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Early-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

Background and AimHemostasis in cirrhosis is dynamic and balanced. Thromboelastography (TEG) assesses global coagulation status. We aimed to assess whether TEG-guided blood product transfusions result in lower blood product requirements in patients with cirrhosis undergoing invasive liver-related procedures as compared to the conventional standard of care (SOC).MethodsIn this open-label, randomized controlled trial, cirrhosis patients with coagulopathy, undergoing invasive liver-related procedures, were randomized to either TEG-guided blood product transfusion or SOC. The primary outcome was difference in the amount of fresh frozen plasma (FFP) and platelet units transfused between the two groups. The secondary outcome was procedure-related bleeding complications within 5 days and any complications until 28 days.ResultsFrom November 2017 till June 2019, 58 patients were recruited (29: TEG and 29: SOC). Most common procedures performed were percutaneous liver biopsy (n = 48), followed by transjugular intrahepatic portosystemic shunt (n = 2), percutaneous acetic acid injection (n = 2), and transarterial chemoembolization (n = 2). There were no differences in baseline demographics, hemostatic profile, and types of procedures between the two groups. Only nine patients in TEG group received transfusions compared to all patients in SOC (31% vs 100%; P < 0.001). In TEG group, six (20.7%) received FFP (P = 0.753 vs. SOC), two (6.9%) received platelets (P < 0.001 vs. SOC), and 1(3.4%) patient received both FFP and platelet (P ≥ 0.999 vs. SOC) transfusion. None of the patients in either group developed procedure-related bleeding complications until 5 days post-procedure. The complication rates at 28-day follow-up were similar between the groups.ConclusionTEG-guided blood product transfusion strategy reduces blood product transfusion without increased risk of bleeding in cirrhotic patients undergoing invasive liver-related procedures (CTRI/2017/12/010822).

INTRODUCTION:Limited evidence exists on the optimal strategy to correct iron deficiency anemia after variceal bleeding (VB) in cirrhosis. This trial compared the efficacy and safety of intravenous ferric carboxymaltose (IV-FCM) with those of oral iron therapy in this cohort.METHODS:In this open-label, single-center, randomized controlled trial, eligible patients with hemoglobin <10 g/dL and iron deficiency (ferritin <100 ng/mL) after VB received either IV-FCM (1,500-2,000 mg) divided into 2 doses (n = 48) or oral carbonyl iron (100 mg elemental iron/day) (n = 44) for 3 months. The primary outcome was change in hemoglobin at 3 months. Secondary outcomes included improvement in anemia (last hemoglobin >12 g/dL), normalization of iron stores (ferritin >100 ng/mL), liver-related adverse events, adverse drug reactions, and changes in quality of life (CLDQOL questionnaire).RESULTS:Baseline characteristics, including median Child-Turcotte-Pugh score 7 (interquartile range [IQR] 6-9), Model for End-Stage Liver Disease score 12 (IQR 10-17), blood hemoglobin (8.25 ± 1.06 g/dL), and ferritin (30.00 ng/mL [15.00-66.50]), were comparable in both arms. The median increase in hemoglobin at 3 months in the IV and oral arms was 3.65 g/dL (IQR 2.55-5.25) and 1.10 g/dL (IQR 0.05-2.90 g/dL) (P < 0.001), respectively. Iron stores normalized in 84.6% and 21% of the IV and oral arms, respectively (P < 0.001). Anemia improved in 50% and 21.9% in the IV and oral arms, respectively (P < 0.009). Patients in the IV arm showed a significant improvement in all domains of CLDQOL. Liver-related adverse events were comparable in both arms. Transient mild/moderate hypophosphatemia developed in 43% of patients receiving IV-FCM.DISCUSSION:Intravenous iron replacement is efficacious and safe to treat iron deficiency anemia after VB in patients with cirrhosis.

Limited data exist on long-term outcomes of patients with compensated cirrhosis presenting with acute variceal bleeding (AVB) as an index and lone decompensating event. This study aimed to evaluate the incidence of further decompensation, survival, and risk factors of mortality in these patients. Patients with otherwise compensated cirrhosis presenting with AVB as their index decompensating event (n = 463) were analyzed in this single-center retrospective study. The incidence of individual decompensation events and survival was estimated using competing risk analysis. Risk factors for poor outcomes were identified. The mean age was 47.4 (13.2) years, with most patients (86.5%) being males. Alcohol-related liver disease (42.3%) and viral cirrhosis (22.4%) were the main etiologies with a median Model for End-Stage Liver Disease score of 14 (11-15) at baseline. Over a median follow-up of 42 (24-62) months, 292 patients experienced further decompensations: ascites (n = 283; 96.9%), rebleeding (n = 157; 53.8%), and hepatic encephalopathy (n = 71; 24.3%). Most events occurred with similar frequency across different etiologies, except acute-on-chronic liver failure, which was more common in nonviral cirrhosis (Gray test, P = 0.042). Patients with viral and nonviral cirrhosis had similar survival (5-year survival: 91% and 80.1%, respectively; P = 0.062). Patients with early further decompensations (onset <6 weeks of index AVB event) (n = 40) had a higher mortality (52.5% vs 20.2% for late decompensations; P < 0.001). Active alcohol consumption (hazard ratio [HR]: 9 [5.31-15.3], P < 0.001), high white blood cell count at presentation (HR: 2.5 [1.4-4.4], P = 0.001), and early decompensation (HR: 6.2 [3.6-10.6], P < 0.001) predicted poor survival. Despite a high incidence of further decompensation, 5-year survival of patients at this stage of cirrhosis is more than 80% across all etiologies in the absence of early further decompensation and active alcohol consumption.

In patients with cirrhosis, highly prevalent vitamin D deficiency and low bone mineral density (BMD) increase the burden of disease, and role of vitamin D supplementation is not clear. So, our aim was to determine the effect of vitamin D supplementation on vitamin D level and BMD in patients with cirrhosis. Patients with cirrhosis (18-60 years) of any etiology were enrolled. We measured serum 25(OH)D, parathyroid hormone, thyroid-stimulating hormone, free T4, bone-specific alkaline phosphatase, insulin-like growth factor (IGF)-1, and health-related quality of life at entry and at 1 year; however, serum calcium was measured at 3-month interval. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine and left hip neck at entry and after 1 year. Statistical analysis was performed according to intention-to-treat analysis. Of 390 screened patients with cirrhosis, 164 participants (82 in each group) were randomized. There was significant increase in 25(OH)D levels in intervention group after 1 year (33.7 [24.3-45.7] ng/mL vs 23.1 [17-28.2] ng/mL; P < 0.001) when compared with placebo. The mean difference in BMD at lumbar spine and left hip neck was not significantly changed after 1 year of intervention with vitamin D between both groups. There was no significant change in both the groups in levels of calcium, thyroid-stimulating hormone, parathyroid hormone, free T4, IGF-1, and bone-specific alkaline phosphatase and quality of life. Supplementation with vitamin D for 1 year improves vitamin D levels but did not result in improvement in BMD at lumbar spine and left hip neck in patients with cirrhosis.

Both transient elastography (TE)-based and non-TE-based criteria exist for detection of varices needing treatment (VNT) in patients with asymptomatic advanced chronic liver disease (CLD). However, their performance in clinical settings at different risk thresholds of detection of VNT and in regions where elastography is not widely available is unknown. We aimed to validate existing noninvasive criteria in our patients with CLD and identify best TE- and non-TE-based criteria for VNT screening at usual risk thresholds. Patients with compensated advanced CLD (cACLD) who underwent esophagogastroduodenoscopy and TE within 3 months were included. Diagnostic performance of Baveno VI, expanded Baveno VI, platelet-model for end-stage liver disease, and platelet-albumin (Rete Sicilia Selezione Terapia-hepatitis C virus) criteria were estimated. Decision curve analysis was conducted for different predictors across range of threshold probabilities. A repeat analysis including all patients with compensated CLD (cACLD and non-cACLD) was performed to simulate absence of TE. A total of 1,657 patients (cACLD, 895; non-cACLD, 762) related to hepatitis B virus (38.2%), hepatitis C virus (33.4%), nonalcoholic steatohepatitis (14.7%), and alcohol (11.8%) were included. Baveno VI identified maximum VNT (97.3%) and had best negative predictive value (96.9%), followed by platelet-albumin criteria. Expanded Baveno VI and platelet-model for end-stage liver disease had intermediate performance. At threshold probability of 5%, Baveno VI criteria showed maximum net benefit, and platelet-albumin criteria was next best, with need for 95 additional elastographies to detect 1 additional VNT. Similar results were obtained on including all patients with compensated CLD irrespective of TE. Baveno VI criteria maximizes VNT yield at 5% threshold probability. An acceptable alternative is the platelet-albumin criteria in resource-limited settings.

Background & objectives: Vitamin D plays an important role in bone metabolism, and liver is the intermediary site of vitamin D metabolism. The purpose of this study was to study the prevalence of vitamin D deficiency and bone health in patients with cirrhosis. Methods: Prospectively, serum 25-hydroxy vitamin D [25(OH)D] level were assessed in cirrhotics by chemiluminescence method. Endocrine Society Clinical practice guideline was used to define deficiency and insufficiency of vitamin D. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry and the World Health Organization criteria was used to define osteoporosis and osteopenia. The lowest T score at the left hip neck or lumbar spine was taken as osteoporosis or osteopenia. The Child-Turcotte-Pugh score was used to assess the severity of cirrhosis. Results: Cirrhotics (n=350, male: 278, compensated: 210) were included. Mean serum 25(OH)D level was 8.75 ng/ml. The prevalence of vitamin D deficiency (VDD) and low-BMD (osteopenia and osteoporosis) was 89.4 and 86 per cent, respectively. VDD, insufficiency and osteoporosis was found in 86.7, 11.9 and 33.8 per cent, respectively, in patients with compensated cirrhosis; and 93.6, 3.6 and 40 per cent, respectively, in patients with decompensated cirrhosis. Body mass index of >25 kg/m2 was protective for bone health. Interpretation & conclusions: VDD and low-BMD is prevalent in Indian patients with cirrhosis and should be looked for in patients with cirrhosis for its prevention.