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.

Treatment of HCV infection with direct-acting antiviral agents. Real life experiences from the Euro-Asian region.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is a common disease that causes liver cirrhosis, hepatocellular carcinoma, and extra hepatic manifestations with high mortality and morbidity rates. This study aimed to present real-life experiences and results of treatment of HCV infection with direct-acting antiviral agents (DAAs) from the Euro-Asian region, including Turkey and Azerbaijan. MATERIALS AND METHODS: A total of 1224 patients with chronic HCV infection were treated with DAAs in accordance with the international guidelines for the management of HCV infection. The mean age was 58.74±14.75 years, with 713 (58.25%) females. The genotypes of the patients were as follows: genotype 1b, 83.36% (n=1024); genotype 1a, 8.08% (n=99); genotype 2, 2.85% (n=35); genotype 3, 3.34% (n=41); genotype 4, 1.71% (n=21); and combined genotypes, 0.32% (n=4). Approximately 808 patients were treated with sofosbuvir-based DAAs with or without Ribavirin for 12 or 24 weeks, whereas 416 patients were treated with the Paritaprevir, Ombitasvir, Ritonavir.Dasabuvir (PROD) regimen with or without Ribavirin for 12 weeks or 24 weeks. RESULTS: At the end of follow-up examinations, 1183 patients (97.93%) had sustained virological response (SVR), 17 (1.40%) died of reasons unrelated to the treatment regimen, 12 had recurrence after treatment, and 129 (10.67%) had adverse events like anemia, itching, and weakness. CONCLUSION: In this large cohort of HCV-infected patients, treatment with DAAs yielded a high overall SVR rate of 97.93%. DAAs were safe and well-tolerated. Thus, the elimination of HCV infection is no longer a dream worldwide.

Real-world efficacy and safety of Ledipasvir + Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience.

BACKGROUND/AIMS: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population. MATERIAL AND METHODS: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)±ribavirin (RBV) orombitasvir/paritaprevir/ritonavir±dasabuvir (PrOD)±RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed. RESULTS: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90±54.60 U/L to 17.00±14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51±4.54 to 7.32±3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0±16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%). CONCLUSION: LDV/SOF or PrOD±RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.

Prognostic factors in patients with advanced extrahepatic cholangiocarcinoma: A single center experience.

Extrahepatic cholangiocarcinoma (ECC) is an aggressive malignancy causing a lot of fatalities and comorbidities. Endoscopic biliary stenting (EBS) is mostly needed for ECC. In this study, we aimed to investigate the prognostic factors for the overall survival (OS) and the factors predicting the patients eligible for chemotherapy after EBS in ECC.We retrospectively screened 153 advanced ECC patients who underwent EBS for jaundice to make the patients eligible for chemotherapy. Patient's clinical and laboratory parameters were recorded. OS was estimated by the Kaplan-Meier method. All parameters were assessed by binary logistic regression analysis to predict which patients are eligible for chemotherapy.The median OS of all patients was 12.0 months (10.1-13.8). The median OS of the patients treated with chemotherapy was 13.0 months (12.0-14.0), while it was 4.0 months (2.3-5.7) for patients unable for chemotherapy after EBS. Albumin, aspartate aminotransferase (ALT) and carbohydrate antigen 19-9 (CA 19-9) values were independent prognostic factors for OS. Higher albumin and lower prothrombin time (PT) levels were independent parameters to predict the patients eligible for chemotherapy after EBS.Being suitable for chemotherapy was the main determinant for prolonged survival and albumin and PT levels were independent predictors for chemotherapy eligibility after EBS. Albumin, ALT, and CA 19-9 values were independent prognostic factors for OS in ECC.

Assessment of histopathological alterations in patients with chronic hepatitis B infection following long-term oral antiviral therapy.

OBJECTIVES: To evaluate the histopathological changes in the liver after oral antiviral therapy in patients with chronic hepatitis B. METHODS: A total of 79 HBeAg-negative and positive patients who had been on lamivudine, entecavir, or tenofovir disoproxil for at least 3 years prior to inclusion were enrolled between March 2015 and 2016, retrospectively. There were 23 patients on lamivudine, 21 patients on entecavir, and 35 on tenofovir. All patients underwent a follow-up liver biopsy. Biochemical, serological, virological and histopathological data were recorded in all patients and were compared after at least 3 years of treatment with oral antiviral agents. Results: Histological activity index scores were reduced in patients who received lamivudine (p=0.011), entecavir (p=0.002), and tenofovir (p=0.001). Also, in contrast with a significant improvement in fibrosis scores in lamivudine (p=0.033) and tenofovir (p=0.001) groups no improvements were found in patients who received entecavir (p=0.090). Conclusion: Long term treatment with oral antiviral agents was associated with biochemical, virological, serological, and histopathological improvements. Long-term use of anti-viral agents as well as continuous suppression of HBV DNA are prerequisites for histopathological improvement.

Relationship between liver injury and serum cytokeratin 18 levels in asymptomatic hepatitis B virus carriers and in patients with chronic hepatitis B infection.

BACKGROUND AND STUDY AIMS: Apoptosis represents a well-known mechanism of cell death involved in most chronic liver injuries. Our aim was to investigate the serum fragment level of cytokeratin 18 (CK18), M30, in asymptomatic hepatitis B virus (HBV) carriers and patients with chronic hepatitis B (CHB) and to evaluate the relationship between serum M30 levels and the severity of hepatic injury. PATIENTS AND METHODS: Asymptomatic HBV carriers (n=169), patients with CHB (n=100), and healthy control subjects (n=43) were enrolled in the study. Serum CK18 (M30) levels were analysed in all subjects. Liver biopsy for histopathological assessment was performed in asymptomatic HBV carriers and in patients with CHB infection. RESULTS: Serum CK18 (M30) levels were significantly higher in asymptomatic HBV carriers (198.77±77.62U/L) than in healthy control subjects (146.92±40.18U/L). Patients with CHB (283.02±147.45U/L) had significantly higher CK18 (M30) levels than asymptomatic HBV carriers (p=0.001). The diagnostic efficacy of CK18 (M30) levels in distinguishing patients with HBeAg-negative CHB from asymptomatic HBV carriers was found to be moderate (c-statistics: 0.695), and the diagnostic cut-off value of CK18 (M30) was 262U/L (specificity: 85%, sensitivity: 48%, positive likelihood ratio: 3.35, and negative likelihood ratio: 0.60). There was a positive correlation between serum CK18 (M30) levels and histological activity index scores in asymptomatic HBV carriers and patients with CHB. CONCLUSIONS: Serum CK18 (M30) levels may be a valuable indicator in distinguishing asymptomatic HBV carriers from patients with HBeAg-negative CHB when considered together with ALT and HBV-DNA levels.

Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program

Abstract: Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. Aim. To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and methods. Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. Results. Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. Conclusions. Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Daclatasvir plus asunaprevir dual therapy for chronic HCV genotype 1b infection: results of Turkish early access program.

 Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. AIM: To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. MATERIAL AND METHODS: Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. RESULTS: Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. CONCLUSIONS: Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Are serum quantitative hepatitis b surface antigen levels, liver histopathology and viral loads related in chronic hepatitis b-infected patients?

BACKGROUND/AIMS: Fluctuations in hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels complicate assessment of the phases of chronic hepatitis B (CHB) infection and correct identification of the inactive HBV carrier state. In this study, we aimed to examine the role of HBsAg quantification (qHBsAg) in the identification of the phases of HBV and to evaluate its association with liver histopathology. PATIENTS AND METHODS: Inactive HBV carriers (IC) (n = 104) and CHB patients (n = 100) were enrolled in the study. Demographic characteristics of patients were evaluated; biochemical parameters and serum qHBsAg levels were studied, and liver biopsy and histopathology were assessed. RESULTS: Serum qHBsAg levels were found to be significantly low in IC (5150.78 ± 8473.16 IU/mL) compared with the HBeAg-negative CHB (7503.21 ± 8101.41 IU/mL) (P = 0.001) patients. The diagnostic accuracy of qHBsAg to differentiate HBeAg-negative CHB from IC was found to be moderate (c-statistic: 0.695) and the cutoff level for qHBsAg in diagnosis was found as 1625 IU/mL (specificity: 80%; sensitivity: 49%). No correlation was noted between serum qHBsAg level and ALT, histologic activity index (HAI), and fibrosis in IC and CHB. A moderate and positive correlation was observed between the serum qHBsAg level and HBV-DNA in HBeAg-positive CHB patients. CONCLUSIONS: Serum qHBsAg levels may prove to be useful in the differentiation between IC and HBeAg-negative CHB when used in conjunction with HBV DNA. Furthermore, patients diagnosed solely on the basis of HBV DNA and ALT may present with higher grade and stage of liver histopathology than expected.

A Case of Early detected Multidrug-resistant Acinetobacter baumannii Infection after Liver Transplantation.

Invasive bacterial infections have become the leading cause of morbidity and mortality among solid organ transplant recipients (SOTRs). Acinetobacter baumannii can cause a serious infection in SOTRs. Multidrug-resistant A. baumannii (MDR-Ab) represents a major problem in liver transplant recipients. Here, we presented a respiratory infection related to MDR-Ab pathogenesis in a patient who underwent liver transplantation due to acute hepatic failure. Accordingly, it has been emphasized that infections after the liver transplantation should be accomplished after due consideration of all relevant facts with a multidisciplinary approach. HOW TO CITE THIS ARTICLE: Balkan A, Balkan Y, Mete AÖ. A Case of Early detected Multidrug-resistant Acinetobacter baumannii Infection after Liver Transplantation. Euroasian J Hepato-Gastroenterol 2016;6(2):170-172.

Transnasal endoscopy is preferred by transoral endoscopy experienced patients.

BACKGROUND & AIMS: Both unsedated transoral endoscopy (TOE) and sedated TOE have some drawbacks in clinical practice. Unsedated transnasal endoscopy (TNE) has been suggested as an alternative to both methods. This study aimed to determine the advantages of TNE in patients who have previously undergone unsedated conventional TOE. METHODS: Patients who had received an unsedated TOE in the last 12 months and were scheduled for a second upper endoscopy were included. They were randomized to undergo either unsedated TOE, using a standard endoscope, or unsedated TNE, using an ultrathin endoscope. Post-procedure, patients were asked to complete a questionnaire to assess pain, discomfort and acceptability of the procedure, and to compare the current procedure with their previous unsedated TOE. Endoscope insertion rate, procedure duration, and side-effects were recorded. RESULTS: Each group included 50 patients. With the exception of nasal pain, the tolerability and acceptance were significantly greater in the unsedated TNE group. Significantly more TNE patients (82%) found the current endoscopic procedure to be better than their previous TOE when compared with patients who had received a second TOE (12%). A repeat procedure was significantly more acceptable for TNE patients when compared to the TOE group (68% vs.16%). The duration of endoscopy was significantly shorter in TOE than in TNE (p<0.05). Endoscope insertion failed in 4% and mild epistaxis was observed in 4% of TNE patients. CONCLUSION: Unsedated TNE was better tolerated in endoscopy experienced patients when compared with unsedated TOE. The majority of patients found TNE more acceptable and preferable to TOE, suggesting that TNE should become a more common practice in clinics when applicable.

Ascites as an initial presentation of spontaneously ruptured hydatid cyst.

We describe the diagnosis of a 77-year-old woman admitted to our outpatient department with a 3-month history of abdominal bloating and distension. Abdominal computed tomography revealed a large cystic lesion in the posterior segment of the right hepatic lobe, with a separated germinal layer and widespread ascites with dense internal echoes and septal appearance. The result of a serum Echinococcus indirect haemagglutination test was positive and findings were indicative of the spontaneous rupture of a hydatid cyst into the peritoneal cavity without trauma. Ascites is rarely seen in the course of hydatid disease, but can result from cyst rupture into the peritoneal cavity. This should be considered in the differential diagnosis of ascites, especially in areas such as Turkey, where hydatid disease in endemic.

High prevalence of transfusion-transmitted virus infection in patients with chronic liver diseases in an endemic area of hepatitis B and C virus.

OBJECTIVE: To determine the prevalence and clinical impact of transfusion-transmitted virus (TTV) DNA in patients with chronic liver diseases in the Southeast Anatolia region of Turkey where hepatitis B and C viral infections are endemic. SUBJECTS AND METHODS: Patients diagnosed with chronic liver disease by clinical, biochemical and histologic means were enrolled in the study. Serum samples of 60 patients (19 males, 41 females) with chronic liver diseases, and of 45 healthy volunteer blood donors as a control group were collected. The chronic liver disease group consisted of 11 patients with hepatitis B, 44 with hepatitis C and 5 with chronic liver disease of unknown etiology. Presence of TTV DNA was investigated by the polymerase chain reaction. Using a scoring system histological grading of inflammation and staging of fibrosis were performed only in the chronic hepatitis C group. RESULTS: TTV DNA was detected in 47 (78%) patients with chronic liver disease and 5 (11%) volunteers in the control group. The difference was statistically significant (p < 0.001). Ten of the 11 (91%) patients with hepatitis B, 32 of 44 (73%) of those with hepatitis C-related chronic liver disease, and 5 of 5 (100%) of the patients with cryptogenic liver disease were positive for TTV DNA. CONCLUSION: TTV is highly prevalent in patients with chronic liver diseases in Southeast Anatolia, Turkey but no pathogenic effect attributable to TTV infection was detected.