ribavirin to peginterferon or interferon, authors performed a systematic review on the available literatures. EVIDENCE ACQUISITION: Trials were identified through electronic database, manual searches of journals and bibliographies and approaching authors of trials. Randomized trials that enrolled patients with a diagnosis of thalassemia and chronic hepatitis C infection treated with interferon or peginterferon with or without ribavirin were included. Two investigators independently evaluated the trials for inclusion criteria, risk of bias and data extraction. The primary outcomes were sustained virological response (SVR), liver-related morbidity, mortality and adverse events. The odds ratios from each trial were calculated individually and in the subgroup analysis of trials. Data were analyzed with fixed-effect model. RESULTS: Three randomized clinical trials with 92 patients were included. All three trials had unclear risk of bias. Compared with peginterferon monotherapy, adding ribavirin to peginterferon had significant beneficial effect on sustained virological response (OR = 3.44, 95% CI: 1.18 - 10.06). There was no significant difference between combination therapy and monotherapy in the end of treatment achievement response. Other than about 30% increase in blood transfusion due to anemia that returned to normal level 2 - 3 months after treatment, there was no significant increase in side effects followed by adding ribavirin to pegylated interferon (Peg-IFN). Data were insufficient to determine the impact of genotype, viral load and age on the response to treatment. CONCLUSIONS: Compared with monotherapy, adding ribavirin to treatment is more effective in removing hepatitis C virus from the bloodstream in patients with thalassemia, it is also more effective in reducing the relapse rate after treatment. Except the increase in blood transfusion, there was no significant increase in side effects followed by adding ribavirin.