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Objective: To identify patients with biliary atresia (BA) with extremely poor outcomes of bile drainage surgery using the infant BA liver fibrosis (iBALF) score, a liver fibrosis marker based on standard blood analysis., Background: Although primary liver transplantation is beginning to be considered as an alternative to bile drainage surgery in patients with BA, those most likely to benefit from this procedure have not yet been identified., Methods: The medical records of 380 patients with BA with bile drainage surgery between 2015 and 2019 were collected for retrospective analysis from 60 participating hospitals. To predict native liver survival at age 1 year, a receiver operating characteristic curve was drawn for the iBALF score. The cutoff value was determined as the point indicating >99% sensitivity., Results: The median age at surgery was 56 days (range: 4-183 days), and native liver survival at age 1 year was achieved in 258 (67.9%) patients. An iBALF score of 5.27 was chosen as the cutoff, and 18 patients (4.7%) were found to have an iBALF score >5.27; of these, only 2 (95% CI: 1.4%-34.7%) had native liver survival at age 1 year, indicating a significantly poorer outcome than in the other patients (95% CI: 65.7%-75.4%). Moreover, patients with an iBALF score >5.27 had significantly higher mortality and younger age at salvage liver transplantation., Conclusions: Patients with BA having a preoperative iBALF score >5.27 had extremely poor outcomes of bile drainage surgery and may be considered candidates for primary LTx., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors have no conflicts of interest to declare.

Background: Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT., Methods: This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis., Results: Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P  < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P  < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P  < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P  < 0.001) but not other etiologies of cirrhosis., Conclusions: Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. Roughly a quarter of paediatric patients with NAFLD develop nonalcoholic steatohepatitis and fibrosis. Here, we evaluated the diagnostic accuracy of previously published noninvasive fibrosis scores to predict liver fibrosis in a large European cohort of paediatric patients with NAFLD., Methods: The 457 patients with biopsy-proven NAFLD from 10 specialized centers were included. We assessed diagnostic accuracy for the prediction of any (F ≥ 1), moderate (F ≥ 2) or advanced (F ≥ 3) fibrosis for the AST/platelet ratio (APRI), Fibrosis 4 score (FIB-4), paediatric NAFLD fibrosis score (PNFS) and paediatric NAFLD fibrosis index (PNFI)., Results: Patients covered the full spectrum of fibrosis (F0: n = 103; F1: n = 230; F2: n = 78; F3: n = 44; F4: n = 2). None of the scores were able to accurately distinguish the presence of any fibrosis from no fibrosis. For the detection of moderate fibrosis, area under the receiver operating characteristic curve (AUROC) were: APRI: 0.697, FIB-4: 0.663, PNFI: 0.515, PNFS: 0.665, while for detection of advanced fibrosis AUROCs were: APRI: 0.759, FIB-4: 0.611, PNFI: 0.521, PNFS: 0.712. Fibrosis scores showed no diagnostic benefit over using ALT ≤ 50/ > 50 IU/L as a cut-off., Conclusions: Established fibrosis scores lack diagnostic accuracy to replace liver biopsy for staging of fibrosis, giving similar results as compared to using ALT alone. New diagnostic tools are needed for Noninvasive risk-stratification in paediatric NAFLD., (© 2023 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose of Review: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity, but is also common in individuals with a normal body mass index (BMI), who also experience the hepatic inflammation, fibrosis, and decompensated cirrhosis associated with NAFLD progression. The clinical evaluation and treatment of NAFLD in this patient population are challenging for the gastroenterologist. A better understanding of the epidemiology, natural history, and outcomes of NAFLD in individuals with normal BMI is emerging. This review examines the relationship between metabolic dysfunction and clinical characteristics associated with NAFLD in normal-weight individuals., Recent Findings: Despite a more favorable metabolic profile, normal-weight NAFLD patients exhibit metabolic dysfunction. Visceral adiposity may be a critical risk factor for NAFLD in normal-weight individuals, and waist circumference may be better than BMI for assessing metabolic risk in these patients. Although screening for NAFLD is not presently recommended, recent guidelines may assist clinicians in the diagnosis, staging, and management of NAFLD in individuals with a normal BMI., Summary: Individuals with a normal BMI likely develop NAFLD as a result of different etiologies. Subclinical metabolic dysfunction may be a key component of NAFLD in these patients, and efforts to better understand this relationship in this patient population are needed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic disorders arising due to mutations in alpha-1 antitrypsin (AAT) gene affecting primarily the lung and the liver. This review summarizes the pathophysiology and clinical manifestation of different AATD genotypes and discusses the recent therapeutic developments. The focus is on the severe, rare homozygous Pi∗ZZ and the common heterozygous Pi∗MZ genotype., Recent Findings: Pi∗ZZ individuals harbor an up to 20 times higher risk of liver fibrosis and cirrhosis than noncarriers and liver transplantation is currently the only available therapeutic option. AATD constitutes a proteotoxic disorder arising from hepatic AAT accumulation and the currently most promising data come from a phase 2, open-label trial of fazirsiran, a hepatocyte-targeted siRNA. Pi∗MZ subjects display an increased risk of advanced liver disease and at the latter stage, a faster deterioration than individuals without AAT mutation., Summary: Although the fazirsiran data offer a glimpse of hope to AATD patients, a consensus on appropriate study endpoint, a careful patient selection as well as monitoring of long-term safety will be essential for an approval., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the performances of MRE and TE for predicting severe complications after HR in patients with HCC., Summary of Background Data: LSM may have the potential to predict outcomes after HR in HCC patients., Methods: Consecutive patients who underwent HR for HCC between 2017 and 2019 were retrospectively enrolled. Before HR, LSM was performed in all patients using both MRE and TE. All postoperative complications were assessed using the comprehensive complication index (CCI). Severe postoperative complications were defined as a CCI ≥26.2. The performances of MRE and TE for predicting high CCI and diagnosing liver fibrosis were compared using the area under the receiver-operating-characteristic curve (AUROC). Uni-/multivariable logistic regression analyses were used to identify factors associated with high CCI., Results: Among the 208 enrolled patients, 28 patients (13.5%) had high CCI. For detecting high CCI, MRE had an AUROC of 0.874 [95% confidence interval (CI), 0.821-0.916], which was significantly higher than the AUROC of TE (0.756; 95% CI, 0.692-0.813) ( P = 0.020). MRE outperformed TE in detecting fibrosis of ≥F2 (AUROC: 0.935 vs 0.767; P = 0.008), ≥F3 (AUROC: 0.902 vs 0.774; P = 0.001) and F4 (AUROC: 0.916 vs 0.767; P < 0.001). LSM by MRE was independently associated with high CCI (odds ratio, 4.207 per kPa; 95% CI, 1.862-9.504; P < 0.001), whereas LSM by TE was not., Conclusions: MRE better predicted severe postoperative complications than TE in HCC patients who underwent HR. LSM by MRE was independently associated with high CCI after HR., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Obesity-related fatty liver disease impacts long-term adolescent liver health. We examined transient elastography assessed hepatic steatosis and fibrosis distributions and relationships with body composition and lifestyle factors in a United States national adolescent population sample., Methods: Liver stiffness and controlled attenuation parameter (CAP) were assessed on 1080 non-Hispanic white, non-Hispanic black, non-Hispanic Asian, and Hispanic boys and girls aged 12-19 years in the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Participants underwent anthropometry and dual-energy x-ray absorptiometry (DXA)., Results: Compared with girls, boys had higher mean CAP (223.7 dB/m vs 215.3 dB/m) and liver stiffness (5.1 kPa vs 4.9 kPa). CAP and liver stiffness increased markedly with body mass index (BMI). In multivariable-adjusted analysis, CAP in the upper quartile was associated with Hispanic and non-Hispanic Asian ethnicity and increased BMI, waist-to-hip ratio, systolic blood pressure, and sedentary time, and decreased physical activity and Healthy Eating Index-2015 score. In multivariable-adjusted analysis, liver stiffness in the upper quartile was associated with male sex, non-Hispanic black ethnicity, and increased BMI, alanine aminotransferase, CAP, and serum cotinine. DXA total percent fat and trunk fat percent were positively related to CAP ( P &lt; 0.001 for each), but not to liver stiffness with multivariable adjustment. Results were similar with CAP and liver stiffness as continuous characteristics., Conclusions: In US adolescents, increased anthropometric and DXA body composition measures and lifestyle factors were associated with higher CAP and liver stiffness. Transient elastography and similar noninvasive markers may be utilized for early detection of liver disease in high-risk pediatric populations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Hyaluronic acid (HA), type III procollagen III (PC-III), type IV collagen IV (IV-C), and laminin (LN) have certain diagnostic value for hepatobiliary diseases. No published studies have compared the diagnostic accuracy of these 4 indicators for the diagnosis of congenital biliary atresia (CBA) in infants. This study aimed to investigate the diagnostic value of HA, PC-III, IV-C, and LN in infants with CBA. From January 2017 to December 2020, 185 infants with nonphysiological jaundice in the Second Department of General Surgery at the Children's Hospital of Hebei were enrolled in this study. Forty-six infants with CBA (CBA group) and 139 infants without CBA (noncongenital biliary atresia group) were diagnosed using ultrasonography, magnetic resonance imaging, intraoperative exploration, and intraoperative cholangiography. The levels of HA, PC-III, IV-C, and LN in the 2 groups were statistically analyzed. The diagnostic accuracy was determined using receiver operating characteristic curves and by calculating the area under the curve. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors. Compared to the noncongenital biliary atresia group, the levels of HA, PC-III, IV-C, and LN were significantly increased in the CBA group (P <.05). The receiver operating characteristic analysis showed the optimal cutoff values for HA, PC-III, IV-C, and LN were 162.7, 42.5, 199.7, and 101.2 ng/mL, and the area under the curves were 0.892, 0.762, 0.804, and 0.768, respectively. The sensitivity values for the diagnosis of CBA were 76.82%, 71.61%, 70.32%, and 72.28%, and the specificity values for the diagnosis of biliary atresia were 70.22%, 70.44%, 66.34%, and 68.71%, respectively. In the multivariate model, HA ≥162.7 ng/mL (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 3.15-8.37), PC-III ≥42.5 ng/mL (OR = 4.61, 95% CI: 2.54-7.16), IV-C ≥199.7 ng/mL (OR = 5.02, 95% CI: 2.98-7.64), and LN ≥101.2 ng/mL (OR = 6.25, 95% CI: 2.41-10.07) remained associated with the occurrence of CBA. HA, PC-III, IV-C, and LN have high accuracy for the diagnosis of CBA in infants, and these factors are potential diagnostic biomarkers for CBA., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: A new noninvasive medical device based on ultrasound elastography such as the Shear Wave Elastography (SWE) was designed in order to measure the liver hardness. The purpose of this work was to evaluate the correlation of the results of the liver elasticity measurements obtained by Fibroscan® (FS) and SWE for patients with chronic liver diseases., Methods: Between January and October 2017, the patients who were followed during this period of time underwent noninvasive assessments of liver fibrosis by SWE in the intercostal spaces during abdominal ultrasound procedures and/or FS. The correlation between FS and SWE was estimated and tested at a 0.05 significance level., Results: Four hundred and seventy-six patients were included in this study. The main etiologies of chronic liver disease were non alcoholic fatty disease (NAFLD), chronic viral hepatitis B (HBV) and chronic viral hepatitis C (HCV). All patients underwent a SWE and 167 among them underwent a FS procedure. The patients who were followed revealed a median FS measurement of 5.80 kpa (Q25 = 4.90 kPa; Q75 = 8 kPa) and a median SWE measurement of 7.00 kPa (Q25 = 6.10 kPa; Q75 = 8.10 kPa). We could observe a significant correlation between the FS and SWE measurements (0.49; P = .001) in the total cohort. The average absolute difference between the measurements of these 2 methods was of 2.54 kPa (sd = 3.39). There was no significant correlation for patients with NAFLD no matter whether they presented with signs of suspected non alcoholic steatohepatitis (NASH) or not (R = 0.20; P = .108). All patients intending to perform the examination were able to undergo the SWE, allowing 33.3% of the patients who failed the FS to have a noninvasive evaluation of their fibrosis., Conclusion: The SWE technique proved to be as efficient as the FS one for the evaluation of the liver fibrosis in real life situation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hyponatremia before liver transplant (LT) increases risk of post-LT neurological complications in patients with decompensated cirrhosis, but it is unknown to what extent change in sodium from pre- to post-LT influences risk of central nervous system (CNS) sequelae. We assessed the relationship between pre- to post-LT delta sodium and prevalence of CNS complications during LT hospitalization., Methods: We performed retrospective single-center chart review of 1265 adults with cirrhosis who underwent LT (2011-2020). Delta sodium is defined as the difference between  maximum sodium within 48 h post-LT and lowest sodium within 7 d pre-LT. Primary outcomes are post-LT CNS events during same hospitalization-encephalopathy, delirium, seizure, coma, osmotic demyelination syndrome, or other altered mental status, determined by International Classification of Diseases codes. Secondary outcome is length of hospital stay post-LT (LOS). Logistic regression modeled association between delta sodium and post-LT CNS outcomes; negative binomial regression modeled LOS., Results: Median age was 59 y, 36% were female, and median Model for End-Stage Liver Disease score was 20. Median delta sodium was 8 mmol/L (interquartile range, 5-11). One hundred ninety-four (15%) experienced post-LT CNS complications. In multivariable analysis, controlling for confounders including pre-LT hyponatremia, every 5 mmol/L increase in delta sodium associated with 47% greater odds of CNS complication (95% confidence interval, 22%-77%). Delta sodium also associated with 7% increased LOS in adjusted regression (95% confidence interval, 3%-12%)., Conclusions: Adult LT recipients with higher perioperative delta sodium shifts displayed a higher risk of post-LT CNS complications, even after adjusting for pre-LT sodium. LT recipients, even those with pre-LT hyponatremia, may benefit from maintenance of stable serum sodium levels to minimize post-LT CNS complications., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Nonalcoholic fatty liver is a complication of pancreaticoduodenectomy (PD); however, liver fibrosis after PD is not well documented. Therefore, we estimated the hepatic fibrotic index of nonalcoholic fatty liver after PD., Methods: We retrospectively examined the electronic medical records of patients who had underwent PD and had computed tomography (CT) records preoperatively and 6 months postoperatively between 2011 and 2019 at the Shiga University of Medical Science Hospital., Results: Overall, 115 patients were enrolled. After 6 months from PD, body mass index significantly decreased from 21.90 to 19.57 kg/m2 (-10.6%). The Fibrosis-4 (FIB-4) index significantly increased from 1.756 to 2.384 (P &lt; 0.001). The FIB-4 grade significantly worsened. Contrarily, neither the albumin-bilirubin (ALBI) score nor the ALBI grade demonstrated significant differences. The CT attenuation value significantly decreased (P &lt; 0.001) from 57.6 to 49.5. Multivariate analysis predicted a high preoperative FIB-4 index, high ALBI index, and hypo-CT attenuation value (&lt;30 HU) as risk factors for a high postoperative FIB-4 index., Conclusions: The FIB-4 index worsened when the follow-up period was only 6 months, regardless of the eternalness in the ALBI score. Liver fibrosis should be assessed using the FIB-4 index for a long-term survivorship after PD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Transfusion-associated iron overload may cause liver fibrosis. We compared transient elastography (TE) and aspartate aminotransferase-platelet ratio index (APRI), noninvasive markers for hepatic fibrosis, to liver histology in children and young adults with sickle cell disease (SCD) who were iron overloaded (cohort 1). Age-matched subjects with SCD but without iron overload (cohort 2) were enrolled for APRI and TE assessments. Nineteen subjects ages 10 to 21 years were transfused for a mean of 9.67 years, had a mean serum ferritin of 4899±2849 ng/mL, and a liver iron concentration of 15.56±10.12 mg/g dry liver weight by R2-magnetic resonance imaging. Mean APRI was 0.33±0.13 in cohort 1 and 0.27±0.10 in cohort 2. The mean liver stiffness measures (LSM) in cohort 1, assessed by TE, was 8.46±3.95 kPa, ranging from 3.5 to 14.6 kPa (expected normal <7 kPa). Cohort 2 had a mean LSM of 5.72±1.74 kPa (4.6 to 8.7 kPa). There was a good correlation between LSM and histologic fibrosis (t value 6.94, P<0.0001). There was no significant correlation between APRI and histologic fibrosis and between APRI and LSM. A high LSM suggests liver fibrosis in children and adults with SCD with iron overload and may merit histologic confirmation especially if persistent., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: One fifth of patients with nonalcoholic fatty liver disease (NAFLD) may progress to nonalcoholic steatohepatitis (NASH), which can increase the risk of cirrhosis, cancer, and death. To date, reported predictors of NASH progression have been heterogeneous.We identified determinants of fibrosis progression in patients with NASH in the United States using physician-reported data from the real-world Global Assessment of the Impact of NASH (GAIN) study, including demographics and clinical characteristics, NASH diagnostic information, fibrosis stage, comorbidities, and treatment. We developed a logistic regression model to assess the likelihood of fibrosis progression since diagnosis, controlling for sociodemographic and clinical variables. An iterative nested model selection approach using likelihood ratio test determined the final model.A total of 989 patients from the GAIN US cohort were included; 46% were women, 58% had biopsy-proven NAFLD, and 74% had fibrosis stage F0-F2 at diagnosis. The final multivariable model included age, years since diagnosis, sex, employment status, smoking status, obesity, fibrosis stage, diagnostic biopsy, Vitamin E, and liver transplant proposed at diagnosis. Odds of progression were 17% higher (odds ratio, 1.17 [95% CI: 1.11-1.23]; P < .001) with each year since NASH diagnosis, 41% lower (0.59 [0.38-0.90]; P = .016) for women than men, 131% higher (2.31 [1.30-4.03]; P = .004) for smokers versus non-smokers, and 89% higher (1.89 [1.26-2.86]; P = .002) with obesity. Odds of progression were also higher with part-time, retired, unemployed, and unable to work due to NASH status versus full-time employment, and when a liver transplant was proposed at diagnosis.Disease duration and severity, obesity, smoking, and lack of full-time employment were significant determinants of fibrosis progression. These findings can support clinical and health-policy decisions to improve NASH management in the US., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which includes diabetes mellitus and hyperlipidemia. A fraction of NAFLD patients develop nonalcoholic steatohepatitis, leading to cirrhosis associated with various serious complications, including hepatocellular carcinoma, gastroesophageal varices, cardiovascular events, and other organ malignancy. Although the incidence of chronic viral hepatitis with associated complications has gradually decreased as highly effective antiviral therapies have been established, the number of patients with steatohepatitis has been increasing.This retrospective study examined data of 229 patients from 22 hospitals in our region. We examined 155 cases of chronological data and assessed the development of liver fibrosis and evaluated hepatic reserve-related markers such as platelet count, FIB-4 index, prothrombin time, and serum albumin concentration. We analyzed the relationship of these chronological changes and the incidence of NAFLD related serious complications.Data related to liver fibrosis progression, albumin, and prothrombin time were significantly associated with the occurrence of serious complications associated with cirrhosis. We compared 22 event and 133 nonevent cases of chronological changes in the data per year and found that serum albumin concentration was significantly lower in the group that developed serious complications (event cases: -0.21 g/dL/year, nonevent cases: -0.04 g/dL/year (P < .001)). This albumin decline was only the associated factor with the event incidence by multivariate analysis (P < .01).Annual decline in serum albumin concentration in patients with NAFLD is associated with serious events from the outcome of multicenter retrospective study. This highlights its potential utility as a surrogate marker to assess the efficacy of prediction of NAFLD related serious events., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Bariatric surgery has been reported to improve non-alcoholic steatohepatitis (NASH), which is a frequent comorbidity in morbidly obese patients. We performed a retrospective cohort study to estimate the therapeutic effect of sleeve gastrectomy (SG), the most common bariatric surgery in Japan, on obese patients with NASH by comparing the findings of paired liver biopsies.Eleven patients who underwent laparoscopic SG for the treatment of morbid obesity, defined as body mass index (BMI) > 35 kg/m2, from March 2015 to June 2019 at Hiroshima University Hospital, Japan, were enrolled. All patients were diagnosed with NASH by liver biopsy before or during SG and were re-examined with a second liver biopsy 1 year after SG. The clinical and histological characteristics were retrospectively analyzed.One year after SG, body weight and BMI were significantly reduced, with median reductions in body weight and BMI of-22 kg and -7.9 kg/m2, respectively. Body fat was also significantly reduced at a median of 13.7%. Liver-related enzymes were also significantly improved. On re-examination by paired liver biopsy, liver steatosis improved in 9 of the 11 patients (81.8%), ruling out of the pathological diagnosis of NASH. However, fibrosis stage did not significantly improve 1 year after SG. The non-alcoholic fatty liver disease activity score was significantly reduced in 10 of 11 patients (90.9%).Pathological improvement or remission of NASH could be achieved in most morbidly obese Japanese patients 1 year after SG., Competing Interests: Conflict of interest and source of funding: EM is currently receiving a grant from Grants-in-Aid for Scientific Research and Development from the Ministry of Health, Labor, and Welfare and the Ministry of Education Culture Sports Science and Technology (JSPS KAKENHI grant number 18K15814). KC received a grant from the Japan Agency for Medical Research and Development (grant number JP20fk0210040). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. None of the remaining authors were declared., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States and increasing globally. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), can lead to cirrhosis and complications of end-stage liver disease. No FDA-approved therapy for NAFLD/NASH exists. Treatment of NAFLD/NASH includes effective and sustained life-style modification and weight loss. This review reports on the recent findings of bariatric surgery in the management of NASH., Recent Findings: NAFLD, at all stages, is common in those who meet indication for bariatric surgery. Bariatric surgery resolves NAFLD/NASH and reverses early stages of fibrosis. Although randomized controlled trials of bariatric surgery in NASH are infeasible, studies defining the metabolic changes induced by bariatric surgery, and their effect on NASH, provide insight for plausible pharmacologic targets for the nonsurgical treatment of NASH., Summary: Resolution of NASH and fibrosis regression can occur after bariatric surgery. Although the exact mechanism(s) underlying the improvement of NASH and hepatic fibrosis following bariatric surgery is not fully elucidated, emerging data on this topic is vitally important for lending insight into the pharmacotherapies for NASH for patients who are not otherwise suitable candidates for bariatric surgery., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We present the case of a successful liver transplant in a young adult patient with cholestasis and cirrhosis secondary to severe pyruvate kinase (PK) deficiency. Liver transplant resulted in resolution of liver dysfunction, decreased need for blood transfusions and eligibility for bone marrow transplantation. This case represents the third reported patient in the literature with severe PK deficiency who successfully underwent liver transplant as a result of profound cholestasis and liver failure. Explant pathology demonstrated a lack of significant iron deposition indicating that PK deficiency predisposes the liver to injury independent of transfusion-related iron overload., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The platelet-albumin-bilirubin (PALBI) grade plays critical role in evaluating liver function. However, the change of PALBI grade from the preoperative to postoperative period in predicting patient outcomes after hepatectomy remains unclear.A total of 489 HCC patients who underwent hepatectomy in West China Hospital between January, 2010 and June, 2016 were analyzed retrospectively.ΔPALBI grade was calculated by PALBI grade at the first postoperative month - preoperative PALBI grade.ΔPALBI >0 was considered as stable; otherwise, worse PALBI grade was considered. Kaplan- Meier method and Cox proportional hazard regression analyses were performed for survival analysis. Prognostic model was constructed by nomogram method.Three hundred forty two patients and 147 patients were classified into training group and validation group, respectively. In the training group, results from Cox model suggested that worse PALBI grade (HR 1.328, 95% CI 1.010-1.746, P = .042), tumor size (HR 1.460, 95% CI 1.058-2.015, P = .021), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P < .001), and high alpha-fetoprotein level (AFP, HR 1.364, 95% CI 1.044-1.781, P = .023) negatively influenced postoperative recurrence. Similarly, worse PALBI grade (HR 1.403, 95% CI 1.020-1.930, P = .038), tumor size (HR 1.708, 95% CI 1.157-2.520, P = .007), MVI (HR 1.914, 95% CI 1.375-2.663, P < .001), and presence of cirrhosis (HR 1.773, 95% CI 1.226-2.564, P = .002) had negatively impacts on overall survival. Patients with worse PALBI grade had worse recurrence free (RFS) and overall survival (OS). The prognostic model incorporating the change of PALBI grade constructed in training group and tested in the validation group could perform well in predicting the outcomes.Postoperative change of PALBI grade was independently risk factor related with prognosis. Prognostic model incorporating the change of PALBI grade might be a useful index to predict the prognosis of HCC patients following hepatectomy., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Early stage of cirrhosis is of great value in the diagnosis and management in patients with chronic liver disease (CLD). Recent studies have shown that quantitative liver surface nodularity (LSN) score based on imaging techniques can be used to predict the early cirrhosis stage noninvasively, with varied diagnostic accuracy and limited sample size. Hence, this study will evaluate the diagnostic accuracy of LSN in the prediction of early cirrhosis., Methods: We will conduct a comprehensive search in PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases to identify eligible studies. The literature screening, data extraction, data analysis, and quality assessment will then be carried out. The summary receiver-operating-characteristic (ROC) and pooled sensitivity, specificity will be calculated to summarize the diagnostic performance of LSN using a random-effect model. A meta-regression analysis will be performed to investigate the underlying cause of the heterogeneity., Results: This study will evaluate the diagnostic accuracy of LSN score in the identification of early cirrhosis, which may further determine whether this method can be used as an alternative in the assessment of CLD patients., Conclusions: This study will help to determine the diagnostic accuracy and summarize the recent evidence on this issue., Study Registration: INPLASY2020100096., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Advances in treatment of cystic fibrosis (CF) have increased survival and thereby prevalence of patients with liver disease, making chronic liver disease one of the major complications of CF. We describe the prevalence of liver fibrosis, portal hypertension, and liver decompensation by extended screening for cystic fibrosis-related liver disease (CFLD) including ultrasound, elastography, and an extended panel of biochemical markers., Methods: A cross sectional study of CFLD in all pediatric CF patients (1-18 years) from the Copenhagen CF Center. Screening for liver disease included physical examination, biochemical analysis, Vibration-Controlled Transient Elastography (FibroScan), conventional ultrasound, and Real-Time Shear Wave elastography (SWE). Patients were scored according to Williams ultrasound scoring scale (WUSS) within 6 months., Results: A total of 84 consecutive patients (male sex 46.4%, median age 10.4 years) were included. Eight patients (9.5%) had both ≥2 abnormal results of sonographic methods and ≥2 abnormal biochemical results and were in this study categorized as having manifest CFLD. Manifest CFLD patients were significantly older and had a higher mean value of APRI, but no differences in gender, z-height, z-weight, z-BMI, FEV1%, or mean value of bilirubin or albumin were found., Conclusions: In total, 8 patients (9.5%) in this pediatric CF population were categorized as having CFLD according to both biochemical and sonographic tests. Consistency was found among the results of FibroScan and SWE. We suggest WUSS and either FibroScan or SWE, combined with GGT as diagnostic markers for CFLD.

Background: Chronic hepatitis B is often complicated with different degrees of hepatic fibrosis, which affects the quality of life. Nucleoside analogs are recommended by almost all guidelines in the world for the treatment of chronic hepatitis B. At present, there is no specific and effective chemical and biological agents for hepatic fibrosis. In China, Chinese compound prescription combined with nucleoside analogs have been used to treat hepatic fibrosis of chronic hepatitis B patients in more and more cases, and good results have been achieved. Several Chinese compound prescriptions that have been made into proprietary Chinese medicine for the convenience of use. This article aims to systematically evaluate the efficacy and safety of Chinese medicine compounds assisting nucleoside analogs in the treatment of hepatic fibrosis in chronic hepatitis B patients., Method: The following databases will be searched from their inception to September 2019: PubMed, EMBASE, EBSCOhost, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), VIP Database, Wanfang Database. Languages are limited to Chinese and English. The study includes randomized controlled trials using Chinese compound prescription combined with entecavir and Chinese compound prescription combined with tenofovir disoproxil fumarate to treat hepatic fibrosis of chronic hepatitis B patients. The primary outcomes including effective rate and biochemical parameters (levels of hyaluronic acid, laminin, pre-type-III collagen and type IV collagen will be tested. Additional outcomes include liver function indexes (levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin) and levels of hepatitis B virus DNA. Stata14.0 software will be used for meta-analysis., Result: The efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs for hepatic fibrosis of chronic hepatitis B patients will be assessed from the effective rate, biochemical parameters, liver function indexes, and levels of hepatitis B virus DNA., Conclusion: The conclusion of this study will be used to evaluate the efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs in the treatment of hepatic fibrosis of chronic hepatitis B patients, as well as the adjuvant effectiveness of Chinese compound prescriptions in combined therapy., Prospero Registration Number: CRD42020156859.

Objective: This study sought to compare trends in the development of cirrhosis between patients with NAFLD who underwent bariatric surgery and a well-matched group of nonsurgical controls., Summary of Background Data: Patients with NAFLD who undergo bariatric surgery generally have improvements in liver histology. However, the long-term effect of bariatric surgery on clinically relevant liver outcomes has not been investigated., Methods: From a large insurance database, patients with a new NAFLD diagnosis and at least 2 years of continuous enrollment before and after diagnosis were identified. Patients with traditional contraindications to bariatric surgery were excluded. Patients who underwent bariatric surgery were identified and matched 1:2 with patients who did not undergo bariatric surgery based on age, sex, and comorbid conditions. Kaplan-Meier analysis and Cox proportional hazards modeling were used to evaluate differences in progression from NAFLD to cirrhosis., Results: A total of 2942 NAFLD patients who underwent bariatric surgery were identified and matched with 5884 NAFLD patients who did not undergo surgery. Cox proportional hazards modeling found that bariatric surgery was independently associated with a decreased risk of developing cirrhosis (hazard ratio 0.31, 95% confidence interval 0.19-0.52). Male gender was associated with an increased risk of cirrhosis (hazard ratio 2.07, 95% confidence interval 1.31-3.27)., Conclusions: Patients with NAFLD who undergo bariatric surgery are at a decreased risk for progression to cirrhosis compared to well-matched controls. Bariatric surgery should be considered as a treatment strategy for otherwise eligible patients with NAFLD. Future bariatric surgery guidelines should include NAFLD as a comorbid indication when determining eligibility.

Objectives: Chronic hepatitis B virus infection is a major cause of morbidity and mortality. The aim of the study is to describe the hepatic histology in children chronically infected with hepatitis B virus living in the United States and Canada., Methods: Liver biopsies of 134 treatment-naïve children with chronic hepatitis B virus infection were scored for inflammation, fibrosis, and other histological features, and correlated with clinical and laboratory data., Results: Sixty percentage of subjects acquired the infection vertically, 51% were male, and 69% were hepatitis B e antigen-positive at the time of the biopsy. Hepatitis B DNA levels were generally high (mean 7.70 log IU/mL), as was serum alanine aminotransferase (median 120 U/L). Using the Ishak-modified histology activity index scoring system, interface hepatitis was mild in 31%, moderate in 61%, and severe in 6%. Lobular inflammation was mild in 54%, moderate in 29%, and marked in 7%. Portal inflammation was mild in 38% and moderate in 62% of subjects. Eighteen percentage had no fibrosis, 59% had portal expansion without bridging fibrosis, 19% had bridging fibrosis, and 4% had cirrhosis. Alanine aminotransferase positively correlated with inflammation and fibrosis. Neither age, duration of infection, nor Hepatitis B virus DNA levels correlated with fibrosis. Fibrosis-4 index did not correlate with fibrosis but correlated with inflammation. Aspartate aminotransferase/platelet ratio index correlated with both inflammation and fibrosis., Conclusions: Chronic hepatitis B virus infection results in significant inflammation and fibrosis during childhood. Serum alanine aminotransferase is a strong indicator of the severity and extent of hepatic inflammation and fibrosis.

To evaluate the diagnostic power of red cell distribution width-to-lymphocyte ratio (RLR) for HBV-related liver cirrhosis via a retrospective cohort study.Seven hundred fifty healthy controls, 327 chronic hepatitis B (CHB) patients, and 410 patients with HBV-related liver cirrhosis (HBV-LC) were enrolled in this study. RLR, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), AST to platelet ratio index (APRI), and fibrosis index based on the 4 factors (FIB-4) were compared between the 3 groups. The predictive powers of RLR and RDW for HBV-related liver cirrhosis and patient prognosis were evaluated using AUROC.Patients with HBV-related liver cirrhosis had higher RLR, FIB-4, NLR, RDW, APRI, and lower LMR compared with the control and CHB groups. RLR in the HBV-LC group was significantly higher than both CHB and control groups (both P < .05). While RLR in the CHB group was also higher than the control group, the difference was not statistically significant (P > .05). The AUROC of RLR for predicting HBV-related liver cirrhosis was 0.87, and was superior to RDW (0.81), FIB-4 (0.79), and APRI (0.60). With an optimized cut-off value (10.87), RLR had the highest sensitivity (0.88) and specificity (0.72), and was superior to RDW (0.86, 0.64), FIB-4 (0.80, 0.65), and APRI (0.85, 0.48) as a biomarker. For all 3 groups, RLR was negatively correlated (all P < .05) with serum platelet (PLT) and was positively correlated (all P < .05) with FIB-4 and APRI. There was no significant statistical difference in RLR for patients in HBV-LC group who had different prognosis (P > .05).The RLR, a routinely available, inexpensive, and easily calculated measure, can be used as a predictor of HBV-related liver cirrhosis, but not as a predictor of prognosis for patients with liver cirrhosis. Use of RLR may reduce the need for frequent liver biopsies in CHB patients.

Liver steatosis could affect the accuracy of FibroScan in patients with chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD). This study aimed to assess the accuracy and cut-off values of FibroScan for diagnosing liver fibrosis and cirrhosis in patients with concomitant CHB and NAFLD.A total of 116 patients with concomitant CHB and NAFLD who underwent FibroScan test and liver biopsy were retrospectively enrolled. Liver fibrosis was staged according to the METAVIR scoring system. Calculations of the areas under receiver-operating characteristic curves (AUROC) were performed and compared for the staging of liver fibrosis.The AUROCs for FibroScan, gamma-glutamyl transpeptidase to platelet ratio (GPR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4), and NAFLD Fibrosis Score (NFS) were 0.87, 0.73, 0.69, 0.57, and 0.57 for the diagnosis of significant liver fibrosis (METAVIR ≥ F2); 0.89, 0.77, 0.75, 0.68, and 0.60 for severe liver fibrosis (METAVIR ≥ F3); and 0.94, 0.86, 0.80, 0.74, and 0.63 for cirrhosis (F4), respectively. The cutoff values of FibroScan for staging liver fibrosis with sensitivity at least 90% were: 8.0 kPa for significant liver fibrosis, and 10.5 kPa for cirrhosis. The cutoff values of FibroScan for staging liver fibrosis with specificity at least 90% were: 10.8 kPa for significant liver fibrosis, and 17.8 kPa for cirrhosis.FibroScan provides high value for the diagnosis of liver fibrosis and cirrhosis in patients with concomitant CHB and NAFLD.

Purpose of Review: Liver disease in cystic fibrosis (CF) usually develops before puberty, is often asymptomatic and slowly progressive. Multilobular cirrhosis develops in approximately 5-10% of patients by the age of 18, and is a significant contributor to the morbidity and mortality. No therapy, including ursodeoxycholic acid and cystic fibrosis transmembrane conductance regulator correctors or potentiators, has proven effective to prevent or halt the progression of liver disease towards cirrhosis and portal hypertension. This review provides the current knowledge in the epidemiology of CF liver disease and development of noninvasive tools to assess liver disease severity and progression overtime in order to optimize clinical management and therapeutic options., Recent Findings: Liver disease not only develops during childhood but also later in the lifetime of patients with CF; the incidence of cirrhosis with portal hypertension increases progressively reaching 10% by age 30. Several noninvasive tools to measure liver stiffness as an indirect measure of fibrosis are being investigated, and show promising results for the assessment of early stages of liver fibrosis and disease progression., Summary: Identifying noninvasive biomarkers is fundamental to improving early diagnosis, monitoring disease evolution and measuring treatment effects. A prerequisite is the use of consistent definitions for CF- liver disease (LD) in clinical trials.

Background: Hepatic fibrosis (HF) is the common pathological basis of chronic liver disease (CLD). Many data indicate that serum vitamin D (VD) levels in patients with liver fibrosis are significantly lower than those without liver fibrosis, and lower level of serum 1,25(OH)2D3 is also an independent risk factor for patients with liver fibrosis combined with other diseases. VD has the functions of anti-fibrosis, regulating cell proliferation and differentiation, anti-inflammatory, and immune regulation, Therefore, serum 1,25(OH)2D3 level may be negatively correlated with the progression of liver fibrosis. But there is absent convincing evidence-based medicine to confirm the efficacy of VD supplementation for CLD. Thus, we aimed to conduct this meta-analysis to summarize the efficacy of VD supplementation on the progression of fibrosis in patients with CLD., Methods: The study only selects clinical randomized controlled trials of VD supplementation for CLD. We will search each database from the built-in until September 2020. The English literature mainly searches Cochrane Library, Pubmed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and gray literature. Two researchers worked independently on literature selection, data extraction and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on the heterogeneity. The serum VD level, hepatic function and serological indexes of hepatic fibrosis were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this Meta-analysis was conducted by RevMan software version 5.3., Results: This meta-analysis will further determine the beneficial efficacy of VD supplementation on the progression of fibrosis in patients with CLD., Conclusion: This study determines the positive efficacy of VD supplementation for CLD., Ethics and Dissemination: This review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines or peer-reviewed journals., Registration Number: INPLASY202040054.

Purpose of Review: This review will describe the natural history of alcohol-related liver disease (ArLD) in light of recent data that have synthesized existing knowledge on this topic and described new research cohorts to improve our understanding of progression and outcomes in ArLD., Recent Findings: ArLD occurs after a threshold of alcohol consumption, but this threshold is lowered by the presence of comorbid factors of which obesity is the most common. The most common stage of ArLD is alcohol-related steatosis: this is associated with a low rate of progression to cirrhosis (3%/year) and nonliver-related morbidity is more likely (4 versus 1%/year). In contrast, alcohol-related steatohepatitis or cirrhosis is more dangerous with higher rates of both nonliver and liver-related mortality. Hepatocellular carcinoma occurs at approximately 3%/year amongst people with ArLD cirrhosis., Summary: These data allow an understanding of ArLD to accurately counsel patients and also to guide public health policies. Awareness of the shortcomings of the available data, highlighted in a recent systematic review, will inform the design of further research in particular to describe the multiple interacting factors that may cause ArLD to regress or progress.

Although serum bile acids and total cholesterol (TC) are closely related to liver cirrhosis, the potential diagnostic value of total bile acid-to-cholesterol ratio (TBA/TC) for liver fibrosis is unclear. The present study aimed to evaluate the value of TBA/TC in the diagnosis of cirrhosis and the relationship between TBA/TC and significant liver fibrosis in chronic hepatitis B virus (HBV) infected patients without cholestasis.667 patients with alkaline phosphatase (ALP) ≤ 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) ≤ 3 ULN were rigorously included in this cross-sectional study. Liver biopsy was performed in 32 patients and METAVIR scoring system was used to evaluate liver fibrosis stage. Liver ultrasound elastography was performed in 138 patients, significant fibrosis was defined as fibrosis ≥ F2. Multiple logistic regression as well as receiver operating characteristic (ROC) curves analyses were performed.Compared to patients with non-cirrhosis, TBA and TBA/TC were significantly higher in cirrhosis while TC was significantly lower (all P < .001). In multivariate analysis, TBA/TC was also independently associated with cirrhosis [odds ratio (OR) = 1.102, 95% confidence interval (CI): 1.085-1.166]. The area under the curve (AUC) of TBA/TC (0.87) was almost equivalent to the aspartate aminotransferase to platelet ratio index (APRI, AUC = 0.84) and fibrosis 4 score (FIB-4, AUC = 0.80), and the optimal cut-off value for TBA/TC to diagnose cirrhosis was 2.70. Among the patients performed liver biopsy, TBA/TC were significantly higher both in significant fibrosis and cirrhosis as well as significantly correlated with fibrosis stage (all P < .001). Furthermore, In patients performed liver ultrasound elastography, TBA/TC was also independently associated with significant fibrosis (OR = 1.040, 95% CI: 1.001-1.078).Assessment of TBA/TC could serve as an additional marker of significant liver fibrosis and cirrhosis in non-cholestatic chronic HBV infection.

Liver cirrhosis is a common chronic progressive liver disease in clinical practice, and intravoxel incoherent motion (IVIM) is a promising magnetic resonance method to assess liver cirrhosis, so our purpose was to investigate association of liver-lobe-based IVIM-derived parameters with hepatitis-B-related cirrhosis and its severity, and esophageal and gastric fundic varices. Seventy-four patients with hepatitis-B-related cirrhotic and 25 healthy volunteers were enrolled and underwent upper abdominal IVIM diffusion-weighted imaging with b-values of 0, 20, 50, 80, 100, 200, 400, 600, and 800 s/mm. IVIM-derived parameters (D, pure molecular diffusion; D, pseudo diffusion; and f, perfusion fraction) of left lateral lobe (LLL), left medial lobe (LML), right lobe (RL), and caudate lobe (CL) were assessed statistically to show their associations with cirrhosis and its severity, and esophageal and gastric fundic varices. In this research, we found that D, D, and f values of LLL, LML, RL, and CL were lower in cirrhotic liver than in normal liver (all P-values <.05). D, D, and f values of LLL, LML, RL, and CL were inversely correlated with Child-Pugh class of cirrhosis (r = -0.236 to -0.606, all P-values <.05). D of each liver lobe, D of LLL and CL, and f of LLL, LML, and CL in patients with esophageal and gastric fundic varices were lower than without the varices (all P-values <.05). D values of RL and CL could best identify cirrhosis, and identify esophageal and gastric fundic varices with areas under receiver-operating characteristic curve of 0.857 and 0.746, respectively. We concluded that liver-lobe-based IVIM-derived parameters can be associated with cirrhosis, and esophageal and gastric fundic varices.

In the absence of liver biopsy and transient elastography (TE), aspartate aminotransferase to platelet ratio (APRI), fibrosis-4 score (FIB-4), and gammaglutamyl transpeptidase to platelet ratio (GPR) are simple and inexpensive methods for the detection of liver fibrosis., Aims: We compared the performance of APRI, FIB-4, and GPR scores against TE in predicting the presence of liver fibrosis and cirrhosis, determined the optimal cut-off values for fibrosis and cirrhosis prediction, and reviewed the need for further TE assessment in resource-limited areas in China., Methods: TE and basic laboratory tests were performed in 2014 consecutive patients with chronic hepatitis B (CHB), and then compared to APRI, FIB-4, and GPR., Results: For the detection of significant fibrosis, the areas under the receiver operating characteristic (AUROC) curves for APRI, FIB-4, and GPR were 0.83, 0.75, and 0.77, respectively. For the detection of cirrhosis, the AUROC curves for APRI, FIB-4, and GPR were 0.90, 0.84, and 0.84, respectively. The cutoff of APRI was 0.35, with 78% sensitivity and 63% negative predictive value (NPV), to exclude significant fibrosis (F ≥ 2). At an APRI of 0.6, results showed a 94% specificity, 100% positive predictive value (PPV) and 7.9 positive likelihood ratio (PLR) in detecting significant fibrosis. Thus, patients with an APRI of <0.35 or >0.6 demonstrated correct prediction of liver fibrosis. These results translated to 1250 out of the 2014 patients avoiding the need for TE with a diagnostic accuracy of >80%., Conclusions: The APRI score accurately assessed fibrosis and reduced the need for TE in almost two-thirds of Chinese patients with CHB.

Background: Chronic viral hepatitis b and its related complications have caused serious harm to human health and become a worldwide public health problem. Hepatitis b cirrhosis is one of the most common complications in Asia. Traditional Chinese medicine combined with antiviral therapy has become the first choice for clinical treatment of hepatitis b Cirrhosis. Biejia Pill is an effective prescription of traditional Chinese medicine in treating Compensatory period of cirrhosis, and there are more and more clinical reports about its validity in treating Compensatory period of cirrhosis. Therefore, we designed this study protocol to evaluate the adjuvant role of Biejia Pill in the treatment of Compensatory period of cirrhosis., Method: Electronic Databases, PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc, (CBM), will be systematically searched from inception to July 2019. Randomized controlled trials (RCTs) on Biejiajian Pill combined with Entecavir and Entecavir alone against Compensatory period of hepatitis b cirrhosis will be included; inclusion and exclusion criteria will be used to screen the trials. liver fibrosis biomarkers including ECM or its metabolites (serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), and type IV collagen (IV-C)) will be measured as primary outcomes. Liver function, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms will be measured as secondary outcomes. RevMan5 software will be used for literature quality evaluation and data synthesis and analysis., Result: To evaluate the efficacy and safety of Biejiajian Pill in combination therapy by observing the outcomes of serum liver fibrosis markers, adverse reactions and liver function., Conclusion: This study protocol will be used to evaluate the efficacy and safety of Biejia Pill in combination with entecavir in the treatment of Compensatory period of hepatitis b cirrhosis, as well as the adjuvant treatment of Biejia Pill in combination.PROSPERO registration number: CRD42019135402.

Rationale: Despite vast improvements in technique, several complications still challenge surgeons and medical practitioners alike, including biliary and vascular complications, acute and chronic rejection, and disease recurrence., Patient Concerns: A 59-year-old man was admitted to hospital on July, 2016. He had hepatitis B cirrhosis related recurrent hepatocellular carcinoma and underwent living donor liver transplantation in our hospital., Diagnosis: At the time of admission, the patient's spirit, diet, sleep, normal urine and stool, and weight did not change significantly. The test indicators are as follows: total bilirubin: 100.1 μmol/L, direct bilirubin: 65.0 μmol/L. Emergency CT in the hospital after admission showed that hepatic artery pseudoaneurysm formation after liver transplantation was observed., Interventions: This patient underwent minimal invasive endovascular treatment. The demographic, clinical, and laboratory data were collected and reviewed. He was treated successfully by endovascular stent grafting and thrombolytic treatment., Outcomes: The blood concentration of tacrolimus (FK506) was 6.3 ng/mL total bilirubin 19.6 μmol/L before discharge. The changing of total bilirubin and direct bilirubin were investigated (Fig. 1). The patient recovered well and was discharged 2 weeks later. The patient is doing well and regularly followed up., Lessons: Coil embolization of aneurysmal sac or placement of a stent graft is a minimally invasive alternative to surgery and definitively excludes a bleeding hepatic artery pseudoaneurysm. This technique can be considered as an effective treatment option for hepatic artery pseudoaneurysm instead of a difficult surgical repair.

This study aim was to evaluate whether plasma D-dimer levels could serve as a novel prognostic biomarker for 1-month mortality in patients with HBV-related decompensated cirrhosis (HBV-DeCi).This was a retrospective study that enrolled 132 HBV-DeCi patients. Univariate and multivariate regression models were used to identify risk factors for mortality. The area under the receiver operating characteristic curve was calculated to estimate and compare the predictive values of different prognostic markers.In the present study, the plasma D-dimer levels were higher in the nonsurviving group than in the surviving group. Additionally, the D-dimer level was positively correlated with the model for end-stage liver disease (MELD) score. The results of multivariate analysis showed that both the MELD score and D-dimer level are independent predictors of 1-month mortality in HBV-DeCi patients (both P < .01).Plasma D-dimer can be considered a new additional prognostic marker for 1-month mortality in HBV-DeCi patients.

We investigated associations between inflammatory marker levels and hepatitis C virus (HCV)-related compensated liver cirrhosis risk in patients with chronic hepatitis C (CHC) infection in China. We used a case-control design and data from the records of 110 Chinese patients with CHC and cirrhosis for the study; 458 CHC patients who did not have a diagnosis of cirrhosis were matched to the case group by age and sex characteristics. We also investigated fatty liver disease risk factors. The group of patients with CHC infection and cirrhosis had lower platelet-to-lymphocyte ratio (PLR) values (60.63 [44.09, 89.31]) compared with the control group patients (80.24 [57.85, 111.08]). The results indicated that the group of patients with cirrhosis had higher 4-factor fibrosis index and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values compared with the group of patients with CHC-only (1.66 [0.98, 2.60] vs 0.71 [0.45, 1.17], respectively; P < .001 and 2.12 [0.97, 4.25] vs 0.99 [0.51, 2.01], respectively; P < .001). Compared with the control group, the AST/alanine aminotransferase ratio (AAR) values in the group of patients with cirrhosis were significantly higher (P < .001). Logistic regression analysis that included model adjustment for demographic characteristics and other factors that could affect cirrhosis risk revealed that greater 1/PLR values were associated with an increased odds of having cirrhosis (adjusted odds ratio [AOR], 95% confidence interval [CI] 0.991 [0.985-0.996]); APRI and AAR values were also independent predictors of the presence of compensated cirrhosis. We found that compared with the patients with CHC-only, the triglyceride, cholesterol, and low-density lipoprotein cholesterol levels in the patients with both CHC and fatty liver disease were significantly higher. The multivariate analysis of the risk of fatty liver development in patients with CHC infection found that cholesterol level was a statistically significant risk factor (AOR [95% CI] 1.380 [1.089-1.750], P = .008). Increased 1/PLR, APRI, and AAR values were associated with increased risks for development of cirrhosis in this population of Chinese patients with CHC infection. Higher cholesterol levels increased the risk of development of fatty liver disease in patients with CHC.

Nonalcoholic fatty liver disease is a growing condition among adolescent and adult populations, present in around 20%-30% of people in the United Kingdom. Nonalcoholic fatty liver disease is known as a silent disease and over many years may go on to cause nonalcoholic steatohepatitis. In the future it may become a leading contributor to cirrhosis, liver transplantation, and mortality. In recent years, programs have been set up to raise awareness of this condition with the first International NASH (nonalcoholic steatohepatitis) Day taking place in 2018; nevertheless, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis is still not clearly understood by many. An extensive review has shown a lack of nursing literature on this topic, and effective specialist nurse input for this patient group should be a key component in tackling this growing epidemic in the years to come.

To investigate the differences in bone mineral density between patients with liver cirrhosis and healthy control, and to analyze the risk factors of hepatic osteoporosis in patients with HBV related liver cirrhosis.A total of 189 patients with liver cirrhosis and 207 health controls were enrolled. The bone mineral density of lumbar spine and femoral neck was examined by dual energy X-ray absorptiometry. -2.0

Background: We aimed to assess the association between red cell distribution width-to-platelet ratio (RPR) and hepatic fibrosis in nonalcoholic fatty liver disease., Methods: The 388 subjects fulfilling the diagnostic criteria of Nonalcoholic fatty liver disease (NAFLD) were enrolled in this cross-sectional study. Red cell distribution, platelet, and other clinical and laboratory parameters were measured., Results: NAFLD patients with advanced fibrosis had significantly higher RPR than those without fibrosis (P < .001). Spearman correlation analysis showed that RPR were significantly correlated with age, sex, creatinine, hemoglobin, white blood cell, and advanced fibrosis (all with P < .05). Multivariate logistic regression analysis showed that RPR was an independent factor predicting advanced fibrosis (fibrosis-4 calculator ≥1.3) in NAFLD patients (OR: 5.718, 95%CI: 3.326-9.830, P < .001)., Conclusions: Our findings suggested that RPR were significantly associated with advanced fibrosis in nonalcoholic fatty liver disease patients.

Ultrasound is routinely used during the evaluation of liver cirrhosis. Inter-observer variability is considered a major drawback. This retrospective study investigated the accuracy of ultrasound in diagnosing compensated cirrhosis (i.e., modified Knodell F3, F4) in chronic hepatitis C (CHC) patients in real world clinical practice. Consecutive treatment-naive CHC patients who underwent liver biopsy (LB) prior to interferon therapy from 1997 to 2010 were enrolled. Ultrasound was performed by 30 hepatologists prior to LB. Ultrasound-identified cirrhosis was defined as small liver size, nodular liver surface and coarse liver parenchyma. LB was used as a reference, and the diagnostic accuracy of ultrasound was assessed and compared. Fibrosis was scored according to the modified Knodell classification. A cohort comprising 1738 patients, including 922 men and 816 women with a mean age of 52.5 years, was analyzed in the present study. The distribution of the patients' modified Knodell scores was F0 = 336, F1 = 489, F2 = 165, F3 = 315, F4 = 433. Ultrasound-identified cirrhosis was noted in 283 patients. Using ultrasound-identified cirrhosis to predict compensated cirrhosis, the sensitivity was 34.0%, the specificity was 97.1%, the positive predictive value was 89.8%, the negative predictive value was 66.1%, the positive likelihood ratio was 11.6, and the negative likelihood ratio was 0.68. The area under the ROC curve (AUROC) was 0.66.Despite being affected by inter-observer variability, ultrasound is highly specific in diagnosing compensated cirrhosis in CHC patients in real world clinical practice. However, the sensitivity is low.

The aim of our study was to investigate the efficiency and feasibility of shear-wave elastography (sound touch elastography [STE], sound touch quantification [STQ]) compared with transient elastography (FibroScan) assessment in noninvasively and quantitatively identifying the degree of liver fibrosis. A total of 158 patients with chronic hepatitis B were included, and all accepted STE, STQ, and FibroScan assessments. Young's modulus (kPa) of STE, STQ, and FibroScan were evaluated, and the diagnostic performance of the 3 techniques on liver fibrosis stage was compared. The final diagnosis was based on histological findings from liver biopsy. Of all these patients, 36 patients were categorized as G/S < 2, and 122 were as G/S ≥ 2 according to Scheuer G/S scoring system. STEmean and STQmean measurements were positively correlated with liver fibrosis stage with high correlation (r = 0.852 and r = 0.803, respectively). Receiver operating characteristic analysis of STE, STQ, and FibroScan revealed that the areas under the curve of STE and STQ were markedly increased compared with that of FibroScan when differentiating early stage of liver fibrosis (S1, S2). It was concluded that shear-wave elastography (STE, STQ, and FibroScan) performs well in evaluation of liver fibrosis in patients with chronic hepatitis B, and the efficacies of STE and STQ are better than that of FibroScan.

The aim of this study was to investigate the features, treatment, and prognosis of early versus late recurrence of centrally located hepatocellular carcinoma (CL-HCC) after mesohepatectomy (MH).Three hundred forty eight patients with CL-HCC undergoing MH were included. Data on clinicopathological characteristics, initial surgical details, timing and sites of tumor recurrence, management after recurrence, and long-term outcomes were analyzed.The optimal cutoff value to differentiate early (71 patients, 64.5%) versus late (39, 35.5%) recurrence was defined as 12 months. Patients with early recurrence (ER) had higher alpha fetoprotein (AFP) level (P < .001), more advanced tumor stage (P = .024), and higher incidence of microvascular invasion (MVI, P = .001). Patients with ER had higher incidence of local tumor recurrence (P = .027) and higher average number of recurrent nodules (P = .016) than patients with LR. Patients after ER showed a better overall survival (from date of diagnosis of recurrence) than after late recurrence (LR). Patients with ER had less chances of curative treatment (14.1% vs 41.0%, P = .004) after tumor recurrence than patients with LR. Multivariable analyses revealed that liver cirrhosis (P < .001) and tumor differentiation (P < .001) were associated with an increased likelihood of LR, while multiple tumor number (P = .005), type IV classification (P = .012), and MVI (P < .001) were independent risk factors related to ER.ER and LR after MH for CL-HCC were associated with different risk predictors and prognosis. Data on the timing of recurrence may inform decisions about postoperative adjuvant treatment, as well as help to predict long-term survival for these patients.

Purpose of Review: Hepatitis C virus (HCV) infection has been the leading cause of cirrhosis in the United States now for the last several decades. With the introduction of highly effective direct acting antiviral (DAA) drugs, cure rates are now almost 100%. With this explosion of effective therapy, it is possible that many patients with HCV may have reversion in fibrosis. The purpose of this review is, therefore, to report on recent findings in this field., Recent Findings: Older data that examined the effect of interferon-based HCV therapy indicate that fibrosis reverses after HCV eradication. More recent work in the DAA era similarly indicates that fibrosis is reversible. A caveat is that DAA therapy causes rapid viral clearance, and appears to lead to rapid reductions in inflammation. Some tools (such as transient elastography), which may also reflect the inflammatory response, and thus may 'overestimate' of fibrosis reversal. However, emerging data suggesting improved outcomes in patients with cirrhosis after HCV clearance support the concept that even cirrhosis reverses in some patients., Summary: Fibrosis (and cirrhosis) reversion, to some extent, occurs after HCV clearance. This topic is vitally important and information continues to emerge; more data on this subject are expected and needed.

Background: Liver cirrhosis is one of the end-stage chronic liver diseases. Individuals with chronic hepatitis B (CHB) are at an increased risk of developing liver cirrhosis. Practice guidelines underline that Nucleos(t)ide analogs (NAs) should be the first-line treatment for hepatitis B virus (HBV)-related cirrhosis. However, prolonged use of NAs may lead to drug resistance and kidney impair and does not reverse the fibrosis of liver. Fufang Biejia Ruangan Tablet (RGT), as a traditional Chinese medicine (TCM), has been proved to be effective in the treatment of liver fibrosis. Hence, we will perform meta-analysis in order to evaluate the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB., Methods: To search for relative literatures up to February 2019 by computer from the following databases: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodicals Database, Chinese BioMedical Database and Wanfang Data. Included criteria are randomized controlled trials and cohort studies of hepatic fibrosis in patients with CHB treated by RGT. The primary outcome measures include biochemical and virological parameters. We will use Stata 13.0 software for data synthesis, sensitivity analysis, meta regression, subgroup analysis, and risk of bias assessment. The reporting bias will be assessed by a funnel plot and the funnel plot symmetries will be evaluated by Begg and Egger tests. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence., Results: This systematic review will provide a synthesis of RGT for hepatic fibrosis in patients with CHB from various evaluation aspects including biochemical and virological parameters, HBV DNA levels HBeAg status and seroconversion, adverse events incidence., Conclusion: The systematic review will provide evidence to assess the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB., Prospero Registration Number: ROSPERO CRD 42018095122.

Background: Whether continued, accelerated liver fibrosis progression occurs following acute hepatitis C virus infection (AHCVI) in HIV-positive MSM is unknown., Design and Methods: HIV-positive MSM from the AIDS Therapy Evaluation in the Netherlands and MSM Observational Study for Acute Infection with Hepatitis C-cohorts with primary AHCVI and at least one fibrosis-4 (FIB-4) measurement less than 2 years before and 1 year after estimated AHCVI were included. Mixed-effect linear models were used to evaluate (time-updated) determinants of FIB-4 levels over time. Determinants of transitioning to and from FIB-4 ≤ 1.45 and > 1.45 were examined using multistate Markov models., Results: Of 313 MSM, median FIB-4 measurements per individual was 12 (interquartile range  = 8-18) and median follow-up following AHCVI was 3.5 years (interquartile range = 1.9-5.6). FIB-4 measurements averaged at 1.00 [95% confidence interval (CI) = 0.95-1.05] before AHCVI, 1.31 (95% CI = 1.25-1.38) during the first year of AHCVI and 1.10 (95% CI = 1.05-1.15) more than 1 year after AHCVI. Mean FIB-4 more than 1 year after AHCVI was higher for chronically infected patients compared with those successfully treated (P = 0.007). Overall FIB-4 scores were significantly higher with older age, lower CD4 cell count, longer duration from HIV-diagnosis or AHCVI, and nonresponse to HCV-treatment. At the end of follow-up, 60 (19.2%) and eight MSM (2.6%) had FIB-4 between 1.45-3.25 and ≥ 3.25, respectively. Older age, lower CD4 cell count and detectable HIV-RNA were significantly associated with higher rates of progression to FIB-4 > 1.45, whereas older age, longer duration from HIV-diagnosis and nonresponse to HCV-treatment were significantly associated with lower rates of regression to FIB-4 ≤ 1.45., Conclusion: In this population of HIV-positive MSM, FIB-4 scores were higher during the first year of AHCVI, but FIB-4 ≥ 3.25 was uncommon by the end of follow-up. Well controlled HIV-infection appears to attenuate FIB-4 progression.

Not only alcoholic cirrhosis related to cardiac dysfunction, cirrhosis caused by nonalcoholic etiology including hepatitis B virus (HBV) infection also related to impaired cardiac health. The aims of present study were to perform a noninvasive evaluation of cardiac function and to evaluate exercise performance in HBV related cirrhotic patients without typical symptoms of cardiac disease.Seventy-nine HBV related cirrhotic patients and 103 matched subjects without a previous history of cardiac involvement were recruited. Clinical examination and cardiac health evaluation were performed. The incidence, risk factors of cardiac dysfunction and exercise tolerance were investigated.A correlation between QTc interval and model for end-stage liver disease score (R = 0.239, P = .018) was detected, however, the connection between QTc prolongation and the severity of liver disease was uncertain. Patients with HBV related cirrhosis had a tendency toward left ventricular wall thickening (P = .007). Forty-one patients (51.90%) were in accordance with the definition of cirrhotic cardiomyopathy, and a significant increase in the incidence of cardiac diastolic dysfunction (CDD) could be found with increasing Child-Pugh grade (P = .004). HBV related cirrhotic patients with CDD had a higher level of pro-brain natriuretic peptide (P = .025), international normalized ratio (P = .010) Child-Pugh score (P = .020), and a higher proportion of ascites (P < .001). The higher Child-Pugh score (odds ratio = 1.662, P = .010) was an independent diagnostic predictor of CDD. The cardiac depression and exercise tolerance also got worse with increasing Child-Pugh score (P < .001).Impaired cardiac health was common in HBV related cirrhotic patients. Cardiogenic factors must be carefully considered in the integral therapy of cirrhosis. Hepatology physicians should lay emphasis on exercise training in daily life.

The prevalence of nonalcoholic liver disease (NAFLD) is increasing worldwide in conjunction with the epidemic increase in obesity and metabolic risk factors. Consequently, NAFLD has become a leading indication for liver transplantation. Although genetic factors play an important role in the pathogenesis of NAFLD, detrimental lifestyle trends favoring a calorically unrestricted diet rich in carbohydrates and unsaturated fat, prolonged sedentary periods or limited physical activity have major metabolic implications. In aggregate these physiological dysregulations constitute the main risk factors for the metabolic syndrome and NAFLD. The cornerstone of the treatment of NAFLD, is lifestyle changes, including modifications to diet and physical activity, to reduce body weight and liver fat, however adherence is notoriously poor and the epidemic of NAFLD continues to grow unimpeded. In the face of this unmet clinical need, the pharmacologic therapy of NAFLD has been expanding as the varied mechanistic pathways of NAFLD are elucidated. Beyond these approaches to treating NAFLD, the prevention of other liver diseases is additionally important. Chief among these is alcoholic liver disease, and heavy use is detrimental irrespective of underlying NAFLD. However, the impact of mild to moderate alcohol use in patients with mild or nonadvanced forms NAFLD is undefined. This article summarizes the results of the International Liver Transplantation Society consensus meeting on NAFLD in liver transplantation. It describes the available evidence and provides consensus guidance on the lifestyle and pharmacologic therapies of NAFLD, and the consensus position on alcohol use in patients with NAFLD.