Is mean platelet volume a simple marker of non-alcoholic fatty liver disease?

BACKGROUND: Due to the increasing prevalence of non-alcoholic fatty liver disease (NAFLD), there was a need to establish non-invasive tests for its detection. Mean platelet volume (MPV) is an inexpensive, practical and easily accessible marker of inflammation in many disorders. Our study was aimed at investigating the relationship between MPV and both NAFLD and liver histology. METHODS: Total 290 patients with biopsy-proven NAFLD (n = 124) and 108 control patients were included in the study. To exclude the effect of other diseases on MPV, we included 156 patient controls in our study. Those whohave liver-related diseases and those who use drugs that may cause fatty liver were not included in the study. Liver biopsy was performed for those whose alanine aminotransferase level persisted for >6 months above the upper limits. RESULTS/CONCLUSION: We found that MPV was significantly higher in the NAFLD group compared with the control group, and MPV had an independent predictive value for the development of NAFLD. We determined that the number of platelets was significantly lower in the NAFLD group compared with that in the control group. We compared MPV values histologically with both stage and grade in all patients with biopsy-proven NAFLD and found that MPV had a significant positive correlation with stage. We observed a positive correlation between MPV and non-alcoholic steatohepatitis grade, but this was not statistically significant. MPV can be useful because it is simple, easy to measure, cost-effective, and routinely tested in daily practice. MPV can be used as a simple marker of NAFLD and an indicator of fibrosis-stage in NAFLD.

Hepatocellular Carcinoma in Cirrhotic Versus Noncirrhotic Livers: Clinicomorphologic Findings and Prognostic Factors.

BACKGROUND: Hepatocellular carcinoma mostly develops in a cirrhotic (80%) background. The clinical features of cirrhotic hepatocellular carcinoma and non-cirrhotic hepatocellular carcinoma also differ. We aimed to determine the clinicopathologic features, tumor characteristics, treatment options, and overall survival after diagnosing hepatocellular carcinoma and prognostic factors effective on survival of hepatocellular carcinoma developing in cirrhotic and non-cirrhotic conditions. METHODS: In our study, 220 patients aged over 18 years who were histologically diagnosed as having hepatocellular carcinoma were included. The patients were divided into 2 groups as cirrhotic and non-cirrhotic. RESULTS: When the tumor morphologies were examined in our study, it was observed that they were mostly solitary in both groups. Cirrhotic hepatocellular carcinomas had significantly higher rates of invasion than the non-cirrhotic group (35.3% vs. 20.3%, respectively) (P <.05). The survival rate was found to be better in the non-cirrhotic group (17.5 months vs. 11.5 months) (P <.05). Age, maximal tumor diameter, and morphologically infiltrative tumor character were found to be independent risk factors affecting survival in patients with cirrhosis. Portal vein invasion, alfa-fetoprotein, and the absence of an underlying risk factor in the etiology were observed as independent risk factors affecting survival in patients with non-cirrhosis. CONCLUSION: Cirrhotic hepatocellular carcinoma and non-cirrhotic hepatocellular carcinoma had different clinicopathologic features and risk factors. We analyzed that treatment choice trends were different between the 2 groups. We also observed that the factors that affected survival were different between the 2 groups.

Prognostic value and morphological findings of overexpression of glypican-3 in hepatocellular carcinoma.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the seventh most common cancer all worldwide and is second in cancer-related deaths. In HCC, whose prognosis is still not good despite current treatments, there is a need for prognostic markers as well as early diagnosis. Glypican (GPC)-3 has been proposed as a potential serologic and histochemical marker specific to HCC. This study aimed to determine the relationship between GPC3 overexpression and HCC prognosis and clinicomorphologic features. MATERIALS AND METHODS: In total 152 patients who were diagnosed as a result of hepatectomy, lobectomy or liver transplantation were enrolled. The patients were divided into two groups, GPC3-positive (overexpression) (>10%) and GPC3-negative (<10%). The demographic data of the patients, tumor characteristics and survival times were recorded. RESULTS: Survival was significantly lower in the GPC3+ group. In the multivariate analysis, hepatitis C, AFP, tumor number, tumor focality, portal vein tumor thrombosis and GLP3 positivity were found to be independent risk factors for survival. CONCLUSION: Our study shows that GPC3 overexpression is a poor prognostic factor in HCC. GPC3 positivity were found to be an independent risk factor for survival.

Prognostic factors of elderly patients with hepatocellular carcinoma: should we be more courageous in treatment?

OBJECTIVES: Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis, its incidence increases with age. The risk of developing HCC is highest in the seventh decade. In this study, we aimed to determine the clinicopathological differences, treatment choices, survival times, and effective prognostic factors of HCC in the elderly and young populations. METHODS: All patients aged ≥18 years who were diagnosed histologically between 2016 and 2020 were included in the study. Patients were divided into two groups: <70 years and ≥70 years. The clinicopathological differences, treatment choices, survival times, and effective prognostic factors of HCC were compared in the elderly and young populations. RESULTS: A total of 407 patients were evaluated. There were 164 patients (40.3%) in the geriatric age group. There was no significant difference in the female/male ratio, the laboratory values, survival time between the two groups. There was no significant difference between the two groups in terms of tumor focality and portal vein invasion ( P > 0.05). The presence of NAFLD, maximal tumor diameter (MTD), and portal invasion were found to be significant for survival according to the univariate analysis in elderly group ( P < 0.05). In the multivariate analysis, presence of NAFLD etiologically, and MTD independent risk factors were observed in elderly group ( P < 0.05). CONCLUSION: If the clinicomorphological features of the tumor and prognostic risk factors can be determined by examining the patients in detail, all treatments can be easily applied in the geriatric group.

Treatment With Balloon Angioplasty of Chronic Portal Vein Thrombosis.

The therapeutic options in portal vein thrombosis cases of young age and low weight, as in this case, are limited. Interventional radiologists also have minimal experience in pediatric patients. There are no reported cases anywhere worldwide, especially in this age group. However, we think that balloon angioplasty can be safely applied in cases in which esophageal variceal bleeding cannot be controlled using traditional treatment.

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.

HBV flare associated with immunosuppressive treatments: it is still dangerous in the third-generation antivirals era.

BACKGROUND: There are limited data about the mortality and morbidity of patients with HBV flare related to immunosuppressive treatments (IST) in the third-generation antivirals era. Herein, we performed a multi-centric study in patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and evaluated their clinical course. METHODS: The study group included patients who were referred to gastroenterology or infectious disease specialists at eight different hospitals in Turkey. HBV flare was defined as at least a threefold elevation in alanine aminotransferase (ALT) levels above the upper limit of normal range. The demographic data, IST protocol, virological markers, liver tests, international normalized ratio (INR), HBV DNA, reactivation risk profile according to AGA guideline, MELD and MELD-Na scores were retrospectively evaluated. The primary aim of the study was to determine the liver-related mortality, including transplantation, at 12 weeks and factors predicting it. Secondary aims were to compare ETV and TDF with respect to mortality and time to ALT, bilirubin normalization and HBV DNA undetectability. RESULTS: The study group included 40 patients (29 males, mean age: 57 ±12 years). Twenty-five patients (62.5%) had a high risk of reactivation. Twenty-six patients received TDF and 14 patients received ETV treatment. Eight (20%) patients developed acute liver failure and one patient (2.5%) underwent living donor liver transplantation. Seven patients died due to liver-related complications, revealing a mortality rate of 17.5%. In multivariate analysis, total bilirubin levels at the onset, ALT levels and delta-MELD score at the first week were the independent risk factors for liver related mortality (HR: 1.222, 1.003, 1.253 and 95% CI: 1.096, 1.362; 1.001, 1.004 and 1.065, 1.470, respectively). There was no significant difference between the TDF and ETV groups with respect to time to normalize ALT and bilirubin levels, HBV DNA undetectability and mortality rates (16% and 21.4%, respectively). CONCLUSIONS: HBV flare associated with IST has a high mortality in the third-generation antivirals era. High total bilirubin at the onset and high ALT and delta-MELD score at the first week predict poor prognosis.

Hemosuccus pancreaticus A case report and review of the literature.

Hemosuccus pancreaticus is a rare clinical condition, defined as a bleeding from an artery around the pancreas or a lesion on the pancreas, to the pancreatic duct. The intensity of bleeding can vary from occult bleeding to life threatening massive acute bleeding. In this article, we aimed to present a 68-year-old man who presented to our clinic with recurrent upper gastrointestinal bleeding and abdominal pain. Endoscopy revealed hemorrhage from ampulla vateri, CT angiographic examination showed an aneurysm of the splenic artery and that the splenic artery was connected to the pancreatic duct.Splenectomy and subtotal pancreatectomy was performed on the patient. The patient was discharged with healing. Hemosuccus pancreaticus should be kept in mind in patients with a history of pancreatitis and peripancreatic aneurysm and upper gastrointestinal bleeding.The early diagnosis and treatment of HP is life-saving. In this study, we aimed to review the basic symptoms and clinical findings, along with the diagnosis and treatment methods of HP. KEY WORDS: Gastrointestinal bleeding, Pancreas, Splenic Artery.

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.

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.

C-reactive protein and hepatocellular carcinoma: analysis of its relationships to tumor factors.

C-reactive protein (CRP) is a blood marker for inflammation and is an independent prognostic factor for many human cancers. Combined with albumin levels, it forms the basis of the Glasgow Index for cancer prognosis. We reviewed the literature on CRP and HCC and also evaluated blood CRP levels and combination CRP plus albumin levels in a large HCC cohort. In order to understand the prognostic significance of CRP, we retrospectively examined a large HCC cohort and examined the relationship of CRP levels to tumor parameters. We report, that CRP alone and CRP plus albumin combined as well, significantly correlated with parameters of HCC aggressiveness, such as maximum tumor dimension (MTD), portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels, both as individual parameters and all parameters together (Aggressiveness Index). This extends current thinking, to suggest a possible explanation for the usefulness of blood CRP levels in HCC prognostication.

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.

The dynamic and clinical significance of autoantibodies and immunoglobulins in liver transplant recipients.

Little is known about autoantibody pattern in liver transplantation (LT). The aim of the study was to examine autoantibodies (AAB) and immunoglobulins in patients with end-stage liver disease before and after LT. Patients with LT who underwent post-LT biopsies between 10/2008 and 8/2011 were enrolled. AAB were assessed at the time of LT and liver biopsy. Demographics, serum immunoglobulins, AAB, and liver histology (explant, post-LT biopsies) were analyzed. Two hundred and twenty patients (M/F 143/77; age at LT 54 (19-73)) were included; AAB and immunoglobulins were evaluated in 76 patients. Length of follow-up from LT was 285 (30-1462) days. Sixty-one percent of patients had hepatitis C (HCV); 83% developed recurrent HCV. A significant decrease in IgG, IgA, IgM (p < 0.001 each), anticardiolipin antibodies IgG and IgM (p = 0.02), and beta-2 microglobulin (p = 0.004) was observed post-LT. HCV patients had higher IgG (p = 0.005), rheumatoid factor (p = 0.044) before LT; elevated IgM was associated with increased inflammation in the explant (p = 0.007). Lower IgG levels and antismooth muscle antibodies were present before LT in a higher percentage in patients who would develop recurrent HCV (p = 0.004, p = 0.077, respectively). In conclusion, AAB change significantly after LT and have a different pattern in HCV. Some immunological markers are associated with HCV recurrence and advanced inflammation on explant.

Relationship between IL28B gene rs8099917 polymorphism and SVR in Turkish patients with hepatitis C virus genotype 1.

BACKGROUND AND OBJECTIVE: The hepatitis C virus (HCV) which infects 3% of the world's population is a global challenge. Recently, genome-wide association studies (GWAS) have identified that the IL28B gene rs8099917 polymorphism was associated with the response to the pegylated-interferon alpha/ribavirin (PegIFNα/RBV) combination therapy in patients infected with HCV genotype 1. IL28B gene rs8099917 polymorphism should be determined before beginning treatment of HCV-infected patients to predict an individual's response. The aims of this study were to analyze the correlation between IL28B gene rs8099917 (T/G) polymorphism and PegIFNα/RBV therapy outcome in the Turkish population. METHODS: Genotypes of the IL28B gene rs8099917 (T/G) single nucleotide polymorphism (SNP) were determined in 308 patients with HCV infection by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. One group consisted of 148 patients with a sustained virological response (SVR), whereas the second group consisted of 160 nonresponders (non-SVR). RESULTS: Allele and genotype associations of IL28B gene rs8099917 polymorphism with a sustained virological response were observed in comparisons between the SVR and non-SVR groups (P<0.001). In addition, the characteristics of the subjects did not differ between these two groups except for age and fibrosis stage (P<0.05). Additionally, neither SVR nor rs80999917 genotypes were associated by HCV RNA levels. CONCLUSIONS: In conclusion, the rs8099917 polymorphism was thus found strongly associated with a sustained virological response to therapy in Turkish patients infected with HCV genotype 1. Consequently, we suggest determining IL28B gene rs8099917 polymorphism of patients with HCV genotype 1 before onset of treatment.

The role of interleukin 28B gene polymorphism in Turkish patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Multiple risk factors lead to hepatocellular carcinoma (HCC) including viral infections, mutation and single nucleotide polymorphisms (SNPs). Interleukin 28B (IL28B) gene rs12979860 polymorphism has been shown to be associated with HCC in the different populations, but its association with HCC has not been investigated in the Turkish population. We investigated whether the rs12979860 polymorphism of IL28B gene affects the risk of HCC. MATERIAL AND METHOD: We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 187 confirmed HCC patients and 208 healthy subjects (cancer and viral infection negative) in the Turkish population. RESULTS: The allele and genotype analysis showed no significant differences between the risk of HCC and IL28B gene rs12979860 polymorphism (OR = 1.10; 95% 0.59-2.08 P = 0.76 for genotype). However, in the HBV-related HCC subgroup, the TT genotype increased a 1.46-fold the risk of developing HCC, but not statistically significant (OR = 1.46; 95% 0.71-2.97 P = 0.30). Furthermore, no significant differences were found between clinical findings, and sex in comparison with the IL28B genotypes in HCC group (P > 0.05). CONCLUSION: Our results suggest, for the first time, that no significant association were found between IL28B rs12979860 genotypes with the risk of developing HCC in Turkish patients. Further independent investigations are required to clarify the possible role of IL28B gene rs12979860 polymorphism on the risk of developing HCC in a larger series and also in patients of different ethnic origins.

Endoscopic closure of ERCP-related duodenal perforations by using endoclips: a case series.

Duodenal wall perforations are traditionally managed surgically. There are isolated case reports or small case series reporting successful endoscopic closure of duodenal perforations. Endoscopic closure techniques include the use of endoclips, fibrin glue, and endoloops. Herein we report the largest series containing 4 cases of successful endoscopic closure of iatrogenic duodenal perforations related to endoscopic retrograde cholangiopancreatography by using endoclips and briefly review the endoscopic methods used in the closure of perforations in the light of current literature.

Major predictors for difficult common bile duct stone.

BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography has become the standard treatment for common bile duct stones worldwide. However, there are only a few reports with small number of patients concerning the factors that contribute to the technical difficulty of endoscopic retrograde cholangiopancreatography in these patients. In this study we aimed to investigate these factors in a large group of patients. MATERIALS AND METHODS: All patients with a naiïve papilla (n=1850) who underwent endoscopic retrograde cholangiopancreatography during a study period of 2 years were prospectively evaluated. Of these, 757 patients with common bile duct stones were included in the study. Following successful cannulation, patients who needed either more than one episode for stone extraction or mechanical lithotripsy, extracorporeal shock wave lithotripsy, or patients in whom stone extraction could not be achieved endoscopically and underwent surgery were regarded as having "difficult stones". Age, sex, laboratory parameters, endoscopic and cholangiographic findings were recorded in all patients. Predictive factors for difficult stones were investigated using univariate and multivariate analysis. RESULTS: The study group consisted of 432 women and 325 men with a mean age of 60±16 years (range, 4-96). Of the total 757 patients, 654 (86.4%) had easy and 103 (13.6%) had difficult stones. Endoscopic stone extraction was successful in 98.1% of patients. A stricture distal to the stone (OR: 8.248), smaller common bile duct/stone diameter ratio (OR: 0,348), stone diameter (OR: 1,187) stone impaction (OR: 1,117) and higher bilirubin levels (OR: 1,1) were found to be independent predictors of difficult stone extraction on multivariate analysis. CONCLUSION: Endoscopic retrograde cholangiopancreatography is a very effective method for the treatment of common bile duct stones. Presence of a stricture distal to the stone, smaller common bile duct/stone diameter ratio, stone diameter, impacted stone, and higher bilirubin levels are significant predictors of difficult stone.