Evaluation of the effectiveness of drug-eluting transarterial chemoebolization in hepatocellular carcinoma.

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.

Characteristics of patients with hepatocellular carcinoma: A multicenter study.

Background and Aim: The aim of the present study was to examine the etiology of hepatocellular carcinoma (HCC) by underlying cause and determine the characteristics and clinical features of patients with HCC. Materials and Methods: The study comprised 1802 HCC patients diagnosed and followed up by Liver Diseases Outpatient Clinics in 14 tertiary centers in Turkey between 2001 and 2020. Results: The mean age was 62.3±10.7 years, and 78% of them were males. Of the patients, 82% had cirrhosis. Hepatitis B virus (HBV) infection was the most common etiology (54%), followed by hepatitis C virus (HCV) infection (19%) and nonalcoholic fatty liver disease (NAFLD) (10%). Of the patients, 56% had a single lesion. Macrovascular invasion and extrahepatic spread were present in 15% and 12% of the patients, respectively. The median serum alpha-fetoprotein level was 25.4 ng/mL. In total, 39% of the patients fulfilled the Milan Criteria. When we compared the characteristics of patients diagnosed before and after January 2016, the proportion of NAFLD-related HCC cases increased after 2016, from 6.6% to 13.4%. Conclusion: Chronic HBV and HCV infections remain the main causes of HCC in Turkey. The importance of NAFLD as a cause of HCC is increasing.

Palliative care in cirrhotic patients: Brief summary of recent AASLD guidance.

Palliative care in decompensated cirrhotic patients is a developing concept which should be used in cirrhotic patients during the advanced and terminal stages. Hepatologists and liver transplant teams mostly ignore the patients palliative care issues while intensively dealing with the liver diseases and its complications. This review is a brief summary of the recently published guidance discussing the palliative care, symptom based treatments and end of life with a collaborative and standartized approach which is recommended to all health care workers of cirrhotic patients.

Mutation Spectrum of Familial Adenomatous Polyposis Patients in Turkish Population: Identification of 3 Novel APC Mutations.

BACKGROUND: Familial adenomatous polyposis (OMIM #175100) and MUTYH-associated polyposis (OMIM #608456) are rare cancerprone disorders characterized by hundreds of adenomatous polyps in the colon and rectum, which have a high probability of malignant transformation. Attenuated familial adenomatous polyposis is a variant of familial adenomatous polyposis, which is a term used for the condition in which patients have less than 100 colorectal polyps. Germline heterozygous Adenomatous polyposis coli (APC) and biallelic MUTYH (mutY DNA glycosylase) pathogenic variations are responsible for familial adenomatous polyposis and MUTYH-associated polyposis respectively. The aim of this study is to discuss the clinical manifestations of patients having pathogenic APC and MUTYH variations. METHODS: We included 27 probands who have more than 10 colonic polyps in this study. After evaluation of their clinical and family histories, the probands were screened for APC and MUTYH variations via next generation sequencing. The family members of the probands carrying pathogenic variations were screened via Sanger sequencing. RESULTS: Among 27 probands, pathogenic APC and MUTYH variations were detected in 3 and 6 probands respectively. In the APC gene, 3 novel truncating variations (p.Leu360*, p.Leu1489Phefs*23, and p.Leu912*) were detected in 3 unrelated probands. In the MUTYH gene, only 2 distinct pathogenic variations were detected (p.Pro295Leu and p.Glu480del) in the homozygous or compound heterozygous state. CONCLUSION: In this study, molecular etiology was clarified in 9 familial polyposis patients. The p.Pro295Leu and p.Glu480del variations seem to be common in the Turkish population and may be considered as a first-step genetic test in Turkish familial polyposis patients showing autosomal recessive inheritance. However more studies are needed to reveal the exact frequency of these variations.

Proposal and Validation of a Novel Scoring System for Hepatocellular Carcinomas Beyond Curability Borders.

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.

Surveillance Strategies for Hepatocellular Carcinoma: Recent Advances and the Shifting Paradigm.

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.

Hepatocellular Carcinoma in Non-cirrhotic Liver Arises with a More Advanced Tumoral Appearance: A Single-Center Cohort Study.

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.

Recommendations for Reopening Endoscopy Units in Turkey: A Set-up Plan from a Tertiary Center in Istanbul.

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.

Evaluation of the Association between Programmed Cell Death-1 Gene Polymorphisms and Hepatocellular Carcinoma Susceptibility in Turkish Subjects. A Pilot Study.

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.

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology.

BACKGROUND & AIMS: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. METHODS: A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. RESULTS: Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). CONCLUSIONS: Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. CLINICALTRIALS. GOV NUMBER: NCT03056612. LAY SUMMARY: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk.

External validation of the Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients.

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.

Surveillance of hepatocellular carcinoma in cirrhotic patients: Current knowledge and future directions.

Patients with cirrhosis are at the highest risk to develop hepatocellular carcinoma (HCC), with a variable annual risk of 1-8%. Currently, biannual abdominal ultrasound (USG) with or without alpha fetoprotein (AFP) is the recommended HCC surveillance strategy of major professional liver societies for all cirrhotic patients. However, the effectiveness of USG and AFP has been a sprawling subject of debate due to conflicting results and the low quality of the evidence. The role of cross-sectional imaging is controversial due to potential harm and cost-effectiveness concerns. Several novel serum biomarkers have been introduced for HCC screening, but have yet to be validated for various geographic regions. A risk-stratified algorithm is needed to increase the yield of HCC surveillance by distinguishing a high-risk group that requires more intense screening with cross-sectional imaging and serum biomarkers, and a low-risk group, where the standard surveillance strategy is continued. In this review, the strengths and concerns related to standard USG-based surveillance strategy are discussed, as well as efforts to increase the effectiveness of surveillance.

Annual contrast-enhanced magnetic resonance imaging is highly effective in the surveillance of hepatocellular carcinoma among cirrhotic patients.

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.

Evaluation of depression, anxiety and quality of life in hepatitis C patients who treated with direct acting antiviral agents.

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.

Impact of Education Provided by Nurses on Quality of Life, Anxiety, and Depression in Patients Receiving Hepatitis C Virus Therapy.

The aim of this study was to determine the impact of education provided by a nurse on quality of life, anxiety, and depression in patients receiving hepatitis C virus (HCV) therapy. The total number of patients receiving HCV treatment was 25 patients (18 females and 7 males). Organized patient lectures addressed transmission routes of HCV, effects of virus on the liver, interferon treatment, treatment complications and care, and psychosocial problems faced by patients with HCV and their families. Lectures were followed by interviews in small groups including 3-4 patients each and repeated 3 months after. Data were collected by patient surveys, Hospital Anxiety-Depression Scale, and Short Form (SF)-36 Health Survey (SF-36). There were no significant differences between pre- and posteducation for the SF-36 domains, namely role physical, health perception, social functioning, role emotion, and mental health, whereas there were significant differences between pre- and posteducation for the SF-36 domains, namely physical function, bodily pain, and vitality. Pre-education depression and anxiety scores were higher than posteducation depression and anxiety scores. Specific educational programs provided by nurses improved patients' quality of life and decreased anxiety and depression in patients receiving HCV therapy. These findings support the importance of educational programs provided by nurses for HCV patients.

Quantitative assessment of liver fibrosis by digital image analysis: Relationship to Ishak staging and elasticity by shear-wave elastography.

OBJECTIVE: To analyze the relationship between fibrosis staged by Ishak stage and quantified by digital image analysis (DIA), and to reveal the optimum performance of shear-wave elastography (SWE) using quantitative DIA measurements as a comparative histological standard. METHODS: The proportionate area (PA) of fibrosis was measured by DIA from images of the PA of trichrome-stain (TPA) of 168 chronic hepatitis patients. SWE was performed in 105 patients. The accuracy of SWE for predicting the fibrosis defined by quantitative PA thresholds (≥ 2.5%, ≥ 5%, ≥ 10% and ≥ 20%, respectively) and by Ishak stages was measured using the area under the receiver operating characteristic curve (AUROC). RESULTS: DIA was proven to be highly reproducible (interclass correlation coefficient 0.926). The TPA range corresponding to each Ishak stage was large, widened as stages progressed, and reached its greatest extent in cirrhosis. TPA magnified at ×50 ranges 11.9-56% for Ishak stage F5-6. A good correlation between TPA and elasticity was presented for more advanced fibrosis (TPA ≥10%, rs = 0.732, P = 0.000) than milder fibrosis (TPA <10%, rs = 0.308, P = 0.006). With the advance of fibrosis either by stages or PA thresholds the discriminative accuracy of SWE gradually increased, but was less satisfactory for milder fibrosis. CONCLUSIONS: DIA may serve as a reproducible and reliable quantitative standard for surrogate tests for liver fibrosis. The performance and correlation of SWE with the fibrotic extent were better for advanced fibrosis, but less satisfactory for milder fibrosis.