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Background: Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non‐cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. Methods: A retrospective cohort of consecutive patients diagnosed with pathology‐confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug‐associated, miscellaneous or idiopathic. Long‐term mortality was analysed using Kaplan‐Meier estimation and Cox regression models. Results: One hundred and sixty‐seven consecutive patients with pathology‐confirmed NRH were analysed over a 15‐year period and followed for a median time of 50 months (1–306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension‐related complications at diagnosis were common, with ascites present in one‐third of patients. Overall transplant‐free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. Conclusions: The rates of liver‐related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver‐related outcomes do not appear to differ based on associated, possibly causal, conditions. [ABSTRACT FROM AUTHOR]

Short telomere syndrome is a genetically inherited syndrome resulting in premature telomere shortening. This premature shortening of telomeres can result in hematologic, pulmonary, vascular, gastrointestinal, and hepatic manifestations of disease. Identifying patients with short telomere syndrome can be a clinical challenge due to the multitude of potential manifestations and lack of widely available diagnostic tests. In this review, we will highlight hepatic manifestations of short telomere syndrome with a focus on diagnosis, testing, and potential treatments. [ABSTRACT FROM AUTHOR]

Over the past 2 decades, the concept of acute-on-chronic liver failure (ACLF) has been proposed as an alternate path in the natural history of decompensated cirrhosis. ACLF thus is characterized by the presence of a precipitating event (identified or unidentified) in subjects with underlying chronic liver disease leading to rapid progression of liver injury and ending in multi-organ dysfunction characterized by high short-term mortality. Multiple organ failure and an increased risk for mortality are key to the diagnosis of ACLF. The prevalence of ACLF ranges from 24% to 40% in hospitalized patients. The pathophysiological basis of ACLF can be explained using the following 4-part model: predisposing event, injury caused by a precipitating event, response to injury, and organ failure. Although several mathematic scores have been proposed for identifying outcomes with ACLF, it is as yet unclear whether these organ failure scores are truly prognostic or only reflective of the dying process. Treatment paradigms continue to evolve but consist of early recognition, supportive intensive care, and consideration of liver transplantation before onset of irreversible multiple organ failure. [ABSTRACT FROM AUTHOR]

Background/Objectives: Circulating endothelial cells (CECs) are indicative of vascular injury and correlate with severity of vascular diseases. A pilot study showed that the ratio of CEC to platelet count (CEC/PC) was effective in predicting cirrhosis. Therefore, we evaluated CEC/PC in a larger cohort of patients, correlated it with cirrhosis, and compared its operating characteristics with previously described biomarker for cirrhosis, the AST/platelet ratio index (APRI). Methods: Fifty-three patients with cirrhosis, 20 matched healthy controls, and 9 patients with noncirrhotic liver disease were recruited. Peripheral blood sample was collected and analyzed to enumerate nucleated CEC CD146+, CD105+, CD45– using a commercial assay. Results: Median CEC counts were significantly higher in patients with cirrhosis (62 cells/4 mL, interquartile range [IQR]: 43.5–121) as compared with controls (31 cells/4 mL, IQR: 22.2–40). The CEC/PC was also significantly elevated in cirrhotics (0.69, IQR: 0.39–1.48) compared with controls (0.12, IQR: 0.09–0.20) and noncirrhotics (0.21, IQR: 0.08–0.43). Receiver operator characteristic (ROC) analysis revealed that CEC cutoff value of ≥37 cells/4 mL showed sensitivity of 81% and specificity of 75% for differentiating cirrhosis from controls (area under the curve [AUC]: 0.80; 95% confidence interval [CI] 0.67–0.91). The CEC/PC ratio cutoff value of ≥0.23 showed sensitivity of 91% and specificity of 82% (AUC: 0.92; 95% CI 0.83–0.99). The APRI cutoff value of ≥0.4 showed sensitivity of 94% and specificity of 85% for differentiating cirrhosis from control patients (AUC: 0.96; 95% CI 0.90–1.0). A product of CEC and APRI, termed CAPRI (CEC-APRI), effectively distinguished patients with cirrhosis from controls; with cutoff value of ≥12.7, showing higher sensitivity of 98% and specificity of 85% (AUC: 0.98; 95% CI 0.96–1.0). Conclusion: The CEC/PC ratio is significantly elevated in patients with cirrhosis and demonstrates comparable operating characteristics to previously described APRI. Furthermore, CAPRI, compiled as product of CEC to APRI showed outstanding ability to distinguish patients with cirrhosis from controls, although larger studies are necessary for validation. [Copyright &y& Elsevier]

Clinical vignette A 51-year-old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia with no significant fibrosis or necroinflammatory activity. Hepatic venous pressure gradient was elevated at 31 mmHg, consistent with clinically significant portal hypertension. The clinical course was complicated by refractory gastric variceal bleeding requiring a surgical portosystemic shunt. Approximately seven years after the initial presentation, the patient developed progressive dyspnoea and a diagnosis of idiopathic pulmonary fibrosis was made. Contrast-enhanced echocardiogram was not suggestive of hepatopulmonary syndrome or portopulmonary hypertension. Given this new diagnosis a telomere biology disorder was suspected. A flow-fluorescence in situ hybridisation analysis for telomere length assessment revealed telomere lengths below the first percentile in both lymphocytes and granulocytes. Next generation sequencing analysis identified a heterozygous mutation involving the hTERT gene (Histidine983Threonine). The lung disease unfortunately progressed in the subsequent two years, leading to the patient’s death nine years after his initial presentation with portal hypertension. During those nine years two brothers also developed idiopathic pulmonary fibrosis. The questions that arise from this case include: I. What are telomere biology disorders? II. What are the hepatic manifestations of telomere biology disorders? III. How are telomere biology disorders diagnosed? IV. Are there any potential therapeutic options for telomere biology disorders? [ABSTRACT FROM AUTHOR]