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.

Possible relationship between IL28B rs12979860 and TLR2 -196 to -174 del/ins polymorphisms and the liver fibrosis stage in hepatitis C patients.

It has been shown that host factors play an important role in the progression of hepatitis C virus (HCV) infection. Toll-like receptor 2 (TLR2) del and interleukin 28B (IL28B) T alleles can mediate liver inflammation and pathogenesis of hepatocellular carcinoma. In the present study, the possible relationship between the IL28B rs12979860 C/T and TLR2 -196 to -174 del/ins gene variants and different fibrosis stages and host factors in hepatitis C patients was investigated. IL28B and TLR2 polymorphisms in the blood of 50 hepatitis C patients at different stages of fibrosis (24 mild/moderate, 26 advanced) and 24 healthy controls were examined by RT-qPCR. The highest frequency of the TLR2 del (26.9%) and IL28B T (46.2%) alleles was found in hepatitis C patients with the most advanced fibrosis, and the lowest frequency was found in healthy controls. There was a statistically significant difference between hepatitis C patients with advanced fibrosis and healthy controls in terms of the TLR2 del (p = 0.0062) and IL28B T (p = 0.0017) allele frequencies. However, no statistically significant difference was found between the mild/moderate fibrosis and severe fibrosis patient groups in terms of genotype or IL28B and TLR2 polymorphisms (p > 0.05). In addition, there was a significant difference between patients with mild/moderate or advanced fibrosis who carried the TLR2 del allele together with the IL28B CT genotype and healthy controls. The present study emphasizes that the TLR2 and IL28B gene variants cannot be single biomarkers for the determination of fibrosis stage in hepatitis C infection but together can play an important role in predicting severe disease.

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.

Circulating vascular adhesion protein-1(VAP-1): a possible biomarker for liver fibrosis associated with chronic hepatitis B and C.

Vascular adhesion protein-1 (VAP-1) is a multifunctional protein that plays a role in chronic liver diseases and fibrogenesis. The present study aimed to investigate the possible association of VAP-1 levels with the severity of disease progression in chronic hepatitis (CH) B and C patients with differing stages of fibrosis (F0-4), CHB/CHC-related cirrhosis, and hepatocellular carcinoma (HCC). The VAP-1 concentration in patient sera was determined by ELISA. The VAP-1 levels were compared between the F0 group and the F1, F2, F3, F4, cirrhosis, and HCC groups of CHB patients and between the F1 group and the F2, F3, F4, cirrhosis, and HCC groups of CHC patients. The levels of VAP-1 were significantly increased in CHB patients with progressive stages of fibrosis, with the highest concentration being found in those with stage F4 (severe fibrosis). A statistically significant difference was found between F0 and F4 in patients with CHB, but no statistically significant difference was observed between F1 and F4 in patients with CHC. Interestingly, there was no statistically significant difference in VAP-1 levels between patients with cirrhosis and HCC (either CHB or CHC, independently). Moreover, no relationship was found between VAP-1 and ALT levels in either CHC or CHB patients. In general, the VAP-1 levels were significantly higher in CHB than in CHC patients (P < 0.01). In conclusion, we suggest that the VAP-1 level may be a noninvasive biomarker for monitoring the severity of fibrogenesis in patients with hepatitis B infection.

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.

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.

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.

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.

Effectiveness of Sedoanalgesia in Percutaneous Liver Biopsy Premedication.

AIM: Percutaneous needle liver biopsy (PLB) is frequently associated with pain and anxiety. This may discourage the patients for biopsy, and rebiopsies, if needed. We planned a study to investigate the efficacy of additional analgesia or sedation for PLB. MATERIALS AND METHODS: The study has been designed as a single-center, prospective study. The PLB was planned for 18- to 65-year-old consecutive patients who were included in the study. The patients were divided into three premedication groups as control, Meperidine, and Midazolam. Hospital Anxiety and Depression Scale (HADS) was used to measure each subject's anxiety level. Fifteen minutes before the biopsy, 1 mL 0.9% NaCl subcutaneously (sc), 1 mg/kg (max 100 mg) Meperidine sc, or 0.1 mg/kg (max 5 mg) Midazolam intravenously was administered to patients respectively. Then PLB was done with 16 G Menghini needle. The day after, the patients were asked about feelings regarding biopsy. RESULTS: Groups were similar by gender and age. The HADS scores prior to PLB and on visual analog scale (VAS, 1-10 points) score during PLB were similar. In the three groups, 7, 12, and 7 patients, respectively, experienced no pain. Other patients explained pain as mild or moderate or severe. The number of patients who agreed for possible rebiopsy was higher in Meperidine and Midazolam groups than in the control group. CONCLUSION: Premedication with Meperidine or Midazolam in PLB would improve patients' tolerance, comfort, and attitude against a possible repeat PLB.How to cite this article: Sezgin O, Yaras S, Ates F, Altintas E, Saritas B. Effectiveness of Sedoanalgesia in Percutaneous Liver Biopsy Premedication. Euroasian J Hepato-Gastroenterol 2017;7(2):146-149.