Acute pancreatitis in Turkey: Results of a nationwide multicenter study.

BACKGROUND: Acute pancreatitis (AP) is the most common gastrointestinal disease requiring hospitalization, with significant mortality and morbidity. We aimed to evaluate the clinical characteristics of AP and physicians' compliance with international guidelines during its management. METHODS: All patients with AP who were hospitalized at 17 tertiary centers in Turkey between April and October 2022 were evaluated in a prospective cohort study. Patients with insufficient data, COVID-19 and those aged below 18 years were excluded. The definitions were based on the 2012 revised Atlanta criteria. RESULTS: The study included 2144 patients (median age:58, 52 % female). The most common etiologies were biliary (n = 1438, 67.1 %), idiopathic (n = 259, 12 %), hypertriglyceridemia (n = 128, 6 %) and alcohol (n = 90, 4.2 %). Disease severity was mild in 1567 (73.1 %), moderate in 521 (24.3 %), and severe in 58 (2.6 %) patients. Morphology was necrotizing in 4.7 % of the patients. The overall mortality rate was 1.6 %. PASS and BISAP had the highest accuracy in predicting severe pancreatitis on admission (AUC:0.85 and 0.81, respectively). CT was performed in 61 % of the patients, with the majority (90 %) being within 72 h after admission. Prophylactic NSAIDs were not administered in 44 % of the patients with post-ERCP pancreatitis (n = 86). Antibiotics were administered to 53.7 % of the patients, and 38 % of those received them prophylactically. CONCLUSIONS: This prospective study provides an extensive report on clinical characteristics, management and outcomes of AP in real-world practice. Mortality remains high in severe cases and physicians' adherence to guidelines during management of the disease needs improvement in some aspects.

Oral Ritlecitinib and Brepocitinib for Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2b Study.

BACKGROUND & AIMS: The efficacy and safety of ritlecitinib (oral JAK3/TEC family kinase inhibitor) and brepocitinib (oral TYK2/JAK1 inhibitor) as induction therapy were assessed in patients with active, moderate-to-severe ulcerative colitis. METHODS: This phase 2b, parallel-arm, double-blind umbrella study randomized patients with moderate-to-severe ulcerative colitis to receive 8-week induction therapy with ritlecitinib (20, 70, 200 mg), brepocitinib (10, 30, 60 mg), or placebo once daily. The primary endpoint was total Mayo Score (TMS) at week 8. RESULTS: Of 319 randomized patients, 317 received ritlecitinib (n = 150), brepocitinib (n = 142), or placebo (n = 25). The placebo-adjusted mean TMSs (90% confidence interval) at week 8 were -2.0 (-3.2 to -0.9), -3.9 (-5.0 to -2.7), and -4.6 (-5.8 to -3.5) for ritlecitinib 20, 70, and 200 mg, respectively (P = .003, P < .001, P < .001), and -1.8 (-2.9 to -0.7), -2.3 (-3.4 to -1.1), and -3.2 (-4.3 to -2.1) for brepocitinib 10, 30, and 60 mg, respectively (P = .009, P = .001, P < .001). Estimates (90% confidence interval) for placebo-adjusted proportions of patients with modified clinical remission at week 8 were 13.7% (0.5%-24.2%), 32.7% (20.2%-45.3%), and 36.0% (23.6%-48.6%) for ritlecitinib 20, 70, and 200 mg, respectively, and 14.6% (1.9%-25.7%), 25.5% (11.0%-38.1%), and 25.5% (11.0%-38.1%) for brepocitinib 10, 30, and 60 mg, respectively. Adverse events were mostly mild, and there were no serious cases of herpes zoster infection. Infections were observed with brepocitinib (16.9% [12.5%-23.7%]), ritlecitinib (8.7% [5.2%-13.4%]), and placebo (4.0% [0.2%-17.6%]). One death due to myocardial infarction (ritlecitinib) and 1 thromboembolic event (brepocitinib) occurred; both were considered unrelated to study drug. CONCLUSIONS: Ritlecitinib and brepocitinib induction therapies were more effective than placebo for the treatment of moderate-to-severe active ulcerative colitis, with an acceptable short-term safety profile. CLINICALTRIALS: gov number: NCT02958865.

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.

A New Risk-Scoring System for Colorectal Cancer and Polyp Screening by Turkish Colorectal Cancer and Polyp Study Group.

BACKGROUND: Colorectal cancer is one of the most commonly diagnosed types of cancer worldwide. An early diagnosis and detection of colon cancer and polyp can reduce mortality and morbidity from colorectal cancer. Even though there are a variety of options in screen- ing tests, the question remains on which test is the most effective for the early detection of colorectal cancer. In this prospective study, we aimed to develop a simple, useful, effective, and reliable scoring system to detect colon polyp and colorectal cancer. METHODS: We enrolled 6508 subjects over the age of 18 from 16 centers, with colonoscopy screening. The age, smoking status, alcohol consumption, body mass index, polyp incidence, polyp size, number and localization, and pathologic findings were recorded. RESULTS: The age, male gender, obesity, smoking, and family history were found as independent risk factors for adenomatous polyp. We have developed a new scoring system which can be used for these factors. With a score of 4 or above, we found the following: sensitivity 81%, specificity 40%, positive predictive value 25.68%, and negative predictive value 89.84%, for adenomatous polyp detection; and sensitivity 96%, specificity 39%, positive predictive value 3.35%, negative predictive value 99.29%, for colorectal cancer detection. CONCLUSION: Even though the first colorectal cancer screening worldwide is generally performed for individuals over 50 years of age, we recommend that screening for colorectal cancer might begin for those under 50 years of age as well. Individuals with a score ≥ 4 must be included in the screening tests for colorectal cancer.

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.

Irritable Bowel Syndrome on Inflammatory Bowel Disease in Deep Remission: No Relation with Remission Deepening and Inflammation.

BACKGROUND: The aim of the study was to establish the frequency of irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in clinical, endoscopic, and histologic remission and in relation to both the depth of remission and inflammation markers. METHODS: Patients with ulcerative colitis (UC) and with Crohn's disease (CD) in clinical remission for at least 6 months were enrolled in the study. All of the patients underwent colonoscopy, and biopsy specimens were taken to evaluate endoscopic and histopathologic remission. Patients were evaluated according to Rome III criteria for IBS. Fecal calprotectin level and blood samples for C-reactive protein (CRP), sedimentation rate, and fibrinogen levels were studied. RESULTS: IBS frequency was 20.9% in UC cases and 28.9% in CD cases in clinical remission. Rates with and without endoscopic remission in UC (20.5% vs. 22.2%, P = .727) and CD (25% vs. 33.3%, P = .837, respectively) were not different. Similarly, rates with and without histopathologic remission in UC (15.7% vs. 26.6%, P = .723), and CD (21.4% vs. 33.3%, P = .999) were not statistically different. Also, it was not related to inflammation markers. CONCLUSION: IBS frequency among IBD patients with remission was in a substantial rate; these rates kept up with the process of deep remission and even complete mucosal healing and were irrelevant to inflammation.

Serum levels of inflammatory markers CRP, ESR and albumin in relation to survival for patients with hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma is associated with several chronic inflammatory conditions. It is increasingly understood that the inflammation may be part of the carcinogenic process and prognostically important. OBJECTIVE: To evaluate the serum levels of three inflammation markers in relation to survival in HCC patients. METHODS: We retrospectively examined the serum levels of CRP, albumin and ESR, both singly and in combination, in relation to patient survival. RESULTS: Survival worsened with increase in CRP or ESR or decrease in albumin levels. Combinations of CRP plus albumin or CRP plus ESR were associated with an even greater range of survival (3-fold), together with significant differences in maximum tumor diameter (PVT) and percent of patients with portal vein thrombosis (PVT). The triplet of CRP plus albumin plus ESR was associated with a sevenfold difference in survival, comparing low vs high parameter levels. These significant differences were found in patients with small or large tumors. CONCLUSIONS: Combinations of CRP with albumin or ESR or all three parameters together significantly related to differences in survival and to differences in MTD and percent PVT, in patients with both small and large size HCCs.

EP-01: Association of genetic polymorphisms of OATP with susceptibility to hepatocellular carcinoma in hepatitis C patients who achieved SVR by direct acting antivirals.

OBJECTIVES: Simeprevir, daclatasvir, ledipasvir, paritaprevir and ritonavir are all substrates and inhibitors of the organic anion transporting polypeptide (OATP1B1 transporter, whereas sofosbuvir, ombitasvir and dasabuvir are not substrates. The purpose of this study is to evaluate the association of organic anion transporting polypeptide (OATP) gene polymorphism and hepatocellular carcinoma in Hepatitis C patients who achieved SVR by direct acting antivirals. MATERIALS & METHODS: Four single-nucleotide polymorphisms (SNPs) (388 A>G, 521 T>C, 334 T>G, and 699 G>A) within the OATP gene were genotyped by PCR-RFLP in 200 patients with chronic HCV infection (CHC) treated with DAAs, Laboratory work up and abdominal ultrasound was performed at baseline, at 12 weeks after end of treatment and then at every 6 months of follow up (FU). RESULTS: The overall SVR12 rate was 99.5%. The SVR12 rate was similar between the patients with HCC and those without HCC (100% vs 99.4%, p=0.49). HCC developed in 10 (5%) of the patients, approximately 11 (6-36 months) after the end of the treatment. No significant differences were found regarding OATP gene polymorphisms among the case groups (including CHC and HCC) and no matter in comparisons of alleles, genotypes, or haplotypes. Similar insignificant results were also observed when subgroup analyses were performed in different gender. CONCLUSION: Our observation suggests that SNPs 388 A>G, 521 T>C, 334 T>G, and 699 G>A of OATP gene might not contribute to the development of HCC in Hepatitis C patients who achieved SVR by direct acting antivirals. Keywords: Hepatitis C, hepatocellular carcinoma, organic anion transporting polypeptide.

The impact of direct-acting antiviral treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients: temporary? permanent?

BACKGROUND/AIMS: In previous studies that investigated the impact of direct-acting antiviral (DAA) treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients have been compared to baseline values with either end of treatment or post-treatment values. The results are inconsistent. We evaluated patients throughout the treatment and after treatment. MATERIALS AND METHODS: 121 patients were included in the study. 93 patients were treated with sofosbuvir/ledipasvir±Ribavirin (RBV), and 28 patients were treated with ombitasvir/paritaprevir/ritonavir+dasabuvir±RBV. Total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG) and homeostatic model assessment-insulin resistance (HOMA-IR) levels were measured at the onset of treatment, after the1st month of treatment, at the end of treatment, and 6 and 12 months after the end of treatment. RESULTS: 117 patients were genotype 1. Sustained virological response was 98.4%. HOMA-IR values during treatment were significantly higher than at the beginning of treatment (p=0.0001). At 12 months there was a decrease in HOMA-IR, but this was not statistically significant (p=0.2048). TC and LDL levels were significantly increased in the first month of treatment (TC; 159±30, 180±34 mg/dl; LDL; 84±28, 100±30 mg/dl, respectively) (p<0.0001) and this increase was present during and after treatment. There was no statistically significant increase in TG (p=0120). Both treatment regimens showed similar effects on HOMA-IR, TC, and LDL. CONCLUSION: Patients with HCV treated with DAAs drugs showed increased IR, TC, and LDL cholesterol levels during treatment. After the end of treatment, IR goes back to normal, while the elevated TC and LDL levels persist indefinitely.

NS5A resistance - associated substitutions in chronic hepatitis C patients with direct acting antiviral treatment failure in Turkey.

OBJECTIVES: Chronic hepatitis C (CHC) is now a more curable disease with new direct acting antivirals (DAA). Although high sustained virologic response rates, failures still occur in DAA regimens. Our objective in this study was to characterize the real-life presence of clinically relevant resistance - associated substitutions (RASs) in the HCV NS5A gene in CHC patients whose DAA regimen has failed. METHODS: The study enrolled 53 CHC patients who experienced failure with DAA regimen as the prospective longitudinal cohort between 2017-2019. Genotypic resistance testing was performed via the viral population sequencing method and The Geno2pheno HCV tool was used for RAS analysis. RESULTS: The most frequent failure category was relapse (88%) followed by non-responder (12%). For a total of 36% of patients, RASs was detected in NS5A, Y93H was the most detected RAS in GT1b infected patients (89%). CONCLUSIONS: This study establishes an HCV failure registry for Turkey in which samples were combined with clinical, virologic and molecular data of adult patients whose DAA therapy failed. RASs can occur in CHC patients with DAA treatment failures. Evaluation of RAS after DAA failure is very important before re-treatment is initiated to prevent virologic failure.

Significant decrease in liver stiffness detected by two dimensional shear-wave elastography after treatment with direct-acting antiviral agents in patients with chronic Hepatitis C.

BACKGROUND/AIMS: Two-dimensional shear-wave (2D-SWE) elastography is one of the noninvasive methods for the evaluation of liver fibrosis. The purpose of this study is to investigate the changes in liver stiffness (LS) by employing 2D-SWE as well as its correlation with noninvasive fibrosis markers in patients with chronic hepatitis C (CHC), who are undergoing direct-acting antiviral (DAA) therapy. MATERIALS AND METHODS: The researchers included all the patients with CHC who are scheduled for DAA treatment in this study. 2D-SWE measurements were performed at baseline, end of treatment (EOT), and 12 weeks after the treatment. According to the latest EFSUMB guidelines, elastography measurements were performed during the ultrasonographic evaluation and recorded in kilopascals (unit). The correlation between biochemical and viral responses, and noninvasive fibrosis scores (FIB-4, AST-to-platelet ratio index (APRI)) was also evaluated. RESULTS: This study employed 230 patients who underwent treatment with DAAs between September 2016 and September 2017. However, 131 patients were able to complete the study, of which 48 (36.6%) were male and 83 (63.4%) were female. The mean age was 65.0 (±11.18) years. Both EOT and sustained viral response (SVR) had the same rate of 99.2% (130/131). The SWE measurement (mean) values at pretreatment, EOT, and 12 weeks after treatment was 12.92, 10.45, and 9.07 kPa, respectively (p<0.05), whereas the APRI scores were 0.76, 0.39, and 0.30, respectively (p<0.05). Additionally, the FIB-4 scores at pretreatment, EOT, and 12 weeks after treatment were 2.98, 2.43, and 2.03, respectively (p<0.05). The results of liver stiffness measurements (LSM) were similar in all the groups of cirrhotic, noncirrhotic, treatment-experienced, and treatment-naive patients. CONCLUSION: DAA treatments in the patients with CHC led to almost a complete SVR and a considerable decrease in LS in a short time.

Evaluation of hypertriglyceridemia-induced acute pancreatitis: A single tertiary care unit experience from Turkey.

BACKGROUND/AIMS: This study aimed to determine the frequency of hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) and assess different clinical and prognostic features in these patients. MATERIALS AND METHODS: The patients who were hospitalized with AP due to HTG (HTG-AP) between January 2005 and December 2014 were retrospectively evaluated in the clinic. The patients with AP due to non-HTG (non-HTG-AP) were also investigated during the same period. RESULTS: Of 635 patients with AP admitted to the clinic, 33 (5.2%) had HTG-related AP. Mean triglyceride levels were 2653 mg/dL (range: 439-13700 mg/dL). Mean Ranson score at the time of admission was 1.5, and the APACHE II score was 4.63. The mean duration of hospitalization was 4.4 days (range: 2-14 days). One of these patients died on the sixth day of hospitalization due to multiple-organ failure. Patients with a triglyceride level of >1000 mg/dL were younger, had a longer hospital stay, and had a higher recurrence rate. Compared with non-HTG-AP, HTG-AP was observed at a younger age (57.4±17.3 vs. 37.6±14.8, p<0.05, respectively) and more frequently in males (45.2% vs. 57.6%, p<0.05, respectively). The frequency of multiple AP in patients with HTG-AP was higher than non-HTG-AP (63.4% vs. 7.6%, respectively). CONCLUSION: HTG-AP was observed at a younger age and was responsible for most cases of recurrent pancreatitis. The duration of hospitalization was long, and the risk of recurrence and mortality were high in patients with HTG-AP having a triglyceride level >1000 mg/dL.

Real-life results of treatment with ombitasvir, paritaprevir, dasabuvir, and ritonavir combination in patients with chronic renal failure infected with HCV in Turkey.

BACKGROUND/AIMS: As the most common liver disease in hemodialysis patients, chronic hepatitis C (CHC) can cause cirrhosis and hepatocellular carcinoma, even increase in renal-related mortality. In Turkey, the frequency of anti-hepatitis C virus (HCV) antibodies in hemodialysis patients ranged from 31.4% to 51%. Until recently, the mainstay of the CHC treatment for these patients was pegylated interferon with potential toxicities and low sustained virological response. The 3D regimen, a combination of four drugs (ombitasvir, paritaprevir, dasabuvir, and ritonavir), has recently been used for patients with chronic kidney disease infected with genotype 1a and 1b HCV. The aim of the present study was to present results of 3D treatment for patients with hemodialysis-dependent chronic renal failure (CRF) who were chronically infected with HCV. MATERIALS AND METHODS: Overall, 25 patients with hemodialysis-dependent CRF who were infected with genotype 1a/1b HCV have been treated using the 3D regimen in our gastroenterology clinic between July 2016 and October 2017. Three patients were administered additional ribavirin 200 mg/day. Serum HCV RNAs, blood chemistry, blood count, and side effects were recorded at 0, 4, and 12 weeks. RESULTS: All 25 patients completed and well tolerated their planned treatment. At the end of 4 weeks, the viral response (defined as HCV RNA clearance) rate was 92%. At the end of 12 weeks of treatment and 3 months after treatment, viral response rates were both 100%. CONCLUSION: We observed that the treatment with 3D regimen in hemodialysis patients infected with genotype 1 hepatitis C is highly effective and well tolerated.

Inflammatory markers C-reactive protein and PLR in relation to HCC characteristics.

INTRODUCTION: Several markers of systemic inflammation, including blood C-reactive protein, platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) have been identified as independent prognosticators for hepatocellular carcinoma (HCC). METHODS: To attempt to understand the significance of these markers, they were examined in relation to 4 tumour parameters, namely maximum tumour diameter (MTD), tumour multifocality, portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels. RESULTS: Using linear and logistic regression models, we found that C-reactive protein and PLR on single variables, were statistically significantly related to the tumour parameters. In a logistic regression final model, CRP was significantly related to MTD, AFP and PVT, and the Glasgow Index significantly related to MTD and AFP. Results of the area under the receiver operating characteristic curves (ROC), showed that the areas for PLR and CRP were statistically significant for high versus low MTD and for presence versus absence of PVT. CRP alone was significant for high versus low AFP. CONCLUSIONS: These analyses suggest that the prognostic usefulness of the inflammatory markers PLR and CRP (but not NLR) may be due to their reflection of parameter values for tumour growth and invasiveness.

Patients Lost after Anti-HCV-Positive Finding in a Tertiary Care University Hospital: Increased Awareness and Action is Necessary to Eradicate HCV.

OBJECTIVES: Though there is a global effort to eradicate hepatitis C infection (HCV), several obstacles remain. Many patients infected with the virus are not detected or go untreated. The goal of this study was to identify any barriers to treatment and any difficulties contributing to the elimination of HCV infection at a tertiary care university hospital. METHODS: This was a retrospective review. The hospital data system was searched for records of patients admitted to the hospital for any reason from between 2013 and 2018 who were screened for viral markers and determined to be anti-HCV positive. The follow-up performed was then analyzed. RESULTS: Viral marker testing was requested for 65,853 patients during the study period. Of those, 64.735 (98.3%) were found to be anti-HCV negative and 1118 (1.7%) were anti-HCV positive. In all, 392 (35.06%) were detected in the gastroenterology department, 417 (37.3%) were patients in the infectious diseases department, and 309 (27.64%) were identified in other clinics, including emergency services, the blood bank, and others. There were 30/392 (7.65%) patients admitted to the gastroenterology clinic who declined a biopsy and/or treatment. In other clinics, 88/309 (28.5%) patients were identified who were not treated for HCV and not followed up because they were not referred to the related specialty department. CONCLUSION: It was determined that there was a significant gap in referring patients to the appropriate specialized department following an anti-HCV positive finding and thus to appropriate follow-up and treatment programs.

C-Reactive Protein and Platelet-Lymphocyte Ratio as Potential Tumor Markers in Low-Alpha-Fetoprotein Hepatocellular Carcinoma.

The hepatocellular carcinoma (HCC) tumor marker alpha-fetoprotein (AFP) is only elevated in about half of the HCC patients, limiting its usefulness in following the effects of therapy or screening. New markers are needed. It has been previously noted that the inflammation markers C-reactive protein (CRP) and platelet-lymphocyte ratio (PLR) are prognostically important and may reflect HCC aggressiveness. We therefore examined these 2 markers in a low-AFP HCC cohort and found that for HCCs > 2 cm, both markers significantly rise with an increasing maximum tumor diameter (MTD). We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index value for each marker, and their area-under-the-curve values for each MTD group. Patients were dichotomized into 2 groups based on the CRP and PLR from the receiver-operating characteristic curve analysis. In the logistic regression models of the 4 different MTD patient groups, CRP and PLR levels were statistically significant to estimate MTD in univariate logistic regression models of MTD groups > 2 cm. CRP and PLR were then combined, and the combination was statistically significant to estimate MTD groups of 3-, 4-, and 5-cm cutoffs. CRP and PLR thus have potential as tumor markers for low-AFP HCC patients, and possibly for screening.

Macroscopic Portal Vein Thrombosis in HCC Patients.

Macroscopic portal vein invasion (PVT) by hepatocellular carcinoma (HCC) in the liver is one of the most important negative prognostic factors for HCC patients. The characteristics of a large cohort of such patients were examined. We found that the percent of patients with PVT significantly increased with increasing maximum tumor diameter (MTD), from 13.7% with tumors of MTD <5cm to 56.4% with tumors of MTD >10cm. There were similar numbers of HCC patients with very large tumors with and without PVT. Thus, MTD alone was insufficient to explain the presence of PVT, as were high AFP levels, since less than 50% of high AFP patients had PVT. However, the percent of patients with PVT was also found to significantly increase with increasing blood alpha-fetoprotein (AFP) levels and tumor multifocality. A logistic regression model that included these 3 factors together showed an odds ratio of 17.9 for the combination of MTD>5.0cm plus tumor multifocality plus elevated AFP, compared to low levels of these 3 parameters. The presence or absence of macroscopic PVT may therefore represent different HCC aggressiveness phenotypes, as judged by a significant increase in tumor multifocality and AFP levels in the PVT positive patients. Factors in addition to MTD and AFP must also contribute to PVT development.

HCC with low- and normal-serum alpha-fetoprotein levels.

A large database of 1773 HCC patients in Turkey was examined. 41.9% had alpha-fetoprotein (AFP) levels <20 IU/ml and an additional 16.123% had values between 20-100 IU/ml. This 58% of the cohort (<100 IU/ml AFP levels) was examined in detail. 66% of patients with small (<5 cm) HCCs had low AFP, compared to 49% of patients with larger (>5 cm) HCCs. The mean diameter (MTD) of larger MTD, low AFP tumors was 8.4cm. Therefore, factors other than AFP must contribute to HCC tumor growth. Larger tumors in low AFP patients had both higher platelet levels and increased PVT percent. Linear regression analysis for both MTD and multifocality showed that platelet numbers and presence of PVT were significant variables; whereas for PVT, significant variables were albumin, alkaline phosphatase and MTD. Comparisons between patients with AFP levels <20, 20-<100, 100-<1000 and >1000 IU/ml showed the most significant tumor finding was an increase in PVT percent between each group, and to a lesser extent, MTD. Thus, low- or normal-AFP HCCs constitute the majority of patients and have slightly lower MTD and much lower PVT percent than HCCs associated with elevated blood AFP levels. New, non-AFP markers are thus needed, especially for small HCCs.

Characteristics of Hepatocellular Carcinoma Aggressiveness Factors in Turkish Patients.

A large cohort of hepatocellular carcinoma (HCC) patients from several collaborating Turkish institutions were examined for the tumor parameters of maximum diameter (MTD), portal vein thrombosis (PVT), and α-fetoprotein (AFP) levels. A relationship was found between MTD and blood platelet levels. Patients with large ≥5 cm tumors who had normal platelet levels had significantly larger tumors, higher percent of PVT, and significantly lower blood total bilirubin and liver cirrhosis than similar ≥5 cm tumor patients having thrombocytopenia. A comparison of patients with and without PVT showed significantly larger tumors, greater multifocality, blood AFP, and C-reactive protein levels, and, interestingly, lower HDL levels in the patients with PVT. Fifty-eight percent of the total cohort had AFP levels ≤100 IU/mL (and 42.1% had values ≤20 IU/mL). These patients had significantly smaller tumors, less tumor multifocality and percent PVT, lower total bilirubin, and less cirrhosis. There was considerable geographic heterogeneity within Turkey in the patterns of HCC presentation, with areas of higher and lower hepatitis B virus, hepatitis D virus, cirrhosis, and tumor aggressiveness parameters. Turkish patients thus have distinct patterns of presentation, but the biological relationships between MTD and both platelets and bilirubin levels are similar to the relationships that have been reported in other ethnic patient groups.