Pancreatic Steatosis Is Associated with Both Metabolic Syndrome and Pancreatic Stiffness Detected by Ultrasound Elastography.

INTRODUCTION: There is increasing evidence that pancreatic steatosis (PS) is associated with metabolic syndrome (MS). However, it is not known whether it is associated with PS grade and pancreatic stiffness, or not. We aimed to evaluate the relationship between PS and its grade detected by transabdominal ultrasound, and pancreatic stiffness determined by two-dimensional shearwave elastography (2D-SWE), whether it has clinical significance and its relationship with MS. METHODS: Patients with and without PS were evaluated prospectively. RESULTS: Patients with PS had higher odds ratio for MS (OR 5.49). Also, ultrasonographic grade of PS was associated with MS parameters and hepatosteatosis. Pancreatic SWE value was significantly higher in PS group and positively correlated with PS grade, liver fat, MS, number of MS criteria. DISCUSSION/CONCLUSION: PS and its grade were associated with MS. In this first comprehensive PS-SWE study, we found that pancreas stiffness increased in the presence of PS, in correlation with PS grade and MS.

Controlling Nutritional Status (CONUT) Score and Prognostic Nutritional Index (PNI) Are Good Candidates for Prognostic Markers for Acute Pancreatitis.

Background and Objectives: It has been demonstrated that parameters such as the Controlled Nutrition Status (CONUT) score and Prognostic Nutrition Index (PNI) are beneficial for the assessment of patients' nutrition. In this study, our objective was to investigate the potential benefits of CONUT and, as a prognostic marker of acute pancreatitis, the PNI. Materials and Methods: The data of 361 patients were analysed retrospectively. The PNI and CONUT scores of these patients were retrospectively calculated. They were categorised as CONUT-high (≥3) and CONUT-low (≤2). A PNI ≥ 45 was considered high and a PNI < 45 low. The AP severity and organ failure due to disease were evaluated based on Atlanta 2012. Results: According to the CONUT score, it was found that 209 patients had normal to mild, whereas 152 patients had severe malnutrition. A total of 293 patients had mild AP and 68 thereof had severe AP. The patients with a high CONUT score used more antibiotics, were hospitalised more in intensive care units and experienced organ failure more frequently. There were no intensive care hospitalisations, mortalities, surgical needs and local complications among the patients with a higher PNI score. Conclusions: CONUT and the PNI have proven to be useful prognostic markers not only for predicting nutritional status but also for estimating the severity and results of AP.

The course and prognostic value of increased pancreas stiffness detected by ultrasound elastography during acute pancreatitis.

BACKGROUND: In this study, we determined the pancreatic stiffness (PS) changes in the course of acute pancreatitis (AP) by ultrasound elastography and evaluated its relation with prognosis. MATERIAL/METHODS: Pancreatic shear wave velocity measurements (SWM) were evaluated at the time of admission to the hospital, following clinical improvement, and one-month after for AP patients and compared to healthy volunteers. Its relationship with clinical severity indexes was evaluated. RESULTS: The pancreatic SWM value in the healthy group was 7.72 ± 2.50 kPa, and in AP group was 10.97 ± 2.26 kPa (p = 0.000). There was no difference between mild and severe pancreatitis. The mean SWM was 8.96 ± 1.53 kPa after disease remission, and 8.83 ± 1.24 kPa after 1-month. CONCLUSIONS: PS increases significantly during AP and decreases with clinical improvement, but this was still higher than controls, and it kept its elevation after 1-month. We think that larger, long-term studies are needed to determine the clinicopathological significance of this.

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.

Mesenchymal stem cells suppress hepatic fibrosis accompanied by expanded intrahepatic natural killer cells in rat fibrosis model.

Natural killer (NK) cells have antifibrotic effects. We have evaluated the influence of rat bone marrow-mesenchymal stem cell (BM-MSC) treatment on liver histology, biochemical liver function tests, systemic immunoregulatory state and NK cell distribution in liver and peripheral blood in rat model of common bile duct (CBD) ligation and compared the results with the control group. Rats were divided into three groups: (1) CBD ligated (CBDL) rats received phosphate-buffered saline (CBDL + PBS group) or (2) MSC (CBDL + MSC group) and sham-operated rats received MSC (healthy + MSC group). We found significantly decreased fibrosis scores with BM-MSC treatment in CBDL rats compared to the control (CBDL + PBS) group while no fibrosis developed in sham operated (healthy + MSC) group. BM-MSC treatment has decreased the inflammation as reflected by the significantly decreased T cell proliferation and inflammatory cytokine concentrations from splenocyte culture and liver tissue itself compared to CBDL + PBS. NK cells both in parenchyme and portal areas decreased significantly in liver and blood in CBDL + PBS compared to healthy + MSC while they were found to be increased in CBDL + MSC compared to CBDL + PBS rats. In conclusion, BM-MSCs may suppress hepatic fibrosis accompanied by expanded intrahepatic NK cells in CBDL rats. Thus, our animal study shows that MSC treatment holds great promise for treatment of patients with end-stage liver diseases through a possible mechanism by adopting the NK cell population and new studies investigating the role of NK cells and clinical fibrosis are warranted.Trial registration number: Marmara University Animal Care and Use Committee approval code: 73.2013.mar.

Appraising diagnostic performance of ELF test by pathological staging and digital quantification of liver fibrosis.

INTRODUCTION AND OBJECTIVES: A crucial issue when appraising the performance of non-invasive markers is the limitations of the reference standard they are compared to. Digital image analysis (DIA) was suggested as a reproducible approach expressing fibrosis numerically as a proportionate area (PA) (%). We aimed to evaluate ELF test with direct reference to PA (%), thereby explore the improvement in accuracy to discriminate significant fibrosis which may actually have been underestimated by categorical pathological staging. MATERIALS AND METHODS: PA (%) data were obtained by DIA of trichrome-stained liver biopsies of 52 chronic hepatitis patients. Paired serum samples of patients and additional 36 controls were performed to measure ELF test. Diagnostic performance characteristics of ELF test was derived in predicting significant fibrosis in the patient cohort, and also, in distinguishing healthy controls from patients with significant fibrosis. RESULTS: We found an AUROC value of 0.73 for ELF to predict significant fibrosis as assessed by DIA and a lower AUROC value of 0.66 when assessed by conventional pathology. Importantly, ELF test provided considerably high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis defined by Ishak F≥2 and TPA≥5% (AUROCs 0.93 and 0.94, respectively) with optimal ELF cut-off point of 8.4 for both. CONCLUSIONS: Digital quantification could represent a better reference standard than conventional pathology allowing a better discriminatory capability for ELF test. ELF test provided high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis suggesting a role as a screening strategy in the community setting.

First Week HCV RNA Level Under the Pegylated Interferon and Ribavirin Treatment Predicts Sustained Virological Response.

This study was planned to investigate whether the decrease in the hepatitis C virus (HCV) RNA levels at the first week of combined pegylated interferon and ribavirin treatment of naive genotype 1 patients with HCV was predicting sustained virologic response (SVR). Fifty-two patients were enrolled into the study. HCV RNA levels were measured at the baseline, first, fourth, and 12th weeks of treatment. Thirty-four patients achieved SVR, which basal, first week, and fourth week HCV RNA levels were log 5.57, log 3.65, and log 1.92, respectively. Eighteen patients could not achieve SVR, which basal, first week, and fourth week HCV RNA levels were log 6.22, log 5.45, and log 3.84, respectively (P < 0.05). Patients were distributed in 2 groups according to the amount of decrease in HCV RNA levels at the first week as less or more than 1.5 log. There were 20 patients with ≥1.5 log decrease in the HCV RNA levels at the first week. They were named as patients with very rapid virologic response (VRVR). All patients (100%) with VRVR were achieved SVR. In only 14 (44%) of the 32 patients without VRVR, SVR was achieved. In 16 (84%) of the 19 patients with rapid virologic response and 33 (79%) of the 42 patients with early virologic response, SVR was achieved. A ≥1.5 log decrease (VRVR) in HCV RNA levels of patients with HCV at the first week of combined pegylated interferon and ribavirin treatment predicts SVR very strongly.

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.

Partial virological response to three different nucleotide analogues in naive patients with chronic hepatitis B.

BACKGROUND: The definition of partial virological response (PVR) was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Whether this rationale can be applied to all nucleotide analogues (NA) is not clear. This study was undertaken to analyze PVR influence on therapeutic outcomes during lamivudine, entecavir or tenofovir monotherapy in NA-naive patients with chronic hepatitis B in routine clinical practice. METHODS: We retrospectively analyzed 150 NA-naive patients with chronic hepatitis B. These subjects received lamivudine, entecavir or tenofovir monotherapy between February 2001 and July 2013. RESULTS: Sixty-nine patients were treated with lamivudine, 35 with entecavir, and 46 with tenofovir. The median therapeutic duration was 19.5 (6-147) months. PVR rates at 24 weeks were similar among three NAs (lamivudine 33.3%, entecavir 35.0%, tenofovir 32.4%, P=0.981). For all three NAs, patients with a higher baseline viral load or HBeAg-positive status had a higher serum viral positive rate tested by polymerase chain reaction at week 24 and 48. Cumulative probability of virological breakthrough (VBR) for patients treated with lamivudine was 67% at 5 years, and PVR at 24 weeks was the independent risk factor for VBR (HR: 3.09; 95% CI: 1.09-8.74; P=0.034); also lamivudine treated patients older than 50 years seemed to have a tendency for VBR (HR: 2.80; 95% CI: 0.99-8.18; P=0.052). A majority of entecavir and tenofovir partial responders achieved and maintained virological response with prolonged monotherapy, except one entecavir treated patient who experienced VBR due to resistance mutations. CONCLUSIONS: Management strategy for lamivudine treatment should include adaptation of regimen according to PVR as an on-treatment response parameter due to its relation with unacceptably high VBR probability. Similar conclusion should not be directly related to entecavir or tenofovir treatment.

Does Genetic Variation in PNPLA3, TM6SF2 and HSD17B13 have a Role in the Development or Prognosis of Hepatocellular Carcinoma in Turkish Patients with Hepatitis B?

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.

Prognostic implication of serum vascular endothelial growth factor in advanced hepatocellular carcinoma staging.

BACKGROUND: Staging systems have considerable impact on hepatocellular carcinoma (HCC) treatment approaches and outcomes. There is an unmet need to improve their stratification ability. We have evaluated four commonly used staging systems and assessed whether angiogenic biomarker vascular endothelial growth factor (VEGF) could improve their prognostic stratification. MATERIAL AND METHODS: Four staging systems; Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh were evaluated in 78 HCC patients; their stratification abilities were detected by Kaplan-Meier curves and log-rank test; their accuracies of predicting survival were compared with the concordance index. Serum VEGF levels were measured using ELISA method. Recursive partitioning was used to determine the optimal VEGF cutoff. The prognostic significance of VEGF cutoff and other parameters were analyzed using univariate and multivariate models. RESULTS: None of the staging systems demonstrated better discriminatory ability in predicting survival. The four staging systems did not reveal significant differences in probability of survival across their intermediate-advanced stages. Optimal cutoff identified for VEGF was 445 pg/mL. In advanced HCC, VEGF level (p = 0.004) and in early HCC, bilirubin level (p = 0.009) were identified as the independent prognostic factors. Survival comparison with high and low VEGF levels was significant for advanced HCC, while insignificant for early disease. CONCLUSION: Staging systems with conventional parameters did not provide good prognostic stratification for survival in advanced HCC population. Serum VEGF level was an independent predictor of survival in advanced HCC, and provided more survival homogeneity within the advanced stages of conventional staging systems.

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.

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.

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.

Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease.

OBJECTIVE: The novel adipokines omentin, chemerin, and adipsin are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histological phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Serum levels of omentin, chemerin, and adipsin were assayed by enzyme-linked immunosorbent assay in 99 patients with biopsy-proven NAFLD and 75 control subjects. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. RESULTS: Adipsin levels did not differ between patients and controls, whereas both omentin and chemerin levels were significantly higher in patients with biopsy-proven NAFLD than in controls (both p values <0.001). Serum omentin levels were significantly associated with C-reactive protein (r = 0.29, p < 0.01) and the degree of hepatocyte ballooning (r = 0.27, p < 0.01), whereas chemerin showed a modest association with liver fibrosis (r = 0.22, p = 0.04). After stepwise linear regression analysis adjusting for potential confounders, serum omentin levels retained their independent significance as a predictor of hepatocyte ballooning in patients with NAFLD (ß = 1.42; t = 2.79, p < 0.01). CONCLUSIONS: Our results suggest that serum omentin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of hepatocyte ballooning.

Serum zinc-α2-glycoprotein concentrations in patients with non-alcoholic fatty liver disease.

BACKGROUND: Evidence suggests that zinc-α(2)-glycoprotein (ZAG) might serve as a biomarker for human metabolic alterations. We measured serum ZAG in patients with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined its association with clinical, biochemical, and histological phenotypes. METHODS: Serum ZAG was determined using ELISA in 90 patients with biopsy-proven NAFLD and 81 controls. RESULTS: Serum ZAG concentrations did not differ in patients with NAFLD (median 61 µg/mL; interquartile range: 56-73 µg/mL) compared with healthy controls (median 66 µg/mL; interquartile range: 56-78 µg/mL, Mann-Whitney U-test, p=NS). However, among patients with NAFLD serum ZAG concentrations were significantly higher in males and in those with the metabolic syndrome. After stepwise linear regression analysis, serum ZAG concentrations were the only independent predictor of the number of metabolic syndrome components in patients with NAFLD (ß=0.22; t=2.001, p<0.05). CONCLUSIONS: In summary, the hypothesis of an association between NAFLD and serum ZAG concentrations is not supported by the present results. However, ZAG remains an interesting molecule for further research in the field of human metabolic disorders.

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.