Evaluation of patients with positive anti-mitochondiral antibody and normal alkaline phosphatase levels for primary biliary cholangitis.

Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease typically diagnosed by elevated cholestatic liver enzymes and a positive anti-mitochondrial antibody (AMA) test. The clinical importance of AMA positivity in patients with normal cholestatic liver enzymes is unclear. The aim of this study was to determine the relationship between PBC and AMA positivity detected in individuals with normal cholestatic enzyme levels. The files of patients with AMA and/or AMA-M2 positivity between 2009 and 2018 and whose alkaline phosphatase (ALP) levels were below upper limit of normal (ULN) at initial admission were retrospectively analyzed. The ALP levels were normal in all patients. All patients had AMA positivity demonstrated by indirect immunofluorescence (IIF) or AMA-M2 positivity demonstrated by ELISA. A total of 16 patients underwent liver biopsy and seven (43.75%) showed changes consistent with those with PBC. A total of 12 patients were diagnosed with PBC and were treated and followed up with this diagnosis. People with AMA positivity and normal cholestasis enzyme levels are closely associated with PBC. Some of these patients were diagnosed with PBC as a result of biopsy and some were diagnosed by clinical and laboratory findings during follow-up.. The patients with an AMA titration of 1/20 were not associated with PBC. In our study, results similar to the studies confirmed by biopsies were obtained. In this regard, there is a need for prospective and retrospective studies with longer follow-up periods.

Psychometric tests, critical flicker frequency, and inflammatory indicators in covert hepatic encephalopathy diagnosis.

Background and Aim: Hepatic encephalopathy (HE) is a frequent complication of liver diseases. Systemic inflammation is key for HE pathogenesis. The main goal of the study was to investigate the role of psychometric tests, critical flicker frequency (CFF), and comparative evaluation of inflammatory indicators for the diagnosis of covert HE (CHE). Materials and Methods: The study was a prospective, nonrandomized, case-control study with a total of 76 cirrhotic patients and 30 healthy volunteers. The West Haven criteria were used to determine the occurrence of CHE in cirrhotic patients. Psychometric tests were applied to healthy and cirrhotic groups. CFF, venous ammonia, serum endotoxin, IL-6, IL-18, tumor necrosis factor alpha (TNF-α) levels, and hemogram parameters were evaluated for cirrhotic patients. Results: CFF values and psychometric tests were found to accurately discriminate CHE positives from CHE negatives (p<0.05). When the control group was excluded, the digit symbol test and the number connection A test failed, unlike CFF and other psychometric tests. Using CFF, a 45 Hz cutoff value had 74% specificity and 75% sensitivity. Basal albumin levels (p=0.063), lymphocyte-to-monocyte ratio (LMR) (p=0.086), and neutrophil-to-lymphocyte ratio (p 0.052) were significant, albeit slightly, among CHE groups. Basal albumin levels had 50% sensitivity and 71% specificity when 2.8 g/dL was used as a cutoff value to determine CHE. Conclusion: Both psychometric tests and CFF can be useful in diagnosing CHE. Using cytokine and endotoxin levels seems to be inadequate to diagnose CHE. Using LMR and albumin levels instead of psychometric tests for diagnosing CHE can be promising.

Noninvasive Risk Stratification for Nonalcoholic Fatty Liver Disease Among Living Liver Donor Candidates: A Proposed Algorithm.

To reduce waitlist mortality, living donor liver transplantation (LDLT) has increased over the past decade in the United States, but not at a rate sufficient to completely mitigate organ shortage. As a result, there are ongoing efforts to expand the living liver donor pool. Simultaneously, the prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population has increased, which has significant implications on the pool of potential living liver donors. As such, a clinical assessment algorithm that exhaustively evaluates for NAFLD and fibrosis is critical to the safe expansion of LDLT. An ideal algorithm would employ safe and noninvasive methods, relying on liver biopsy only when necessary. While exclusion of NAFLD and fibrosis by noninvasive means is widely studied within the general population, there are no well-accepted guidelines for evaluation of living donors using these modalities. Here we review the current literature regarding noninvasive NALFD and fibrosis evaluation and propose a potential algorithm to apply these modalities for the selection of living liver donors.

The importance of antioxidant status in gastric intestinal metaplasia.

BACKGROUND: Oxidative stress status in different cancer types was investigated before, but not studied in gastric intestinal metaplasia to the best of our knowledge. Purpose of this study is to examine whether there is a difference between oxidative stress status in patients with intestinal metaplasia (IM) compared to individuals without IM, we compared the serum levels of disulfide (SS), total thiol (TT) and native thiol (NT). METHODS: This was a prospective, non-randomized casecontrol study including 67 patients with histopathologically confirmed IM and 60 individuals demographically matched in terms of age, gender, BMI, smoking status, and chronic diseases as control group. RESULTS: The mean NT, TT and NT to TT (NT/TT) ratios were statistically significantly higher in IM group compared to controls ((351.71 ± 81.9 mol/L vs. 271.82 ± 54.13 mol/L, p=0.000), (391.5 ± 92.69 mol/L vs. 308.59 ± 55.53 mol/L, p=0.000) and (0.89 ± 0.6 vs. 0.87 ± 0.29, p=0.022), respectively). The mean SS to TT (SS/TT) ratio was significantly lower in IM group than control group (0.050 ± 0.31 vs. 0.060 ± 0.014, P=0.022). Median SS and mean SS/NT ratio was similar in both groups (16.3 (3.3-78) vs. 18.3 (10-32.7), p=0.271 and 0.055 ± 0.041 vs. 0.070 ± 0.019, p=0.068, respectively). In ROC analysis, cut off value of SS/NT for IM was found 0.062, in regression analysis, SS/NT <0.062 was found as an independently prognostic marker for IM (OR, 2.38; 95%CI: 1.168-4.865, P=0.017). CONCLUSIONS: SS/NT ratio lower than 0.062 was found as an independently prognostic marker for IM. This ratio could help to distinguish which patients should be followed closely for gastric cancer.

Predictive value of FibroScan in detecting liver fibrosis in HBeAg negative patients with chronic hepatitis B whose HBV DNA 2000-20000 IU/ml with ALT 1-2 times the upper limit of normal and those with HBV DNA >20000 IU/ml and normal ALT.

Objective: In hepatitis B infection, it is difficult to make a treatment decision in patients with slightly elevated transaminases and HBV DNA level between 2000 and 20000 IU/ml, and in those with normal ALT, despite high levels of HBV DNA. Objectives: In HBeAg negative patients whose HBV DNA levels were between 2000 and 20000 IU/ml with ALT 1-2 times the upper limit of normal (ULN) and those with HBV DNA >20000 IU/ml and normal ALT, the concordance between liver fibrosis in biopsy and liver stiffness measured by transient elastography with FibroScan® (FS) was investigated, and diagnostic value of FS to predict the liver fibrosis was tested. Methods: The patients were selected from the outpatient hepatology clinics between the dates of November 2014 and October 2016 among those who were taken liver biopsy. Transient elastography was obtained within 3 months after liver biopsy. The diagnostic value of FS in detecting advanced fibrosis or moderate to advanced (MTA) fibrosis was investigated for each group. Results: In 38 patients with HBV DNA 2000-20000 IU/ml and ALT 1-2×ULN, advanced fibrosis was detected in only one patient (2.6%) on liver biopsy, sensitivity of FS to show advanced fibrosis is 100%, specificity 78.3%, and diagnostic accuracy rate 79%. The area under curve was determined to be 0.892. In detecting MTA fibrosis, these values are 100%, 62%, 71%, and 0.810, respectively. Of 79 patients with HBV DNA >20000 IU/ml and normal ALT, five had advanced (5.5%) and 18 had MTA (23%) fibrosis. Sensitivity of FS in detecting advanced fibrosis was 100%, specificity 87.8%, and accuracy 88.6%, and these values for MTA fibrosis were 85.7%, 81%, and 82.3%, respectively. Conclusion: Because of false negativity in a few patients with HBV DNA >20000 IU/ml in detecting MTA, FS may be combined with other non-invasive techniques. Negative predictive values of FS in predicting advanced or MTA fibrosis were very high, while positive predictive values were low. However, FS may save several patients from liver biopsy.

Recurrence of hepatocellular carcinoma following deceased donor liver transplantation: case series.

AIM: We aimed to study the clinical and pathological characteristics of liver transplant recipients with hepatocellular carcinoma recurrence. METHODS: We reviewed the data for 26 patients who had tumor recurrence after deceased donor liver transplant for hepatocellular carcinoma at the Johns Hopkins Hospital from January 2005 to December 2015. RESULTS: In total, 88% of recipients were males. The mean age was 59 years. On explant, poor differentiation was detected in 43%, while 73% had microvascular invasion. Overall, 62% were diagnosed to be outside of Milan criteria. Out of these, 15% met the criteria for downstaging. Twenty (77%) patients had pre-transplant alpha fetoprotein levels ≥ 20 ng/mL. In 54% of patients, the location of hepatocellular carcinoma (HCC) recurrence was extrahepatic, followed by intrahepatic in 31% and both intra- and extrahepatic in 15%. The post-transplant tumor recurrence was diagnosed at a mean of 427 days (range 34-1502). Fifty percent of HCC recurrences were diagnosed within one year following liver transplant. Twenty (77%) patients received treatment for their recurrent HCC: external radiation (n = 10), surgical resections (n = 8; brain 4, spine 2, bone 1, and Whipple surgery 1), sorafenib (n = 7), locoregional therapy (n = 5). Overall, 24 out of 26 (92%) recipients died within four years after the transplant. CONCLUSION: HCC recurrence after liver transplant is infrequent. More than fifty percent of HCC recurrences following liver transplant are extrahepatic. Despite better recipient selection for liver transplant, the curative options are limited in recurrent cases and associated with extremely poor outcomes.

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.

From cirrhosis to hepatocellular carcinoma: An investigation into hepatitis C viral oncogenesis.

Background and Aim: Hepatitis C is a leading cause of chronic liver disease and hepatocellular carcinoma (HCC). Understanding the evolution and biology of HCC among HCV patients may lead to novel therapeutic avenues and risk stratification. Material and Methods: Using meta-analysis platform STARGEO, we performed two separate meta-analyses as follows: 357 HCV-related HCC tumor samples with 220 adjacent non-tumor samples and 92 HCV-related cirrhotic liver samples with 53 healthy liver samples as a control. Then, we analyzed the signature in Ingenuity Pathway Analysis. Results: HCV cirrhosis analysis demonstrated LPS/IL-1 mediated inhibition of RXR function, LXR/RXR activation, sirtuin signaling, IL-10 signaling and hepatic fibrosis/stellate cell activation as top canonical pathways. IL1ß, TNF, and TGF-ß1 were top upstream regulators. Cellular morphologic and signaling changes were noted through the up-regulation of RGS1/2, WNT receptor FZD7, the TGF-ß1-induced gap junction gene GJA1, and the zinc finger transcription factor repressor SNAI2. Apoptosis was inhibited through the down-regulation of OMA1. Metabolic dysfunction was noted through the down-regulation of SCLY and CBS. HCV-related HCC analysis showed FXR/RXR and LXR/RXR signaling, LPS/IL1-mediated inhibition of RXR activation, and melatonin degradation as top canonical pathways. Conclusion: Our results suggest that the genetic changes in the setting of chronic HCV infection predispose patients to developing HCC.

A possible link between luteinizing hormone and macrophage migration inhibitory factor levels in polycystic ovary syndrome.

PURPOSE: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that plays a role in metabolic and inflammatory processes. Increasing evidence suggests that there is a link between MIF and ovulation. We aimed to evaluate plasma MIF levels in women with polycystic ovary syndrome (PCOS) and to determine whether MIF levels differ between the follicular phase and mid-cycle of the menstrual cycle in eumenorrheic women. METHODS: Ninety women with PCOS and 80 age- and BMI-matched healthy eumenorrheic women were consecutively recruited into this prospective observational study. For all subjects, plasma MIF levels in the early follicular phase were measured by ELISA; for the 40 healthy controls, MIF levels were also measured during mid-cycle of the same menstrual cycle. RESULTS: Plasma MIF levels were significantly higher in women with PCOS than in eumenorrheic women (14.16 ± 1.59 vs. 10.39 ± 0.70 ng/ml; p < 0.001). MIF levels were significantly higher at mid-cycle than in the follicular phase in eumenorrheic women (11.15 ± 0.61 vs. 10.56 ± 0.82 ng/ml; p < 0.001). MIF was positively correlated with BMI, high sensitivity C-reactive protein (hs-CRP), and homeostasis model assessment of insulin resistance (HOMA-IR) in both groups. MIF was positively correlated with luteinizing hormone (LH) and free-testosterone only in the PCOS group. Binary logistic regression analyses revealed that the odds ratio (OR) for PCOS independently increases linearly with elevated MIF (OR = 1.385, 95% CI = 1.087-1.764, p = 0.017). CONCLUSION: MIF may play a crucial role in the reproductive system in women, including the development of PCOS and normal ovulation.