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World Journal of Gastrointestinal... Apr 2024Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection...
BACKGROUND
Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.
AIM
To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.
METHODS
This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023.
RESULTS
Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC.
CONCLUSION
Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.
PubMed: 38660636
DOI: 10.4251/wjgo.v16.i4.1596 -
BioMed Research International 2020The role of -fetoprotein (AFP) in the surveillance and diagnosis of hepatocellular carcinoma (HCC) has been questioned in recent years due to its low sensitivity and... (Meta-Analysis)
Meta-Analysis
The role of -fetoprotein (AFP) in the surveillance and diagnosis of hepatocellular carcinoma (HCC) has been questioned in recent years due to its low sensitivity and specificity. In addition to AFP, several new serum biomarkers, such as lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-gamma-carboxy prothrombin (DCP), have also been identified as useful HCC serological markers. However, the exact diagnostic value of the combinations of these biomarkers for detecting HCC in patients with liver disease remains unclear. Thus, we performed the current meta-analysis to assess performance of AFP+AFP-L3%+DCP for diagnosing HCC. Studies were systematically searched in PubMed, Embase, the Cochrane Library, CNKI, and WanFang Data databases. After full-text evaluation, 13 studies from 11 articles focusing on the combination of the three serum biomarkers for HCC detection were enrolled. Random-effects models were used due to the presence of heterogeneity. The pooled sensitivity and specificity for AFP+AFP-L3%+DCP were 88% and 79%, respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.91, and the diagnostic odds ratio (DOR) was 28.33 (95% CI 16.78-47.83). Subgroup analysis showed that the pooled sensitivity and specificity of AFP+AFP-L3%+DCP in the diagnosis of HCC versus cirrhosis patients were 0.81 and 0.82, respectively. In conclusion, the combination of AFP, AFP-L3%, and DCP may prove to be useful in the diagnosis and screening of HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Prothrombin; alpha-Fetoproteins
PubMed: 33015170
DOI: 10.1155/2020/5087643 -
The Cochrane Database of Systematic... Apr 2021Hepatocellular carcinoma (HCC) occurs mostly in people with chronic liver disease and ranks sixth in terms of global instances of cancer, and fourth in terms of cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatocellular carcinoma (HCC) occurs mostly in people with chronic liver disease and ranks sixth in terms of global instances of cancer, and fourth in terms of cancer deaths for men. Despite that abdominal ultrasound (US) is used as an initial test to exclude the presence of focal liver lesions and serum alpha-foetoprotein (AFP) measurement may raise suspicion of HCC occurrence, further testing to confirm diagnosis as well as staging of HCC is required. Current guidelines recommend surveillance programme using US, with or without AFP, to detect HCC in high-risk populations despite the lack of clear benefits on overall survival. Assessing the diagnostic accuracy of US and AFP may clarify whether the absence of benefit in surveillance programmes could be related to under-diagnosis. Therefore, assessment of the accuracy of these two tests for diagnosing HCC in people with chronic liver disease, not included in surveillance programmes, is needed.
OBJECTIVES
Primary: the diagnostic accuracy of US and AFP, alone or in combination, for the diagnosis of HCC of any size and at any stage in adults with chronic liver disease, either in a surveillance programme or in a clinical setting. Secondary: to assess the diagnostic accuracy of abdominal US and AFP, alone or in combination, for the diagnosis of resectable HCC; to compare the diagnostic accuracy of the individual tests versus the combination of both tests; to investigate sources of heterogeneity in the results.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic-Test-Accuracy Studies Register, Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, until 5 June 2020. We applied no language or document-type restrictions.
SELECTION CRITERIA
Studies assessing the diagnostic accuracy of US and AFP, independently or in combination, for the diagnosis of HCC in adults with chronic liver disease, with cross-sectional and case-control designs, using one of the acceptable reference standards, such as pathology of the explanted liver, histology of resected or biopsied focal liver lesion, or typical characteristics on computed tomography, or magnetic resonance imaging, all with a six-months follow-up.
DATA COLLECTION AND ANALYSIS
We independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS-2 checklist. We presented the results of sensitivity and specificity, using paired forest-plots, and tabulated the results. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double-checked all data extractions and analyses.
MAIN RESULTS
We included 373 studies. The index-test was AFP (326 studies, 144,570 participants); US (39 studies, 18,792 participants); and a combination of AFP and US (eight studies, 5454 participants). We judged at high-risk of bias all but one study. Most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time-interval between the index test and the reference standard was rarely defined. Most studies with AFP had a case-control design. We also had major concerns for the applicability due to the characteristics of the participants. As the primary studies with AFP used different cut-offs, we performed a meta-analysis using the hierarchical-summary-receiver-operating-characteristic model, then we carried out two meta-analyses including only studies reporting the most used cut-offs: around 20 ng/mL or 200 ng/mL. AFP cut-off 20 ng/mL: for HCC (147 studies) sensitivity 60% (95% CI 58% to 62%), specificity 84% (95% CI 82% to 86%); for resectable HCC (six studies) sensitivity 65% (95% CI 62% to 68%), specificity 80% (95% CI 59% to 91%). AFP cut-off 200 ng/mL: for HCC (56 studies) sensitivity 36% (95% CI 31% to 41%), specificity 99% (95% CI 98% to 99%); for resectable HCC (two studies) one with sensitivity 4% (95% CI 0% to 19%), specificity 100% (95% CI 96% to 100%), and one with sensitivity 8% (95% CI 3% to 18%), specificity 100% (95% CI 97% to 100%). US: for HCC (39 studies) sensitivity 72% (95% CI 63% to 79%), specificity 94% (95% CI 91% to 96%); for resectable HCC (seven studies) sensitivity 53% (95% CI 38% to 67%), specificity 96% (95% CI 94% to 97%). Combination of AFP (cut-off of 20 ng/mL) and US: for HCC (six studies) sensitivity 96% (95% CI 88% to 98%), specificity 85% (95% CI 73% to 93%); for resectable HCC (two studies) one with sensitivity 89% (95% CI 73% to 97%), specificity of 83% (95% CI 76% to 88%), and one with sensitivity 79% (95% CI 54% to 94%), specificity 87% (95% CI 79% to 94%). The observed heterogeneity in the results remains mostly unexplained, and only in part referable to different cut-offs or settings (surveillance programme compared to clinical series). The sensitivity analyses, excluding studies published as abstracts, or with case-control design, showed no variation in the results. We compared the accuracy obtained from studies with AFP (cut-off around 20 ng/mL) and US: a direct comparison in 11 studies (6674 participants) showed a higher sensitivity of US (81%, 95% CI 66% to 90%) versus AFP (64%, 95% CI 56% to 71%) with similar specificity: US 92% (95% CI 83% to 97%) versus AFP 89% (95% CI 79% to 94%). A direct comparison of six studies (5044 participants) showed a higher sensitivity (96%, 95% CI 88% to 98%) of the combination of AFP and US versus US (76%, 95% CI 56% to 89%) with similar specificity: AFP and US 85% (95% CI 73% to 92%) versus US 93% (95% CI 80% to 98%).
AUTHORS' CONCLUSIONS
In the clinical pathway for the diagnosis of HCC in adults, AFP and US, singularly or in combination, have the role of triage-tests. We found that using AFP, with 20 ng/mL as a cut-off, about 40% of HCC occurrences would be missed, and with US alone, more than a quarter. The combination of the two tests showed the highest sensitivity and less than 5% of HCC occurrences would be missed with about 15% of false-positive results. The uncertainty resulting from the poor study quality and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results.
Topics: Abdomen; Adult; Bias; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Chronic Disease; Confidence Intervals; Cross-Sectional Studies; Female; Humans; Liver Diseases; Liver Neoplasms; Male; Sensitivity and Specificity; Ultrasonography; alpha-Fetoproteins
PubMed: 33855699
DOI: 10.1002/14651858.CD013346.pub2 -
Heliyon Aug 2023Traditional Chinese medicine and radiofrequency ablation are becoming increasingly important in the treatment of primary liver cancer. However, the clinical outcome of...
BACKGROUND & AIMS
Traditional Chinese medicine and radiofrequency ablation are becoming increasingly important in the treatment of primary liver cancer. However, the clinical outcome of traditional Chinese medicine plus radiofrequency ablation is contentious. This study aimed to conduct a meta-analysis of randomized controlled clinical trials to address this gap.
METHODS
Short-term efficacy, alpha-fetoprotein level, immune function, liver function, and quality of life outcomes in patients with primary liver cancer treated with Chinese herbal medicine adjuvant radiofrequency ablation were systematically reviewed.
RESULTS
Eighteen randomized controlled clinical trials with 1488 patients with primary liver cancer were included. The combination treatment significantly increased the objective remission rate and quality of patient survival compared to the control group. Combination treatment significantly improved immunity and liver function factors, including CD3, CD4, CD4/CD8, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and albumin levels. However, there were no statistical differences in CD8 levels across treatments. Trial sequential analysis showed that the cumulative Z-curve of the Objective response rate crossed the conventional and test sequence monitoring boundaries; however, it did not cross the required information size line.
CONCLUSIONS
Traditional Chinese medicine combined with radiofrequency ablation for primary liver cancer can effectively reduce alpha-fetoprotein and improve clinical efficacy, immune function, liver function, as well as the quality of life.
PubMed: 37554780
DOI: 10.1016/j.heliyon.2023.e18591 -
Medicine Sep 2021The present network meta-analysis was conducted to perform an indirect comparison among ramucirumab, regorafenib, and cabozantinib in patients with advanced... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety for second-line treatment with ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma progressed on sorafenib treatment: A network meta-analysis.
BACKGROUND
The present network meta-analysis was conducted to perform an indirect comparison among ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma (HCC) progressed on sorafenib treatment.
METHODS
A systematic review through Medline, Embase, and Cochrane library was developed, with eligible randomized clinical trials been included. Hazard ratios (HRs) including progression-free survival (PFS), overall survival (OS), odds ratios of disease control rate (DCR), objective response rate (ORR), and adverse events were compared indirectly with network meta-analysis using random model in software STATA version 13.0.
RESULTS
A total of 4 randomized clinical trials including 2137 patients met the eligibility criteria and enrolled. Indirect comparisons showed that there was no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among agents of regorafenib, cabozantinib, and ramucirumab in advanced HCC patients with elevated α-fetoprotein (AFP) (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib was the only agent associated with significant superiority in OS, compared with placebo (hazard ratio 0.67, 95% CI, 0.50-0.90).
CONCLUSIONS
The present network meta-analysis revealed that there might be no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among regorafenib, cabozantinib, or ramucirumab in advanced HCC patients with elevated AFP (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib might be associated with significant superiority in OS, compared to placebo, which need further investigation in clinical practice.
Topics: Anilides; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Drug Administration Schedule; Humans; Liver Neoplasms; Neoplasm Metastasis; Phenylurea Compounds; Pyridines; Randomized Controlled Trials as Topic; Sorafenib; Ramucirumab
PubMed: 34559096
DOI: 10.1097/MD.0000000000027013 -
BMC Gastroenterology Mar 2023The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis.
METHODS
36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software.
RESULTS
The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74-0.83),0.85(95%CI 0.80-0.89),5.4(95%CI 3.8-7.5), 0.25(95%CI 0.20-0.31), 22(95%CI 13-35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64-0.81),0.70(95%CI 0.49-0.85),2.40(95%CI 1.3-4.7),0.38(95%CI 0.23-0.61),6(95%CI 2-19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis.
CONCLUSION
The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Membrane Proteins; Liver Cirrhosis; Fibrosis; Biomarkers, Tumor
PubMed: 36964524
DOI: 10.1186/s12876-023-02685-8 -
Case Reports in Surgery 2018Primary hepatic lymphomas (PHLs) are rare liver tumors, frequently misdiagnosed preoperatively. As these tumors could be successfully treated with chemotherapy, their...
INTRODUCTION
Primary hepatic lymphomas (PHLs) are rare liver tumors, frequently misdiagnosed preoperatively. As these tumors could be successfully treated with chemotherapy, their early recognition is essential, potentially, to avoid useless surgery. We report on the case of a cirrhotic patient with hemochromatosis who presented a PHL, initially diagnosed as a hepatocellular carcinoma (HCC), and we analyze recent data from the literature on this subject.
CASE PRESENTATION AND REVIEW OF THE LITERATURE
A 45 mm liver tumor was found is a 68-year-old man with alcohol cirrhosis and hemochromatosis. At imaging, the diagnosis of HCC was suspected according to vascular characteristics and the presence of cirrhosis. FDG PET scan showed a solitary hypermetabolic liver tumor. Tumor markers were negative. Surgery consisted in left lateral hepatectomy. At pathology, the diagnosis of the primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type was demonstrated. Twenty-two articles reporting 33 cases of true PHL of MALT type were found. Presentation lacked specific symptoms (70% asymptomatic). Half of patients were suspected to have other etiologies of liver mass (HCC, intrahepatic cholangiocarcinoma), and thus diagnosis was established postoperatively. In the patient, diagnosis was made by preoperative biopsy, and chemotherapy was first-line treatment.
DISCUSSION
Preoperative diagnosis of PHL, and particularly of primary hepatic MALT lymphoma, is challenging. This case illustrates that PHL remains to be considered among the differential diagnosis of isolated solid liver tumors. Further, it indicates that biopsy could be still indicated in case of suspected HCC in cirrhotic patients, particularly in the presence of unusual findings such as the combination of a FDG PET scan positive tumor in the absence of elevated alpha-fetoprotein.
PubMed: 29850362
DOI: 10.1155/2018/9183717 -
The Cochrane Database of Systematic... Feb 2019Hepatocellular carcinoma, also called malignant hepatoma, is a primary malignancy of the liver. Despite regular surveillance conducted in high-risk populations, most... (Meta-Analysis)
Meta-Analysis
Transcatheter arterial chemoembolisation followed by three-dimensional conformal radiotherapy versus transcatheter arterial chemoembolisation alone for primary hepatocellular carcinoma in adults.
BACKGROUND
Hepatocellular carcinoma, also called malignant hepatoma, is a primary malignancy of the liver. Despite regular surveillance conducted in high-risk populations, most people with hepatocellular carcinoma are diagnosed at an advanced stage. Consequently, only a minority of people with the disease are suitable for surgical resection when diagnosed.
OBJECTIVES
To compare the beneficial and harmful effects of transcatheter arterial chemoembolisation (TACE) followed by three-dimensional conformal radiotherapy (3-DCRT) versus TACE alone in adults with primary hepatocellular carcinoma, considered unsuitable for surgical resection.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science up to 31 May 2018. We checked reference lists for all included studies and related reviews for further relevant articles.
SELECTION CRITERIA
We included all randomised clinical trials comparing TACE followed by 3-DCRT versus TACE alone in people with primary hepatocellular carcinoma.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as suggested by Cochrane. We presented the results of the fixed-effect model in the absence of statistical heterogeneity. Otherwise, we reported the results from the random-effects model meta-analysis. We assessed risk of bias of the included trials using bias risk domains and presented the review results incorporating the methodological quality of the trials using GRADE. Our main conclusions were based on the analysis up to three years' follow-up.
MAIN RESULTS
We identified eight randomised clinical trials (632 participants) that fulfilled our inclusion criteria. All eight trials were at high risk of bias, and we rated the evidence as low to very low certainty. The mean age ranged from 16 years to 78 years. The proportion of men ranged from 60% to 75% and the proportion of people with stage III primary hepatocellular carcinoma ranged from 22% to 85%. The median follow-up duration was 12 months (2 months to 38 months).TACE followed by 3-DCRT compared with TACE alone may have reduced all-cause mortality at three years' follow-up (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.73 to 0.88; 552 participants; 7 trials; low-certainty evidence). TACE followed by 3-DCRT compared with TACE alone may reduce the proportion of participants without tumour response (complete response plus partial response) (RR 0.49, 95% CI 0.39 to 0.61; 632 participants; 8 trials; low-certainty evidence). Data, from one trial on health-related quality of life, favoured the TACE followed by 3-DCRT group, but the provided data were ill-defined (very low-certainty evidence). None of the trials reported serious adverse events. The results on non-serious adverse events were as follows: TACE followed by 3-DCRT compared with TACE alone showed no difference in the results for proportion of participants with leukopenia (RR 1.12, 95% CI 0.92 to 1.34; 438 participants; 5 trials; very low-certainty evidence) and serum transaminases elevation (RR 1.67, 95% CI 0.66 to 4.27; 280 participants; 4 trials; very low-certainty evidence). However, the proportion of participants with total bilirubin elevation was larger in the TACE followed by 3-DCRT group than in the TACE alone group (RR 2.69, 95% CI 1.34 to 5.40; 172 participants; 2 trials; very low-certainty evidence). The rate of participants with serum alpha-fetoprotein (AFP) without decline or normalisation was significantly lower in the TACE followed by 3-DCRT group than in the TACE group, but these data were from one trial only (Chi² = 7.24, P = 0.007; very low-certainty evidence).
AUTHORS' CONCLUSIONS
TACE followed by 3-DCRT may be associated with lower all-cause mortality and increased tumour response, despite the increased toxicity expressed by a higher rise of total bilirubin. Our review findings should be considered with caution because of the methodological weaknesses in the included trials, resulting in low- to very low-certainty evidence. Data on serious adverse events and health-related quality of life are lacking. We are also very much uncertain in the results of the reported non-serious adverse events. High-quality trials are needed to assess further the role of TACE followed by 3-DCRT for unresectable hepatocellular carcinoma.
Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Cause of Death; Chemoembolization, Therapeutic; Combined Modality Therapy; Female; Humans; Liver Neoplasms; Male; Middle Aged; Radiotherapy, Conformal; Randomized Controlled Trials as Topic; Young Adult
PubMed: 30776082
DOI: 10.1002/14651858.CD012244.pub2