GP73 level in patients with chronic hepatitis B: Relationship with liver biopsy, levels of ALT, AST and HBV DNA.

BACKGROUND/AIMS: In this study, we investigated the Golgi protein 73 (GP73) level in Hepatitis B and determined the correlation between Hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, and liver histopathology. Materials and. METHODS: GP73 levels were estimated by enzyme-linked immunosorbent assay in serum samples from patients. Liver biopsy specimens were examined by the same pathologist. RESULTS: : This study included a total of 127 patients who underwent liver biopsy. Of patients, 85% were HBeAg negative. HBV DNA level was median 134667 IU/mL (2247-170000000 IU/mL), Liver biopsy results revealed a mean Histological Activity Index (HAI) grade of 7.7 ± 3.4 and a mean fibrosis stage of 2.25 ± 1.06 gr/dL. GP73 was as follows: a mean of 14.8 ± 7.9 ng/mL and a median of 12.9 (4.8-50.1) ng/mL. A weak correlation between GP73 level and AST (r = 0.236, P = 0.11), fibrosis stage (r = 0.287, P = 0.002), and HAI grade (r = 0.218, P = 0.016) was noted. No statistically significant correlation was detected between GP73 and ALT (r = 0.16, P = 0.08), HBV DNA (r = 0.13, P = 0.08). CONCLUSION: Although recent studies revealed a strong correlation and increased GP73 levels in accordance with HAI scores and the fibrosis grade of liver, we detected a weak correlation between serum GP73 levels and HAI scores, fibrosis stage, and AST. This may be due to the insufficient number of patients with higher HAI grading and fibrosis staging in our study. Therefore, we concluded that, in cases of low-moderate fibrosis and HAI grading, GP73 seemed not to be useful and a reliable marker to replace liver biopsy.

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.

Using vibration controlled transient elastography and FIB-4 to assess liver cirrhosis in a hepatitis C virus infected population.

ABSTRACT: We assessed the performance characteristics of the Fibrosis-4 (FIB-4) score in a veteran population with chronic hepatitis C virus (HCV) infection and used vibration controlled transient elastography (VCTE) as the gold standard.All VCTE studies were performed by a single operator on United States veterans with HCV infection presenting for care at the Atlanta VA Medical Center (AVAMC) over a 2 year period. VCTE liver stiffness measurements (LSM) were categorized as cirrhotic if LSM was >12.5 kPa and non-cirrhotic if LSM was ≤12.5 kPa. FIB-4 scores ≤3.25 were considered non-cirrhotic and scores >3.25 were considered cirrhotic. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the FIB-4 score. A second analysis was done which identified and excluded indeterminate FIB-4 scores, defined as any value between 1.45 and 3.25.When FIB-4 was used to screen for liver cirrhosis using VCTE as the gold standard, sensitivity was 42%, specificity was 88%, PPV was 62%, and NPV was 76%. When indeterminate FIB-4 scores were excluded from the analysis, sensitivity was 95%, specificity was 61%, PPV was 62%, and NPV was 94.4%. In a veteran population with chronic HCV infection, we found the sensitivity of the FIB-4 score to be unacceptably low for ruling out liver cirrhosis when using a binary cutoff at 3.25. Using a second staging method like VCTE may be an effective way to screen for liver cirrhosis in persons with chronic HCV, especially when the FIB-4 score is in the indeterminate range.

ACR appropriateness criteria radiologic management of portal hypertension

Cirrhosis is a heterogeneous disease that cannot be studied as a single entity and is classified in two main prognostic stages: compensated and decompensated cirrhosis. Portal hypertension, characterized by a pathological increase of the portal pressure and by the formation of portal-systemic collaterals that bypass the liver, is the initial and main consequence of cirrhosis and is responsible for the majority of its complications. A myriad of treatment options exists for appropriately managing the most common complications of portal hypertension, including acute variceal bleeding and refractory ascites. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis.

BACKGROUND AND AIMS: The usefulness of APRI or FIB-4 is well established as a non-invasive liver fibrosis marker at a point of diagnosis in patients with chronic liver disease. However, their applicability for the monitoring of progression of liver fibrosis over time is yet to be determined. We aimed to clarify the feasibility of APRI and FIB-4 for the longitudinal evaluation of liver fibrosis in patients with chronic hepatitis B and C. METHODS: This is a multi-center retrospective and prospective cohort study, enrolling 1029 patients with HCV and 384 patients with HBV who were histologically diagnosed by liver biopsy. The observation period of retrospective and prospective study was 14 and 12 years, respectively. The APRI and FIB-4 were traced back in cases of histologically diagnosed cirrhosis, and those were prospectively analyzed after biopsy in cases diagnosed as F3 of METAVIR score, respectively. RESULTS: The averaged APRI and FIB-4 exhibited time-dependent increase in the retrospective study of hepatitis C patients (increase by 0.09/year in APRI and 0.29/year in FIB-4). In the prospective study of untreated hepatitis C patients, such increases were 0.14/year in APRI and 0.40/year in FIB-4, respectively. Neither the average of APRI nor FIB-4 showed a specific tendency with hepatitis B patients and treatment-experienced hepatitis C patients. CONCLUSION: The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.

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.

Clinical significance of serum human epididymis protein 4 in liver fibrosis: An experimental study.

BACKGROUND: Human epididymis protein 4 (HE4) has been identified as marker for renal fibrosis. Present study aimed to investigate the clinical significance of serum HE4 in liver fibrosis. METHODS: Serum from 65 liver fibrosis patients, 68 hepatic patients without fibrosis, and 50 controls was collected respectively. Serum HE4 levels were measured by chemiluminescence immunoassay and compared among the groups. The relationships between serum HE4 levels and the clinical characteristics of liver fibrosis were also analyzed. A receiver operator characteristic curve was plotted to investigate the diagnostic efficacy of serum HE4 for liver fibrosis. Child-Pugh (C-P) score and liver fibrosis score were also evaluated. Data were analyzed by statistical software 13.0. RESULTS: Serum HE4 levels were significantly higher in liver fibrosis than that of controls [105.35 (82.64, 164.18) vs 46.2 (39.9, 58.9) pmol L, P = .00] and hepatic patients without liver fibrosis [105.35 (82.64, 164.18) vs 51.00 (44.02, 65.65) pmol L, P < .01]; Serum HE4 levels in liver fibrosis patients with C-P class C were significantly higher than those with C-P class A [143.75 (106.50, 186.08) vs 81.42 (69.73, 99.26) pmol L, P = .005] and C-P class B [143.75 (106.50, 186.08) vs 113.10 (88.92, 169.50) pmol L, P = .01]; the diagnostic sensitivity and specificity of serum HE4 levels for liver fibrosis detection were 87.5% and 81.1%, at a cutoff value of 69 pmol L; Serum HE4 levels in alcoholic liver fibrosis were higher than that of liver fibrosis with hepatitis B virus infection [131.30 (100.67, 228.35) vs 89.46 (73.74, 116.45) pmol L, P < .01]. CONCLUSION: Serum HE4 was closely correlated with C-P class and might be a potential marker for liver fibrosis.

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.

Image Processing Pipeline for Liver Fibrosis Classification Using Ultrasound Shear Wave Elastography.

The purpose of this study was to develop an automated method for classifying liver fibrosis stage ≥F2 based on ultrasound shear wave elastography (SWE) and to assess the system's performance in comparison with a reference manual approach. The reference approach consists of manually selecting a region of interest from each of eight or more SWE images, computing the mean tissue stiffness within each of the regions of interest and computing a resulting stiffness value as the median of the means. The 527-subject database consisted of 5526 SWE images and pathologist-scored biopsies, with data collected from a single system at a single site. The automated method integrates three modules that assess SWE image quality, select a region of interest from each SWE measurement and perform machine learning-based, multi-image SWE classification for fibrosis stage ≥F2. Several classification methods were developed and tested using fivefold cross-validation with training, validation and test sets partitioned by subject. Performance metrics were area under receiver operating characteristic curve (AUROC), specificity at 95% sensitivity and number of SWE images required. The final automated method yielded an AUROC of 0.93 (95% confidence interval: 0.90-0.94) versus 0.69 (95% confidence interval: 0.65-0.72) for the reference method, 71% specificity with 95% sensitivity versus 5% and four images per decision versus eight or more. In conclusion, the automated method reported in this study significantly improved the accuracy for ≥F2 classification of SWE measurements as well as reduced the number of measurements needed, which has the potential to reduce clinical workflow.

Nonalcoholic Fatty Liver Disease: An Important Consideration for Primary Care Providers in Hawai'i.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is a broad term for both non-alcoholic fatty liver (NAFL), which describes simple fatty liver without inflammation, and non-alcoholic steatohepatitis (NASH), the more severe phenotype with hepatocellular inflammation. The population of Hawai'i is particularly vulnerable to the NAFLD and obesity epidemics due to its large proportions of high-risk ethnic minorities exposed to varying degrees of westernization. Unfortunately, primary care providers (PCPs) often face a lack of awareness on the diagnosis and disease spectrum of NAFLD. Early initiation of treatment for NAFLD is crucial to slow its progression and prevent liver-related morbidity and mortality. This review aims to raise awareness for NAFLD among PCPs in Hawai'i by summarizing the disease's epidemiology, diagnosis, and treatment. The diagnostic workup of NAFLD in the primary care setting involves exclusion of other liver disease etiologies and staging assessment of fibrosis and steatosis through non-invasive means such as serum biomarkers or elastography. Patients with overt signs and symptoms of cirrhosis or a high likelihood of advanced hepatic fibrosis should be referred to liver disease specialists. The role of PCPs in NAFLD management involves facilitating weight loss through therapeutic lifestyle modifications and treatment of comorbid cardiovascular conditions. Evidence-based pharmacologic therapies for NAFLD are available, such as vitamin E and pioglitazone, with more currently in development.

Plasma IP-10 and IL-6 are linked to Child-Pugh B cirrhosis in patients with advanced HCV-related cirrhosis: a cross-sectional study.

We aimed to evaluate the association of plasma biomarkers linked to inflammation (bacterial translocation, inflammatory response, and endothelial dysfunction), coagulopathy, and angiogenesis with the severity of liver cirrhosis (assessed by the Child-Pugh-Turcotte score, CTP) and Child-Pugh B cirrhosis (CTP 7-9) in patients with advanced hepatitis C virus (HCV)-related cirrhosis. We carried out a cross-sectional study in 97 patients with advanced HCV-related cirrhosis (32 HCV-monoinfected and 65 HIV/HCV-coinfected). Plasma biomarkers were measured by ProcartaPlex multiplex immunoassays. The outcome variable was the CTP score and the Child-Pugh B cirrhosis (CTP 7-9). HIV/HCV-coinfected patients and HCV-monoinfected patients with advanced HCV-related cirrhosis had near-equivalent values of plasma biomarkers. Higher values of plasma biomarkers linked to an inflammatory response (IP-10, IL-8, IL-6, and OPG), endothelial dysfunction (sVCAM-1 and sICAM-1), and coagulopathy (D-dimer) were related to higher CTP values. The most significant biomarkers to detect the presence of Child-Pugh B cirrhosis (CTP 7-9) were IP-10 (p-value= 0.008) and IL-6 (p-value=0.002). The AUC-ROC values of IP-10, IL-6, and both biomarkers combined (IP-10+IL-6) were 0.78, 0.88, and 0.96, respectively. In conclusion, HIV infection does not appear to have a significant impact on the analyzed plasma biomarkers in patients with advanced HCV-related cirrhosis. However, plasma biomarkers linked to inflammation (inflammatory response and endothelial dysfunction) were related to the severity of liver cirrhosis (CTP score), mainly IP-10 and IL-6, which discriminated patients with Child-Pugh B concerning Child-Pugh A.

Prevalence of steatosis and fibrosis in young adults in the UK: a population-based study.

BACKGROUND: The estimated worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) in adults is 25%; however, prevalence in young adults remains unclear. We aimed to identify the prevalence of steatosis and fibrosis in young adults in a sample of participants recruited through the Avon Longitudinal Study of Parents and Children (ALSPAC), based on transient elastography and controlled attenuation parameter (CAP) score. METHODS: In this population-based study, we invited active participants of the ALSPAC cohort to our Focus@24+ clinic at the University of Bristol (Bristol, UK) between June 5, 2015, and Oct 31, 2017, for assessment by transient elastography with FibroScan, to determine the prevalence of steatosis and fibrosis. FibroScan data were collected on histologically equivalent fibrosis stage (F0-F4) and steatosis grade (S0-S3); results with an IQR to median ratio of 30% or greater were excluded for median fibrosis results greater than 7·1 kPa, and CAP scores for steatosis were excluded if less than ten valid readings could be obtained. Results were collated with data on serology (including alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase) and exposures of interest: alcohol consumption (via the Alcohol Use Disorder Identification Test for Consumption [AUDIT-C] and the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for alcohol use disorder), body-mass index (BMI), waist-to-height ratio, socioeconomic status (based on predefined ALSPAC markers), and sex. We used logistic regression models to calculate odds ratios (ORs) for the effect of exposures of interest on risk of steatosis and fibrosis, after dichotomising the prevalences of fibrosis and steatosis and adjusting for covariates (excessive alcohol intake [hazardous drinking, AUDIT-C score ≥5; or harmful drinking, evidence of alcohol use disorder], social class, smoking, and BMI). FINDINGS: 10 018 active ALSPAC participants were invited to our Focus@24+ clinic, and 4021 attended (1507 men and 2514 women), with a mean age of 24·0 years (IQR 23·0-25·0). 3768 CAP scores were eligible for analysis. 780 (20·7% [95% CI 19·4-22·0]) participants had suspected steatosis (S1-S3; ≥248 dB/m), with 377 (10·0%) presenting with S3 (severe) steatosis (≥280 dB/m). A BMI in the overweight or obese range was positively associated with steatosis when adjusted for excessive alcohol consumption, social class, and smoking (overweight BMI: OR 5·17 [95% CI 4·11-6·50], p<0·0001; obese BMI: 27·27 [20·54-36·19], p<0·0001). 3600 participants had valid transient elastography results for fibrosis analysis. 96 participants (2·7% [95% CI 2·2-3·2]) had transient elastography values equivalent to suspected fibrosis (F2-F4; ≥7·9 kPa), nine of whom had values equivalent to F4 fibrosis (≥11·7 kPa). Individuals with alcohol use disorder and steatosis had an increased risk of fibrosis when adjusted for smoking and social class (4·02 [1·24-13·02]; p=0·02). INTERPRETATION: One in five young people had steatosis and one in 40 had fibrosis around the age of 24 years. The risk of fibrosis appears to be greatest in young adults who have harmful drinking patterns and steatosis. A holistic approach to the UK obesity epidemic and excessive drinking patterns is required to prevent an increasing health-care burden of adults with advanced liver disease in later life. FUNDING: Medical Research Council UK, Alcohol Change UK, David Telling Charitable Trust.

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.

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.

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.