Machine learning for individualized prediction of hepatocellular carcinoma development after the eradication of hepatitis C virus with antivirals.

BACKGROUND AND AIMS: Accurate risk stratification for hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) is necessary for optimal surveillance. We aimed to develop and validate a machine learning (ML) model to predict the risk of HCC after achieving an SVR in individual patients. METHODS: In this multicenter cohort study, 1742 patients with chronic hepatitis C who achieved an SVR were enrolled. Five ML models were developed including DeepSurv, gradient boosting survival analysis, random survival forest (RSF), survival support vector machine, and a conventional Cox proportional hazard model. Model performance was evaluated using Harrel' c-index and was externally validated in an independent cohort (977 patients). RESULTS: During the mean observation period of 5.4 years, 122 patients developed HCC (83 in the derivation cohort and 39 in the external validation cohort). The RSF model showed the best discrimination ability using seven parameters at the achievement of an SVR with a c-index of 0.839 in the external validation cohort and a high discriminative ability when the patients were categorized into three risk groups (P <0.001). Furthermore, this RSF model enabled the generation of an individualized predictive curve for HCC occurrence for each patient with an app available online. CONCLUSIONS: We developed and externally validated an RSF model with good predictive performance for the risk of HCC after an SVR. The application of this novel model is available on the website. This model could provide the data to consider an effective surveillance method. Further studies are needed to make recommendations for surveillance policies tailored to the medical situation in each country. IMPACT AND IMPLICATIONS: A novel prediction model for HCC occurrence in patients after hepatitis C virus eradication was developed using machine learning algorithms. This model, using seven commonly measured parameters, has been shown to have a good predictive ability for HCC development and could provide a personalized surveillance system.

Endoscopic balloon dilation for the prevention of severe strictures caused by acute esophageal necrosis.

A 58-year-old man who had the history of alcohol dependence was referred to our emergency center due to severe nausea, vomiting, and subsequent onset of chest and back pain. Esophagogastroduodenoscopy (EGD) showed black-appearing esophagus mucosa extending from the cervical esophagus to the esophagogastric junction with clear margins, a condition typically referred to as a black esophagus. Alcohol abuse was considered an important factor associated with acute esophageal necrosis in this patient. After admission, he received fluid resuscitation and proton-pump inhibitors, with restriction of oral intake and treatment of alcohol dependence. Follow-up EGDs and endoscopic balloon dilation were performed for the management of esophageal narrowing before the development of severe strictures. Strictures were successfully treated endoscopically without complications such as perforation.

Reevaluation of Gastric Cancer Screening by Levin's Equation.

INTRODUCTION: This study aimed to reevaluate the effectiveness of fluoroscopy and endoscopy in reducing gastric cancer mortality at the population level. METHODS: Crude and age-adjusted mortality rates of gastric cancer and the introduction rates of gastric cancer screening were extracted from the Cancer Registry and Statistics database. The population-attributable risk (PAR) percent of no screening for gastric cancer mortality was calculated using Levin's equation. The PAR of each mortality rate in the no-screening group was estimated as follows: mortality × PAR%. The Jonckheere-Terpstra test for trends and linear regression were performed to compare the PAR of gastric cancer mortality rates among the decades. RESULTS: The PAR of crude and age-adjusted mortality rates in the no-screening group significantly decreased in the total population ( P for trend <0.001), as well as individually in the male ( P for trend <0.001) and female ( P for trend <0.001) populations. The PAR of the crude mortality rate in the female population significantly decreased in 2000-2009 and 2010-2019, compared with that in 1980-1989. There was no significant difference in the PAR of crude mortality rate in the male population among the decades. The PAR of the age-adjusted mortality rate significantly decreased in 2000-2009 and 2010-2019, compared with that in 1980-1989, in the male and female populations. DISCUSSION: PAR% and PAR of no screening for gastric cancer mortality could be estimated using Levin's equation, and the effectiveness of the present gastric cancer screenings with fluoroscopy and endoscopy has been decreasing, especially in the female population.

Impact of Obesity and Heavy Alcohol Consumption on Hepatocellular Carcinoma Development after HCV Eradication with Antivirals.

BACKGROUND AND AIMS: It remains unclear whether obesity increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C who achieved a sustained virological response (SVR) with antiviral therapy. METHODS: In this multicenter cohort study, we enrolled patients with chronic hepatitis C who achieved SVR with interferon (IFN)-based therapy (IFN group) or direct-acting antiviral (DAA) therapy (DAA group) between January 1, 1990, and December 31, 2018. The patients underwent regular surveillance for HCC. Cumulative incidence of and the risk factors for HCC development after SVR were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis, respectively. RESULTS: Among 2,055 patients (840 in the IFN group and 1,215 in the DAA group), 75 developed HCC (41 in the IFN group and 34 in the DAA group) during the mean observation period of 4.1 years. The incidence rates of HCC at 1, 2, and 3 years were 1.2, 1.9, and 3.0%, respectively. Multivariate analysis revealed that in addition to older age, lower albumin level, lower platelet count, higher alpha-fetoprotein level, and absence of dyslipidemia, obesity (body mass index ≥25 kg/m2) and heavy alcohol consumption (≥60 g/day) were independent risk factors for HCC development, with adjusted hazard ratio (HR) of 2.53 (95% confidence interval [CI]: 1.51-4.25) and 2.56 (95% CI: 1.14-5.75), respectively. The adjusted HR was not significant between the 2 groups (DAA vs. IFN; HR 1.19, 95% CI: 0.61-2.33). CONCLUSIONS: Obesity and heavy alcohol consumption increased the risk of HCC development after SVR.

[Edema in liver disease].

Patients with advanced cirrhosis show an abnormal regulation of extracellular fluid volume, resulting in the accumulation of fluid as ascites or edema. As portal hypertension develops, splanchnic arterial vasodilation also does due mainly to the production of nitric oxide (NO). Splanchnic arterial vasodilation decreases effective arterial blood volume, leading to fluid accumulation and renal function abnormalities which are a consequence of the homeostatic activation of vasoconstrictor and antinatriuretic factors. And the net effect is retention of sodium and water as well as renal vasoconstriction. The portal hypertension and splanchnic hyperdynamic circulation elevate the pressure of the splanchnic capillary circulation, leading to the accumulation of retained fluid as ascites.

Antiproliferative property of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5.

BACKGROUND & AIMS: Sphingosine 1-phosphate (S1P), a ligand for G protein-coupled endothelial differentiation gene-1 (Edg-1), Edg-3, Edg-5, Edg-6, and Edg-8, elicits a variety of responses by cells. Prominent among these is cell proliferation. S1P is abundantly stored in platelets and released upon their activation, suggesting that S1P plays a pathophysiologic role in vivo. Because the major part of injected S1P was distributed into the liver in mice, we wondered whether the liver would be one of its targets. The effects of S1P on hepatocytes, the major constituent cells in the liver, were examined. METHODS & RESULTS: Northern blot analysis revealed the expression of Edg-1 and Edg-5 messenger RNA (mRNA) in cultured rat hepatocytes, in which S1P decreased DNA synthesis induced by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) without affecting total protein synthesis. This inhibitory effect was attenuated by inactivation of small GTPase Rho with C3 exotoxin but not by inactivation of G(i) with pertussis toxin. Moreover, in the presence of JTE-013, a newly developed and specific binding antagonist for Edg-5, the inhibitory effect was also cancelled. Finally, the administration of S1P after 70% partial hepatectomy in rats reduced the peak of DNA synthesis in hepatocytes with increased Rho activity. Furthermore, Edg-5 but not Edg-1 mRNA expression was enhanced in hepatocytes 24-72 hours after partial hepatectomy, which coincides with decreasing hepatocyte proliferation. CONCLUSIONS: S1P has an antiproliferative property in rat hepatocytes by activating Rho via Edg-5. Our results raise the possibility that S1P is a negative regulator in liver regeneration.