Natural History of Cirrhosis: Changing Trends in Etiology Over the Years.

BACKGROUND AND GOALS: The aims of the present study were to investigate the natural history of cirrhosis and to determine trends in the etiology of cirrhosis. METHODS: Between January 2001 and January 2018, a total of 1,341 patients had been diagnosed with cirrhosis and were included. RESULTS: A total of 898 cirrhotic patients, who were followed up for at least 6 months were included into the analysis. The median age was 54 years. The median Child-Pugh and MELD scores were 7.5 and 11, respectively. Ascites (51%) was the most common causes of decompensation. Chronic viral hepatitis was the most frequent cause of cirrhosis (58%). Hepatitis B virus (HBV) infection was the main etiology (34%), followed by hepatitis C virus (HCV) infection (18%). Among 129 patients with cryptogenic cirrhosis (CC), 60 had metabolic abnormalities. If these 60 patients with CC were considered to have nonalcoholic fatty liver disease (NAFLD)-related cirrhosis, the proportion of NAFLD-related cirrhosis increased from 1.8 to 8.0%. At admission, 74 patients (8%) had been diagnosed with hepatocellular carcinoma (HCC). A new HCC developed in 80 patients during the follow-up period. The probability of developing HCC was 3.9% at 12 months. Logistic regression analysis showed that the development of HCC was significantly associated with older age (p < 0.001), male gender (p < 0.001), viral etiology (p = 0.026), and baseline high aspartate aminotransferase level (p = 0.01). Overall, 104 cirrhotic patients died. CONCLUSION: HBV and HCV remain the leading causes of etiology in cirrhosis and HCC. However, NAFLD-related cirrhosis is recognized as a growing burden.

Evaluation of Magnetic Resonance Elastography and Transient Elastography for Liver Fibrosis and Steatosis Assessments in the Liver Transplant Setting.

BACKGROUND: Liver graft fibrosis affects long-term graft and patient survival in liver transplant recipients. Transient elastography and magnetic resonance elastography are widely used for the assessment of liver fibrosis in routine clinical practice, but are limited in liver transplant settings. The aims of the present study were to evaluate the accuracy of magnetic resonance elastography and transient elastograph in the assessment of liver fibrosis in liver transplant recipients, and to determine the recurrence rates of post-transplant hepatic steatosis and liver fibrosis. METHODS: A total of 126 consecutive liver transplant recipients were included. Magnetic resonance elastography and transient elastography were performed for to measure liver stiffness. RESULTS: The most common cause of liver transplantation was hepatitis B virus-induced cirrhosis (50%). The mean liver stiffness value with transient elastography was 6.1 ± 3.0 kPa, and the mean magnetic resonance elastography value was 2.7 ± 1.0 kPa. A significant positive correlation was found between magnetic resonance elastography and transient elastography in terms of liver stiffness measurement (r = 0.61, P < .001). Obesity and the underlying etiology of liver diseases did not have any significant negative effect on magnetic resonance elastography and transient elastography measurements. During the follow-up, the post-transplant recurrence rates of hepatic steatosis and hepatic fibrosis were 26% and 37%, respectively. The recurrence rates of post-transplant hepatic steatosis and liver fibrosis were slightly higher in recipients with non-alcoholic fatty liver disease-related cirrhosis than those with viral hepatitisrelated etiologies (44% vs 27%, P = .43; 44% vs 30%, P = .45, respectively). CONCLUSION: Magnetic resonance elastography and transient elastography are accurate in assessing liver fibrosis in the liver transplant setting. Obesity and the underlying etiology of primary liver disease do not influence the measurements.

The prevalence of metabolic-associated fatty liver disease in the Turkish population: A multicenter study.

Background and Aim: The objective of the present study was to investigate the prevalence of metabolic-associated fatty liver disease (MAFLD) in patients with dyspepsia. Materials and Methods: A total of 909 consecutive patients who presented with dyspepsia at 8 tertiary care centers in Turkey between March 2019 and December 2019 were included. Results: The median age was 47 years. Among them, 30.3% of the patients were obese, 18.8% had type 2 diabetes mellitus (T2DM), 35.1% had metabolic syndrome, 84.8% had dyslipidemia, and 23.9% had hypertension. The prevalence of MAFLD was 45.5%. Among the patients with MAFLD, the prevalence of obesity, T2DM, metabolic syndrome, dyslipidemia, and hypertension was 43.3%, 24.9%, 52.5%, 92.3%, and 31.9%, respectively. MAFLD was significantly associated with all of the metabolic comorbidities (p<0.001). The median Fibrosis-4 Index score of the MAFLD patients was 0.88 (range: 0.1-9.5). Of note, 53 patients with hepatic steatosis did not meet the MAFLD criteria. Conclusion: The results of the present study indicated that there was a significantly high prevalence of MAFLD observed in daily clinical practice in Turkey. Early diagnosis and prevention efforts should be implemented to reduce disease progression, and a region-based strategy is recommended.

Determination of Turkish norms of psychometric tests for diagnosing minimal hepatic encephalopathy and proposal of a high sensitive screening test battery.

BACKGROUND: Psychometric hepatic encephalopathy score (PHES) needs local standardization. AIMS: This study aimed at standardizing PHES for Turkish patients and compare them with German norms; to determine minimal hepatic encephalopathy (mHE) prevalence with two different methods [PHES battery and Critical Flicker Frequency (CFF)] and to assess whether sub-tests of the battery can be used for screening for mHE. METHODS: Healthy volunteers (n = 816; 400 male) and cirrhotics (n = 124; 58 male) were included. For mHE diagnosis PHES score threshold was set at ≤ - 5 points and that of CFF at < 39 Hz. For comparing German and Turkish norms, datasets were combined. Multiple backward procedure was applied to assess effects of age, sex and education on single tests of the battery. Receiver operating characteristic (ROC) curves were created for assessing diagnostic capabilities of subtests of the battery. RESULTS: PHES norms for Turks were developed. MHE prevalence in compensated cirrhotics was 29.8% and 27.4% with PHES and CFF tests, respectively, with low compatibility (kappa coefficient 0.389); mHE prevalence decreased to 16% when both tests were combined. Turks performed worse vs Germans in the digit symbol (DS) and serial dotting (SD) subtests but performed better in other subtests. In ROC analyzes of subtests, the combination of DS + SD tests achieved an AUROC of 0.974 versus PHES. CONCLUSIONS: Use of two methods for diagnosing mHE is important for research purposes. From a clinical perspective, sensitivity with acceptable specificity may suffice for screening instruments for mHE. Combined use of DS and SD subtests of the PHES battery appears suitable for this purpose.

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.

MR Enterography in Crohn's disease complicated with enteroenteric fistula.

OBJECTIVE: In this retrospective study, we aimed to evaluate MR enterography (MRE) findings, MR index of activity (MaRIA) and laboratory markers in Crohn patients with enteroenteric fistula. METHODS: Institution's electronic medical records (laboratory, pathology, ileocolonoscopy results and discharge summary) were reviewed and MR images retrieved from the PACS were reanalyzed in Crohn patients assessed at Gastroenterology Clinic of our university between July 2011 and July 2016. MR enterography and clinic parameters of 38 Crohn patients with enteroenteric fistula and 48 Crohn patients without enteroenteric fistula were compared. RESULTS: Of the findings, perienteric inflammation was seen only in fistula group. The mean wall thickness was significantly greater; perienteric fluid, mural hyperenhancement, cecal contraction, thickening of ileocecal valve, and colonic involvement were significantly more common in fistula patients. There was no significant difference between groups with regards to MaRIA index and perianal disease. In patients with enteroenteric fistula, there was significant association between the presence of hypoalbuminemia and presence of ileitis at ileocolonoscopy. In the overall study population, there was a positive correlation between the MaRIA and CRP values at the time of the MRE. CONCLUSIONS: Perienteric mesenteric inflammation and fluid collection are common in enteroenteric fistulization. MaRIA indices and laboratory findings of patients with enteroenteric fistula are not significantly different from those without fistulas.

Two cases with HSS/DRESS syndrome developing after prosthetic joint surgery: does vancomycin-laden bone cement play a role in this syndrome?

We report two cases of hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (HSS/DRESS) syndrome following systemic and local (via antibiotic laden bone cement (ALBC)) exposures to vancomycin. Both cases developed symptoms 2-4 weeks after the initiation of treatment. They responded to systemic corticosteroid treatment and were cured completely. Various drug groups may cause HSS/DRESS syndrome, and vancomycin-related cases do not exceed 2-5% of the reported cases. Almost all of these cases developed the syndrome following systemic exposure to vancomycin. ALBC seems to be the safer antibiotic administration method, as systemic antibiotic levels did not reach a toxic threshold level. However, local administration may not always be sufficient for bone-related/joint-related infections; these infections may require systemic antibiotics as well. As HSS/DRESS syndrome can mimic infectious diseases, it must be considered during differential diagnosis before suspecting failure of treatment and initiation of a different antibiotic course.