UNASSIGNED: Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intra-hepatic fat without significant alcohol intake. Multifactorial pathogenesis is reported to be involved. Reduced lysosomal acid lipase (LAL) activity is suggested as one of the novel-involved pathogenic mechanisms. This review summarizes the available evidence on the role of LAL activity in NAFLD pathogenesis.
UNASSIGNED: Four databases namely, PubMed/Medline, Science direct, Cochrane Library, and Google scholar were searched to identify relevant observational records evaluating the role of LAL activity in the pathogenesis of NAFLD. All studies were assessed for their quality by using Newcastle-Ottawa Scale or The Joanna Briggs Institute Critical Appraisal tools for cohort and cross-sectional studies, respectively. The estimates of LAL activity and other clinical outcomes were expressed as mean (SD) and number (%) as presented in the primary studies.
UNASSIGNED: A total of nine good quality studies with 1711 patients with NAFLD and 877 controls from different groups (healthy volunteers, alcoholics, cryptogenic cirrhosis, and HCV-positive) were included. From the NAFLD group, 59.55% were males and the overall mean age ranged between the studies from 12.6 ± 8.5 months in pediatrics to 58.90 ± 13.82 years in adults. In the NAFLD group, the LAL activity varied from 0.53 ± 0.08 to 1.3 ± 0.70 (nmol/spot/hr) between the studies which was less than all control groups except cryptogenic cirrhosis patients (0.5 ± 0.15 nmol/spot/hr). Of the other outcomes of interest, ALT, AST, total cholesterol, triglyceride, and LDL cholesterol were found elevated in NAFLD patients than in controls.
UNASSIGNED: The current evidence suggests a potential correlation of reduced LAL activity with NAFLD pathogenesis according to its severity. Large-scale studies are recommended, more importantly in patients with NAFLD having no metabolic or genetic involvement. Further LAL can act as a new non-invasive diagnostic biomarker to identify that specific NAFLD subgroup.

Close follow-up of patients with liver cirrhosis has led to increased detection of hepatocellular carcinoma (HCC) at an early stage, especially with magnetic resonance imaging (MRI) innovations. We report the case of a 70-year-old man, with a recent history of liver cirrhosis due to chronic hepatitis C virus (HCV) complicated by hepatocellular carcinoma (HCC), and for whom trans-arterial chemoembolization (TACE) was planned, as the patient was assigned Child B7 at admission. Angiography performed during the first TACE cycle shows not only the \"tumor blush\" corresponding to previously detected HCC but also an additional small foci of HCC uptake seen within a large dysplastic nodule giving the appearance of \"nodule-within-nodule.\" Early detection of hepatocellular carcinoma improves prognosis. Hence, it is essential to be aware of all early aspects of HCC, including the nodule-within-nodule appearance on cross-sectional imaging, and also in angiography, as in this case.

UNASSIGNED: Non-alcoholic steatohepatitis (NASH) is associated with increased mortality and a high clinical burden. NASH adversely impacts patients\' health-related quality of life (HRQoL), but published data on the humanistic burden of disease are limited. This review aimed to summarise and critically evaluate studies reporting HRQoL or patient-reported outcomes (PROs) in populations with NASH and identify key gaps for further research.
UNASSIGNED: Medline, EMBASE, the Cochrane Library and PsycINFO were searched for English-language publications published from 2010 to 2021 that reported HRQoL/PRO outcomes of a population or subpopulation with NASH.
UNASSIGNED: Twenty-five publications covering 23 unique studies were identified. Overall, the data showed a substantial impact of NASH on HRQoL, particularly in terms of physical functioning and fatigue, with deterioration of physical and mental health as NASH progresses. Prevalent symptoms, including fatigue, abdominal pain, anxiety/depression, cognition problems, and poor sleep quality, adversely impact patients\' ability to work and perform activities of daily living and the quality of relationships. However, some patients fail to attribute symptoms to their disease because of a lack of patient awareness and education. NASH is associated with high rates of comorbidities such as obesity and type 2 diabetes, which contribute to reduced HRQoL. Studies were heterogeneous in terms of diagnostic methods, population, outcomes, follow-up time, and measures of HRQoL/utility. Most studies were rated \'moderate\' at quality assessment, and all evaluable studies had inadequate control of confounders.
UNASSIGNED: NASH is associated with a significant HRQoL burden that begins early in the disease course and increases with disease progression. More robust studies are needed to better understand the humanistic burden of NASH, with adequate adjustment for confounders that could influence outcomes.
UNASSIGNED: Non-alcoholic steatohepatitis (NASH) has a significant impact on quality of life, with individuals experiencing worse physical and mental health compared with the general population. NASH and its symptoms, which include tiredness, stomach pain, anxiety, depression, poor focus and memory, and impaired sleep, affect individuals\' relationships and ability to work and perform day-to-day tasks. However, not all patients are aware that their symptoms may be related to NASH. Patients would benefit from more education on their disease, and the importance of good social networks for patient health and well-being should be reinforced. More studies are needed to better understand the patient burden of NASH.

UNASSIGNED: Spinal metastases (SM) are a frequent complication of cancer and may lead to pathologic vertebral compression fractures (pVCF) and/or metastatic epidural spinal cord compression (MESCC). Based on autopsy studies, it is estimated that about one third of all cancer patients will develop SM. These data may not provide a correct estimation of the incidence in clinical practice.
UNASSIGNED: This systematic review (SR) aims to provide a more accurate estimation of the incidence of SM, MESCC and pVCF in a clinical setting.
UNASSIGNED: We performed a SR of papers regarding epidemiology of SM, pVCF, and MESCC in patients with solid tumors conform PRISMA guidelines. A search was conducted in the PubMed and Web of Science database using the terms epidemiology, prevalence, incidence, global burden of disease, cost of disease, spinal metastas*, metastatic epidural spinal cord compression, pathologic fracture, vertebral compression fracture, vertebral metastas* and spinal neoplasms. Papers published between 1975 and august 2021 were included. Quality was evaluated by the STROBE criteria.
UNASSIGNED: While 56 studies were included, none of them reports the actual definition used for MESCC and pVCF, inevitably introducing heterogenity. The overall cumulative incidence of SM and MESCC is 15.67% and 2.84% respectively in patients with a solid tumor. We calculated a mean cumulative incidence in patients with SM of 9.56% (95% CI 5.70%-13.42%) for MESCC and 12.63% (95% CI 7.00%-18.25%) for pVCF. Studies show an important delay between onset of symptoms and diagnosis.
UNASSIGNED: While the overall cumulative incidence for clinically diagnosed SM in patients with a solid tumor is 15.67%, autopsy studies reveal that SM are present in 30% by the time they die, suggesting underdiagnosing of SM. Approximately 1 out of 10 patients with SM will develop MESCC and another 12.6% will develop a pVCF. Understanding these epidemiologic data, should increase awareness for first symptoms, allowing early diagnosis and subsequent treatment, thus improving overall outcome.

UNASSIGNED: Acute kidney injury (AKI) is common in the perioperative transplant period and is associated with poor outcomes. Few studies reported a reduction in AKI incidence with terlipressin therapy by counteracting the hemodynamic alterations occurring during liver transplantation. However, the effect of terlipressin on posttransplant outcomes has not been systematically reviewed.
UNASSIGNED: A comprehensive search of electronic databases was performed. Studies reporting the use of terlipressin in the perioperative period of living donor liver transplantation were included. We expressed the dichotomous outcomes as risk ratio (RR, 95% confidence interval [CI]) using the random effects model. The primary aim was to assess the posttransplant risk of AKI. The secondary aims were to assess the need for renal replacement therapy (RRT), vasopressors, effect on hemodynamics, blood loss during surgery, hospital and intensive care unit (ICU) stay, and in-hospital mortality.
UNASSIGNED: A total of nine studies reporting 711 patients (309 patients in the terlipressin group and 402 in the control group) were included for analysis. Terlipressin was administered for a mean duration of 53.44 ± 28.61 h postsurgery. The risk of AKI was lower with terlipressin (0.6 [95% CI, 0.44-0.8]; P = 0.001). However, on sensitivity analysis including only four randomized controlled trials (I2 = 0; P = 0.54), the risk of AKI was similar in both the groups (0.7 [0.43-1.09]; P = 0.11). The need for RRT was similar in both the groups (0.75 [0.35-1.56]; P = 0.44). Terlipressin therapy reduced the need for another vasopressor (0.34 [0.25-0.47]; P < 0.001) with a concomitant rise in mean arterial pressure and systemic vascular resistance by 3.2 mm Hg (1.64-4.7; P < 0.001) and 77.64 dyne cm-1.sec-5 (21.27-134; P = 0.007), respectively. Blood loss, duration of hospital/ICU stay, and mortality were similar in both groups.
UNASSIGNED: Perioperative terlipressin therapy has no clinically relevant benefit.

BACKGROUND: Gastrointestinal candidiasis is often neglected and potentially serious infection in cirrhosis patients. Therefore, we evaluated the prevalence, risk factors, and outcomes of esophageal candidiasis (EC) in cirrhotics and did a systematic review to summarize EC\'s available evidence in cirrhosis.
METHODS: Consecutive patients with cirrhosis posted for esophagogastroduodenoscopy (EGD) at a tertiary care institute were screened for EC (cases) between January 2019 and March 2020. EC was diagnosed on EGD findings and/or brush cytology. Controls (without EC) were recruited randomly, and EC\'s risk factors and outcomes were compared between cases and controls.Four electronic databases were searched for studies describing EC in cirrhosis. Prevalence estimates of EC were pooled on random-effects meta-analysis, and heterogeneity was assessed by I2. A checklist for prevalence studies was used to evaluate the risk of bias in studies.
RESULTS: EC was diagnosed in 100 of 2762 patients with cirrhosis (3.6%). Patients with EC had a higher model for end-stage liver disease (MELD) (12.4 vs. 11.2; P = 0.007), acute-on-chronic liver failure (ACLF) (26% vs. 10%; P = 0.003) and concomitant bacterial infections (24% vs. 7%; P = 0.001), as compared with controls. A multivariable model, including recent alcohol binge, hepatocellular carcinoma (HCC), upper gastrointestinal (UGI) bleed, ACLF, diabetes, and MELD, predicted EC\'s development in cirrhosis with excellent discrimination (C-index: 0.918). Six percent of cases developed the invasive disease and worsened with multiorgan failures, and four patients with EC died on follow-up.Of 236 articles identified, EC\'s pooled prevalence from 8 studies (all with low-risk of bias) was 2.1% (95% CI: 0.8-5.8). Risk factors and outcomes of EC in cirrhosis were not reported in the literature.
CONCLUSIONS: EC is not a rare infection in cirrhosis patients, and it may predispose to invasive candidiasis and untimely deaths. Alcohol binge, HCC, UGI bleed, ACLF, diabetes, and higher MELD are the independent predictors of EC in cirrhosis. At-risk patients with cirrhosis or those with deglutition symptoms should be rapidly screened and treated for EC.

UNASSIGNED: In an attempt to uncover unmet patient needs, this review aims to synthesise quantitative and qualitative studies on patients\' quality of life and their experience of having liver disease.
UNASSIGNED: Three databases (CINAHL, Embase, and PubMed) were searched from January 2000 to October 2020. The methodological quality and data extraction of both quantitative and qualitative studies were screened and appraised using Joanna Briggs Institute instruments for mixed-method systematic reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A convergent, integrated approach to synthesis and integration was used. Studies including patients with autoimmune and cholestatic liver disease, chronic hepatitis B and C, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma were considered.
UNASSIGNED: The searches produced 5,601 articles, of which 95 (79 quantitative and 16 qualitative) were included in the review. These represented studies from 26 countries and a sample of 37,283 patients. The studies showed that patients´ quality of life was reduced. Unmet needs for information and support and perceived stigmatisation severely affected patients\' quality of life.
UNASSIGNED: Our study suggests changes to improve quality of life. According to patients, this could be achieved by providing better education and information, being aware of patients\' need for support, and raising awareness of liver disease among the general population to reduce misconceptions and stigmatisation.
UNASSIGNED: PROSPERO CRD42020173501.
UNASSIGNED: Regardless of aetiology, patients with liver diseases have impaired quality of life. This is associated with disease progression, the presence of symptoms, treatment response, and mental, physical, and social factors such as anxiety, confusion, comorbidities, and fatigue, as well as limitations in daily living, including loneliness, low income, stigmatisation, and treatment costs. Patients highlighted the need for information to understand and manage liver disease, and awareness and support from healthcare professionals to better cope with the disease. In addition, there is a need to raise awareness of liver diseases in the general population to reduce negative preconceptions and stigmatisation.

UNASSIGNED: Individuals with type 2 diabetes (T2DM) are at high risk of developing non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis/cirrhosis. Screening patients with T2DM and normal liver enzymes for NAFLD in primary care remains contentious. Our aim was to develop and assess a primary care pathway integrating two-tier (Fib-4 then transient elastography [TE]) liver fibrosis assessment, irrespective of aetiology, into routine annual review of all patients with T2DM.
UNASSIGNED: All patients aged >35 years with T2DM attending annual review at 2 primary care practices in North East England between April 2018 and September 2019 (n = 467) had Fib-4 requested via the electronic patient record. Those with a Fib-4 score above the \'high-sensitivity\' threshold (>1.3 for ≤65 years and >2.0 for >65 years) underwent TE and were reviewed in secondary care if the liver stiffness measurement (LSM) was >8 kPa. The number of patients identified with advanced disease, service uptake, and predictors of advanced disease were assessed.
UNASSIGNED: A total of 85/467 (18.5%) patients had raised Fib-4; 27/467(5.8%) were excluded as a result of frailty or known cirrhosis. A total of 58/467 (12.2%) were referred for TE. Twenty-five of 58 (43.1%) had an LSM of >8 kPa and 13/58 (22.4%) had an LSM >15 kPa; 4/58 (6.7%) did not attend and 5/58 (9.3%) had an invalid reading. Twenty of 440 (4.5%) patients were found to have advanced liver disease following specialist review, compared to 3 patients previously identified through standard care (odds ratio [OR] 6.71 [2.0-22.7] p = 0.0022). Alcohol (OR 1.05 [1.02-1.08] p = 0.001) and BMI (OR 1.09 [1.01-1.17] p = 0.021) were predictors of advanced disease, particularly drinking >14/21 units/week (p <0.0001).
UNASSIGNED: Incorporating 2-tier assessment of liver fibrosis into routine annual diabetes review in primary care significantly improves identification of advanced liver disease in patients with T2DM.
UNASSIGNED: People with type 2 diabetes are at increased risk of developing non-alcoholic fatty liver disease and developing more significant complications. This study looks at introducing screening for advanced liver disease into the annual diabetes reviews performed routinely in primary care; we found that significantly more people were identified as having significant liver disease through this pathway than with current standard care.

Circular RNAs (circRNAs) are a very interesting class of conserved single-stranded RNA molecules derived from exonic or intronic sequences by precursor mRNA back-splicing. Unlike canonical linear RNAs, circRNAs form covalently closed, continuous stable loops without a 5\'end cap and 3\'end poly(A) tail, and therefore are resistant to exonuclease digestion. The majority of circRNAs are highly abundant, and conserved across different species with a tissue or developmental-stage-specific expression. circRNAs have been shown to play important roles as microRNA sponges, regulators of gene splicing and transcription, RNA-binding protein sponges and protein/peptide translators. Emerging evidence reveals that circRNAs function in various human diseases, particularly cancers, and may function as better predictive biomarkers and therapeutic targets for cancer treatment. In consideration of their potential clinical relevance, circRNAs have become a new research hotspot in the field of tumor pathology. In the present study, the current understanding of the biogenesis, characteristics, databases, research methods, biological functions subcellular distribution, epigenetic regulation, extracellular transport and degradation of circRNAs was discussed. In particular, the multiple databases and methods involved in circRNA research were first summarized, and the recent advances in determining the potential roles of circRNAs in tumor growth, migration and invasion, which render circRNAs better predictive biomarkers, were described. Furthermore, future perspectives for the clinical application of circRNAs in the management of patients with cancer were proposed, which could provide new insights into circRNAs in the future.

Ovaries are a common niche for metastasis. Metastatic malignancies account for 5-30% of all ovarian malignancies. Hepatocellular carcinoma (HCC) is one of the rare malignancies to metastasize to the ovaries. Of all the variants of HCC, fibrolamellar HCC (FLHCC) variant is extremely uncommon and accounts for around 1% of all HCC cases. FLHCC metastasizing to ovaries, at presentation, is an exceptional occurrence. We present a case of a young female who presented with bilateral adnexal masses and was diagnosed as metastatic FLHCC on histopathological examination and confirmed by immunohistochemistry. In addition, a thorough literature review highlighting the previously reported cases is also presented.