Can Interferon Therapy Change the Natural Course of Hepatitis Delta Infection?: a Clinical and Pathological Study.

Chronic delta hepatitis (CDH) has a worse outcome than other types of viral hepatitis. High-dose, long-term alpha interferon (IFN-α) is the approved treatment and may ameliorate the course of infection. We evaluated long-term histological outcomes of CDH patients treated with IFN-α. Patients with histologically proved noncirrhotic CDH who were treated with high-dose IFN-α for at least 1 year were classified as cirrhotic or noncirrhotic at the end of treatment. Noncirrhotic patients also had posttreatment liver biopsies. Patients were designated histologically responsive or nonresponsive on the basis of fibrosis status. Histological, virological, and biochemical courses were analyzed. Forty-eight patients were treated with IFN-α (conventional and/or pegylated) for a median of 24 months with a posttreatment follow-up of 5 years. During the follow-up, cirrhosis developed in 24 patients, 5 of whom were decompensated. There was no difference between pre- and posttreatment fibrosis scores for 24 noncirrhotic patients at the end of follow-up. Among patients, 13% (n = 6) had decreased, 21% (n = 10) had steady, and 16% (n = 8) had increased fibrosis scores. Persistent viral response (PVR) was achieved in 16 patients (33%). Twenty percent of the entire group was histologically responsive (decreasing or steady fibrosis scores with improved necroinflammatory scores), while nearly 80% had histological progression/cirrhosis. PVR was significantly associated with histological response. The long-term natural course of patients who were treated with high dose IFN-α for at least 1 year was evaluated clinically and histologically. Despite the association of PVR with histological response, IFN-α treatment did not change the natural course of CDH; clinical and histological progression continued in two-thirds of the cases despite treatment.

The effect of liver test abnormalities on the prognosis of COVID-19.

INTRODUCTION: COVID-19 caused by the SARS-CoV-2 continues to spread rapidly across the world. In our study, we aim to investigate the relationship between the liver enzymes on admission (AST, ALT, ALP, GGT) and severity of COVID-19. We evaluated course of disease, hospital stay, liver damage and mortality. MATERIALS AND METHODS: Our study included 614 patients who were hospitalized with the diagnosis of COVID-19 between 03.16.20 and 05.12.20. Patients with liver disease, hematological and solid organ malignancy with liver metastases were excluded, resulting in 554 patients who met our inclusion criteria. We retrospectively evaluated liver transaminase levels, AST/ALT ratio, cholestatic enzyme levels and R ratio during hospital admission and these were compared in terms of morbidity, mortality and clinical course. RESULTS: Mean age of 554 subjects were 66.21±15.45 years, 328 (59.2%) were men. The mean values of liver enzymes on admission were AST (36.2±33.6U/L), ALT (34.01±49.34U/L), ALP (78.8±46.86U/L), GGT (46.25±60.05U/L). Mortality rate and need for intensive care unit were statistically significant in subjects that had high ALT-AST levels during their admission to the hospital (p=0.001). According to the ROC analysis AST/ALT ratio was a good marker of mortality risk (AUC=0.713: p=0.001) and expected probability of intensive care unit admission (AUC=0.636: p=0.001). R ratio, which was used to evaluate prognosis, showed a poor prognosis rate of 26.5% in the cholestatic injury group, 36.1% in the mixed pattern group and 30% in the hepato-cellular injury group (p 0.001). CONCLUSIONS: ALT-AST elevation and AST/ALT ratio >1 was associated with more severe course and increased mortality in COVID-19.

A micro-elimination approach to addressing hepatitis C in Turkey.

BACKGROUND: In 2016, WHO passed the Global Health Sector Strategy on Viral Hepatitis (GHSS), calling for its elimination by 2030. Two years later, Turkey approved a strategy to reach the WHO targets. This study reports new national prevalence data, breaks it down by subpopulation, and models scenarios to reach HCV elimination. METHODS: Literature was reviewed for estimates of HCV disease burden in Turkey. They were discussed with stakeholders and used as inputs to develop a disease burden model. The infected population was estimated by sequelae for the years 2015-2030. Three scenarios were developed to evaluate the disease burden in Turkey: a Base 2017 scenario, representing the current standard of care in Turkey; an increased treatment scenario, representing the impact of improved access to DAAs; and a WHO targets scenario, which meet the WHO GHSS viral hepatitis targets of a 65% reduction in mortality and 90% diagnosis rate of the infected population by 2030. RESULTS: At the beginning of 2017, 271,000 viremic infections were estimated. Of these, 58,400 were diagnosed and 10,200 treated. Modelling results showed that, with the current treatment paradigm in Turkey, by 2030 the total number of viremic HCV infections would decline by 35%, while liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis would decrease by 10-25%. In the increased treatment scenario, by 2030 viremic HCV infections would decrease by 50%; liver-related deaths, HCC and decompensated cirrhosis would decrease by 45-70%. In the WHO targets scenario, HCV infections would decrease by 80%; sequelae would decrease by 80-85%. Data on disease burden in micro-elimination target subpopulations are largely unavailable. CONCLUSIONS: To meet the WHO Global Health Sector Strategy targets for the elimination of HCV, Turkey needs to increase treatment. Better data are needed as well as countrywide access to DAAs.

Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort.

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.

Cryptogenic liver cirrhosis and hepatitis E virus (HEV): Are they related?

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis. In recent years, its role in the development of chronic hepatitis and cirrhosis especially in immunosuppressed patients and its wide range of extrahepatic involvement have increased the amount of research on HEV. In this study we aimed to investigate the presence of HEV infection in individuals with cryptogenic cirrhosis. MATERIALS AND METHODS: HEV antibodies were analysed using the Anti HEV enzyme-linked immunosorbent assay (ELISA) kit (anti-HEV ELISA; Diapro Prodiagnostic Bioprobes, Milan, Italy). HEV RNA was isolated with using QIAMP Viral RNA mini kit (QIAGEN, Hilden, Germany). The HEV RNA titre was detected with the Rotor Gene 3000 real time polymerase chain reaction (PCR) system using GenoSen's HEV (Rotor Gene) Quantitative Real Time PCR Kit (Genome Diagnostics Private Limited, the Netherlands). RESULTS: Our study included 21 healthy volunteers (12 males) and 35 cryptogenic cirrhosis patients (19 males). The ages of the patients and the controls were similar (46±12.1 vs. 37.5±9.7years). The mean Child-Pugh score was 8±2.5. The anti HEV immunoglobulin G(IgG) positivity rate was 9.5% and 25.7% in the control and patient groups respectively (p>0.05). HEV RNA positivity was not detected in the control group, but 3 cases (8.6%) in the patient group were positive (p>0.05). The HEV RNA, aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels for these 3 cases were 326.461copies/mL, 91IU/L and 67IU/L; 480copies/mL, 68IU/L and 36IU/L and 72copies/mL, 42IU/L and 24IU/L respectively. There were positive correlations between HEV RNA levels and AST and ALT levels (p<0.05). CONCLUSIONS: Anti HEVIgG and HEV RNA positivity rates are high in cryptogenic cirrhosis although it is not statistically significant and there is a positive correlation between HEV RNA and aminotransferases.

Mutations in Core Gene Region of Hepatitis B Virus in Patients with Chronic Hepatitis B.

BACKGROUND: The HBV core protein plays a major role in host immune response. Mutations occurring in the HBV core gene may cause alterations in the major epitopes being effective in the host immune response. Until now, the persistent effects of core gene mutations on HBV infections have not been fully understood. The aim of this study is to analyze the core gene mutations for epitopes in the T lymphocytes [T helper (Th) and cytotoxic (CTL)] and B cell and C terminal region in patients with chronic hepatitis using ultra-deep pyrosequencing (UDPS) method. METHODS: Eleven patients with chronic hepatitis B infection were included in the study. Amplification of the core gene was performed by a conventional PCR method. Mutations in the epitopes for T lymphocytes (Th and CTL) and B cell and in the C terminal region of HBV core gene were screened by UDPS. These mutations were analyzed in HBeAg positive and negative patients. RESULTS: The minimum percentages of amino acid substitutions were found with 0.9% in HBeAg positive patients and 1.2% in negative patients. The number of missense mutation was higher in patients with HBeAg positive than negative patients (p < 0.005). The number of amino acid substitutions in the region of aa49 - 69 in the Th epitopes was found to be the highest in both HBeAg positive and negative patients. The mutation frequency was higher in the C-terminal region of the core protein compared to the Th, CTL, and B cell regions and these were more common in subjects with high-grade fibrosis. Some types of mutations (V27I, R47H, Y132I, R174STOP, S181P, Q182K) were only detected in subjects with liver cirrhosis. CONCLUSIONS: Unlike literature, our results show that there is no significant increase in number of mutations in the core gene of the virus during the anti-HBe positive period. The role of low abundance variants and mutations in the immune system can be understood using methods such as UDPS in the near future.

Analysis of Hepatitis C Virus NS5A Region in Patients with Cirrhosis Using an Ultra-Deep Pyrosequencing Method.

BACKGROUND: HCV (Hepatitis C Virus) is genetically more diverse than HBV and HIV (Human Immunodeficiency Virus) and exists as quasispecies within infected individuals. This is due to the lack of efficient proofreading of the viral RNA-dependent RNA polymerase. Consequently, quasispecies emerge depending on the mutation rate of the viral polymerase, which may display a high level of genetic variability in a population. In infected individuals, HCV replicates and circulates as quasispecies composed of a complex mixture of different but closely related genomes that undergoes continuous change due to competitive selection and cooperation between arising mutants. The aim of this study is to investigate mutations in the NS5A region as a whole, including ISDR, PKRBD, IRRDR, and V3 of HCV genotype 1b cirrhosis patients being naive and nonresponders, treated with IFN (interferon) + ribavirin (RBN) by using an ultra-deep pyrosequencing method (UDPS). METHODS: During the study, five patients (four females, and one male, mean age 59.8 ± 11 years) with HCV related cirrhosis were analyzed. Three patients received IFN + RBN for six months, but two patients did not receive any therapy. HCV-RNA concentrations in patients' sera were determined using a COBAS AMPLICOR HCV MONITOR Test, Version 2.0. Genotyping was performed by using a commercial reverse hybridization method, Line Probe Assay. The quasispecies for the NS5A region were investigated using UDPS. RESULTS: All five patients were HCV genotype 1b (Mean Child-Pugh score 7.2 ± 1.9, 2 pts Child A, 2 pts Child B, and one pt Child C) but only one patient had hepatocellular carcinoma (HCC). A total of 19 different mutations were detected in each of the five patients (ranging from 3 to 6 mutations per patient). In all five patients, several mutations in the ISDR and PKR-BD regions were detected. On the other hand, mutations in the V3 and IRRDR regions were only detected in one patient. CONCLUSIONS: UDPS is a new sequencing technology and a very sensitive method in detection of quasispecies with low frequency NS5A region mutations. These mutations may affect the antiviral response and development of HCC. However, further studies in larger number of patients should be conducted to clarify this hypothesis.

Tenofovir disoproxil fumarate has a substantial efficacy against multidrug-resistant strains of hepatitis B virus.

BACKGROUND & AIMS: To evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF-R) and suboptimal response to adefovir (ADF-S). METHODS: Nucleos(t)ide analogue (NA)-naïve patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6 months thereafter. The primary outcome measure was complete virological response (CVR) (HBVDNA < 20 IU/ml). CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional hazard model was generated to find out factors independently associated with CVR. RESULTS: A total of 165 patients (118 men, mean age 42 ± 12, 64 HBeAg(+) ) were included in the study. There were 105 patients in NA-naïve, 32 patients in ADF-S and 28 patients in ADF-R groups. All patients in the ADF-R group had multidrug resistance patterns. Mean duration of tenofovir treatment was 29 ± 14 months. CVR rates in NA-naïve, ADF-S and ADF-R groups were 65% vs. 75% vs. 58% at 12th month, 77% vs. 87% vs. 79% at 24th month and 83% vs. 94% vs. 79% at 36th month respectively. According to multivariate Cox regression model, HBeAg positivity (HR = 0.56, 95%CI 0.36-0.86, P = 0.008), high baseline HBVDNA level (HR = 0.64, 95%CI 0.55-0.74, P < 0.001) and ADF-R (HR = 0.47, 95%CI 0.28-0.81, P = 0.006) were independent predictors for CVR. Seven patients encountered mild renal dysfunction and were managed by dose adjustments. CONCLUSION: CVR rates during the follow-up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug-resistant strains of HBV.

Effects of polymorphisms in interferon λ 3 (interleukin 28B) on sustained virologic response to therapy in patients with chronic hepatitis D virus infection.

BACKGROUND & AIMS: We investigated the association between interferon λ 3 (IFNL3) genotype (also known as interleukin 28B) and response to IFNα therapy in patients with chronic hepatitis D virus (HDV) infection. METHODS: We studied IFNL3 genotypes of 32 patients (19 men; median age, 42.5 y) with chronic HDV infection. Nineteen patients (59%) were treated with pegylated IFNα and 13 patients (41%) were treated with standard IFNα, for at least 12 months. Levels of HDV RNA were measured before the initiation of treatment and every 6 months thereafter; patients were followed up for a median time of 16 months (range, 6-164 mo) after treatment ended. We used real-time polymerase chain reaction to classify the IFNL3 polymorphism rs12979860 as CC, CT, or TT, and rs8099917 as TT, GT, or GG. A virologic response was defined as undetectable HDV RNA in serum, and a sustained virologic response (SVR) was defined as undetectable HDV RNA after cessation of treatment until the end of the follow-up period. We evaluated the association between IFNL3 polymorphism and treatment response using univariate and multivariate analyses. RESULTS: After treatment, a response was achieved in 16 patients (50%) and an SVR was achieved in 9 (28%). The percentages of patients with CC, CT, and TT at rs12979860 were 47%, 47%, and 6%, respectively; the percentages of patients with TT, GT, and GG at rs8099917 were 69%, 28%, and 3%, respectively. Rates of SVR were 27%, 27%, and 50% in patients with CC, CT, TT at rs12979860 (P = .78 for CC vs CT vs TT) and 36%, 11%, and 0% in patients with TT, GT, and GG at rs8099917 (P = .30 for TT vs GT vs GG). CONCLUSIONS: The IFNL3 polymorphisms rs12979860 and rs8099917 do not significantly affect responses of patients with chronic HDV infection to treatment with IFNα.

Small bowel mucosal damage in familial Mediterranean fever: results of capsule endoscopy screening.

OBJECTIVE: Familial Mediterranean fever (FMF) is the most common form of autoinflammatory diseases. We aimed to evaluate the small bowel mucosa by capsule endoscopy (CE) in FMF patients for investigation of other possible causes of abdominal pain. MATERIAL AND METHODS: The study group consisted of 41 patients with FMF. A standard questionnaire was used to record the gastrointestinal symptoms, other clinical findings, Mediterranean fever gene (MEFV) mutations, and history of medications including non-steroidal anti-inflammatory drugs (NSAIDs). Gastroscopy, colonoscopy and small bowel CE were performed in all patients, and biopsies were taken from terminal ileum and duodenum. RESULTS: The mean age of the patients was 34 ± 11 years, 63% of them were female, and 76.5% of them were carrying MEFV exon 10 mutations. Only one patient used NSAIDs in addition to colchicine. In endoscopic investigations, gastric erosion was detected in only one patient, and no significant findings were detected in colonoscopy. CE showed small bowel mucosal defects in 44% (erosions in 26.8%, ulcer in 17.1%) and edema in 29.3% of the patients. Most (64%) of the ulcer and erosions were localized to jejunum, and only 24% were in ileum. Mitotic changes as an indirect finding of colchicine toxicity were not different from the changes observed in samples of independent group of patients with irritable bowel syndrome. CONCLUSION: Mucosal defect was observed in half of the FMF patients, which may be associated with underlying inflammation or chronic colchicine exposure. Detection of nonspecific chronic inflammation without mitotic changes supports that mucosal defects may be associated with the autoinflammatory process.

Efficacy of tenofovir in patients with Lamivudine failure is not different from that in nucleoside/nucleotide analogue-naive patients with chronic hepatitis B.

We evaluated the efficacy of tenofovir disoproxil fumarate (TDF) in patients with lamivudine failure (LAM-F) in comparison with that in nucleoside/nucleotide analogue (NA)-naïve patients with chronic hepatitis B (CHB). The criteria for inclusion were being NA naïve or having previous LAM-F and receiving TDF therapy for at least 6 months. Biochemical and virological tests were performed at the baseline, at 3-month intervals in the first year, and every 6 months thereafter. The primary outcome measure for efficacy was a complete virological response (CVR), defined as an HBV DNA level of <20 IU/ml. CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional-hazard model was generated in order to find predictive factors independently associated with the time to a CVR. We included 197 patients in the study (136 males; mean age, 43 ± 12 years; 105 patients were NA naïve). Sixty-five patients had hepatitis B e antigen (HBeAg)-positive CHB. The median duration of TDF treatment was 29 (range, 6 to 52) months. Seventy-one patients (77%) in the LAM-F group were treated with TDF add-on therapy. The CVR rates of the NA-naïve and LAM-F groups were comparable in HBeAg-negative (94% versus 96% at month 36, P = 0.10) and HBeAg-positive patients (67% versus 83% at month 36, P = 0.48). According to the multivariate Cox regression model, only HBeAg positivity (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.26 to 0.59; P < 0.001) and a high baseline HBV DNA level (HR, 0.44; 95% CI, 0.29 to 0.67; P < 0.001) had a significant influence on the time to a CVR. The similar cumulative CVR rates during the follow-up show that TDF has comparable efficacy in lamivudine-experienced and NA-naïve patients, and the presence of resistance mutations did not alter the response rates.

Role of the line probe assay INNO-LiPA HBV DR and ultradeep pyrosequencing in detecting resistance mutations to nucleoside/nucleotide analogues in viral samples isolated from chronic hepatitis B patients.

Despite the effectiveness of nucleoside/nucleotide analogues in the treatment of chronic hepatitis B (CHB), their long-term administration is associated with the emergence of resistant hepatitis B virus (HBV) mutants. In this study, mutations resulting in antiviral resistance in HBV DNA samples isolated from 23 CHB patients (nine treatment naïve and 14 treated previously) were studied using a line probe assay (INNO-LiPA HBV DR; Innogenetics) and ultradeep pyrosequencing (UDPS) methods. Whilst the INNO-LiPA HBV DR showed no resistance mutations in HBV DNA samples from treatment-naive patients, mutations mediating lamivudine resistance were detected in three samples by UDPS. Among patients who were treated previously, 19 mutations were detected in eight samples using the INNO-LiPA HBV DR and 29 mutations were detected in 12 samples using UDPS. All mutations detected by the INNO-LiPA HBV DR were also detected by UDPS. There were no mutations that could be detected by INNO-LiPA HBV DR but not by UDPS. A total of ten mutations were detected by UDPS but not by INNO-LiPA HBV DR, and the mean frequency of these mutations was 14.7 %. It was concluded that, although INNO-LiPA HBV DR is a sensitive and practical method commonly used for the detection of resistance mutations in HBV infection, UDPS may significantly increase the detection rate of genotypic resistance in HBV at an early stage.

Association of the MEFV gene variations with inflammatory bowel disease in Turkey.

BACKGROUND: Association of NOD2 (CARD15) gene mutations with inflammatory bowel diseases (IBD) is well known. We herein aimed to investigate the role of familial Mediterranean fever-associated MEFV variations in IBD patients as additional regional-specific risk factor. STUDY: One hundred thirty-seven (78 female, 56.9%) IBD patients [62 Crohn's disease (CD), 75 ulcerative colitis (UC)] were enrolled into the study. The diagnosis of all patients was confirmed by colonoscopy, histopathology, and the clinical findings. One hundred one healthy donors' samples were used as healthy controls. All patients were genotyped for the most common E148Q, M608I, M694V, and V726A variations of the MEFV and R702W, G908R, and 1007fs of the NOD2. RESULTS: The overall MEFV variation frequency was found to be higher in the IBD (25.5%) patients (28% in UC, 22.6% in CD) compared with controls (9.9%, P=0.006). This association was stronger with the penetrant exon 10 variations (M694V, M680I, V726A; odds ratio =4.5, P=0.001). Contribution of M694V was higher compared with the other variations (14.5% in CD, 17.3% in UC and 3% in controls, odds ratio =6.039, 95% confidence intervals, 1.7-20.7, P=0.002). The overall frequency of 3 NOD2 variants in the IBD group was not different from that of controls. CONCLUSIONS: The results of this study suggest that the MEFV variations may be an additional susceptibility factor for IBD in certain parts of the world where the carrier rate is high, and the genetic background of the IBD patients may show regional changes.

Efficacy and Safety of Sofosbuvir and Ledipasvir for Hepatitis C in Kidney Transplant Recipients: A Single-center Retrospective Observational Study

Background: Treatment using direct-acting antivirals provides high rates of sustained virologic response and a favorable safety profile for patients with chronic hepatitis C virus infection. However, data on the efficacy of direct-acting antivirals in kidney transplant recipients are still limited. Aims: To evaluate the safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination in kidney transplant recipients. Study Design: Retrospective, observational, single-center study. Methods: Data of 29 kidney transplant recipients who received a fixed-dose safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination for 12 or 24 weeks with or without ribavirin were analyzed. The primary outcome was SVR12, which was defined as undetectable HCV-RNA levels 12 weeks after the treatment. Secondary outcomes were graft function, proteinuria, and calcineurin inhibitor trough level variability. Results: The predominant hepatitis C virus genotype was 1b (n = 19, 65.6%). All patients achieved SVR12. No graft failures nor deaths were reported during the study period. Throughout and after the treatment, the levels of aspartate aminotransferase [21 (range: 18-29.5) to 16 (range: 14-20) U/l, p < 0.001] and alanine aminotransferase [22 (range: 15-34) to 14 (range: 12-17.5) U/l, p < 0.001] improved significantly, unlike bilirubin, hemoglobin, and platelet levels. Renal function remained stable. Dose adjustments for calcineurin inhibitors were required. Serious adverse events were not observed. Conclusion: Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. However, cautious monitoring of trough levels of calcineurin inhibitorss is needed due to potential drug-drug interactions during the treatment episode.

Is the Y90-radioembolization treatment effective on the intermediate-advanced stage of hepatocellular carcinoma and what is the albumin-bilirubin score's prediction factor for survival?

Background and Aim: Radioembolization (RE) is a one of the palliative treatments that have been used to down stage and/or increase the survival time in intermediate-advanced stages of HCC. We aimed to evaluate the clinical impact of RE and the clinical use of the albumin-bilirubin (ALBI) score as a predictor for survival in HCC patients. Materials and Methods: Fifty-nine unresectable hepatocellular carcinoma (HCC) patients were enrolled. RE was performed in 28 of them (group 1) and 31 patients were followed up in the natural course (NC) (group 2). Patients were classified according to the Child-Pugh score (only cirrhotic patients), Barcelona clinic liver cancer (BCLC) staging, and ALBI scores were also calculated. Results: All patients in Group 1 were cirrhotic and their BCLC stages were as follows: 60.7% stage B and 39.3% stage C. In Group 2, 83.9% of patients were cirrhotic and their BCLC stages were as follows: 9.7% stage B, 51.6% stage C, and 38.7% stage D. Mortality rates were 82% and 100% in Groups 1 and 2, respectively. The median overall survival (OS) was 13.5 months (95% CI: 10.4-16.6 months) and 4.5 months (95% CI: 3.5-5.5 months) in Groups 1 and 2, respectively (p=0.000). When RE was applied to patients with ALBI Grade 1 and 2, the median OS was statistically higher than in the NC group, respectively (p<0.001, p<0.001). Conclusion: RE is an effective treatment method at the advanced stages of HCC. The ALBI score is a more useful and practical than the other prognostic tools.

Current hepatitis delta virus type 1 (HDV1) infections in central and eastern Turkey indicate a wide genetic diversity that is probably linked to different HDV1 origins.

Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.

The clinical significance of JAK2V617F mutation for Philadelphia-negative chronic myeloproliferative neoplasms in patients with splanchnic vein thrombosis.

Polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF), collectively known as Philadelphia-negative (Ph-negative) chronic myeloproliferative neoplasms (MPNs), MPNs represent the most common causes of splanchnic vein thrombosis (SVT), including Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). The JAK2V617F mutation has been demonstrated in most of the Ph-negative chronic MPNs. The study objective was to assess the diagnostic value of JAK2V617F mutation in patients with SVT in a group of 68 patients with SVT (42 PVT,19 BCS, 7 combined PVT and BCS). By DNA-melting curve analysis, the JAK2V617F mutation was detected in 42.1 % of BCS, 38.1 % of PVT and 71.4 % of combined PVT and BCS groups. Thirteen of 15 (86.6 %) SVT patients with overt MPN and 16 of 53 (30.1 %) SVT patients without overt MPN (patients with either normal blood counts or cytopenias), including 6 of 16 with BCS (37.5 %), 7 of 33 with PVT (21.2 %) and 3 of 4 with combined BCS and PVT (75 %) possessed JAK2V617F mutation. A substantial proportion of patients with SVT were recognized as carriers of the JAK2V617F mutation despite the absence of overt signs of MPN. Receiver Operating Characteristic (ROC) curve analysis determined a platelet count of 190,000 mm(3) (area under the curve; AUC = 0.724, p = 0.002) and a white blood cell (WBC) count of 8,150 mm(3) (AUC = 0.76, p = 0.001) as the best cut-off values for the highest sensitivity and specificity ratios of the JAK2V617F mutation in patients with SVT. A significant positive correlation existed between the JAK2V617F mutational status of SVT patients and the WBC and platelet counts. Our results imply that JAK2V617F mutation screening should be an initial test for MPN in patients with SVT.

Is there any predictor for relapse after treatment withdrawal in autoimmune hepatitis patients in the real life?

BACKGROUNDS AND AIMS: In autoimmune hepatitis, there are uncertainties about whether to discontinue the treatment, when the treatment should be discontinued, and the risks of relapse in the cases where remission is achieved with immunosuppressive therapy. In this study, patients with AIH, whose immunosuppressive treatments were discontinued, were evaluated for the rates of remission and the risk of relapse. MATERIALS AND METHODS: A total of 119 patients, who were diagnosed with AIH based on the AIHG scoring systems between 1990 and 2015, were evaluated. Patients were receiving standard azathioprine and steroid therapy. The treatment was discontinued in patients, who had been receiving treatment for at least 2 years, who had no clinical complaints, and whose aminotransferases were normal and when an increase occurred in AST values more than two times the normal after the treatment was interrupted, the case was considered as a relapse. RESULTS: Among the patients, 83%(n = 99) were women. When the patients were diagnosed with AIH, their mean age was 36 ± 16(8-79) years; 70.6%(n = 84) were type 1, 3.4%(n = 4) type 2, and 26%(n = 31) were autoantibody-negative AIH. At the time of discontinuation, liver biopsy was performed in 8 of the patients and minimal-mild abnormalities were detected. Patients whose treatment was discontinued received treatment for an average of 101 ± 75(range: 24-280, median: 68.5) months; and, they were followed up for an average of 19 (1-110) months during the period without medication. Relapse occurred in 67%(n = 12) of the patients with drug withdrawal. Relapse occurred within the first 12 months in 67% of these patients (n = 8) and developed with an acute hepatitis attack in 42%. None of the clinical, laboratory, and histological data were found to be effective on relapse. CONCLUSION: In patients with AIH, relapse occurs in two-thirds of patients within an average of 19 month after the discontinuation of the medication. Most relapses occur at the early period and they are accompanied by an acute hepatitis attack.

A Case of Budd-Chiari Syndrome Associated With Antiphospholipid Syndrome Treated Successfully by Transjugular Intrahepatic Portosystemic Shunt.

Budd Chiari syndrome (BCS) is defined as obstruction of hepatic venous outflow that can be located anywhere from small hepatic venules up to the entrance of inferior vena cava (IVC) into right atrium. Etiologies of BCS include myeloproliferative disorders, congenital, and acquired hypercoagulable states. Anticoagulation is the mainstay of treatment for all cases of BCS with a demonstrable hypercoagulable state. Interventional radiology procedures such as transjugular intrahepatic portosystemic shunting (TIPS) can be utilized to reduce portal hypertension and to improve complications related to portal hypertension. We present a patient with systemic lupus erythematosus who first presented with fever, weight loss, malar rash, alopecia, livedo reticularis, symmetric polyarthritis, pancytopenia, and class IV lupus nephritis when she was 23 years old. After receiving an induction treatment of cyclophosphamide and glucocorticoids, she received a maintenance treatment of azathioprine. She presented with ascites and abdominal pain when she was 36 and the abdominal imaging revealed reduced calibration of hepatic venules and intrahepatic segment of inferior vena cava. Lupus anticoagulant was positive and anti cardiolipin IgM and IgG were positive. Work up for hereditary hypercoagulable states was negative. Thus, the diagnosis was secondary antiphospholipid syndrome where BCS was the first clinical manifestation of the antiphospholipid syndrome. Patient was anticoagulated with warfarin and received diuretics for ascites. After the ascites became refractory to diuretics and the patient had multiple vertebral compression fractures due to volume overload secondary to ascites, she was successfully treated with TIPS. When control imaging was performed, 50% of stenosis was observed in the stent. Balloon dilation of the stent was performed. Interventional radiology techniques like TIPS can be used in BCS patients secondary to APS, in cases when medical treatment is insufficient to control complications of portal hypertension. In BCS patients secondary to APS, TIPS enables clinical improvement but due to the presence of endothelial dysfunction in APS patients, there is a risk of shunt dysfunction secondary to thrombosis or stenosis secondary to intimal hyperplasia. Therefore, strict anticoagulation and regular follow up of patients after TIPS is recommended. In cases with stent stenosis, reintervention may be necessary.

Cyclosporine Therapy as a Rescue Treatment in Steroid Refractory Acute Severe Ulcerative Colitis: A Real Life Data From a Tertiary Center.

BACKGROUND: Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients. METHODS: Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylpredniso- lone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index. RESULTS: In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy. CONCLUSION: Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive.