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BACKGROUND AND AIMS: Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown. MATERIALS: We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis. RESULTS: The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC. CONCLUSIONS: We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
Subject(s)
17-Hydroxysteroid Dehydrogenases , Carcinoma, Hepatocellular , Genetic Predisposition to Disease , Hepatitis B, Chronic , Lipase , Liver Neoplasms , Membrane Proteins , Polymorphism, Single Nucleotide , Humans , Membrane Proteins/genetics , Lipase/genetics , Female , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/genetics , Liver Neoplasms/virology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , 17-Hydroxysteroid Dehydrogenases/genetics , Case-Control Studies , Hepatitis B, Chronic/genetics , Hepatitis B, Chronic/complications , Prognosis , Adult , Turkey/epidemiology , Risk Factors , Prospective Studies , Phenotype , Genetic Association Studies , Acyltransferases , Phospholipases A2, Calcium-IndependentABSTRACT
Background and Aim: Transarterial Chemoembolization (TACE) therapy is currently considered as first option therapy in the intermediate stage HCC. The purpose of our study is to assess the efficacy and prognostic factors related to the DEB- TACE therapy. Materials and Methods: The data from 133 patients with unresecetable HCC who were treated with DEB-TACE and followed between January 2011-March 2018 were retrospectively evaluated. To assess the efficacy of therapy, control imagings were performed at 30th and 90th days after the procedure. Response rates, survival outcomes, and prognostic factors were investigated. Results: According to the Barcelona staging system, 16 patients (13%) were in the early stage, 58 patients (48%) were in the intermediate stage and 48 patients (39%) were in the advanced stage. There were complete response (CR) in 20 patients (17%), partial response (PR) in 36 patients (32%), stable disease (SD) in 24 patients (21%) and progressed disease (PD) in 35 (30%) patients. Median follow-up time was 14 months (range 1-77 months). Median PFS and OS were 4 months and 11 months, respectively. In multivariate analysis, posttreatment AFP ≥400 ng/ml was found to be an independent prognostic factor on both PFS and OS. Child-Pugh classification and tumor size >7 cm were independent prognostic factors on OS. Conclusion: DEB-TACE is effective and a tolerable treatment method for unresectable HCC patients.
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Optimal scoring system for clinical prognostic factors in patients with unresectable hepatocellular carcinoma (HCC) is currently uncertain. We aimed to develop and externally validate an easy to use tool, particularly for this population, and named it the "unresectable hepatocellular carcinoma prognostic index" (UHPI). We evaluated the data of patients with treatment-naive unresectable HCC who were diagnosed in the training center from 2010 to 2019 (n = 209). A simple prognostic model was developed by assigning points for each covariate in proportion to the beta coefficients in the Cox multivariable model. Predictive performance and distinction ability of the UHPI were further evaluated in an independent European validation cohort (n = 147) and compared with 11 other available models. A simple scoring system was derived, assigning 0.5/1/2 scores for six independent covariates including, the Child-Pugh score, Eastern Cooperative Oncology Group performance status, maximum tumor size, vascular invasion or extrahepatic metastasis, lymph node involvement, and alpha-fetoprotein. The UHPI score, ranging from 0 to 6, showed superior performance in prognosis prediction and outperformed 11 other staging or prognostic models, giving the highest homogeneity (c-index, 6-month and 1-year area under the receiver operator characteristic curves), lowest Akaike information criterion, and -2 log-likelihood ratio values. The UHPI score allocated well the risk of patients with unresectable HCC for mortality within the first year, using two cut-off values (low-risk, <0.5; intermediate-risk, 0.5-2; high-risk, >2). Conclusion: The UHPI score can predict prognosis better than other systems in subjects with unresectable HCC and can be used in clinical practice or trials to estimate the 6-month and 1-year survival probabilities for this group.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/diagnosis , Cohort Studies , Humans , Liver Neoplasms/diagnosis , Prognosis , Proportional Hazards ModelsABSTRACT
Currently, international liver societies recommend screening at-risk individuals for HCC (patients with cirrhosis regardless of etiology, and/or chronic hepatitis B virus, and/or advanced liver fibrosis) with biannual abdominal ultrasound (USG) with or without alpha-fetoprotein (AFP). The global acceptance of USG in surveillance relies on the absence of risks, non-invasiveness, and lower costs. However, the suboptimal performance of USG ± AFP in reaching direct and indirect goals of HCC surveillance highlights the need for alternative surveillance strategies. Several studies targeted contrast-enhanced magnetic resonance imaging techniques, but the main barriers for their entrance to surveillance programs have been concerns about cost-effectivity and long scan times. Overall, the HCC risk stratification appears at hand by several validated multiple score systems, but their optimal performance is obtained only in populations who show highly homogenous clinical, pathological, epidemiologic, etiologic, and therapeutic characteristics, and this limitation poses a major drawback to their sustainable use in clinical practice. We need globally validated and molecular integrated risk stratification tools to shape the future tailored HCC surveillance decision algorithms. A dynamic process for HCC surveillance algorithms awaits us owing to the expected further prospective studies focusing on risk-stratified screening strategy.
Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/epidemiology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/epidemiology , Public Health Surveillance/methods , Carcinoma, Hepatocellular/pathology , Humans , Liver Cirrhosis/complications , Liver Neoplasms/pathology , Risk Assessment , Risk FactorsABSTRACT
In recent years, immune-based therapies have emerged as novel pillars for hepatocellular carcinoma (HCC). The rationale of immune-checkpoint inhibitors (ICIs) trial in HCC originated from the fact that the tumor cells and the infiltrating stromal and immune cells promote an immunosuppressive tumor microenvironment, including the up-regulation of immune checkpoint molecules on their surface. Antibody-based blockage targeting inhibitory checkpoint molecules on cytotoxic T cells, including programmed cell death-1 (PD-1) or its counterpart on antigen-presenting cells has shown strong anti-tumor activity in a subset of HCC patients. Single nucleotide polymorphisms (SNP) of PD-1 gene may affect the PD-1 expression or function, which eventually can cause dysfunctionality of immune balance. Based on the inhibitory role of PD-1 in anti-tumor responses, it has been investigated in several studies as a candidate to test for genetic susceptibility of individuals to HCC. The present paper highlights the knowledge on cross-talks for liver immunology and HCC course, recent studies investigating the role of functional SNPs of PD-1 gene in Turkish HCC population, and the data on already investigated PD-1 inhibitor molecules in clinical trials.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Immune Checkpoint Inhibitors/pharmacology , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Programmed Cell Death 1 Receptor/genetics , Apoptosis , Carcinoma, Hepatocellular/pathology , Humans , Immunotherapy , Liver Neoplasms/pathology , Polymorphism, Single Nucleotide , Programmed Cell Death 1 Receptor/drug effects , TurkeyABSTRACT
AIMS: To evaluate patient profile for epidemiological and clinicopathological characteristics and potential risk/prognostic factors in newly diagnosed hepatocellular carcinoma (HCC) patients across Turkey. METHODS: A total of 547 patients (mean (SD) age 62.6 (10.3) years, 81.9% were males) were included in this registry study. Data on patient characteristics, etiologies of HCC, laboratory values, and tumor characteristics and stages were recorded at study enrollment. RESULTS: HBV infection (68.2%) was the leading etiology, followed by HCV infection (17.2%), HDV infection (5.5%), alcohol (6.4%), and NAFLD (3.5%), as the major etiologies. Considering that 51.6% of the patients had >5 cm HCC, 44% were Child-Pugh B/C and 57% were BCLC B-D, it appears that a significant group of HCC patients were diagnosed at advanced stages. Of 540 patients, 271 (50.2%) were referred or applied with the diagnosis of HCC. Patients with HCC at presentation had larger tumor size (median (min-max) 6.6 (0-30) vs. 4.8 (0-90) cm, P < .001) and more advanced BCLC stage (Stage C-D in 40.8% vs. 26.4%, respectively, P = .005), compared to patients who were diagnosed during follow-up. CONCLUSIONS: Our findings revealed that HBV infection was the leading etiology and a moderate-to-advanced disease was evident in more than half of patients at the time of diagnosis. HCC patients diagnosed at follow-up had smaller tumor size and earlier BCLC stage.
Subject(s)
Abdominal Pain/etiology , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Non-alcoholic Fatty Liver Disease/complications , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/epidemiology , Female , Humans , Liver Neoplasms/epidemiology , Male , Middle Aged , Prospective Studies , Registries , Turkey/epidemiology , Weight LossABSTRACT
BACKGROUND: A small proportion of all hepatocellular carcinomas (HCCs) arise in a non-cirrhotic liver (NCL). However, our knowledge about the HCCs developing in a NCL is scarce. This study was undertaken to investigate the characteristics and survival course of this patient group. METHODS: We retrospectively analyzed the database of patients with HCC at a tertiary center during a 10-year period (2009-2019). All demographic, clinical, laboratory, and tumoral features with survival outcomes were compared between the HCC-CL and HCC-NCL groups. RESULTS: Out of 384 HCC cases, 11.2% (n = 43) had no cirrhosis. The dominant etiology in the HCC-NCL group was hepatitis B virus (n = 26, 60.5%), followed by non-alcoholic fatty liver disease (n = 10, 23.2%), and hepatitis C virus (n = 7, 16.3%). The maximum tumor diameter was approximately 2 times larger in the HCC-NCL group (HCC-NCL: 90 mm vs. HCC-CL: 46.5 mm, P < .001). The proportion of patients with vascular (HCC-NCL: 27.9% vs. HCC-CL: 8.6%, P < .001) and extrahepatic invasion (HCC-NCL: 14% vs. HCC-CL: 3%, P = .001) were prominently higher in the HCC-NCL group. Patients with HCC-NCL were less often detected in early-curable stages (BCLC 0-A) than those in the HCC-CL group (HCC-NCL: 16.3% vs. HCC-CL: 34.9%, P = .004). The overall survival was not different between the 2 groups (HCC-NCL: 19.4 ± 9.8 months vs. HCC-CL: 17.5 ± 2.3 months, P = .581). CONCLUSION: HCC in NCL is diagnosed at more advanced tumoral stages with larger tumor size and more often with vascular and extrahepatic spread. Despite the preserved liver functions, the overall survival is not prolonged in HCCs without cirrhosis, due to the late recognition.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/pathology , Humans , Liver Cirrhosis/epidemiology , Liver Neoplasms/epidemiology , Liver Neoplasms/pathology , Neoplasm Staging , Retrospective StudiesABSTRACT
In the midst of Coronavirus-19 (COVID-19) pandemic, endoscopic procedures have been separated for only urgent and semi-urgent cases for the last few months to prevent transmission in endoscopy units. This approach will perhaps resolve the burden of elective procedures in the months ahead of us. As we observe a downtrend in new cases of COVID-19 in Turkey, a strategy for reopening endoscopy units is required. We are stepping into a time period where we should not only re-provide the essential services to our patients but also maintain the safety of healthcare workers and preserve the valuable personal protective equipment as well. Herein, we aim to share the available knowledge in performing endoscopy during the pandemic and the set-up plan of a tertiary center in Istanbul for reopening the endoscopy unit in the era of the COVID-19 pandemic.
Subject(s)
COVID-19/prevention & control , Endoscopy/standards , Infection Control/standards , Tertiary Care Centers/standards , Health Personnel/standards , Humans , Infection Control/methods , Personal Protective Equipment/standards , Personal Protective Equipment/supply & distribution , SARS-CoV-2 , TurkeyABSTRACT
Background and Aim: The coexistence of metabolic-associated fatty liver disease (MAFLD) in the course of chronic hepatitis B virus infection increases liver-related morbidity. A positive correlation was found between positive hepatitis B core antibody (anti-HBc) and the risk of cirrhosis and hepatocellular carcinoma (HCC) in MAFLD. The relationship between anti-HBc positivity and MAFLD progression to fibrosis, cirrhosis, and liver-related outcomes was determined. Materials and Methods: This is a retrospective study including 242 patients with biopsy-proven MAFLD, 130 patients with clinically diagnosed MAFLD-related cirrhosis, and 62 patients with MAFLD-related or cryptogenic HCC. Anti-HBc antibody results were compared with clinical outcomes. Results: Anti-HBc positivity was associated with fibrosis severity (p=0.005). Anti-HBc was positive in 19 (20.2%), 33 (25.8%), 53 (35.3%), and 27 (43.5%) patients with F0-F1 fibrosis, F2-F3 fibrosis, cirrhosis (F4), and HCC, respectively. Median steatosis score was grade 3 in anti-HBc positive patients and grade 2 in negative patients (p=0.07). Anti-HBc positivity was not associated with significant fibrosis (≥F2), cirrhosis, and any liver related complications including HCC. Conclusion: Higher anti-HBc positivity was found in MAFLD patients with advanced fibrosis and cirrhosis compared to patients with early stage fibrosis. No relation was found between anti-HBc positivity and development of cirrhosis, HCC or other liver related complications.
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BACKGROUND/AIMS: Room air (RA) and carbon dioxide (CO2) are widely used to insufflate the colon to examine the mucosa in colonoscopy. Pain, discomfort, and bloating can be seen during and after colonoscopy secondary to bowel distention. This study aimed to investigate the effect of CO2 on post-procedure pain sensation (PPPS) in comparison with RA. MATERIALS AND METHODS: Patients were randomly assigned to the RA and CO2 insufflation groups in a 1:1 ratio. The visual analog scale (VAS) was used to measure the pain before and after the colonoscopy. VAS score of 0 was accepted as the absence of pain and above 0 was accepted as the presence of pain. The primary outcome was to investigate the effect of CO2 insufflation on PPPS. Secondary outcomes were to investigate the other contributing factors affecting PPPS and the effect of CO2 on PPPS in patients with inflammatory bowel disease (IBD). RESULTS: A total of 204 patients were enrolled in the study. No significant difference in PPPS was seen between the 2 groups at any point in time after the colonoscopy. Furthermore, there was no significant difference in pain sensation between the CO2 and RA groups in patients with IBD. When we investigated the other contributing factors to pain sensation, body-mass index (BMI) was found to be significant at 30 minutes and BMI and colonoscopy time were found to be significant at 6 hours afterwards. CONCLUSION: We found no favorable effect of CO2 insufflation on PPPS in colonoscopy, including in patients with IBD.
Subject(s)
Abdominal Pain/etiology , Colonoscopy , Inflammatory Bowel Diseases/surgery , Insufflation/adverse effects , Pain, Procedural/etiology , Adult , Air , Body Mass Index , Carbon Dioxide/administration & dosage , Female , Humans , Inflammatory Bowel Diseases/complications , Insufflation/methods , Male , Middle Aged , Operative Time , Pain Measurement , Prospective StudiesABSTRACT
BACKGROUND AND AIMS: Programmed cell death-1 (PD-1) has a vital role in regulating T-cell function, and immune escape mechanism of cancer cells. It was shown that there could be a relationship between single nucleotide polymorphisms (SNPs) in the PD-1 gene and susceptibility to hepatocellular carcinoma (HCC) based on various studies. We aimed to investigate the role of three SNPs within the PD-1 gene in susceptibility to HCC in the Turkish population. METHODS: Single nucleotide polymorphisms of PD-1.1, 1.5, and 1.6 were genotyped by using TaqMan Allelic Discrimination Assays in blood samples of 137 HCC and 136 control subjects, matched for age and gender. The genotype, allele and haplotype frequencies were compared in HCC and control groups using logistic regression analysis. RESULTS: Genotype distributions of PD-1.1, PD-1.5 and PD-1.6 SNPs were in Hardy-Weinberg equilibrium. No significant difference was observed in the genotype distribution of PD-1.1, PD-1.5 and PD-1.6 polymorphisms among gender and age-matched HCC (M/F: 96/41; mean age: 61.4 ±11.7 years) and control group (M/F: 94/42; mean age: 61.4±10.1). In the haplotype analysis of PD-1.1/PD-1.5/PD-1.6, no significant difference was found among HCC and control group adjusted for sex and age (all p values>0.1). CONCLUSION: Our findings, firstly reporting the association of PD-1.5 polymorphism with HCC, and PD-1.1 and PD-1.6 with HCC in the Turkish population, suggest that PD-1 polymorphisms are not predisposing factors for HCC development. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , Programmed Cell Death 1 Receptor/genetics , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Pilot Projects , TurkeyABSTRACT
OBJECTIVES: Toronto hepatocellular carcinoma risk index is developed to stratify cirrhotic patients according to 10-year hepatocellular carcinoma risk. We aimed to validate the performance of Toronto hepatocellular carcinoma risk index in a large Turkish cohort. MATERIALS AND METHODS: We retrospectively reviewed the database of 1287 cirrhotic patients followed-up in a 10-year period (February 2008 to January 2018). All patients were stratified into three groups based on the Toronto hepatocellular carcinoma risk index score as follows: low-risk, < 120; intermediate risk, 120 to 240; and high risk, > 240. Area under the curve and optimal cutoff value of Toronto hepatocellular carcinoma risk index were obtained from receiver operator curve. To reveal the parameters related with hepatocellular carcinoma development, logistic regression analysis was conducted. The cumulative incidences of hepatocellular carcinoma were calculated using the Kaplan-Meier method, and the curves were compared using the log-rank test. RESULTS: Out of 403 enrolled patients, 57 developed hepatocellular carcinoma. The median Toronto hepatocellular carcinoma risk index value was higher in hepatocellular carcinoma (+) group comparing to hepatocellular carcinoma (-) group [267 (70-366) vs. 224 (36-366), P < 0.001]. Out of 57 detected hepatocellular carcinomas, 45 (78.9%) were high risk, 11 (19.3%) were intermediate risk, and only one (1.8%) was low risk at the entry. The area under the curve of the Toronto hepatocellular carcinoma risk index to predict hepatocellular carcinoma was 0.750 (95% confidence interval, 0.683-0.817, P < 0.001). The optimal cutoff value of Toronto hepatocellular carcinoma risk index was 239.5, giving a sensitivity of 78.9% and specificity of 62.7%. As a result, Toronto hepatocellular carcinoma risk index remained to be the only significant parameter that has an affect on hepatocellular carcinoma development [adjusted-odds ratio: 1.016 (95% confidence interval, 1.007-1.024), P<0.001]. CONCLUSION: The present study validated the performance of Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients to predict hepatocellular carcinoma risk, which can be considered as a tool for personalized surveillance.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Retrospective Studies , Risk FactorsABSTRACT
Background and Aim: Hepatocellular carcinoma (HCC) is a life-threatening condition of the liver, often concurrent with vitamin D deficiency. In this study, we investigated the relationship between HCC patients' vitamin D levels and overall survival. Materials and Methods: We retrospectively enrolled patients that were being followed on their HCC diagnosis. We collected and examined data on patients' 25-OH vitamin D levels one month before diagnosis or at any point thereafter. We took levels below 10 ng/mL to indicate severe deficiency, levels between 10 ng/mL and 20 ng/mL to indicate moderate deficiency, and levels between 20 ng/mL and 30 ng/mL to indicate mild deficiency. We then analyzed the effects of vitamin D levels on patients' survival for each of these brackets. Results: We included 85 patients in our survival analyses. We found 9 ng/mL to be the significant cutoff vitamin D level for survival. Vitamin D levels were lower in cases of advanced disease. Univariate analysis showed that advanced Barcelona Clinic Liver Cancer (BCLC) grades, vitamin D levels below 9 ng/mL, and alpha-fetoprotein (AFP) levels above 400 ng/dL had a negative significant effect on survival. Multivariate analysis showed that only advanced BCLC grades and AFP levels above 400 ng/dL had a negative significant effect. Conclusion: In our study's cohort, HCC grades and AFP levels had a substantial negative impact on patients' overall survival. We found no connection, however, between vitamin D levels and overall survival.
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BACKGROUND/AIMS: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population. MATERIAL AND METHODS: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)±ribavirin (RBV) orombitasvir/paritaprevir/ritonavir±dasabuvir (PrOD)±RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed. RESULTS: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90±54.60 U/L to 17.00±14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51±4.54 to 7.32±3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0±16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%). CONCLUSION: LDV/SOF or PrOD±RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.
Subject(s)
Anilides/administration & dosage , Antiviral Agents/administration & dosage , Benzimidazoles/administration & dosage , Cyclopropanes/administration & dosage , Fluorenes/administration & dosage , Hepatitis C, Chronic/drug therapy , Lactams, Macrocyclic/administration & dosage , Proline/analogs & derivatives , Ritonavir/administration & dosage , Sofosbuvir/administration & dosage , Sulfonamides/administration & dosage , Valine/administration & dosage , Aged , Drug Therapy, Combination , Female , Hepacivirus/drug effects , Humans , Male , Middle Aged , Proline/administration & dosage , Prospective Studies , Retrospective Studies , Treatment Outcome , TurkeyABSTRACT
OBJECTIVES: Biannual ultrasonography, a globally accepted surveillance method, has low sensitivity in detecting early-stage hepatocellular carcinoma (HCC). We aimed to investigate the effectiveness of a surveillance strategy using annual contrast-enhanced MRI to detect HCCs at early-stage. MATERIALS AND METHODS: We reviewed the data of 294 patients with consistent annual contrast-enhanced MRI and biannual alpha fetoprotein (AFP) surveillance between 2008 and 2017. Patients were stratified for HCC risk as low-intermediate-high risk group using Toronto risk score. HCCs were classified according to Barcelona Clinic Liver Cancer staging system. RESULTS: Thirty-five (11.9%) HCCs were detected with annual surveillance MRI. Of those, 30 (85.8%) were early-stage and 15 (42.9%) were very early-stage. The majority of patients (82.9%) with surveillance detected HCC were high risk at the entry. MRI had sensitivity of 83.3 and 80% with a specificity of 95.4 and 91.4%, for detecting early and very early-stage HCC, respectively. Addition of AFP to MRI displayed similar sensitivity and specificity rates to detect early and very early HCCs. The area under the curve of MRI alone and combination with AFP was not statistically different (Any-HCC: 0.905 vs. 0.924; Early-HCC: 0.853 vs. 0.885; Very early-HCC: 0.838 vs. 0.885, respectively, all P values >0.2). CONCLUSION: Annual MRI strategy demonstrated a satisfactory performance in the surveillance of HCC, in terms of detecting most of the lesions in earlier curable stages and indicating high sensitivity with no additional benefit of biannual AFP. New risk stratified screening algorithms may further increase the yield of HCC surveillance among cirrhotic patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Cirrhosis/diagnostic imaging , Liver Neoplasms , Magnetic Resonance Imaging/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/epidemiology , Early Detection of Cancer/methods , Female , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/epidemiology , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Assessment , Watchful Waiting/methods , alpha-Fetoproteins/analysisABSTRACT
BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is known to impair the quality of life (QoL). Increased levels of anxiety and depression have been found in HCV infection with a prevalence of 28% and 33%, respectively. Our aim was to investigate depression, anxiety, and QoL of chronic hepatitis C (CHC) patients before and after treatment with a direct-acting antiviral agent (DAAA). MATERIALS AND METHODS: In this study, enrolled CHC patients who had undergone DAAA treatment in our out-patient clinic. We administered the Hospital Anxiety and Depression (HAD) questionnaire to measure the severity of the anxiety and depression symptoms and the Short Form-36 (SF-36) questionnaire to measure the QoL at the beginning and at the end of the treatment. RESULTS: Pretreatment anxiety and depression scores showed a statistically significant difference from the post treatment scores (p=0.000 and p=0.029 respectively). When we compared the SF-36 subitems before and after the treatment, a statistical significance was found in physical functioning (p=0.026), physical role limitation (p=0.009), bodily pain (p=0.011), general health (p=0.017), social functioning (p=0.006), and emotional role limitation (p=0.007). Also, an improvement was seen in the vitality (p=0.488) and mental health (p=0.714), which was not statistically significant. CONCLUSION: Depression got minimally worse in the male group despite an improvement in CHC. Anxiety scores were improved with treatment in the cirrhotic and non-cirrhotic groups significantly. A decrease in anticipatory anxiety may be related to the high treatment success with DAAA. Nearly all the subitems of the QoL scores were improved after treatment and these were more common in the female group. Elimination of HCV may itself decrease the number of patients who need psychiatric treatment.
Subject(s)
Antiviral Agents/therapeutic use , Anxiety/etiology , Depression/etiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Quality of Life , Aged , Diagnostic Self Evaluation , Female , Hepatitis C, Chronic/psychology , Humans , Male , Middle AgedABSTRACT
The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.