Search

Yang An,1– 3,* Xiangbo Xu,1– 3,* Tianshu Ren,1– 3,* Zhenhua Tong,1,4,* Fernando Gomes Romeiro,5 Andrea Mancuso,6 Xiaozhong Guo,1 Xingshun Qi1 1Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, 110840, People’s Republic of China; 2Postgraduate College, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China; 3Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110840, People’s Republic of China; 4Section of Medical Service, General Hospital of Northern Theater Command, Shenyang, 110840, People’s Republic of China; 5Department of Internal Medicine, Botucatu Medical School, UNESP – Univ Estadual Paulista. Av. Prof. Mário Rubens Guimarães Montenegro, s/n Distrito de Rubião Jr, Botucatu, Brazil; 6Medicina Interna 1, ARNAS-Civico, Di Cristina-Benfratelli, Palermo, Italy*These authors contributed equally to this workCorrespondence: Xingshun Qi; Xiaozhong Guo Email xingshunqi@126.com; guo_xiao_zhong@126.comBackground and Aim: Long-term use of non-selective beta blockers (NSBBs) is essential for the prevention of esophageal variceal bleeding in liver cirrhosis but may impair the patient’s adherence. The present study aimed to investigate the adherence to NSBBs to prevent variceal bleeding in cirrhotic patients.Methods: All patients who had an indication of NSBBs for the prophylaxis of variceal bleeding between February 2018 and June 2019 were screened. Clinical pharmacists gave pre-medication education and recorded the adherence to NSBBs during the patients’ hospitalizations. Factors associated with poor adherence were evaluated by univariate logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. The relationship between poor adherence during follow-up and variceal bleeding after discharge was also evaluated.Results: Overall, 108 patients were screened, of whom 12 were intolerant to NSBBs. Among the 96 remaining patients who could take NSBBs, the average change of heart rate after NSBBs was − 10.49 b.p.m. Twenty-two (22.9%) patients had poor adherence to NSBBs due to their refusal to take NSBBs (n = 2), complete forgetfulness to take NSBBs (n = 10), and refusal or forgetfulness to monitor heart rate (n = 10). Univariate logistic regression analysis demonstrated that only older age was significantly associated with poor adherence (OR: 1.065, 95% CI: 1.019– 1.114, P = 0.005). Patients with poor adherence during follow-up were more likely to develop variceal bleeding after discharge.Conclusion: A significant proportion of cirrhotic patients had poor adherence to NSBBs during their hospitalizations. Further studies should explore how to improve the patient’s adherence to NSBBs.Keywords: liver cirrhosis, esophageal varices, non-selective beta blockers, adherence, risk factors

Marina P Okoshi,1 Fernando G Romeiro,1 Paula F Martinez,1,2 Silvio A Oliveira Jr,1,2 Bertha F Polegato,1 Katashi Okoshi11Internal Medicine Department, Botucatu Medical School, Sao Paulo State University, UNESP, Sao Paulo, Brazil; 2School of Physiotherapy, Federal University of Mato Grosso do Sul, Campo Grande, BrazilAbstract: Cachexia and muscle wasting are frequently observed in heart failure patients. Cachexia is a predictor of reduced survival, independent of important parameters such as age, heart failure functional class, and functional capacity. Muscle and fat wasting can also predict adverse outcome during cardiac failure. Only more recently were these conditions defined in International Consensus. Considering that heart failure is an inflammatory disease, cardiac cachexia has been diagnosed by finding a body weight loss >5%, in the absence of other diseases and independent of other criteria. Muscle wasting has been defined as lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean for healthy individuals between 20 years and 30 years old from the same ethnic group. The etiology of heart failure-associated cachexia and muscle wasting is multifactorial, and the underlying physiopathological mechanisms are not completely understood. The most important factors are reduced food intake, gastrointestinal alterations, immunological activation, neurohormonal abnormalities, and an imbalance between anabolic and catabolic processes. Cachexia and muscle wasting have clinical consequences in several organs and systems including the gastrointestinal and erythropoietic systems, and the heart, previously affected by the primary disease. We hope that a better understanding of the mechanisms involved in their physiopathology will allow the development of pharmacological and nonpharmacological therapies to effectively prevent and treat heart failure-induced cachexia and muscle wasting before significant body weight and muscle wasting occurs.Keywords: heart failure, prognosis, anorexia, inflammatory activation, cardiac wasting

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB., Methods: A total of 368 cirrhotic patients presenting with AUGIB who are highly suspected to be from AVB will be enrolled. They will be stratified according to the severity of liver function and clinical presentation at admission and then randomly assigned at a 1:1 ratio into early (within 12 h after admission) and delayed (within 12-24 h after admission) endoscopy groups within each stratum. The primary outcomes include the rates of 5-day failure to control bleeding after admission and 6-week rebleeding. The secondary outcomes include 6-week mortality and incidence of adverse events., Conclusion: Considering existing evidence originates from non-randomized studies, this RCT will provide high-quality evidence to uncover whether cirrhotic patients with AVB should undergo early endoscopy to control bleeding and improve survival., Trial Registration: ClinicalTrials.gov identifier: NCT06031402., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Objectives: Muscle loss is one of the phenotypic criteria of malnutrition, is highly prevalent in patients with cirrhosis, and is associated with adverse outcomes. Mid-arm muscle circumference (MAMC) estimates the skeletal muscle mass and is especially helpful in cases of fluid overload. This study aimed to propose MAMC cutoff points for patients with cirrhosis and demonstrate its association with 1-year mortality., Methods: This is an analysis of cohort databases from five reference centers in Brazil that included inpatients and outpatients with cirrhosis aged ≥18 y. The nutritional variables obtained were the MAMC (n = 1075) and the subjective global assessment (n = 629). We established the MAMC cutoff points stratified by sex based on the subjective global assessment as a reference standard for malnutrition diagnosis, considering the sensitivity, specificity, and Youden index. An adjusted Cox regression model was used to test the association of MAMC cutoff points and 1-year mortality., Results: We included 1075 patients with cirrhosis, with a mean age of 54.8 ± 11.3 y; 70.4% (n = 757) male. Most patients had alcoholic cirrhosis (47.1%, n = 506) and were classified as Child-Pugh B (44.7%, n = 480). The MAMC cutoff points for moderate and severe depletion were ≤21.5 cm and ≤24.2 cm; ≤20.9 cm and ≤22.9 cm for women and men, respectively. According to these cutoff points, 13.8% (n = 148) and 35.1% (n = 377) of the patients had moderate or severe MAMC depletion, respectively. The 1-year mortality rate was 17.3% (n = 186). In the multivariate analysis adjusted for sex, age, MELD-Na, and Child-Pugh scores, a severe depletion in MAMC was an independent increased risk factor for 1-year mortality (HR: 1.71, 95% CI: 1.24-2.35, P < 0.001). Each increase of 1 cm in MAMC values was associated with an 11% reduction in 1-year mortality risk (HR: 0.89, 95% CI: 0.85-0.94, P < 0.001)., Conclusions: Low MAMC classified according to the new cutoff points predicts mortality risk in patients with cirrhosis and could be used in clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by continuous inflammation of the colonic mucosa. Autoimmune hepatitis (AIH) is a chronic liver disease characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis, and favorable response to immunosuppression. An association between IBD and AIH is uncommon, and experts have suggested that in patients with overlapping IBD and AIH, the anti-tumor necrosis factor agents can be used. Therefore, this study reports a rare case of a patient with liver cirrhosis due to AIH and UC refractory to conventional treatment and discusses the risks and benefits of using anti-tumor necrosis factor in both conditions., Patient Concerns: A 28-year-old female presented with symptoms of diarrhea, abdominal pain, asthenia, and inappetence, accompanied by abdominal collateral circulation, anemia, alteration of liver enzymes, and elevation of C-reactive protein levels., Diagnoses: The patient underwent a liver biopsy, which was consistent with liver cirrhosis due to AIH. Colonoscopy showed an inflammatory process throughout the colon, compatible with moderately active UC., Interventions: The patient received mesalazine, azathioprine, and corticotherapy, with no control of the inflammatory process. Faced with refractoriness to drug treatment and side effects of corticosteroids with an increased risk of severe infection due to cirrhosis, we opted to use infliximab for the treatment of UC. The patient presented with a clinical response and infliximab therapy was maintained., Outcomes: Eight months after starting infliximab therapy, the patient developed pneumonia with complications from disseminated intravascular coagulation and died., Lessons Subsections: AIH is a rare cause of elevated transaminase levels in patients with UC. The best treatment to control the 2 conditions should be evaluated with vigilance for the side effects of medications, mainly infections, especially in patients with cirrhosis., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Peptic ulcer is the most common source of non-variceal bleeding. However, it remains controversial whether the outcomes of cirrhotic patients with peptic ulcer bleeding differ from those with variceal bleeding., Methods: Cirrhotic patients with acute gastrointestinal bleeding (AGIB) who underwent endoscopy and had an identifiable source of bleeding were retrospectively screened from an international multicenter cohort. Logistic regression analyses were performed to explore the impact of peptic ulcer bleeding on in-hospital death and 5-day failure to control bleeding. Propensity score matching (PSM) analysis was performed by matching age, gender, Child-Pugh score, and model for end-stage liver disease score between the peptic ulcer bleeding and variceal bleeding groups., Results: Overall, 1535 patients were included, of whom 73 (4.7%) had peptic ulcer bleeding. Multivariate logistic regression analyses showed that peptic ulcer bleeding was not independently associated with in-hospital death (OR = 2.169, p  = 0.126) or 5-day failure to control bleeding (OR = 1.230, p  = 0.680). PSM analyses demonstrated that both in-hospital mortality (9.7% vs. 6.3%, p  = 0.376) and rate of 5-day failure to control bleeding (6.9% vs. 5.4%, p  = 0.787) were not significantly different between the two groups., Conclusions: The impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients is similar to that of variceal bleeding.

Rationale and Objectives: Hepatocellular carcinoma (HCC) treatment often requires transarterial chemoembolization (TACE). However, TACE efficacy is controversial in the presence of portal vein thrombosis (PVT). Although transarterial radioembolization (TARE) benefit was previously documented in PVT, neither the objective tumor response (OTR) after TARE with Iodine-131-lipiodol ( 131 I-lipiodol) nor the PVT effect on the results of locoregional therapies was accurately measured in prospective clinical trials. The aim of this study was to compare OTR and survival obtained by TARE with 131 I-lipiodol versus TACE in patients with cirrhosis and HCC, as well as between those with and without PVT., Materials and Methods: 33 patients were included, from whom 38 tumors were assessed. OTR was quantified by a special algorithm to measure hypervascular HCC tissue., Results: 19 tumors received each therapy. Nine subjects (27%) had PVT, most of them in the TARE group (p = 0.026). Mean OTR according to the tumor volumes was 24.2% ± 56% after TARE and 32.8% ± 48.9% after TACE, with no difference between the treatments (p = 0.616). Similar values were also observed between those with and without PVT (p = 0.704). Mean survival was 340 days and did not differ between the two treatments (p = 0.596), but was 194 days in PVT cases (p = 0.007)., Conclusions: This is the first study in which OTR obtained by TARE with 131 I-lipiodol is accurately measured. Additionally, PVT impact on survival after TARE and TACE was precisely documented. Although the TARE group had more PVT subjects (who had shorter survival), TARE and TACE achieved similar OTR and OS rates., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fernando Gomes Romeiro reports financial support was provided by São Paulo Research Foundation (FAPESP). Fernando Gomes Romeiro reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this review is to determine the costs and benefits of non-invasive liver tests vs liver biopsy in patients with chronic liver diseases., Introduction: Hepatic diseases can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. In the past, liver biopsy was the only option for diagnosing fibrosis degree. Liver biopsy is an invasive procedure that depends on the sample size to be able to deliver an accurate diagnosis. In recent years, non-invasive liver tests have been increasingly used to estimate liver fibrosis degree; however, there is a lack of economic assessments of technology implementation outcomes., Inclusion Criteria: This review will include partial (cost studies) and complete economic evaluation studies on hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease that compare non-invasive liver tests with liver biopsies. Studies published in English, French, Spanish, German, Italian, or Portuguese will be included. No date limits will be applied to the search., Methods: This review will identify published and unpublished studies. Published studies will be identified using MEDLINE (PubMed), Cochrane Library (CENTRAL), Embase, Web of Science, Scopus, and LILACS. Sources of unpublished studies and gray literature will include sources from health technology assessment agencies, clinical practice guidelines, regulatory approvals, advisories and warnings, and clinical trial registries, as well as Google Scholar. Two independent reviewers will screen and assess studies, and extract and critically appraise the data. Data extracted from the included studies will be analyzed and summarized to address the review objective using narrative text, and the JBI dominance ranking matrix., Review Registration: PROSPERO CRD42023404278., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 JBI.)

Liver diseases cause a significant burden on public health worldwide. In spite of great advances during recent years, there are still many challenges in the diagnosis and treatment of liver diseases. During recent years, artificial intelligence (AI) has been widely used for the diagnosis, risk stratification, and prognostic prediction of various diseases based on clinical datasets and medical images. Accumulative studies have shown its performance for diagnosing patients with nonalcoholic fatty liver disease and liver fibrosis and assessing their severity, and for predicting treatment response and recurrence of hepatocellular carcinoma, outcomes of liver transplantation recipients, and risk of drug-induced liver injury. Herein, we aim to comprehensively summarize the current evidence regarding diagnostic, prognostic, and/or therapeutic role of AI in these common liver diseases., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Budd-Chiari syndrome (BCS) and sinusoidal obstruction syndrome (SOS) are two major vascular disorders of the liver, of which both can cause portal hypertension related complications, but their locations of obstruction are different. BCS refers to the obstruction from the hepatic vein to the junction between the inferior vena cava and right atrium, which is the major etiology of post-sinusoidal portal hypertension; by comparison, SOS is characterized as the obstruction at the level of hepatic sinusoids and terminal venulae, which is a cause of sinusoidal portal hypertension. Both of them can cause hepatic congestion with life-threatening complications, especially acute liver failure and chronic portal hypertension, and share some similar features in terms of imaging and clinical presentations, but they have heterogeneous risk factors, management strategy, and prognosis. Herein, this paper reviews the current evidence and then summarizes the difference between primary BCS and SOS in terms of risk factors, clinical features, diagnosis, and treatment.

Background: Liaoning score has been developed and validated to predict the risk of esophageal varices in liver cirrhosis. This study aimed to further modify the Liaoning score by combining clinical and laboratory parameters to predict the long-term outcome of cirrhotic patients., Methods: First, 474 cirrhotic patients were retrospectively enrolled from Shenyang, China as the training cohort. Independent predictors for death were identified by competing risk analyses, and then a new prognostic model, called as modified Liaoning score, was developed. Its performance was externally validated at three centers from Fuzhou, China ( n  = 1944), Jinan, China ( n  = 485), and São Paulo, Brazil ( n  = 221)., Results: Age, total bilirubin (TBIL), albumin (ALB), serum creatinine (SCr), and Liaoning score were independently associated with death in the training cohort. Modified Liaoning score = 0.159×Liaoning score + 0.010×TBIL(µmol/L)+0.029×age(years)+0.011×SCr(µmol/L)-0.037×ALB(g/L). The area under curve of modified Liaoning score was 0.714 (95%CI = 0.655-0.773), which was higher than that of Child-Pugh score (0.707, 95%CI = 0.645-0.770), MELD score (0.687, 95%CI = 0.623-0.751), and Liaoning score (0.583, 95%CI = 0.513-0.654). A modified Liaoning score of ≥ 1.296 suggested a higher cumulative incidence of death in liver cirrhosis ( p  < 0.001). Modified Liaoning score still had the highest prognostic performance in Chinese and Brazilian validation cohorts., Conclusions: Modified Liaoning score can be considered for predicting the long-term outcome of cirrhotic patients.

Background:  Direct oral anticoagulants (DOACs) are effective for the management of thromboembolic disorders. However, bleeding remains a major concern in cirrhotic patients receiving DOACs., Methods:  PubMed, EMBASE, and Cochrane Library databases were searched. The incidence of bleeding episodes in cirrhotic patients receiving DOACs was pooled. Odds ratios (ORs) were calculated to compare the incidence of bleeding episodes in cirrhotic patients who received DOACs versus those who received conventional anticoagulants and did not receive anticoagulants., Results:  Twenty-nine studies were included. All bleeding, major bleeding, fatal bleeding, gastrointestinal bleeding, and intracranial hemorrhage episodes were observed in 310/2,469, 100/1,388, 2/611, 166/1,886, and 5/1,147 cirrhotic patients receiving DOACs, respectively. Their pooled incidences were 13, 6, 0, 8, and 0%, respectively. They became higher in subgroup analyses of studies with advanced age, a longer treatment duration, and Child-Turcotte-Pugh class C. Compared with conventional anticoagulants, DOACs were associated with lower incidences of all bleeding (OR = 0.71, 95% confidence interval [CI] = 0.52-0.98) and major bleeding (OR = 0.55, 95% CI = 0.37-0.83) in cirrhotic patients, but not those of fatal bleeding (OR = 0.21, 95% CI = 0.04-1.28), gastrointestinal bleeding (OR = 0.78, 95% CI = 0.52-1.17), or intracranial hemorrhage (OR = 0.36, 95% CI = 0.12-1.12). The incidences of all bleeding (OR = 1.04, 95% CI = 0.22-4.79) and major bleeding (OR = 0.96, 95% CI = 0.26-3.61) did not significantly differ between cirrhotic patients with portal vein thrombosis (PVT) who received DOACs and those who did not receive anticoagulants., Conclusion:  DOACs carry a low risk of bleeding in liver cirrhosis. Age, treatment duration, and Child-Turcotte-Pugh class may be associated with bleeding in cirrhotic patients receiving DOACs. The risk of bleeding is not increased by DOACs in cirrhotic patients with PVT., Competing Interests: None declared., (Thieme. All rights reserved.)

Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy., Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications., Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion., Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated., Impact and Implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion., Competing Interests: ZB, NM-S, FGR, AM, and CAP declare no potential conflicts of interest that pertain to this work. FT’s laboratory received research grants from Gilead, Allergan, Bristol-Myers Squibb and Inventiva. MB, MP, MI, YJW, FGN, RT, CNF, AEM, KP, TT, and SPS declared no potential conflicts of interest concerning the publication of this article. AM received grant funding from Gilead (clinical trials), Inventiva, Intercept, and Novo-Nordisk; and was a member of the advisory board (Gilead). SKS received research funding from Novartis, Durect, Fibronostics, and Gilead. LR, HM, EC, GBLS, LY, S, YY, EV, and AK declared no potential conflicts of interest concerning the publication of this article. FW received grant support from Grifols. RJ is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma. He is also the founder of Yaqrit Discovery, a spin-off company from University College London, Hepyx Limited, and Cyberliver. He has research collaborations with Yaqrit Discovery, has received speaker fees from Grifols, and is a consultant for Ambys, Takeda, and Bioconvergent Health. AOB declared no potential conflicts of interest concerning the publication of this article. MB declared the following potential conflicts of interest with respect to the publication of this article: personal fees from CLS Behring GmbH (consultant, speaker), Grifols SA (consultant, speaker), Takeda (consultant, speaker), PPTA (speaker), and Octapharma (speaker). XQ declared no potential conflicts of interest concerning the publication of this article. He received a governmental grant from the Young and Middle-aged Scientific and Technological Innovation Talents Support Plan Project of Shenyang (RC210011), which does not influence the publication of this article, for holding the final advisory meeting of the position statement. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Introduction: The role of human albumin (HA) infusion in cirrhotic patients has been increasingly recognized. This paper aims to summarize the evidence from meta-analyses regarding HA infusion for the management of cirrhosis and its complications., Methods: A systematic search in the PubMed, EMBASE, and Cochrane library databases, and in reference lists was conducted. All relevant meta-analyses were identified and their findings were reviewed. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist was used to evaluate the methodological quality and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to assess the quality of evidence for significant outcomes., Results: Among 300 papers initially identified, 18 meta-analyses have been included. Short- and long-term HA infusion at high doses decreased the mortality of patients with decompensated cirrhosis. In cirrhotic patients with ascites, long-term HA infusion reduced the recurrence of ascites, but not mortality. In cirrhotic patients undergoing large-volume paracentesis (LVP), HA infusion reduced the incidence of post-paracentesis circulatory dysfunction and hyponatremia, but not mortality or renal impairment. In cirrhotic patients with overt hepatic encephalopathy (HE), HA infusion improved the severity of overt HE, but not overall mortality. In cirrhotic patients with spontaneous bacterial peritonitis (SBP), but not those with non-SBP infections, HA infusion reduced the mortality and renal impairment. In cirrhotic patients with type-1 hepatorenal syndrome (HRS), an increment of 100 g in cumulative HA dose increased 1.15-fold survival, but not HRS reversal. In these meta-analyses, the quality of methodology was low or critically low, and that of the evidence was from very low to moderate., Conclusions: Based on the limited evidence from these meta-analyses, HA infusion appears to be beneficial in cirrhotic patients with ascites, overt HE, and SBP and in those undergoing LVP, but not in those with non-SBP infections., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Background: Subcutaneous and visceral adipose tissues are important body components, but their effects on the mortality in patients with liver cirrhosis remain controversial based on the current evidence., Methods: We retrospectively identified 372 eligible patients in whom subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) could be measured by computed tomography images at the third lumbar vertebra. The association of SATI and VATI with the risk of death was evaluated on a continuous scale with restricted cubic spline curves based on Cox proportional hazards models. Cumulative probability of mortality was estimated by Nelson-Aalen cumulative risk curve analyses. Independent predictors of death were evaluated by competing risk analyses after adjusting for age, sex, and model for end-stage liver disease score., Results: Majority of patients were male (69.4%) with a mean age of 55.40 ± 10.68 years. SATI had a U-shaped association with mortality (P for non-linearity <0.001). Cutoff values of SATI were 19.7 and 51.8 cm 2 /m 2 at the points where hazard ratios were just <1.2. SATI was categorized as low (<19.7 cm 2 /m 2 ), moderate (19.7-51.8 cm 2 /m 2 ), and high (>51.8 cm 2 /m 2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate SATI groups (Gray's test, P = 0.052) and high versus moderate SATI groups (Gray's test, P = 0.054). Competing risk analyses demonstrated that low SATI could increase the mortality compared with moderate SATI (subdistribution hazard ratio [sHR] = 1.66, 95% confidence interval [CI]: 0.992-2.78, P = 0.054) and was an independent predictor of death (sHR = 1.86, 95% CI: 1.059-3.28, P = 0.031). Competing risk analyses also demonstrated that high SATI could significantly increase the mortality compared with moderate SATI (sHR = 1.6, 95% CI: 1-2.54, P = 0.049), and was an independent predictor of death (sHR = 2.007, 95% CI: 1.195-3.37, P = 0.0085). VATI had an irregularly shaped association with mortality (P for non-linearity <0.001). Cutoff values of VATI were 9.8 and 40.2 cm 2 /m 2 at the points where hazard ratios were just <1.2. VATI was categorized as low (<9.8 cm 2 /m 2 ), moderate (9.8-40.2 cm 2 /m 2 ), and high (>40.2 cm 2 /m 2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate VATI groups (Gray's test, P = 0.381) and high versus moderate VATI groups (Gray's test, P = 0.787). Competing risk analyses demonstrated that neither low (sHR = 1.27, 95% CI: 0.599-2.7, P = 0.53) nor high VATI (sHR = 0.848, 95% CI: 0.539-1.34, P = 0.48) was an independent predictor of death compared with moderate VATI., Conclusions: Both excessive deficiency and accumulation of subcutaneous adipose tissues negatively influence the outcomes of cirrhotic patients., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Human albumin infusion is effective for controlling systemic inflammation, thereby probably managing some liver cirrhosis-related complications, such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and hepatorenal syndrome. However, its clinical benefits remain controversial., Methods: EMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials (RCTs) regarding use of human albumin infusion in cirrhotic patients were eligible. Mortality and incidence of liver cirrhosis-related complications were pooled. Effect of human albumin infusion on mortality was also evaluated by subgroup analyses primarily according to target population and duration of human albumin infusion treatment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated., Results: Forty-two RCTs were finally included. Meta-analysis showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). Subgroup analyses showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients with SBP (OR = 0.36, 95% CI = 0.20-0.64, p = 0.0005) and HE (OR = 0.43, 95% CI = 0.22-0.85, p = 0.02), but not those with ascites or non-SBP infections or undergoing large-volume paracentesis. Short-term human albumin infusion treatment could significantly decrease short-term mortality (OR = 0.67, 95% CI = 0.50-0.89, p = 0.005), but not long-term mortality. Long-term human albumin infusion treatment could not significantly decrease long-term mortality (OR = 0.72, 95% CI = 0.48-1.08, p = 0.11). In addition, human albumin infusion could significantly decrease the incidence of renal impairment (OR = 0.63, 95% CI = 0.45-0.88, p = 0.007) and ascites (OR = 0.45, 95% CI = 0.25-0.81, p = 0.007), but not infections or gastrointestinal bleeding., Conclusions: Human albumin infusion may improve the outcomes of cirrhotic patients. However, its indications for different complications and infusion strategy in liver cirrhosis should be further explored., (© 2022. Asian Pacific Association for the Study of the Liver.)

Background: Bisphosphonates are the mainstay of osteoporosis treatment, but their use for patients with esophageal varices has been avoided due to the risk of esophagitis, which may cause variceal bleeding. Since most clinical trials assessing osteoporosis treatment last 2-3 years, this study aimed to evaluate a 2-year risedronate treatment for patients with esophageal varices and liver cirrhosis., Methods: The study received Institutional Review Board approval, and the sample was divided into two groups according to bone mineral density (BMD). Cirrhosis severity and endoscopic findings at baseline were similar between the groups. The intervention group had 51 patients with osteoporosis, who received oral risedronate 35 mg weekly plus calcium and vitamin D supplements. The control group had 51 patients with osteopenia, receiving only the supplements. Scheduled esophagogastroduodenoscopies and BMD measurements were carried out., Results: The adjusted esophagitis risk was higher in the intervention group; however, none of the subjects had digestive bleeding. Lumbar spine BMD increased in the intervention group (- 3.06 ± 0.71 to - 2.33 ± 0.90; p < 0.001) and in the control group (- 1.38 ± 0.77 to - 1.10 ± 1.05; p = 0.012). Femoral neck BMD did not change in the intervention group (- 1.64 ± 0.91 to - 1.71 ± 0.95; p = 0.220), but tended to decrease in the control group (- 1.00 ± 0.74 to - 1.09 ± 0.82; p = 0.053)., Conclusion: Oral risedronate was effective and did not cause gastrointestinal bleeding in cirrhotic patients with esophageal varices under endoscopic surveillance., (© 2022. Asian Pacific Association for the Study of the Liver.)

Background: Common variable immunodeficiency (CVID) is a rare disease that affects children and adults and is often difficult to diagnose. Despite being one of the most frequent causes of immunodeficiency, involving gastrointestinal (GI), respiratory, and hematological systems, the disease onset can have heterogeneous and intermittent symptoms, frequently leading to diagnostic delay. GI symptoms are common and can include diarrhea, but the asymptomatic periods lead to overlooking the recurrent pattern. The same can occur with respiratory infections, thus delaying CVID suspicion. The starting point for CVID diagnosis is the decreased gamma globulin levels in serum protein electrophoresis (SPE), also observed through direct immunoglobulin's dosage., Case Presentation: The patient is a 38 years-old man who had intermittent diarrhea and recurrent airway infections for 19 years, but the CVID diagnosis was achieved only after SPE was carried out. At that time, he was already malnourished, and developed other complications related to CVID in a short period., Conclusions: SPE is readily available and inexpensive, but is not part of the laboratory approach in diarrhea. According to the case presented herein, it can be useful for patients with recurrent infections or other clues of the disease., (© 2022. The Author(s).)

This integrative review examined factors associated with hepatitis C treatment adherence. The articles included were published in English, Spanish and Portuguese in the Lilacs, Medline, PsycINFO, Web of Science, Scopus and CINAHL databases, between 2000 and 2019. Initially, 540 publications were found and, after applying the study inclusion criteria, 22 articles were selected. Percentage non-adherence to treatment ranged from 12% to 32%. The variables identified as facilitating adherence were: receiving treatment for psychiatric disorders identified during treatment; knowing about medications and disease; receiving less complex treatment with greater likelihood of cure; fewer adverse events; social support; doctor-patient communication; and/or being in relationships. Barriers to adherence identified were: presence of depressive symptoms and other mental disorders; abuse of alcohol and psychoactive substances; education; age; ethnicity; unemployment; not having a steady partner; stigma; distance from health services; and the complexity and adverse effects of treatment. This review identified gaps in research on adherence.

Background: Setting up new liver transplant (LT) centers is essential for countries with organ shortages. However, good outcomes require experience, because LT learning depends on a high number of surgeries. This study aims to describe how a new center was set up from a partnership between the new center and an experienced one. The step-by-step preparation process, the time needed and the results of the new center are depicted., Material and Methods: The mentoring process lasted 40 months, in which half of the 52 patients included on the transplant list received LT. After the mentorship, a 22-month period was also analyzed, in which 46 new patients were added to the waiting list and nine were operated on., Results: The 30-day survival rates during (92.3%) and after (66.7%) the partnership were similar to the other LT centers in the same region, as well as the rates of longer periods. The waiting time on the LT list, the characteristics of the donors and the ischemia times did not differ during or after the mentorship., Conclusion: The partnership between universities is a suitable way to set up LT centers, achieving good results for the institutions and the patients involved., Competing Interests: The authors declare that they have no conflicts of interest to declare.

Portal vein thrombosis (PVT) is a common complication in liver cirrhosis, especially in advanced cirrhosis. It may be related to a higher risk of liver-related events and liver function deterioration. Imaging examinations can not only provide an accurate diagnosis of PVT, such as the extent of thrombus involvement and the degree of lumen occupied, but also identify the nature of thrombus (i.e., benign/malignant and acute/chronic). Evolution of PVT, mainly including development, recanalization, progression, stability, and recurrence, could also be assessed based on the imaging examinations. This article briefly reviews the pathophysiology, diagnosis, classification, and evolution of PVT with an emphasis on their computed tomography imaging features., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Gastric antral vascular ectasia (GAVE) is an uncommon clinical entity leading to recurrent gastrointestinal bleeding. There is no consensus regarding treatment of GAVE. Endoscopic therapy is the preferred treatment option, but has a fairly high recurrence rate. Surgical resection can completely resolve GAVE, but is invasive with a relatively high risk of postoperative complications. Recently, the role of pharmacotherapy for GAVE has been recognized. However, the evidence is limited to scattered case reports or small case series. This review comprehensively summarizes the efficacy and side effects of drugs commonly used for the treatment of GAVE, including octreotide, cyproheptadine, cyclophosphamide, prednisolone, estrogen-progesterone, thalidomide, bevacizumab, and tranexamic acid., (© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Objective: The aim of this study was to compare the effects of muscle wasting according to measures obtained by different limb muscle mass indexes, to find the best mortality predictor among outpatients with cirrhosis., Methods: Patients with liver cirrhosis (N = 210) were submitted to dual-energy x-ray absorptiometry (DXA). Appendicular muscle mass (AMM), AMM index (AMMI), upper limb muscle mass (ULMM), and ULMM index (ULMMI) were calculated. The Model for End-Stage Liver Disease, anthropometric measures, and the presence of ascites and edema were also registered. Multiple logistic regressions were performed to determine mortality predictors; the area under the receiver operating characteristic curve was used to establish the best cutoff point to predict mortality., Results: The mean follow-up duration was 49 ± 15.59 mo. ULMM and ULMMI were clearly associated with mortality (P = 0.007 and 0.001, respectively), whereas AMM and AMMI were not. After calculating the cutoff points for men and women, the presence of a depleted ULMMI as a categorical variable was associated with a mortality risk 2.5 times higher., Conclusions: The results suggest that using ULMMI is better than AMMI for predicting mortality of outpatients with cirrhosis, thus offering a better measure to detect muscle wasting in this population using DXA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Anemia is one of the most common disorders in the world. Serum iron is an essential element for the synthesis of hemoglobin and contribution of the oxygen-carrying ability of red blood cells (RBCs). Iron sucrose injection may effectively correct iron deficiency, increase iron storage, and then improve anemia. The aim of the present study was to evaluate the therapeutic effect of iron sucrose injection in anemia patients with reduced serum iron concentration., Methods: Overall, 95 anemia patients with digestive and/or liver diseases were included. They were divided according to the infusion of iron sucrose injection during hospitalization. The paired sample t test was used for comparison between last and baseline hemoglobin concentration. The independent sample t test was used for comparison of a dynamic change of hemoglobin concentration between patients who received and did not receive infusion of iron sucrose injection., Results: Iron sucrose injection was infused in 74 (77.90%) patients. Mean hemoglobin concentration after infusion of iron sucrose injection was significantly increased (91.61 vs. 94.98 g/L, P=0.011). Δ Hemoglobin concentration was significantly different between patients who received and did not receive infusion of iron sucrose injection (P=0.007). Mean hemoglobin concentration after infusion of iron sucrose injection remained significantly increased in subgroup analyses of patients with cirrhosis (88.30 vs. 91.98 g/L, P=0.035) and gastrointestinal bleeding (85.70 vs. 92.63 g/L, P<0.01)., Conclusions: Iron sucrose injection can significantly increase the hemoglobin concentration in anemia patients with serum iron concentration below the lower limit of the normal range.

Background: Hepatocellular carcinoma is a relevant cause of mortality worldwide, mainly among patients who have a prior liver disease. In spite of clear recommendations regarding surveillance and screening methods, most patients are still diagnosed only when they are no longer candidates to curative treatment modalities, while others do not achieve the goals of such treatments, thus increasing the need of anticancer drugs. Moreover, when cirrhotic patients begin to receive these drugs, many types of adverse events are seen as a reason to withdrawal, even when there are findings suggesting a good response to the treatment. Case Summary . This case report is about a cirrhotic patient who received many types of treatment, from surgery and chemoembolization during early stages to first- and second-line systemic therapy when the disease turned to be advanced. Since he had no signs of liver dysfunction and suffered tumor progression during sorafenib treatment, regorafenib was initiated. The main findings that make this case important are the adverse events after taking this second-line agent, which would certainly be considered unacceptable and would lead to the drug withdrawal. The reasons why regorafenib was maintained are explained based on clinical and imaging findings, showing how this decision led to an excellent response., Conclusions: The knowledge of the main adverse events described in the pilot clinical trials can avoid unnecessary withdrawal of regorafenib. In addition, some clinical and imaging findings can be deemed as predictors of good response to tyrosine kinase inhibitors., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Gustavo Hideki Kawanami et al.)

Purpose: We aimed to identify prognostic factors for survival and recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for patients with HCC and hepatitis C virus-related cirrhosis (HCV-cirrhosis)., Methods: This retrospective cohort study followed all adult patients with HCV-cirrhosis who underwent LT because of HCC or had incidental HCC identified through pathologic examination of the explanted liver at a university hospital in Rio de Janeiro, Brazil, over 11 years (1998-2008). We used Cox regression models to assess the following risk factors regarding HCC recurrence or death after LT: age, Model for End-stage Liver Disease score, Child-Pugh classification, alpha-fetoprotein (AFP), whether patients had undergone locoregional treatment before transplantation, the number of packed red blood cell units (PRBCU) transfused during surgery, the number and size of HCC lesions in the explanted liver, and the presence of microvascular invasion and necrotic areas within HCC lesions., Results: Seventy-six patients were followed up for a median (interquartile range (IQR)) of 4.4 (0.7-6.6) years. Thirteen (17%) patients had HCC recurrence during the follow-up period, and 26 (34%) died. The median survival time was 6.6 years (95% CI: 2.4-12.0), and the 5-year survival was 52.5% (95% CI: 42.3-65.0%). The final regression model for overall survival included four variables: age (hazard ratio (HR): 1.02, 95% CI: 0.96-1.08, P = 0.603), transplantation waiting time (HR: 1.00, 95% CI: 1.00-1.00, P = 0.190), preoperative AFP serum levels (HR: 1.01, 95% CI: 1.00-1.02, P = 0.006), and whether >4 PRBCU were transfused during surgery (HR: 1.15, 95% CI: 1.05-1.25, P = 0.001). The final cause-specific Cox regression model for HCC recurrence included only microvascular invasion (HR: 14.86, 95% CI: 4.47-49.39, P < 0.001)., Conclusion: In this study of LT for HCV-cirrhosis, preoperative AFP levels and the number of PRBCU transfused during surgery were associated with overall survival, whereas microvascular invasion with HCC recurrence., Competing Interests: The authors declare that they have no conflicts of interest regarding the present manuscript., (Copyright © 2020 Raphael Iglesias de Oliveira Vidal et al.)

Methods: Cirrhotic patients who were consecutively hospitalized between January 2016 and March 2019 were screened. Serum cardiac biomarkers at admission, including N-Terminal pro-B-type natriuretic peptide (NT-pro BNP), high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase (CK), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH), were collected. Acute decompensating events at admission, primarily including ascites, acute gastrointestinal hemorrhage, and acute-on-chronic liver failure (ACLF), were recorded., Results: The NT-pro BNP level was significantly higher in cirrhotic patients with acute decompensating events than in those without any decompensating events (median: 140.75 pg/mL versus 41.86 pg/mL, P < 0.001). The NT-pro BNP level significantly correlated with ascites, acute gastrointestinal hemorrhage, and ACLF. The hs-cTnT level was significantly higher in cirrhotic patients with acute decompensating events than in those without decompensating events (median: 0.008 ng/mL versus 0.006 ng/mL, P = 0.007). The hs-cTnT level significantly correlated with acute gastrointestinal hemorrhage, but not ascites or ACLF. LDH (185.0 U/L versus 173.5 U/L, P = 0.281), CK (71 U/L versus 84 U/L, P = 0.157), and CK-MB (29.5 U/L versus 33.0 U/L, P = 0.604) levels were not significantly different between cirrhotic patients with and without acute decompensating events., Conclusion: The elevated NT-pro BNP level seems to be closely related to the development of acute decompensating events in liver cirrhosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Miaomiao Li et al.)

Background and Aims: Coronavirus disease 2019 (COVID-19) pandemic is ongoing. Except for lung injury, it is possible that COVID-19 patients develop liver injury. Thus, we conducted a systematic review and meta-analysis to explore the incidence, risk factors, and prognosis of abnormal liver biochemical tests in COVID-19 patients., Methods: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases were searched. The incidence of abnormal liver biochemical tests, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), total bilirubin (TBIL), and albumin (ALB), was pooled. Risk ratio (RR) was calculated to explore the association of abnormal liver biochemical tests with severity and prognosis of COVID-19 patients., Results: Forty-five studies were included. The pooled incidence of any abnormal liver biochemical indicator at admission and during hospitalization was 27.2% and 36%, respectively. Among the abnormal liver biochemical indicators observed at admission, abnormal ALB was the most common, followed by GGT, AST, ALT, TBIL, and ALP (39.8%, 35.8%, 21.8%, 20.4%, 8.8%, and 4.7%). Among the abnormal liver biochemical indicators observed during hospitalization, abnormal ALT was more common than AST and TBIL (38.4%, 28.1%, and 23.2%). Severe and/or critical patients had a significantly higher pooled incidence of abnormal liver biochemical indicators at admission than mild and/or moderate patients. Non-survivors had a significantly higher incidence of abnormal liver biochemical indicators than survivors (RR = 1.34, p = 0.04)., Conclusions: Abnormal liver biochemical tests are common in COVID-19 patients. Liver biochemical indicators are closely related to the severity and prognosis of COVID-19 patients.

Background and Aims: Acute upper gastrointestinal bleeding (AUGIB) is one of the most life-threatening emergency conditions. Hemostatic drugs are often prescribed to control AUGIB in clinical practice but have not been recommended by major guidelines and consensus. The aim of this study was to investigate the therapeutic effect of hemostatic drugs on AUGIB in cirrhosis., Methods: All cirrhotic patients with AUGIB who were admitted to our hospital from January 2010 to June 2014 were retrospectively included. Patients were divided into hemostatic drugs and no hemostatic drug groups. A 1 : 1 propensity score matching (PSM) analysis was performed by adjusting age, gender, etiology of liver disease, Child-Pugh score, MELD score, hematemesis, red blood cell transfusion, vasoactive drugs, antibiotics, proton pump inhibitors, and endoscopic variceal therapy. Primary outcomes included 5-day rebleeding and in-hospital mortality., Results: Overall, 982 cirrhotic patients with AUGIB were included (870 in hemostatic drugs group and 112 in no hemostatic drug group). In overall analyses, hemostatic drugs group had a significantly higher 5-day rebleeding rate (18.10% versus 5.40%, P = 0.001) than no hemostatic drug group; in-hospital mortality was not significantly different between them (7.10% versus 4.50%, P = 0.293). In PSM analyses, 172 patients were included (86 patients in each group). Hemostatic drugs group still had a significantly higher 5-day rebleeding rate (15.10% versus 5.80%, P = 0.046); in-hospital mortality remained not significantly different (7.00% versus 3.50%, P = 0.304) between them. Statistical results remained in PSM analyses according to the type of hemostatic drugs., Conclusions: The use of hemostatic drugs did not improve the in-hospital outcomes of cirrhotic patients with AUGIB., Competing Interests: The authors declare that there is no conflict of interest in this study., (Copyright © 2020 Yang An et al.)

Background and Aims: Left-sided portal hypertension (LSPH) is a rare type of portal hypertension, which occurs due to obstruction, stenosis, or thrombosis within the splenic vein. Pancreatic diseases are the most common etiology of LSPH. This study is aimed at reporting our experiences and discussing the presentation, management, and prognosis of LSPH secondary to pancreatic diseases. Patients and Methods . We retrospectively reviewed five patients who were diagnosed with LSPH secondary to pancreatic diseases at our department. We collected the demographic information, history, comorbidities, clinical presentations, laboratory tests, esophagogastroduodenoscopy (EGD), images, and outcome data., Results: Three elderly patients (>60 years old) were diagnosed with pancreatic cancer, of whom one underwent laparoscopic radical distal pancreatectomy and splenectomy, one received chemotherapy, and another one chose conservative management due to multiple systemic metastases. Two younger patients (<40 years old) were diagnosed with acute recurrent pancreatitis and chronic pancreatitis. Four of these five included patients presented with hematemesis and/or melena at our admission. All patients had gastric varices, and one of them also had esophageal varices. One elderly patient with metastatic pancreatic cancer underwent endoscopic variceal treatment as a rescue therapy but finally died of refractory gastrointestinal (GI) bleeding; another younger patient with chronic pancreatitis died of massive GI bleeding; and the remaining three patients survived at their last follow-up., Conclusions: LSPH should be seriously taken into consideration in patients with pancreatic diseases who develop upper GI bleeding. Clinicians should individualize the treatment strategy of LSPH according to the patients' clinical conditions and nature of pancreatic diseases., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Kexin Zheng et al.)

Background: Renal dysfunction is a serious morbidity in cirrhotic patients with acute upper gastrointestinal bleeding (AUGIB). Terlipressin is the first-line treatment choice for acute variceal bleeding and hepatorenal syndrome (HRS). This study aimed to assess the effect of terlipressin on renal function in patients with liver cirrhosis and AUGIB., Methods: We retrospectively reviewed 40 cirrhotic patients with AUGIB treated with terlipressin by an attending physician between January 2016 and June 2018. We analyzed the change of renal function parameters, including cystatin C (CysC) and creatinine (Cr), during the use of terlipressin and after terlipressin was stopped. We also identified the factors associated with renal function improvement in patients without active bleeding during the use of terlipressin., Results: During the use of terlipressin, CysC value was significantly reduced (1.3±0.8 vs. 1.1±0.7, P=0.001); Cr value was reduced, but the reduction was not statistically significant (68.8±24 vs. 65.5±23, P=0.817); the rate of CysC reduction was significantly higher in patients treated with terlipressin than those treated with somatostatin/octreotide (73.1% vs. 0%, P=0.005); the rate of Cr reduction was not significantly different between patients treated with terlipressin and somatostatin/octreotide (61.5% vs. 20%, P=0.148); no factor associated with CysC reduction was identified; higher hemoglobin, red blood cell, and platelet and lower prothrombin time and international normalized ratio at baseline were significantly associated with Cr reduction. After terlipressin was stopped, neither CysC nor Cr value was significantly reduced (P=0.852 and P=0.296)., Conclusions: Terlipressin may be beneficial on preventing renal function impairment in cirrhotic patients with AUGIB., Competing Interests: Conflicts of Interest: The authors have no conflict of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Despite the high prevalence of osteoporosis in liver cirrhosis, the indication of bisphosphonates for patients with esophageal varices has been avoided due to risk of digestive mucosal damage. Therefore, this study aimed to evaluate the safety profile of risedronate treatment for patients with osteoporosis, liver cirrhosis and esophageal varices with low risk of bleeding. A total of 120 patients were allocated into two groups according to their bone mineral density measured by dual-energy X-ray absorptiometry. In the intervention group, 57 subjects with osteoporosis received oral risedronate at 35 mg weekly plus daily calcium and vitamin D supplementation. In the control group, 63 subjects with osteopenia received only calcium and vitamin D. The groups received the treatment for one year and underwent surveillance endoscopies at six and 12 months, as well as a control dual-energy X-ray absorptiometry after a 12-month follow-up. The study received Institutional Review Board approval. The groups had not only comparable Model for End-stage Liver Disease score and esophageal varices degree, but also similar incidence of digestive adverse effects. A significant improvement was achieved in the intervention group in the lumbar spine T score (p < 0.001). The results suggest that risedronate may be safely used in liver cirrhosis and esophageal varices with low bleeding risk under endoscopic surveillance, thus allowing bone mass recovery.

Aim: The present study aimed to identify variables associated with sarcopenia in cirrhotic outpatients using clinical data, anthropometric measures and lab tests. In a single centre prospective study, 261 cirrhotic outpatients were followed on average for 2 years. The diagnostic criteria of sarcopenia were applied according to the current guidelines, combining muscle strength and appendicular muscle mass index., Methods: Age, sex, liver disease aetiology and the Model of End-Stage Liver Disease score were included as independent variables, as well as mid-arm circumference (MAC), body mass index and triceps skinfold. Multiple logistic regression was applied including all independent variables (maximum model). Then, the analysis was performed only with the variables that were significant in the first analysis (parsimonious model). Once the variable most related to sarcopenia was determined by the two models, the area under the receiver operator characteristic curve was calculated. Mortality rates were described for patients with and without sarcopenia., Results: Sarcopenia was diagnosed in 14 subjects (5.36%), and the variable best associated with sarcopenia was MAC (P < 0.01). The 1-year mortality rate of 35.71% found among subjects with sarcopenia was not significantly higher (P = 0.07) than the 15.38% observed among those without this condition., Conclusions: Before examinations requiring ionising radiation, patients with cirrhosis can be submitted to simple screening tools to identify those who have a high risk of sarcopenia, thus promoting a cost-effective assessment., (© 2019 Dietitians Association of Australia.)

Studies comparing gut microbiota profiles of inflammatory bowel disease (IBD) patients have shown several changes in microbiota composition, with marked reduction of local biodiversity relative to that of healthy controls. Modulation of the bacterial community is a promising strategy to reduce the proportion of harmful microorganisms and increase the proportion of beneficial bacteria; this is expected to prevent or treat IBD. The exact mechanism of fecal microbiota transplantation (FMT) remains unknown; however, replacing the host microbiota can reestablish gut microbial composition and function in IBD patients. The present report describes an ulcerative colitis patient who underwent FMT. A 17-year-old male with moderate to severe clinical activity, which was refractory to mesalazine, azathioprine, and infliximab, underwent FMT as alternative therapy. The patient exhibited clinical improvement after the procedure; however, the symptoms returned. A second FMT was performed 8 months after the first procedure, but the patient did not improve. In conclusion, despite the FMT failure observed in this patient, the procedure is a promising therapeutic option for IBD patients, and more in-depth studies of this method are needed.

Background: Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver diseases. It has been reported that traditional Chinese medicine (TCM) may improve liver function, delay disease progression, alleviate symptoms, and improve quality of life in HRS patients. The study aims to systematically review the efficacy of TCM for the treatment of HRS., Methods: Publications were searched electronically from China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, and EMBASE databases. Odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed. The Cochrane Collaboration's tool was used to assess the risk of bias., Results: Fourteen randomized controlled trials involving 788 patients with HRS were included. Random generation sequence was reported in only two studies. Blinding was not used in any study. Compared to conventional treatment without TCM, TCM led to a significant survival benefit during hospitalization (OR: 0.18; 95% CI: 0.08-0.39; P<0.0001), a significantly higher complete response (OR: 3.20; 95% CI: 2.06-4.97; P<0.00001), and a significantly lower no response (OR: 0.20; 95% CI: 0.14-0.30; P<0.00001). Partial response was not significantly different between the two groups (OR: 1.39; 95% CI: 0.90-2.15; P=0.14). Regardless of TCM, blood urea nitrogen and abdominal circumference were significantly decreased, and urine volume was significantly increased after treatment. Compared to conventional treatment without TCM, TCM led to a significantly lower serum creatinine, blood urea nitrogen, bilirubin, plasma ammonia, and abdominal circumference and significantly higher urine volume after treatment. There was significant heterogeneity., Conclusions: TCM might have a better survival and a higher complete response in patients with HRS. However, the quality of published studies was unsatisfactory., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Branched-chain amino acids increase the brain perfusion of patients with hepatic encephalopathy (HE), but the amino acid and the mechanisms involved are still unknown. This study compared brain perfusion and clinical improvement during leucine or isoleucine supplementation. After randomization, 27 subjects with cirrhosis and HE received leucine or isoleucine supplements for one year. Brain single Photon Emission Computed Tomography (SPECT) and dynamic brain scintigraphy (DBS) were performed pretreatment and at 1, 8 and 12 months of supplementation. Brain perfusion was increased only in the isoleucine group at 8 months of treatment by both SPECT and DBS ( p  < 0.001 and p  = 0.05, respectively) and by SPECT at the 12th month ( p  < 0.05). This was associated with hepatic encephalopathy improvement at 8 and 12 months ( p  = 0.008 and 0.004, respectively), which was not observed in the leucine group ( p  = 0.313 and 0.055, respectively). Isoleucine supplementation achieved a better impact on brain perfusion restoration in HE.

Background and Aim: Spontaneous bacterial peritonitis (SBP) is one of the most common complications of liver cirrhosis. Antibiotics are the main treatment regimen of SBP. Traditional Chinese medicine Xuebijing injection has been used in such patients. Our study aimed to overview the efficacy of Xuebijing injection combined with antibiotics for the treatment of SBP., Method: We searched the PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang databases. The search items included "Xuebijing", "peritonitis", "liver cirrhosis", and "random" to identify all relevant randomized controlled trials (RCTs). The Cochrane risk of bias tool was used to assess the study quality. The odd ratios (ORs) with 95% confidence intervals (CIs) were calculated by using a random-effect model. Heterogeneity was also calculated., Results: A total of 9 RCTs were included. The study quality was unsatisfied. The overall (OR = 2.95, 95% CI = 1.97-4.42, p < 0.00001) and complete (OR = 2.18, 95% CI = 1.57-3.04, p < 0.00001) responses were significantly higher in the Xuebijing injection combined with antibiotics group than the antibiotics alone group. The incidence of cirrhosis related complications, including hepatic encephalopathy and hepatorenal syndrome, was lower in the Xuebijing injection combined with antibiotics group than the antibiotics alone group. No significant heterogeneity was observed among studies., Conclusion: Additional use of Xuebijing injection may improve the efficacy of antibiotics for the treatment of SBP in liver cirrhosis. However, due to a low level of current evidence, we did not establish any recommendation regarding the use of Xuebijing injection for the treatment of SBP.

Background: To evaluate the ability of albumin-to-bilirubin (ALBI) score for assessing the in-hospital death in cirrhotic patients., Methods: Overall, 1,067 cirrhotic patients admitted between January 2009 and December 2014 were retrospectively enrolled. We calculated the Child-Pugh, model for end-stage liver disease (MELD), and ALBI scores. We performed receiver operating characteristic curve (ROC) analyses to assess the in-hospital death. We calculated the area under the ROC curve (AUC)., Results: In the overall analysis, all of the three scores can significantly assess the in-hospital death (Child-Pugh score AUC =0.750, 95% CI: 0.713-0.784, P<0.0001; MELD score AUC =0.728, 95% CI: 0.689-0.765, P<0.0001; ALBI score AUC =0.698, 95% CI: 0.667-0.727, P<0.0001). In the subgroup analysis of hepatitis B virus, Child-Pugh and ALBI scores were suitable to assess in-hospital death (Child-Pugh score AUC =0.752, 95% CI: 0.679-0.816, P<0.0001; ALBI score AUC =0.803, 95% CI: 0.751-0.849, P=0.0002) and both were superior to the MELD score (AUC=0.564, 95% CI: 0.483-0.643, P=0.5357). In the subgroup analysis of alcohol abuse, Child-Pugh and MELD scores properly assessed in-hospital death (Child-Pugh score AUC =0.791, 95% CI: 0.727-0.846, P<0.0001; MELD score AUC =0.720, 95% CI: 0.647-0.786, P=0.0023), rather than ALBI score (AUC =0.646, 95% CI: 0.588-0.702, P=0.1360)., Conclusions: ALBI score might be an alternative index for assessing the in-hospital death in patients with liver cirrhosis., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Exposure to biological materials is common among hospital workers, even when preventive measures are suggested. Few studies assessed the incidence of this type of exposure and the impact of preventive measures., Objective: The aim of the present study was to describe occupational exposure to biological materials at Base Hospital of Bauru, São Paulo, Brazil, along one year., Methods: Observational retrospective study conducted with data for 2014, which were analyzed according to epidemiological and occupational exposure characteristics before and after exposure, such as previous immunization and follow up of workers, respectively., Results: Forty-two accidents involving biological materials were recorded; 85.7% affected the nursing staff, mainly nursing technicians. The incidence of accidents involving sharp materials was 83%; the upper limbs were the most frequently affected (81%) body part. Vaccination campaigns and specific care protocols achieved effective results, allowing to avoid disease transmission and reducing the costs associated with the follow up of affected healthcare professionals. Few accidents (17%) occurred during emergency procedures, which shows that most instances of exposure might be prevented through safety measures., Conclusion: The study revealed some aspects of the workers involved, exposure type and follow up after accidents with biological materials at the investigated hospital and discusses measures likely to reduce risk.

Objectives: To identify the value of liver-to-abdominal area ratio (LAAR) score for predicting the in-hospital mortality in advanced cirrhotic patients., Methods: All cirrhotic patients with Child-Pugh class B or C who were admitted between July 2012 and June 2014 and underwent abdominopelvic CT scans were considered in this retrospective observational study. The association of LAAR with in-hospital death was calculated. Receiver operating characteristic curve analysis was performed. The area under curve (AUC) was calculated., Results: In the overall analysis of 128 cirrhotic patients with Child-Pugh class B or C, LAAR score was significantly associated with the risk of in-hospital death (p = 0.012). The AUC of LAAR score for predicting the in-hospital mortality was 0.764 (p < 0.0001). The best cut-off value was 0.29 with a sensitivity of 75% and a specificity of 73.33%. In the subgroup analysis of 37 patients with Child-Pugh class C, LAAR score was significantly associated with the risk of in-hospital death (p = 0.008). The AUC of LAAR score was 0.821. The best cut-off value was 0.29 with a sensitivity of 85.71% and a specificity of 80%. In the subgroup analysis of 80 patients with moderate-severe ascites, LAAR score was not significantly associated with the risk of in-hospital death (p = 0.072). The AUC of LAAR score was 0.684 (p = 0.0158). The best cut-off value was 0.29 with a sensitivity of 75% and a specificity of 63.89%., Conclusion: LAAR score might be effective for predicting the in-hospital death of advanced cirrhosis.

Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment., Competing Interests: Potential Conflict of Interest No potential conflict of interest relevant to this article was reported.