A 42-year-old patient with renal cell carcinoma presenting as low back pain: A case report.

RATIONALE: Renal cell carcinoma (RCC) is the most common renal neoplasm, accounting for 2.4% of all cancers in Korea. Although the usual clinical manifestations of RCC include flank pain, hematuria, and palpable mass, RCC is generally characterized by a lack of early warning signs and is mostly discovered incidentally in advanced stage. This case report describes a 42-year-old Korean man diagnosed with giant RCC who presented with simple back pain. PATIENT CONCERNS: The clinical manifestation of a 42-year-old Korean man was chronic back pain. DIAGNOSES: Contrast-enhanced computed tomography showed a 19.1-cm sized heterogeneous enhancing mass on the right kidney and tumor thrombosis extending into inferior vena cava. INTERVENTION: Due to the large size of the tumor and extensive tumor thrombosis, the multidisciplinary team decided to administer neoadjuvant chemotherapy and an anticoagulant. Following 12 cycles of treatment with nivolumab and cabozantinib, he underwent a right radical nephrectomy with an adrenalectomy and tumor thrombectomy. OUTCOMES: Treatment was successful and posttreatment he started a cancer rehabilitation program. He was followed-up as an outpatient and no longer complains of back pain. LESSONS: RCC can manifest clinically as back pain, with diagnosis being difficult without appropriate imaging modalities. RCC should be included in the differential diagnosis of patients with low back pain, even at a young age.

Identification of patients with favorable prognosis after resection in intermediate-stage-hepatocellular carcinoma.

BACKGROUNDS: It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. METHODS: This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). RESULTS: A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816). CONCLUSIONS: Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.

A risk prediction model for hepatocellular carcinoma in non-alcoholic fatty liver disease without cirrhosis: HCC prediction for non-cirrhotic NAFLD.

BACKGROUND & AIMS: Although non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of hepatocellular carcinoma (HCC), HCC risk in non-cirrhotic NAFLD received little attention. We aimed to develop and validate an HCC risk prediction model for non-cirrhotic NAFLD. METHODS: A nationwide cohort of non-cirrhotic NAFLD patients in Korea was recruited to develop a risk prediction model and validate it internally (n = 409 088). A model using a simplified point system was developed by Cox proportional hazard model. K-fold cross-validation assessed the accuracy, discrimination and calibration. The model was validated externally using a hospital cohort from Asan Medical Center (n = 8721). RESULTS: An 11-point HCC risk prediction model for non-cirrhotic NAFLD was developed using six independent factors of age, sex, diabetes, obesity, serum alanine aminotransferase level and gamma-glutamyl transferase level (c-index 0.75). The average area under receiver operating curves (AUROCs) of the model was 0.72 at 5 years and 0.75 at 10 years. In the external validation cohort, the AUROCs were 0.79 [95% confidence interval [CI], 0.59-0.95] at 5 years and 0.84 (95% CI, 0.73-0.94) at 10 years. The calibration plots showed the expected risks corresponded well with the observed risks. Risk stratification categorized patients into the low (score 0-6), moderate (7, 8) and high (9-11; estimated incidence rate >0.2%/year) risk groups. CONCLUSIONS: A novel HCC risk prediction model for non-cirrhotic NAFLD patients was developed and validated with fair performance. The model is expected to serve as a simple and reliable tool to assess HCC risk and assist precision screening of HCC.

Statin use and the risk of hepatocellular carcinoma among patients with chronic hepatitis B: an emulated target trial using longitudinal nationwide population cohort data.

BACKGROUND: No randomized controlled trials have been completed to see whether statin can decrease hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. We used large-scale, population-based, observational data to emulate a target trial with two groups, statin user and statin non-user. METHODS: Among 1,379,708 nonunique individuals from the Korean National Health Insurance Service data, 2,915 CHB patients with serum cholesterol level of 200 mg/dL or higher who started statin therapy and 8,525 propensity-score matched CHB patients with serum cholesterol level of 200 mg/dL or higher who did not start statin therapy were analyzed for the development of HCC. In addition, liver cancer or liver-related mortality and all-cause mortality were assessed. RESULTS: During follow-up, 207 participants developed HCC. Incidence rate of HCC was 0.2 per 1,000 person-years in the statin user group and 0.3 per 1,000 person-years in the statin non-user group. Fully adjusted hazard ratio (HR) for incident HCC comparing statin user group to statin nonuser group was 0.56 (95% confidence interval [CI]: 0.39 to 0.80). The association between statin use and decreased HCC risk was consistent in all subgroups analyzed. Fully adjusted HR comparing statin user to statin nonuser was 0.59 (95% CI: 0.35 to 0.99) for liver cancer or liver-related mortality and 0.93 (95% CI: 0.78 to 1.11) for all-cause mortality. CONCLUSIONS: Statin might have a benefit for preventing HCC in CHB patients with elevated cholesterol levels. Statin should be actively considered for CHB patients with dyslipidemia.

Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study.

Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.

Effect of lifestyle modification on hepatocellular carcinoma incidence and mortality among patients with chronic hepatitis B.

BACKGROUND: Research exploring the influence of healthier lifestyle modification (LSM) on the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is limited. AIM: To emulate a target trial to determine the effect of LSM on HCC incidence and mortality among patients with CHB by large-scale population-based observational data. METHODS: Among the patients with CHB enrolled in the Korean National Health Insurance Service between January 1, 2009, and December 31, 2017, those aged ≥ 20 years who drank alcohol, smoked cigarettes, and were sedentary were analyzed. Exposure included at least one LSM, including alcohol abstinence, smoking cessation, and regular exercise. The primary outcome was HCC development, and the secondary outcome was liver-related mortality. We used 2:1 propensity score matching to account for covariates. RESULTS: With 48766 patients in the LSM group and 103560 in the control group, the adjusted hazard ratio (HR) for incident HCC and liver-related mortality was 0.92 [95% confidence interval (CI): 0.87-0.96] and 0.92 (95%CI: 0.86-0.99) in the LSM group, respectively, compared with the control group. Among the LSM group, the adjusted HR (95%CI) for incident HCC was 0.84 (0.76-0.94), 0.87 (0.81-0.94), and 1.08 (1.00-1.16) for alcohol abstinence, smoking cessation, and regular exercise, respectively. The adjusted HR (95%CI) for liver-related mortality was 0.92 (0.80-1.06), 0.81 (0.72-0.91), and 1.15 (1.04-1.27) for alcohol abstinence, smoking cessation, and regular exercise, respectively. CONCLUSION: LSM lowered the risk of HCC and mortality in patients with CHB. Thus, active LSM, particularly alcohol abstinence and smoking cessation, should be encouraged in patients with CHB.

Regression of nonalcoholic fatty liver disease is associated with reduced risk of incident diabetes: A longitudinal cohort study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is potentially reversible. However, whether improvement of NAFLD leads to clinical benefits remains uncertain. We investigated the association between regression of NAFLD and the risk of incident diabetes in a longitudinal way. METHODS: A cohort of 11,260 adults who had NAFLD at in an initial exam, had the second evaluation for NAFLD status at 1~2 years from an initial exam were followed up for incident diabetes from 2001 and 2016. NAFLD was diagnosed with abdominal ultrasound. RESULTS: At baseline, NAFLD was regressed in 2,559 participants (22.7%). During 51,388 person-years of follow-up (median 4 years), 1,768 participants developed diabetes. The fully adjusted hazard ratio (HR) for incident diabetes in participants with regressed NAFLD compared to those with persistent NAFLD was 0.81 [95% confidence interval (CI) 0.72-0.92]. When assessed by NAFLD severity, among participants with a low NAFLD fibrosis score (NFS) (< -1.455), participants with regressed NAFLD had a lower risk of incident diabetes than those with persistent NAFLD (HR 0.77, 95% CI 0.68-0.88). However, in participants with an intermediate to high NFS (≥ -1.455), the risk of incident diabetes was not different between NAFLD regression and persistence groups (HR 1.12, 95% CI 0.82-1.51). CONCLUSIONS: Regression of NAFLD was associated with decreased risk of incident diabetes compared to persistent NAFLD. However, the benefit was evident only for NAFLD patients with low NFS. This suggests that early intervention for NAFLD, before advanced fibrosis is present, may maximize the metabolic benefit from NAFLD regression.

Improved on-treatment fibrosis-4 during antiviral therapy and lower hepatocellular carcinoma risk in cirrhotic patients with hepatitis B.

Normalization of serum alanine aminotransferase (ALT) levels is one of the goals of hepatitis B treatment. However, ALT levels in cirrhosis patients might be normal or mildly elevated regardless of ongoing inflammation. Therefore, we examined whether on-treatment ALT and other potential on-treatment indicators could be clinical surrogates of antiviral therapy in HBV-related cirrhosis. A total of 911 patients with HBV-related liver cirrhosis who started treatment with entecavir or tenofovir were analyzed. At 1 year of antiviral therapy, we evaluated 'ALT normalization', 'undetectable serum HBV DNA', 'fibrosis-4 (FIB-4) index improvement', and 'serum HBeAg loss' as potential biomarkers for HCC development. During 6.6 (3.8-10.2) years of follow-up, 222 patients (24.3%) newly developed HCC. Undetectable HBV DNA levels at 1 year were observed in 667 patients (73.2%), and the HCC incidence was significantly lower in this population (adjusted hazard ratio (HR) 0.66, 95% CI 0.50-0.87). Improvement of the FIB-4 index (< 3.25) was associated with a lower risk of HCC in 478 patients with an elevated FIB-4 index (adjusted HR 0.59, 95% CI 0.55-0.82). However, there was no significant difference in HCC risk between those with and without normalization of ALT levels (p = 0.39) among those with elevated ALT levels or between those with and without HBeAg seroconversion (p = 0.55) among HBeAg-positive patients. Therefore, on-treatment FIB-4 levels at 1 year are clinically useful surrogates of antiviral therapy for HBV-related cirrhosis patients.

Clinical Outcomes and Validation of Ursodeoxycholic Acid Response Scores in Patients with Korean Primary Biliary Cholangitis: A Multicenter Cohort Study.

Background/Aims: The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. Methods: A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. Results: After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCA response rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41 (n=97). The area under the receiver operating characteristic curve of URS in predicting UDCA response was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5 years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed according to the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005). Conclusions: URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.

Associations of physical activity domains and muscle strength exercise with non-alcoholic fatty liver disease: a nation-wide cohort study.

It is unclear if various types and domains of exercise have an identical effect on non-alcoholic fatty liver disease (NAFLD). Thus, this study aimed to investigate associations of different physical activity domains and muscle strength exercise with NAFLD using a nation-wide cohort database. Adults aged 20-79 years who participated in the Korean National Health and Nutrition Examination Survey between 2014 and 2018 were analyzed. Hepatic steatosis index was used to identify NAFLD. Physical activity was assessed with the Global Physical Activity Questionnaire. Of 21,015 participants, 4942 (23.5%) had NAFLD. Participants with ≥ 150 min/week of total physical activity had a lower risk of NAFLD than those with < 150 min/week (the fully adjusted OR: 0.86, 95% CI 0.78-0.95). When the individual domain of physical activity was assessed, ≥ 150 min/week of recreation activity was associated with a reduced risk of NAFLD (OR: 0.77, 95% CI 0.67-0.88), whereas ≥ 150 min/week of travel or work activity was not. The fully adjusted OR for NAFLD comparing participants with ≥ 2/week to those with < 2/week of muscle strength exercise was 0.83 (95% CI 0.73-0.94). Muscle strength exercise ≥ 2/week showed a lower risk of NAFLD for all levels of total and each specific domains of physical activity except for ≥ 150 min/week of work activity. An increased level of physical activity and muscle strength exercise was associated with a reduced risk of NAFLD, albeit the effect varied depending on domains of physical activity. Thus, physical activity should be differentiated by domains for the management of NAFLD. Muscle strength exercise could also be a good option for individuals who could not perform moderate-to-vigorous physical activity.

Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome.

BACKGROUND & AIMS: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. METHODS: We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. RESULTS: By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42-1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction = .029) and those without elevated triglycerides levels (P for interaction = .047). CONCLUSION: In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.

The association of non-alcoholic fatty liver disease between parents and adolescent children.

BACKGROUND: Data reporting the heritability of non-alcoholic fatty liver disease (NAFLD) are highly variable. AIMS: To investigate the association of NAFLD between parents and their adolescent children using a nationwide, population-based cohort. METHODS: We analysed 1737 families with both parents and adolescent children aged 12-18 who participated in Korean National Health and Nutrition Examination Surveys (KNHANES) between 2010 and 2019. NAFLD was defined by body mass index and elevated alanine aminotransferase levels in children and by the hepatic steatosis index in parents. RESULTS: The prevalence of NAFLD in adolescent children with either parent with NAFLD was higher than that in those without a parent with NAFLD (10.2% vs. 3.1%, p < 0.001). In a model fully adjusted for demographic, nutritional, behavioural and metabolic risk factors, children with either parent with NAFLD had a higher odds ratio (OR) for NAFLD (OR = 1.75, 95% CI: 1.02-3.00) than those without a parent with NAFLD. Compared to those without a parent with NAFLD, the fully adjusted ORs of NAFLD in children with paternal NAFLD, maternal NAFLD and NAFLD in both parents were 1.80 (95% CI: 1.01-3.20), 2.21 (95% CI: 1.11-4.42) and 2.60 (95% CI: 1.03-6.54), respectively. CONCLUSION: Adolescent children with a parent with NAFLD were at increased risk of NAFLD; risk was higher when both parents had NAFLD. Further studies are needed to explore the benefit of NAFLD screening in children who have a parent with NAFLD.

Incidence and Pattern of Aminotransferase Elevation During Anti-Hypertensive Therapy With Angiotensin-II Receptor Blockers.

BACKGROUND: Angiotensin type II receptor blockers (ARBs) are the most widely used anti-hypertensive drugs. This study aimed to elucidate the likelihood and pattern of ARB-induced liver injury in a hospital-based cohort. METHODS: Data of patients receiving fimasartan (n = 5,543), candesartan (n = 6,406), valsartan (n = 6,040), and losartan (n = 9,126) were retrieved from the clinical data warehouse of two tertiary hospitals. Patients with alanine aminotransferase (ALT) levels > 5 times the upper normal limit were assessed according to the Roussel Uclaf Causality Assessment Method (RUCAM). RESULTS: A total of 27,115 patients were enrolled, including 14,630 (54.0%) men, with a mean age of 64.6 years (standard deviation, 13.6). During 31,717 person-years of ARB therapy, serum ALT levels > 120 IU/L were found in 558 (2.1%) person-years, and levels > 200 IU/L were found in 155 (0.6%) person-years. The incidence of ALT elevation > 120 IU/L per 106 cumulative defined daily doses was 6.6, 3.6, 3.9, and 4.0 in the fimasartan, candesartan, valsartan, and losartan groups, respectively (P = 0.002). An ALT level > 200 IU/L with RUCAM score ≥ 6 was found in 20 patients, suggesting probable drug-induced liver injury for 11 (0.2%) patients receiving fimasartan, five (0.1%) receiving candesartan, four (0.1%) receiving valsartan, and none receiving losartan (P < 0.001). CONCLUSION: Approximately 2% of patients receiving ARB therapy had significant ALT elevation (4.24/106 cumulative defined daily doses [cDDDs]), which was associated with probable ARB-related liver injury in 0.07% of patients (0.15/106 cDDDs). Elevation of ALT was more commonly associated with fimasartan than the other ARBs. Clinicians should be aware of the possibility of ARB-related ALT elevation in patients with unexplained chronic abnormal ALT.

The Association Between Breastfeeding and Nonalcoholic Fatty Liver Disease in Parous Women: A Nation-wide Cohort Study.

BACKGROUND AND AIMS: Breastfeeding has multiple effects on maternal health outcomes. However, the effect of breastfeeding on NAFLD in parous women remains unclear. APPROACH AND RESULTS: A total of 6,893 Korean parous women aged 30-50 years who participated in the Korean National Health and Nutrition Examination Survey were assessed for the association between breastfeeding and NAFLD. Duration of lactation was calculated by dividing the total lactation period by the number of breastfed children. NAFLD was defined by the hepatic steatosis index. Of 6,893 women, 1,049 (15.2%) had NAFLD. Prevalence of NAFLD was 18.3%, 14.3%, 12.3%, 14.4%, and 15.8% in women with a breastfeeding period of <1, ≥1-<3, ≥3-<6, ≥6-<12, and ≥12 months, respectively. In a fully adjusted model, breastfeeding (≥1 month) was associated with reduced NAFLD prevalence (OR, 0.67; 95% CI, 0.51-0.89) after adjusting for metabolic, socioeconomic, and maternal risk factors. Fully adjusted ORs (95% CI) decreased with an increase of breastfeeding duration: 0.74 (0.49-1.11), 0.70 (0.47-1.05), 0.67 (0.48-0.94), and 0.64 (0.46-0.89) for women with ≥1-<3, ≥3-<6, ≥6-<12, and ≥12 months of breastfeeding duration, respectively, compared to women with <1 month of breastfeeding duration. Such an association was also observed in all predefined subgroups without interaction. CONCLUSIONS: Breastfeeding showed a protective effect against NAFLD in later life of parous women, suggesting a maternal benefit of breastfeeding on NAFLD.

Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea.

BACKGROUND: Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. METHODS: A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. RESULTS: A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4-9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. CONCLUSION: Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

Eradication of Helicobacter pylori infection decreases risk for dyslipidemia: A cohort study.

BACKGROUND: Previous studies have suggested a relationship between Helicobacter pylori infection and dyslipidemia; however, large-scale longitudinal studies have not elucidated this association. This study assessed the longitudinal effects of H. pylori infection and eradication on lipid profiles in a large cohort. METHODS: This cohort study included 2,626 adults without dyslipidemia at baseline, who participated in a repeated, regular health-screening examination, which included upper gastrointestinal endoscopy, between January 2009 and December 2018. The primary outcome was incident dyslipidemia at follow-up. RESULTS: During the 10,324 person-years of follow-up, participants with persistent H. pylori infection had a higher incidence rate (130.5 per 1,000 person-years) of dyslipidemia than those whose infections had been successfully controlled (98.1 per 1,000 person-years). In a multivariable model adjusted for age, sex, waist circumference, smoking status, alcohol intake, and education level, the H. pylori eradication group was associated with a lower risk of dyslipidemia than the persistent group (HR, 0.85; 95% CI, 0.77-0.95; p = 0.004). The association persisted after further adjustment for baseline levels of low-density and high-density lipoprotein cholesterol (HR, 0.87; 95% CI, 0.79-0.97; p = 0.014). CONCLUSIONS: H. pylori infection may play a pathophysiologic role in the development of dyslipidemia, whereas H. pylori eradication might decrease the risk of dyslipidemia.

Risk and Risk Score Performance of Hepatocellular Carcinoma Development in Patients With Hepatitis B Surface Antigen Seroclearance.

INTRODUCTION: Hepatocellular carcinoma (HCC) can develop among chronic hepatitis B patients after hepatitis B surface antigen (HBsAg) seroclearance. However, whether HCC risk after HBsAg seroclearance differs between antiviral therapy (AVT)-induced or spontaneous seroclearance cases and ways to identify at-risk populations remain unclear. METHODS: A retrospective cohort of 1,200 adult chronic hepatitis B patients who achieved HBsAg seroclearance (median age: 56 years; 824 men; 165 with cirrhosis; 216 AVT-induced cases) were analyzed. The risk of HCC after HBsAg seroclearance and the performance of 6 HCC prediction models were assessed. RESULTS: During a median of 4.8 years of follow-up (range: 0.5-17.8 years), HCC developed in 23 patients (1.9%). The HCC incidence rate was higher in the AVT-induced cases than that in the spontaneous cases (3.9% vs 0.9% at 5 years). AVT and cirrhosis were independent factors associated with HCC, with HCC incidence rates of 0.5%, 1.2%, 4.0%, and 10.5% at 5 years for spontaneous/no-cirrhosis, AVT-induced/no-cirrhosis, spontaneous/cirrhosis, and AVT-induced/cirrhosis patients, respectively. Among the 6 predictive HCC models tested, Chinese University-HCC score (0.82) showed the highest C-statistics, which was followed by guide with age, gender, HBV DNA, core promoter mutations and cirrhosis (0.81). DISCUSSION: AVT-induced HBsAg seroclearance was associated with higher HCC risk, especially for patients with cirrhosis, indicating that they need careful monitoring for HCC risk. The HCC risk models were able to stratify the HCC risk in patients with HBsAg seroclearance.

Prognosis of hepatocellular carcinoma patients diagnosed under regular surveillance: potential implications for surveillance goal.

AIMS: The goal of hepatocellular carcinoma (HCC) surveillance is to diagnose cancer at an early stage when treatment is likely to provide the best outcome and thereby, reduce mortality. However, no specific criteria define the 'early stage' for tumors diagnosed under HCC surveillance. We aimed to analyze factors that determined the outcome of HCC patients diagnosed under regular surveillance, to find out how early it is necessary to detect tumors during surveillance. METHODS: A retrospective cohort of 874 HCC patients with preserved liver function (Child-Pugh A) who were diagnosed under regular HCC surveillance at Samsung Medical Center from 2014 to 2016 and did not receive liver transplantation as an initial treatment were analyzed. The primary outcome was overall survival (OS). RESULTS: Tumor size, presence of vascular invasion, albumin-bilirubin grade, and initial treatment modality were independent factors for OS in multivariable analysis. When categorized according to the tumor size, the risk of mortality increased for tumors of > 3 cm, while tumors of 2-3 cm showed similar mortality risks as tumors of ≤2 cm. When categorized according to the tumor factors, curative-intent treatment (resection or ablation) can be applied to 84.5% with excellent outcomes (5-year OS rate, 93.4%), for tumors of ≤3 cm without vascular invasion. CONCLUSIONS: When tumors of ≤3 cm were detected and had no vascular invasion, curative-intent treatment was applied for most patients and showed excellent OS. This finding suggests that to detect tumors of <3 cm without vascular invasion may be considered as the goal of HCC surveillance.