A comparative study of cirrhosis sub-staging using the Laennec system, Beijing classification, and morphometry.

There is constant remodeling in a cirrhotic liver resulting in cirrhosis being spatially heterogeneous. The Laennec system, and, more recently the Beijing classification, have been used to sub-classify various degrees of cirrhosis. It is unknown how these two schemes compare with each other, how they are impacted by geographic variation, and how they correlate with clinical outcomes. Five needle biopsies were obtained from 20 explanted cirrhotic HCV livers at the time of transplantation. Collagen proportionate area (CPA) was measured by computerized quantitative morphometry. The Laennec system (4A-4C indicating increasing degrees of cirrhosis) and Beijing classification (P-progressive, R-regressive, I-indeterminate) were assessed and then correlated with CPA. Geographical variation using CPAs was calculated by the coefficient of variation (CoV). CPA of Laennec 4C cirrhosis was higher than 4A (p = 0.00008) or 4B (p = 0.0002). The CPA of the P pattern was greater than the R (p = 0.002) or I patterns (p = 0.037). The mean CoV of the five CPAs was 47.3 ± 4.5%, suggesting a significant degree of geographic variation. There was 100% overlap between the Beijing R pattern and Laennec 4A, and 80% overlap between the P pattern and Laennec 4C. Patients' platelet counts of P pattern were lower than R pattern (p = 0.008) or I pattern (p = 0.024), while Laennec 4C was lower than 4A (p = 0.036) and 4B patients (p = 0.7). There was no correlation between CPA, Laennec stage, or Beijing classification and MELD score, liver weights, total bilirubin, or albumin levels. The Laennec system and the Beijing classification are highly correlated with CPA in cirrhosis. This study confirms that there is a significant degree of geographic variation in terms of fibrosis content and cirrhosis morphology throughout the liver.

Improvement in Liver Stiffness in Pediatric Patients with Hepatitis C Virus after Treatment with Direct Acting Antivirals.

OBJECTIVES: To assess the degree of liver stiffness using transient elastography in Egyptian children infected with hepatitis C virus (HCV) at baseline and 1 year after achievement of sustained virologic response (SVR) with direct acting antivirals. STUDY DESIGN: This prospective study included children infected with HCV who received treatment with sofosbuvir/ledipasvir and achieved SVR. At baseline and 1 year after achievement of SVR, the extent of hepatic fibrosis was assessed by transient elastography using FibroScan to measure liver stiffness, in addition to noninvasive markers including aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. RESULTS: The study included 23 cases that had variable degrees of fibrosis at baseline; their ages ranged between 10 and 18 years. At baseline, 13 patients had F1; 3 patients had F1-F2; 1 patient had F2; 3 patients had F3; 2 had F3-F4; and 2 patients with F4. One year after achievement of SVR, there was a statistically significant improvement in liver stiffness, APRI, and FIB-4 index (P = .03, <.001, .02, respectively). In 13 patients (56.5%), the liver stiffness improved; in 7 patients, it was stationary; and the remaining 3 patients showed mild increase in liver stiffness that was, however, associated with improvement in APRI and FIB-4 index. Comorbid conditions and previous treatment with interferon were not associated with increased liver stiffness 1 year after SVR. CONCLUSIONS: Egyptian children infected with HCV genotype 4 achieved significant regression in liver stiffness after treatment with direct acting antivirals.

Validity of International Classification of Diseases, Tenth Revision, Codes for Cirrhosis.

INTRODUCTION: Accurate identification of patients with cirrhosis is important for research using administrative databases. We aimed to examine the accuracy of several major ICD-10 codes for cirrhosis diagnosis in a large and diverse patient cohort; there is little existing research on this topic. METHODS: Using data from 3,396 patients with chronic liver disease (hepatitis B or C or nonalcoholic fatty liver disease) from 1 university and several community medical centers, we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value, and area under the receiver operating characteristic curve (AUROC) for several major ICD-10 codes for cirrhosis, which was verified by individual chart review. We performed a secondary validation in a general cohort of 1,560 randomly selected patients. RESULTS: While each of the individual study ICD-10 codes were specific (98.08-100%), none of the codes were sufficiently sensitive (0.27-55.70%). PPVs were high in the chronic liver disease cohort (88.41-100%) but lower in the general population (55.53-66.76%). The AUROC for having at least 1 code was higher (0.79) than any code alone (0.50-0.65). DISCUSSION/CONCLUSION: Individual ICD-10 codes are suboptimal for identifying patients with cirrhosis in the general patient population. We recommend conditioning ICD-10 code searches with a chronic liver disease diagnosis code and/or combining diagnostic codes to maximize performance.

Clinical Outcomes of Acute Pancreatitis in Patients with Cirrhosis According to Liver Disease Severity Scores.

BACKGROUND: Literature on acute pancreatitis (AP) outcomes in patients with cirrhosis is limited. We aim to investigate the mortality and morbidity of AP in patients with cirrhosis. METHODS: We conducted a retrospective cohort study, and propensity score matching was done to match cirrhotic with non-cirrhotic patients on a 1:2 basis. Outcomes included inpatient mortality, organs failure, systemic inflammatory response syndrome, and length of hospital stay. We performed subgroup analysis of cirrhotics according to Child-Pugh and MELD scores. Multivariable logistic regression models were tested. RESULTS: From 819 AP patients, cirrhosis prevalence was 4.9% (40). There was no significant difference between cirrhotics and non-cirrhotics for inpatient mortality (7.5% vs. 1.3%, p = 0.1), severe AP (17.5% vs. 7.5%), shock (7.9% vs. 3%), respiratory failure (10% vs. 3.8%), need for intensive care unit (15% vs. 6.3%), systemic inflammatory response syndrome (SIRS) on admission (22.5% vs. 32.5%), and SIRS on day 2 (25% vs. 15%). Cirrhotics had similar rates of pancreatic necrosis, ileus, BISAP score, Marshall score, admission hematocrit, BUN, and hospital length of stay. Finally, cirrhotics who had severe AP, required ICU, and/or die in-hospital appeared to have more severe liver diseases (Child-C, higher MELD score > 17) and had lower AP severity scores (BISAP < 3, Marshall scores < 2). CONCLUSION: In our study, cirrhotics hospitalized with AP had similar morbidity and mortality when compared to non-cirrhotics.

Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis.

BACKGROUND & AIMS: Treatment allocation in patients with hepatocellular carcinoma (HCC) on a background of Child-Pugh B (CP-B) cirrhosis is controversial. Liver resection has been proposed in small series with acceptable outcomes, but data are limited. The aim of this study was to evaluate the outcomes of patients undergoing liver resection for HCC in CP-B cirrhosis, focusing on the surgical risks and survival. METHODS: Patients were retrospectively pooled from 14 international referral centers from 2002 to 2017. Postoperative and oncological outcomes were investigated. Prediction models for surgical risks, disease-free survival and overall survival were constructed. RESULTS: A total of 253 patients were included, of whom 57.3% of patients had a preoperative platelet count <100,000/mm3, 43.5% had preoperative ascites, and 56.9% had portal hypertension. A minor hepatectomy was most commonly performed (84.6%) and 122 (48.2%) were operated on by minimally invasive surgery (MIS). Ninety-day mortality was 4.3% with 6 patients (2.3%) dying from liver failure. One hundred and eight patients (42.7%) experienced complications, of which the most common was ascites (37.5%). Patients undergoing major hepatectomies had higher 90-day mortality (10.3% vs. 3.3%; p = 0.04) and morbidity rates (69.2% vs. 37.9%; p <0.001). Patients undergoing an open hepatectomy had higher morbidity (52.7% vs. 31.9%; p = 0.001) than those undergoing MIS. A prediction model for surgical risk was constructed (https://childb.shinyapps.io/morbidity/). The 5-year overall survival rate was 47%, and 56.9% of patients experienced recurrence. Prediction models for overall survival (https://childb.shinyapps.io/survival/) and disease-free survival (https://childb.shinyapps.io/DFsurvival/) were constructed. CONCLUSIONS: Liver resection should be considered for patients with HCC and CP-B cirrhosis after careful selection according to patient characteristics, tumor pattern and liver function, while aiming to minimize surgical stress. An estimation of the surgical risk and survival advantage may be helpful in treatment allocation, eventually improving postoperative morbidity and achieving safe oncological outcomes. LAY SUMMARY: Liver resection for hepatocellular carcinoma in advanced cirrhosis (Child-Pugh B score) is associated with a high rate of postoperative complications. However, due to the limited therapeutic alternatives in this setting, recent studies have shown promising results after accurate patient selection. In our international multicenter study, we provide 3 clinical models to predict postoperative surgical risks and long-term survival following liver resection, with the aim of improving treatment allocation and eventually clinical outcomes.

The Use of NACSELD and EASL-CLIF Classification Systems of ACLF in the Prediction of Prognosis in Hospitalized Patients With Cirrhosis.

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is defined by the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) consortium and the North American Consortium for the Study of End-Stage Liver Disease (NACSELD) as an acute deterioration of cirrhosis with multiple organ failures and high short-term mortality. However, their diagnostic criteria differ. We aimed to compare these 2 criteria in the prediction of prognosis in hospitalized cirrhosis. METHODS: This was a prospective study of nonelectively hospitalized patients with cirrhosis (N = 468) from a single tertiary hospital between 2016 and 2018. Baseline characteristics, incidence, and types of organ failure and survival data at 7, 28, and 90 days were collected. Prognostic utilities of the 2 criteria were compared. RESULTS: One hundred thirty-seven of 468 patients (29.3%) had EASL-CLIF ACLF, and 35 of 468 (7.4%) had NACSELD ACLF. The 28-day transplant-free survival of ACLF was 58.4% using EASL-CLIF and 37.1% using the NACSELD criteria. In predicting 28-day mortality, the NACSELD criteria demonstrated significantly higher overall accuracy (92.0% vs 85.3%, P < 0.01), specificity (99.7% vs 84.0%, P < 0.001), and positive predictive value (97.1% vs 50.4%, P < 0.001) but lower sensitivity (49.3% vs 92.5%, P < 0.001) and negative predictive value (91.6% vs 98.5%, P < 0.001) than those of EASL-CLIF. The results were similar in predicting 7-day outcome. However, the overall accuracy became similar between NACSELD and EASL-CLIF ACLF criteria in predicting 90-day mortality (86.3% vs 88.7%, P = 0.27) because of the decrease of sensitivity and negative predictive value of NACSELD ACLF criteria. The prognostic performance of these 2 ACLF criteria was similar when applied to patients with or without hepatitis B virus infection as an etiology of cirrhosis. DISCUSSION: There are both caveats and utilities of NACSELD and EASL-CLIF ACLF criteria in prognosis prediction in patients with cirrhosis. NACSED criteria is highly accurate in predicting morality, whereas the EASL-CLIF criteria is more sensitive to identify patients who would benefit from liver transplantation.

Deep learning with ultrasonography: automated classification of liver fibrosis using a deep convolutional neural network.

OBJECTIVES: The aim of this study was to develop a deep convolutional neural network (DCNN) for the prediction of the METAVIR score using B-mode ultrasonography images. METHODS: Datasets from two tertiary academic referral centers were used. A total of 13,608 ultrasonography images from 3446 patients who underwent surgical resection, biopsy, or transient elastography were used for training a DCNN for the prediction of the METAVIR score. Pathological specimens or estimated METAVIR scores derived from transient elastography were used as a reference standard. A four-class model (F0 vs. F1 vs. F23 vs. F4) was developed. Diagnostic performance of the algorithm was validated on a separate internal test set of 266 patients with 300 images and external test set of 572 patients with 1232 images. Performance in classification of cirrhosis was compared between the DCNN and five radiologists. RESULTS: The accuracy of the four-class model was 83.5% and 76.4% on the internal and external test set, respectively. The area under the receiver operating characteristic curve (AUC) for classification of cirrhosis (F4) was 0.901 (95% confidence interval [CI], 0.865-0.937) on the internal test set and 0.857 (95% CI, 0.825-0.889) on the external test set, respectively. The AUC of the DCNN for classification of cirrhosis (0.857) was significantly higher than that of all five radiologists (AUC range, 0.656-0.816; p value < 0.05) using the external test set. CONCLUSIONS: The DCNN showed high accuracy for determining METAVIR score using ultrasonography images and achieved better performance than that of radiologists in the diagnosis of cirrhosis. KEY POINTS: • DCNN accurately classified the ultrasonography images according to the METAVIR score. • The AUROC of this algorithm for cirrhosis assessment was significantly higher than that of radiologists. • DCNN using US images may offer an alternative tool for monitoring liver fibrosis.

Precision pathology analysis of the development and progression of hepatocellular carcinoma: Implication for precision diagnosis of hepatocellular carcinoma.

Outcomes for patients with hepatocellular carcinoma (HCC) remain poor because the condition is often unresponsive to the available treatments. Consequently, the early and precise diagnosis of HCC is crucial to achieve improvements in prognosis. For patients with chronic liver disease, the assessment of liver fibrosis is also important to ascertain both the staging of fibrosis and the risk of HCC occurrence. Early HCC was first described in 1991 in Japan and was defined internationally in 2009. As the concept of early HCC spread, the multistage hepatocarcinogenesis process became accepted. Consequently, improvements in imaging technology made the early diagnosis of HCC possible. At present, the most appropriate therapeutic strategy for HCC is determined using an integrated staging system that assesses the tumor burden, the degree of liver dysfunction and the patient performance status; however, pathological and molecular features are not taken into account. The recent introduction of several new therapeutic agents will change the treatment strategy for HCC. Against this background, HCC subclassification based on tumor cellular and microenvironmental characteristics will become increasingly important. In this review, we give an overview of how pathological analysis contributes to understanding the development and progression of HCC and establishing a precision diagnosis of HCC.

The clinical spectrum of Fontan-associated liver disease: results from a prospective multimodality screening cohort.

AIMS: Liver fibrosis and cirrhosis are a consequence of a Fontan physiology, and determine prognosis. It is unclear whether non-invasive assessment of liver pathology is helpful to provide clinically relevant information. The aims of this study were to assess the spectrum of Fontan-associated liver disease (FALD) and usefulness of non-invasive methods to assess biopsy confirmed liver fibrosis. METHODS AND RESULTS: Hepatic screening of consecutive patients consisted of a blood panel, ultrasonography, elastography, contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) scan, and liver biopsy (scored with Fontan specific fibrosis scores and collagen proportionate area; CPA). Fibrosis parameters, varices, ascites, and splenomegaly were measured on imaging. Thirty-eight of 49 referred patients (27 ± 6.6 years, 73.7% male) underwent the complete screening protocol. Liver fibrosis on biopsy was present in all patients, and classified as severe (Stages 3-4) in 68%. Median CPA was 22.5% (16.9-29.5) and correlated with individual fibrosis scores. ELF® and liver stiffness were elevated, but MELD-XI scores were low in all patients. Fibrosis severity neither correlated to ELF® and liver stiffness, nor to (semi-) quantitative fibrosis parameters on MRI/CT. Varices were present in 50% and hyperenhancing nodules in 25% of patients, both independent of fibrosis stage, but varices were associated with higher CPA values. CONCLUSION: The FALD spectrum includes both hepatic congestion and severe fibrosis, with signs of portal hypertension and hyperenhancing nodules as significant manifestations. Routine imaging, transient elastography, and serum biomarkers are unable to accurately assess severity of liver fibrosis in this cohort. Future research should focus on validating new diagnostic tools with biopsy as the reference standard.

Child-Pugh Classification: Time to Abandon?

The Child-Pugh classification is one of the commonest and oldest bedside tools utilized in estimating prognosis in patients with cirrhosis. However, its usage as a risk prediction tool or indeed a decision-making tool should be revisited. In this review, we discuss some inherent issues with the Child-Pugh classification and present a few contexts in which the current usage of Child-Pugh warrants reassessment, elaborating on its utility in acute variceal bleeding, specifically its role in decision-making on early transjugular intrahepatic portosystemic shunt, as well as its use in the context of hepatocellular carcinoma and drug development and dose adjustment.

Evaluation and comparison of thirty noninvasive models for diagnosing liver fibrosis in chinese hepatitis B patients.

The limitations of liver biopsy have led to the development of indirect noninvasive models for liver fibrosis assessment. We aimed to evaluate and compare the performance of 30 noninvasive models to predict fibrosis stage in treatment-naïve and treated chronic hepatitis B (CHB) patients. A total of 576 Chinese treatment-naïve CHB patients and 236 treated CHB patients who had undergone percutaneous liver biopsy were included in the analysis. Histological grading and staging was assessed by the Ishak scoring system. The diagnostic accuracies of 30 noninvasive models were assessed by area under the receiver operating characteristic curves (AUROCs). In treatment-naïve CHB patients, the AUROCs of the 30 noninvasive models for discriminating significant fibrosis (SF) were less than 0.800, and only the AUROC of the PP score for diagnosing advanced fibrosis (AF) was more than 0.800, while the AUROCs of FIB-4, FibroQ, HB-F, Lok index, PHP score and PP score for predicting cirrhosis were greater than 0.800. In treated CHB patients, only the AUROCs of APRI, GUCI, King's score and Wang I for identifying cirrhosis were more than 0.800. The Spearman correlation analysis identified that only the changes in FCI and Virahep-C model values were weakly correlated with changes in Ishak fibrosis scores before and after treatment (r = 0.206, p = 0.008; r = 0.187, p = 0.016, respectively). In conclusion, in Chinese CHB patients, the 30 existing noninvasive models were not suitable for assessing each stage of fibrosis except cirrhosis before and after antiviral therapy, especially in gauging progression and regression of liver fibrosis following therapy.

Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients.

PURPOSE: We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. METHODS: This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics (ROC) curves. RESULTS: 238 HIV/HCV co-infected and 1937 HCV mono-infected patients were included. Performances of FIB-4 and APRI for the detection of significant fibrosis and cirrhosis proved to be unsatisfactory, with very high false negative and false positive rates among both cohorts. No significant differences were found after stratification of HIV/HCV co-infected patients for BMI < or ≥ 25, ALT < or ≥ 40 IU/L, ALT < or ≥ 80 IU/L, and presence/absence of a bright liver echo pattern on ultrasonography. CONCLUSIONS: Differently from other studies, we detected the unreliability of APRI and FIB-4 for the assessment of liver fibrosis in both HCV mono-infected and HIV/HCV co-infected patients.

Diagnostic Accuracy of Acoustic Radiation Force Impulse (ARFI) and Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein (WFA⁺-M2BP) in Patients with Chronic Liver Disease.

BACKGROUND The present study assessed and compared the diagnostic accuracy of elastography (acoustic radiation force impulse, ARFI) with that of Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA⁺-M2BP) for estimating the stage of hepatic fibrosis in chronic liver disease patients. MATERIAL AND METHODS This retrospective cross-sectional study enrolled 70 chronic liver disease patients who underwent hepatectomy for hepatic tumors. ARFI and WFA⁺-M2BP serum level, underlying liver disease, and laboratory data for all patients were recorded. The stage of fibrosis was determined from a surgical specimen. The area under the receiver operating characteristic (ROC) curves (AUC) was measured to compare the diagnostic accuracy. RESULTS The ARFI and serum WFA⁺-M2BP levels had good performances for detecting severe fibrosis (≥F3). The AUC in characterization of fibrosis stage ≥F3 was 0.79 for ARFI and 0.71 for serum WFA⁺-M2BP levels. When comparing the diagnostic performances between ARFI and serum WFA⁺-M2BP levels for the severity of fibrosis stage, no significant differences were found. Then all patients were divided into 2 subgroups, the AUC for serum WFA⁺-M2BP levels was higher in the hepatitis C virus (HCV) subgroup than in the hepatitis B virus (HBV) subgroup when characterizing fibrosis stages ≥F3. CONCLUSIONS WFA⁺-M2BP is an accurate biomarker and is as good as ARFI in detecting severe fibrosis for chronic liver disease patients.

Diagnostic Method of Liver Cirrhosis Based on MR Image Texture Feature Extraction and Classification Algorithm.

In order to improve the accuracy of cirrhosis staging diagnosis based on MR images, a diagnostic method combining image texture feature extraction and classification algorithm is proposed. Firstly, the liver MR image is preprocessed, the region of interest (ROI) image patch is extracted therefrom, and the ROI image is quantized and compressed by the Lloyd algorithm. Then, the ROI image is filtered by a local binary pattern (LBP) operator, and then the texture feature of a 20-dimensional gray-level co-occurrence Matrix (GLCM) in four directions on the LBP image is extracted. Finally, MR image is classified by performing support vector machine (SVM) and the final diagnosis of liver cirrhosis is obtained. The experimental results show that the proposed method can accurately diagnose liver cirrhosis.

Determination of liver fibrosis stages in Egyptian chronic hepatitis B patients by a noninvasive tool

Background/aim: Hepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF). The prognosis and management of patients with chronic hepatitis B virus depend on the amount and progression of liver fibrosis. Angiopoietin-like protein 2 (Angptl2) is not only a chronic inflammatory mediator, but also a tissue-remodeling factor. The aim of this study is to explore the predictive value of Angptl2 in different fibrosis stages in patients chronically infected with HBV. Materials and methods: Eighty patients with chronic HBV infection undergoing Fibroscan were included. Serum concentrations of Angptl2 were detected using a commercial ELISA kit. Results: Angptl2 levels were significantly associated with liver fibrosis stages (P = 0.02). The area under the curve (AUC) of Angptl2 for distinguishing patients who showed significant fibrosis (F2­F4) was70.2%. Angptl2 with fibrosis-4 (FIB-4) and Angptl2 with AST/platelets ratio (APRI) performed best with an AUC of 92.5%. Conclusion: In patients with chronic HBV infection, Angptl2 level represents a potential biomarker independently associated with fibrosis stages. The combination of Angptl2 with FIB-4 or Angptl2 with APRI performed better than the existing models for diagnosing significant fibrosis.

Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosis.

BACKGROUND & AIMS: The main stages of cirrhosis (compensated and decompensated) have been sub-staged based on clinical, endoscopic, and portal pressure (determined by the hepatic venous pressure gradient [HVPG]) features. Vasodilation leading to a hyperdynamic circulatory state is central in the development of a late decompensated stage, with inflammation currently considered a key driver. We aimed to assess hepatic/systemic hemodynamics and inflammation (by C-reactive protein [CRP]) among the different sub-stages of cirrhosis and to investigate their interrelationship and prognostic relevance. METHODS: A single center, prospective cohort of patients with cirrhosis undergoing per protocol hepatic and right-heart catheterization and CRP measurement, were classified into recently defined prognostic stages (PS) of compensated (PS1: HVPG ≥6 mmHg but <10 mmHg; PS2: HVPG ≥10 mmHg without gastroesophageal varices; PS3: patients with gastroesophageal varices) and decompensated (PS4: diuretic-responsive ascites; PS5: refractory ascites) disease. Cardiodynamic states based on cardiac index (L/min/m2) were created: relatively hypodynamic (<3.2), normodynamic (3.2-4.2) and hyperdynamic (>4.2). RESULTS: Of 238 patients, 151 were compensated (PS1 = 25; PS2 = 36; PS3 = 90) and 87 were decompensated (PS4 = 48; PS5 = 39). Mean arterial pressure decreased progressively from PS1 to PS5, cardiac index increased progressively from PS1-to-PS4 but decreased in PS5. HVPG, model for end-stage liver disease (MELD), and CRP increased progressively from PS1-to-PS5. Among compensated patients, age, HVPG, relatively hypodynamic/hyperdynamic state and CRP were predictive of decompensation. Among patients with ascites, MELD, relatively hypodynamic/hyperdynamic state, post-capillary pulmonary hypertension, and CRP were independent predictors of death/liver transplant. CONCLUSIONS: Our study demonstrates that, in addition to known parameters, cardiopulmonary hemodynamics and CRP are predictive of relevant outcomes, both in patients with compensated and decompensated cirrhosis. LAY SUMMARY: There are two main stages in cirrhosis, compensated and decompensated, each with a main relevant outcome. In compensated cirrhosis the main relevant outcome is the development of ascites, while in decompensated cirrhosis it is death. Major roles of cardiac dysfunction and systemic inflammation have been hypothesized in the evolution of the disease in decompensated patients. In this study, we have shown that these factors were also involved in the progression from compensated to decompensated stage.

Progression and regression of fibrosis in viral hepatitis in the treatment era: the Beijing classification.

In this new era of successful long term suppression of hepatitis B viral replication and consistent eradication of hepatitis C virus the necessity for routine pre-treatment biopsies has often been eliminated. Thus, whether there is utility to perform liver biopsy in chronic viral hepatitis is undergoing re-examination. In response to these changing needs, we have developed a new staging system, the Beijing Classification, for assessment of biopsy specimens from patients with chronic viral hepatitis. The most important novelty of the Beijing Classification is that it includes not only extent (stage) of fibrosis, but the quality of fibrosis, namely if the specimen shows predominantly regressive vs. progressive features (or is indeterminantly balanced between the two), the P-I-R score. This histologic distinction between regressive and progressive fibrosis, while invoked in this particular setting of chronic viral hepatitis, may have applicability to all forms of chronic liver disease. Thus, the review contains a description of the concepts of regression and progression with the aim of empowering pathologists to apply them in histopathologic-clinical correlation research as well as in the specific clinical setting for which it was developed. Also, in light of changing clinical needs, grading of necroinflammatory activity and staging of fibrosis are simplified into three point scales. These simplifications should aid the general diagnostic pathologist in being comfortable and confident in assessing biopsy specimens as the criteria for their distinction are far more precise, with significantly reduced "gray zones" of prior grading/staging systems.

Recommendation for terminology: Nodules without arterial phase hyperenhancement and with hepatobiliary phase hypointensity in chronic liver disease.

LEVEL OF EVIDENCE: 5 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2018;47:1169-1171.

Taurocholic acid is an active promoting factor, not just a biomarker of progression of liver cirrhosis: evidence from a human metabolomic study and in vitro experiments.

BACKGROUND: Previous studies have indicated that bile acid is associated with progression of liver cirrhosis. However, the particular role of specific bile acid in the development of liver cirrhosis is not definite. The present study aims to identify the specific bile acid and explore its possible mechanisms in promoting liver cirrhosis. METHODS: Thirty two cirrhotic patients and 27 healthy volunteers were enrolled. Age, gender, Child-Pugh classification and serum of patients and volunteers were collected. Liquid chromatography tandem mass spectrometry (LC-MS) was utilized to determine concentrations of 12 bile acids in serum. Principal component analysis, fold change analysis and heatmap analysis were used to identify the most changed bile acid. And pathway analysis was used to identify the most affected pathway in bile acid metabolism. Spearman rank correlation analysis was employed to assess correlation between concentrations of bile acids and Child-Pugh classification. Hepatic stellate cells (LX-2) were cultured in DMEM. LX-2 cells were also co-cultured with HepG2 cells in the transwell chambers. LX-2 cells were treated with Na+/taurocholate in different concentrations. Western blot was used to evaluate the expression of alpha smooth muscle actin (α-SMA), type I collagen, and Toll-like receptor 4 (TLR4) in LX-2 cells. RESULTS: Concentrations of 12 bile acids in serum of patients and healthy volunteers were determined with LC-MS successively. Principal component analysis, fold change analysis and heatmap analysis identified taurocholic acid (TCA) to be the most changed bile acid. Pathway analysis showed that TCA biosynthesis increased significantly. Spearman rank correlation analysis showed that concentration of TCA in serum of cirrhotic patients was positively associated with Child-Pugh classification. TCA increased the expression of α-SMA, type I collagen, and TLR4 in LX-2 cells. Moreover, the above effect was strengthened when LX-2 cells were co-cultured with HepG2 cells. CONCLUSIONS: Increased TCA concentration in serum of liver cirrhotic patients is mainly due to increased bile acid biosynthesis. TCA is an active promoter of the progression of liver cirrhosis. TCA promoting liver cirrhosis is likely through activating hepatic stellate cells via upregulating TLR4 expression. TCA is a potential therapeutic target for the prevention and treatment of liver cirrhosis.

Non-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis.

Underlying liver cirrhosis is present in most patients with hepatocellular carcinoma, and liver transplantation is the only treatment strategy to cure both diseases. All other hepatocellular carcinoma treatment strategies have to take into account residual liver function that concurs with the patient's prognosis and might limit their feasibility. In patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B (CPT-B), owing to borderline liver function, any intervention might be offset by liver function deterioration. In this setting, the decision for hepatocellular carcinoma treatment requires a comprehensive assessment of liver function, not restricted to the CPT classification, in addition to a careful evaluation of the prognostic effect of hepatocellular carcinoma compared with cirrhosis. In this Review, we provide an overview of the literature regarding the benefits and harms of non-transplant therapies in patients with hepatocellular carcinoma and CPT-B cirrhosis.