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.

A study on prevention of bleeding complications using lusutrombopag for safe RFA in patients with hepatocellular carcinoma with low platelet counts: prospective observational study.

BACKGROUND: Platelet (PLT) transfusion was the most practical way to increase patients' PLT counts before invasive hepatic procedures such as radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). A novel drug that raises the PLT count by acting on the thrombopoietin receptor has recently become available. METHODS: Lusutrombopag 3 mg was administered daily for 7 days to patients who underwent RFA for liver tumors with low PLT counts (< 50,000 PLT µL- 1). We collected demographic data concerning the patients' liver function and PLT counts. RESULTS: Lusutrombopag was administered to 91 patients, with a median age of 71 years (range 51-86). Forty-two patients had hepatitis C, 12 had hepatitis B, 21 had alcoholic liver disease, 11 had nonalcoholic steatohepatitis, and five had other diseases. The median Child-Pugh score was 7 (range 5-11). Thirty-seven patients had stage I tumors, 41 had Stage II, 12 had stage III, and one had stage IV. PLT count was elevated from 4.4 × 104 ± 1.4 × 104 to 8.6 × 104 ± 2.5 × 104 PLT µL- 1. Lusutrombopag administration prevented PLT transfusions in 84/91 patients (92%). No patient had bleeding complications after RFA. One had portal thrombosis after lusutrombopag administration. Patients who achieved PLT counts of > 50,000 PLT µL- 1 had higher PLT counts before lusutrombopag administration. The degree of splenomegaly did not affect the rate of PLT count elevation. There was no specific adverse effect by administrating lusutrombopag for patients with PLT counts of around 50,000 µL- 1 but > 50,000 µL- 1. CONCLUSIONS: Lusutrombopag administration before RFA was effective and seemed to be relatively safe for hepatocellular carcinoma patients with low PLT counts. TRIAL REGISTRATION: This study was approved by Japanese Red Cross Medical Center Institutional Reseach Comittie (#862, 07/03/2016), and was registered in a publically accessible primary register (#UMIN000046629, registered date: 14/01/2022).

The Efficacy and Safety of EUS-Guided Gallbladder Drainage as a Bridge to Surgery for Patients with Acute Cholecystitis.

BACKGROUND AND AIM: This study aimed to compare the efficacy and safety of endoscopic ultrasound-guided gallbladder drainage and percutaneous transhepatic gallbladder drainage as a bridge to surgery in patients with acute cholecystitis unfit for urgent cholecystectomy. METHODS: This retrospective study included 46 patients who underwent cholecystectomy following endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) or percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis in NTT Tokyo Medical Center. We surveyed 35 patients as the EUS-GBD group and 11 patients as the PTGBD group, and compared the rate of technical success of the cholecystectomy and periprocedural adverse events. A 7-F, 10-cm double pigtail plastic stent was used for ultrasound-guided gallbladder drainage. RESULTS: The rate of technical success of cholecystectomy was 100% in both groups. Regarding postsurgical adverse events, no significant difference was noted between the two groups (EUS-GBD group, 11.4%, vs. PTGBD group, 9.0%; p = 0.472). CONCLUSIONS: EUS-GBD as a BTS seems to be an alternative for patients with AC because it can ensure lower adverse events. On the other hand, there are two major limitations in this study--the sample size is small and there is a risk of selection bias.

Clinical outcomes of permanent stenting with endoscopic ultrasound gallbladder drainage.

BACKGROUND/AIMS: Endoscopic ultrasound gallbladder drainage (EUS-GBD) is gaining attention as a treatment method for cholecystitis. However, only a few studies have assessed the outcomes of permanent stenting with EUS-GBD. Therefore, we evaluated the clinical outcomes of permanent stenting using EUS-GBD. METHODS: This was a retrospective, single-center cohort study. The criteria for EUS-GBD at our institution are a high risk for surgery, inability to perform surgery owing to poor performance status, and inability to obtain consent for emergency surgery. EUS-GBD was performed using a 7-Fr double-pigtail plastic stent with a dilating device. The primary outcomes were the recurrence-free rate of cholecystitis and the late-stage complication-avoidance rate. Secondary outcomes were technical success, clinical success, and procedural adverse events. RESULTS: A total of 41 patients were included in the analysis. The median follow-up period was 168 (range, 10-1,238) days. The recurrence-free and late-stage complication-avoidance rates during the follow-up period were 95% (38 cases) and 90% (36 cases), respectively. There were only two cases of cholecystitis recurrence during the study period. CONCLUSION: EUS-GBD using double-pigtail plastic stent was safe and effective with few complications, even in the long term, in patients with acute cholecystitis.

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.

New microwave ablation system for unresectable liver tumors that forms large, spherical ablation zones.

BACKGROUND AND AIM: The aim of this study was to assess the efficacy of a new microwave ablation (MWA) system, the Emprint Ablation System, for the ablation of unresectable large liver tumors (≥ 30 mm). METHODS: Twenty-one hepatic tumors (mean diameter, 34.7 mm) from 21 patients who underwent percutaneous MWA were included in this cross-sectional study. A volume analyzer based on computed tomography imaging was used for all patients within the month before and month after the procedure to evaluate the shape and volume of ablation zones. In addition, computed tomography imaging was performed again 3 months after the procedure to evaluate the presence of residual tumors and local recurrence. RESULTS: Mean ablation time was 11.3 min, and mean overall procedure time was 33.4 min. An ablated adrenal gland-induced Takotsubo (stress) cardiomyopathy occurred immediately after MWA as a major complication in one patient. Roundness index A, B, and C presented a mean value of 0.94, 0.94, and 1.01, respectively (all values near 1 is a perfect sphere), indicating that a spherical ablation zone was achieved. The mean ablation volume was larger than the volume of tumors (24.5 vs 41.7 cm3 ). Residual tumors were confirmed in only 4.8% of tumors after a single ablation session. There was no local recurrence. CONCLUSIONS: In our experience, the new MWA system provides an effective treatment option for unresectable large liver tumors. However, to ablate the liver tumors safely, it is necessary to consider the surrounding organs, such as the adrenal glands.

Percutaneous ethanol injection for hepatocellular carcinoma: 20-year outcome and prognostic factors.

BACKGROUND: Ethanol injection is the best-known image-guided percutaneous ablation for hepatocellular carcinoma (HCC) and a well-tolerated, inexpensive procedure with few adverse effects. However, there have been few reports on its long-term results. AIMS: We report a 20-year consecutive case series at a tertiary referral centre. METHODS: We performed 2147 ethanol injection treatments on 685 primary HCC patients and analysed a collected database. RESULTS: Final computed tomography demonstrated complete ablation of treated tumours in 2108 (98.2%) of the 2147 treatments. With a median follow-up of 51.6 months, 5-, 10- and 20-year survival rates were 49.0% [95% confidence interval (CI) = 45.3-53.0%], 17.9% (95% CI = 15.0-21.2%) and 7.2% (95% CI = 4..5-11.5%) respectively. Multivariate analysis demonstrated that age, Child-Pugh class, tumour size, tumour number and serum alpha-fetoprotein level were significant prognostic factors for survival. Five-, 10- and 20-year local tumour progression rates were 18.2% (95% CI = 15.0-21.4%), 18.4% (95% CI = 15.2-21.6%) and 18.4% (95% CI = 15.2-21.6%) respectively. Five-, 10- and 20-year distant recurrence rates were 53.5% (95% CI = 49.4-57.7%), 60.4 (95% CI = 56.3-64.5%) and 60.8% (95% CI = 56.7-64.9%) respectively. There were 45 complications (2.1%) and two deaths (0.09%). CONCLUSIONS: Ethanol injection was potentially curative for HCC, resulting in survival for more than 20 years. This study suggests that new ablation therapies will achieve similar or even better long-term results in HCC.

Is it worthwhile to perform capsule endoscopy for asymptomatic patients with positive immunochemical faecal occult blood test?

BACKGROUND: The immunochemical faecal occult blood test (IFOBT) is widely performed for colorectal cancer screening, but the usefulness of IFOBT in the detection of disorders of the small intestine is unknown. The objective of this study was to investigate what proportion of IFOBT-positive subjects with negative colonoscopy and oesophagogastroduodenoscopy has pathologies of the small intestine detected by capsule endoscopy (CE). METHODS: Between October 2008 and June 2010, asymptomatic IFOBT-positive patients with negative total colonoscopy and oesophagogastroduodenoscopy underwent CE. CE findings were classified into three categories: P0 (no abnormalities, or findings without potential for bleeding), P1 (findings with uncertain potential for bleeding), P2 and (findings with high potential for bleeding). RESULTS: Fifty-three patients (37 males, 16 females; 52.1 ± 13.0 years) were included. There were no cases with P2, 19 cases with P1, and 34 cases with P0 (there were no abnormalities in 25 of 34 cases). As a result, lesions in the small intestine were detected in 28 cases. Additional examination was considered necessary for five patients after CE, but no abnormality was detected, and therapeutic intervention was not undertaken in any case. Caecal completion rate was 92.5%. CONCLUSIONS: No significant pathologies of the small intestine were detected in asymptomatic IFOBT-positive cases with negative colonoscopy and oesophagogastroduodenoscopy. CE is of limited use in asymptomatic patients with positive IFOBT.

A prospective randomized trial of lafutidine vs rabeprazole on post-ESD gastric ulcers.

AIM: To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection (ESD) gastric ulcers. METHODS: Patients with gastric tumors indicated for ESD were prospectively studied. After ESD, all patients were treated with intravenous omeprazole for the first 3 d. Patients were then randomly assigned to oral lafutidine or rabeprazole. Ulcer size, ulcer size reduction rate, and ulcer stage were evaluated 4 wk later. Occurrence of complication was monitored throughout the 4-wk period. RESULTS: Sixty five patients were enrolled in the study, and 60 patients were subjected to the final analysis. In the lafutidine group (30 lesions in 29 patients), initial and 4-wk post-ESD ulcer sizes were 33.3 ± 9.2 and 10.5 ± 4.8 mm, respectively. In the rabeprazole group (34 lesions in 31 patients), the values were 34.7 ± 11.3 and 11.8 ± 6.7 mm, respectively. Ulcer size reduction rates in lafutidine and rabeprazole groups were 32.3% and 33.5%, respectively (P = 0.974). Ulcer stage 4 wk post-ESD did not differ significantly between the two groups (P = 0.868). Two cases in the rabeprazole group and no cases in the lafutidine group developed ulcer bleeding during the oral dose period, although the difference of bleeding rate between the two groups was not statistically significant (P = 0.157). CONCLUSION: Lafutidine and rabeprazole have equivalent therapeutic effects on post-ESD gastric ulcers.

[Diagnosis of small bowel carcinoma by capsule endoscopy].

Now in Japan, the use of capsule endoscopy for small bowel is approved only for the diagnosis of obscure gastrointestinal bleeding. Since the small bowel is anatomically difficult to approach, and small bowel carcinomas are often asymptomatic at early stages, they were usually diagnosed only after symptoms such as intestinal stenosis have developed. The advent of capsule endoscopy, however, enabled us to diagnose small bowel carcinoma at an early stage. However, we must be careful of the risk of capsule retention. The combination of capsule endoscopy, double balloon endoscopy, and traditional examination modalities including radiography or computed tomography will make it possible to diagnose and treat small bowel carcinoma at an early stage, and further progress is expected in this field.

Characteristics of small bowel injury in symptomatic chronic low-dose aspirin users: the experience of two medical centers in capsule endoscopy.

BACKGROUND: The antithrombotic effects of low-dose aspirin (LDA) are well established, and it is used for primary and secondary prevention of cardiovascular events. However, the small intestinal toxicity of LDA remains unclear. The aim of this study was to review the characteristics of small bowel injury in long-term LDA users with capsule endoscopy (CE). METHODS: We retrospectively reviewed all chronic LDA users (>3 months) who underwent CE for suspected small bowel diseases from May 2004 to May 2008 at two medical centers. RESULTS: At our institutions, a total of 22 patients (13 males and 9 females, mean age 66.3 years) taking LDA underwent a CE examination. The indications for CE were obscure gastrointestinal bleeding in 21 patients and 1 patient who had abdominal pain. Twenty-one patients (95.5%) had some small bowel mucosal injury. Small bowel erosions were identified in 14 patients (63.6%). This enteropathy was characterized by multiple petechiae, loss of villi, erosions, and ulcers with round, irregular, and punched-out shapes. Two patients had circumferential ulcers with stricture. In most patients, small bowel lesions were multifocal and were evenly distributed in the small bowel. No patients failed to pass the capsule. CONCLUSIONS: This is the first CE report that has studied the characteristics of small bowel injury in chronic LDA users. CE is useful to diagnose small bowel enteropathy associated with LDA.

Ingesting 500 ml of polyethylene glycol solution during capsule endoscopy improves the image quality and completion rate to the cecum.

The benefits of bowel preparation prior to capsule endoscopy (CE) are controversial. The aim of this study was to examine whether ingesting a small amount of polyethylene glycol (PEG) during, not before, the CE procedure improves the image quality and the cecal completion rate. A prospective single-blind controlled study was conducted including 59 patients. The initial 32 patients (group A) received no preparation, and the subsequent 27 patients (group B) ingested 500 ml of PEG starting 30 min after swallowing the capsule. The capsule reached the cecum in 65.6% of the patients in group A and 88.9% of the patients in group B (P = 0.038). The use of PEG during CE examination significantly improved the image quality, and this effect was more pronounced in the distal ileum. Ingesting a small amount of PEG during CE examination significantly improves both the CE image quality and the cecal completion rate.

Rebleeding rate after interventional therapy directed by capsule endoscopy in patients with obscure gastrointestinal bleeding.

BACKGROUND: The precise role of capsule endoscopy in the diagnostic algorithm of obscure gastrointestinal bleeding has yet to be determined. Despite the higher diagnostic yield of capsule endoscopy, the actual impact on clinical outcome remains poorly defined. The aim of this study was to evaluate the follow-up results of patients with obscure gastrointestinal bleeding to determine which management strategies after capsule endoscopy reduced rebleeding. METHODS: All patients in whom the cause of obscure gastrointestinal bleeding was investigated between May 2004 and March 2007 were studied retrospectively. We evaluated the clinical outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy using the rebleeding rate as the primary outcome. RESULTS: Seventy-seven patients with obscure gastrointestinal bleeding underwent capsule endoscopy. Capsule endoscopy identified clinically significant findings that were thought to be the sources of obscure gastrointestinal bleeding in 58.4% of the patients. The overall rebleeding rate was 36.4%. The rebleeding rate was significantly higher among patients with insignificant findings than among those with significant findings (p = 0.036). Among the patients in whom capsule endoscopy produced significant findings, the rebleeding rate of the patients who underwent therapeutic interventions was significantly lower than that in those who did not undergo intervention (9.5% vs 40.0%, p = 0.046). CONCLUSION: Follow-up and further aggressive interventions are necessary for patients with obscure gastrointestinal bleeding and significant capsule endoscopy findings to reduce the chance of rebleeding.

Recurrent hepatocellular carcinoma has an increased risk of subsequent recurrence after curative treatment.

BACKGROUND AND AIM: Local ablation therapy has been shown to be effective for small hepatocellular carcinoma (HCC); however, HCC recurrence is very frequent even after apparently curative treatment. In particular, recurrent HCC may be more prone to subsequent recurrence, although quantitative data are lacking. The aim of this study was to evaluate the difference in the risk for subsequent recurrence, if any, between primary and recurrent cases. METHODS: A retrospective analysis was conducted of 376 patients with HCC (uninodular and 100 ng/mL, treatment other than radiofrequency ablation, HCV antibody positivity, and tumor multinodularity also remained as significant predictors. CONCLUSION: Hepatocellular carcinoma at second or later recurrence is three times as prone to subsequent recurrence as is primary HCC, when compared with adjustment for other tumor and hepatic factors.

Health-related quality of life of chronic liver disease patients with and without hepatocellular carcinoma.

BACKGROUND AND AIM: Impaired health-related quality of life has been reported in patients with cirrhosis and chronic hepatitis. However, only limited data are available concerning the influence of hepatocellular carcinoma. METHODS: Health-related quality of life was assessed in 97 patients with hepatocellular carcinoma who had been treated successfully with percutaneous ablation therapy, and 97 patients with chronic liver disease without hepatocellular carcinoma matched for age and sex, using the Japanese version of Short-Form 36. Raw scores were transformed using norm-based scoring. The relations with objective variables including status of hepatocellular carcinoma and laboratory data were analyzed. RESULTS: Health-related quality of life was lower in both groups than in the general population. Patients with hepatocellular carcinoma and patients in the control group showed similar scores. By multivariate analysis, liver function, especially serum albumin, strongly predicted health-related quality of life, but status of hepatocellular carcinoma did not. CONCLUSIONS: Impaired health-related quality of life was not associated with the presence of hepatocellular carcinoma but dependent on the level of liver function, indicating the importance of preserving liver function in following up patients. Serum albumin level was a useful objective variable to assess health-related quality of life of patients with chronic liver disease.

Changes in hepatic functional reserve after percutaneous tumor ablation for hepatocellular carcinoma: long-term follow up for 227 consecutive patients with a single lesion.

BACKGROUND/AIMS: Percutaneous tumor ablation (PTA), such as ethanol injection, is currently accepted as a potentially curative treatment for hepatocellular carcinoma (HCC). Percutaneous tumor ablation is presumed to be relatively non-invasive, but there are few studies on long-term follow-up of liver function after tumor ablation. METHODS: Changes in liver functions were monitored in 227 consecutive patients treated for a solitary HCC nodule by PTA between 1993 and 1997. The liver function evaluated based on Child-Turcotte classification prior to the initial treatment was Child A in 119 (52.4%) patients, B in 81(35.7%), and C in 27 (11.9%). The follow-up period was 46 +/- 21 months. RESULTS: The five-year survival rates of patients in Child A, B, and C group after treatment were respectively 76%, 45%, and 43%. Annual shift rate of Child A to Child B was 7%, and that of Child B to Child C was 14%. Tumor recurrence significantly affected aggravation of liver function in Child A (P = 0.002) but not in Child B patients (P = 0.55). Tumor size at initial treatment influenced changes of liver function in Child B group patients (P = 0.009). CONCLUSIONS: Preservation of liver function may be essential when treating HCC patients with impaired liver function.

Age-related comparison of the profiles of patients with hepatocellular carcinoma.

BACKGROUND/AIMS: It is not known whether the putative etiologic factors and clinical and pathological features of hepatocellular carcinoma differ between young adults and older patients. Therefore this study aims to evaluate whether the clinicopathological features in young patients with HCC significantly differ from those of elderly patients. METHODOLOGY: A total of 1014 consecutive patients with HCC were divided into two groups based on age. Among them, 73 patients younger than 50 years of age comprised the first group and 941 patients 50 years and older made up the second. Clinical, laboratory, and pathological characteristics were compared between the two age groups. RESULTS: The male: female ratio and the incidence of positive hepatitis B surface antigen were significantly higher in young patients than in elderly patients. Tumor size, pathological grading of the tumor, and the severity of liver disease did not differ between the two groups. Especially in those patients demonstrating positive antibody to hepatitis C virus, alanine aminotransferase was higher in the younger, and platelet count was lower. Younger patients also had a higher ratio of alcohol consumption compared to elderly patients. CONCLUSIONS: There were age-related differences in the clinicopathological characteristics of HCC patients. Concerning hepatocarcinogenesis, male and HBsAg positive patients were at high risk in young. Of the HCV-related HCC patients, heavy drinking may accelerate the progression from chronic hepatitis to cirrhosis and HCC.