Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study.

Background: The majority of patients with hepatocellular carcinoma (HCC) following hepatic resection experience tumor recurrence. Statin use is associated with a reduced risk of HCC development; however, the association between statin use and the prognosis of HCC after resection remains unclear. We aimed to investigate the effect of statin use on the prognosis after hepatic resection among patients with HCC. Methods: A nationwide cohort study was performed with data from the National Health Insurance Service Database in Korea. Among 65,101 HCC patients who underwent hepatic resection between January 2002 and December 2017, we included 21,470 patients. For validation, a hospital-based cohort of 3366 patients with very early or early-stage HCC who received curative-intent hepatic resection between January 2010 and December 2018 was analyzed. Recurrence-free survival (RFS) and overall survival (OS) was compared between statin users and non-users. Findings: Among the nationwide cohort of 21,470 patients, 2399 (11.2%) used statins and 19,071 (88.8%) did not. Among the hospital cohort of 3366 patients, 363 (10.8%) used statins and 3003 (89.2%) did not. In the propensity score-matched nationwide cohort, statin users had better RFS (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.56-0.64; P < 0.001) and OS (HR, 0.49; 95% CI, 0.45-0.53; P < 0.001), with a duration-response relationship. In the propensity score-matched validation hospital cohort, statin treatment was significantly associated with better RFS (HR, 0.73; 95% CI, 0.59-0.90; P = 0.003) and OS (HR, 0.48; 95% CI, 0.32-0.72; P < 0.001). The beneficial effects of statins were more prominent in non-cirrhotics, tumors sized ≥3 cm, tumors with microscopic vascular invasion, or early HCC recurrence (<2 years after resection). Interpretation: Statin use was associated with a better prognosis in a population-based cohort of patients with HCC after hepatic resection, which was further validated in a large hospital-based cohort. Funding: Asan Institute for Life Sciences and Corporate Relations; Korean Association for the Study of the Liver.

Liver Cirrhosis Increases the Risk of Herpes Zoster: A Nationwide Population-Based Cohort Study.

INTRODUCTION: Limited data are available regarding the association between liver cirrhosis (LC) and the risk of herpes zoster (HZ). This study aimed to determine the risk of HZ in patients with LC. METHODS: HZ was defined as the presence of the International Classification of Diseases-10th revision code for HZ and concomitant prescription of antiviral medication. The incidence rates and standardized incidence ratios (SIRs) of HZ in patients with LC were analyzed using data from the Health Insurance Review and Assessment Service in Korea claims database from 2009 to 2019. RESULTS: A total of 504,986 Korean patients with LC were included. The mean age was 52.4 years, and 60.8% were men. Chronic hepatitis B was the most common cause of LC. The incidence rates for HZ and HZ-related hospitalization were 21.6 of 1,000 and 1.81 of 1,000 person-years, respectively. The SIRs for HZ and HZ-related hospitalization were 1.09 (95% confidence interval [CI]: 1.08-1.09) and 1.48 (95% CI: 1.44-1.52), respectively, which were significantly higher than those in the general population. Patients with LC aged 20-29, 30-39, and 40-49 years had SIRs for HZ of 1.41 (95% CI: 1.33-1.48), 1.16 (1.13-1.19), and 1.17 (1.13-1.19), respectively. In multivariable analysis, woman (adjusted hazard ratio [AHR]: 1.48), steroid (AHR: 1.20), immunosuppressant use (AHR: 1.26), and combined comorbidities were associated with an increased risk of HZ among patients with LC. DISCUSSION: Patients with LC, particularly those who are not currently recommended for HZ vaccination, were at an increased risk of HZ and HZ-related hospitalization compared with the general Korean population.

Treatment patterns for hepatocellular carcinoma in patients with Child-Pugh class B and their impact on survival: A Korean nationwide registry study.

BACKGROUND AND AIMS: There are no established practice guidelines for treating hepatocellular carcinoma (HCC) in patients with Child-Turcotte-Pugh (CTP) class B liver function. To evaluate the impact of various initial treatment modalities on these patients, we conducted a nationwide registry study in Korea. MATERIALS AND METHODS: Treatment patterns and overall survival (OS) of patients with HCC and CTP class B according to initial treatment modalities in each Barcelona Clinic Liver Cancer (BCLC) stage were analysed using data from the Korean Primary Liver Cancer Registry between 2008 and 2016. Initial treatment modalities were categorized as standard, alternative treatment and supportive care only, referring to the 2018 BCLC guidelines, irrespective of liver function. RESULTS: Of the 2318 newly diagnosed Korean patients with HCC and CTP class B, 29.7%, 60.3% and 15.6% of patients in BCLC stages A, B and C, respectively, underwent standard treatment. Adjusted OS hazard ratios of alternative treatment referring to standard treatment were 1.55 (95% confidence interval [CI], 1.25-1.94; p < .001) in BCLC-A, 0.82 (95% CI, 0.43-1.56; p = .550) for curative alternative treatment, 1.89 (95% CI, 0.97-3.68; p = .059) for non-curative alternative treatment in BCLC-B, 0.40 (95% CI, 0.28-0.56; p < .001) for curative alternative treatment, 0.84 (95% CI, 0.69-1.02; p = .076) for non-curative alternative treatment for BCLC-C. CONCLUSION: Regardless of BCLC stages, chemoembolization was conducted the most among patients with CTP class B. Treatment in line with the BCLC treatment algorithm resulted in favourable OS outcomes, except for those with BCLC stage C, as systemic therapy showed poor OS.

Natural History of Asymptomatic Esophageal Subepithelial Tumors of 30 mm or Less in Size.

BACKGROUND: No definite guidelines for the management of small esophageal subepithelial tumors (SETs) have been established, because there are limited data and studies on their natural history. We aimed to assess the natural history and propose optimal management strategies for small esophageal SETs. METHODS: Patients diagnosed as esophageal SETs ≤ 30 mm in size between 2003 and 2017 using endoscopic ultrasound (EUS) with a minimal follow-up of 3 months were enrolled, and their esophagogastroduodenoscopy (EGD) and EUS were retrospectively reviewed. RESULTS: Of 275 esophageal SETs in 262 patients, the initial size was < 10 mm, 10-20 mm, and 20-30 mm in 104 (37.8%), 105 (38.2%), and 66 (24.0%) lesions, respectively. Only 22 (8.0%) SETs showed significant changes in size and/or echogenicity and/or morphology at a median of 40 months (range, 4-120 months). Tissues of 6 SETs showing interval changes were obtained using EUS-guided fine needle aspiration biopsy; 1 was identified as a gastrointestinal stromal tumor (GIST) and was surgically resected, while the other 5 were leiomyomas and were regularly observed. Eight SETs showing interval changes were resected surgically or endoscopically without pathological confirmation; 1 was a GIST, 2 were granular cell tumors, and the other 5 were leiomyomas. CONCLUSION: Regular follow-up with EGD or EUS may be necessary for esophageal SETs ≤ 30 mm in size considering that small portion of them has a possibility of malignant potential. When esophageal SETs ≤ 30 mm show significant interval changes, pathological confirmation may precede treatment to avoid unnecessary resection.

The impact of pylorus preservation on the development of nonalcoholic fatty liver disease after pancreaticoduodenectomy: A historical cohort study.

BACKGROUND/PURPOSE: The pathophysiology and associated factors of nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) remain elusive. We aimed to investigate these factors, including the operation type, for NAFLD development after PD. METHODS: This historical cohort study included 786 consecutive patients treated with either classic Whipple operation or pylorus-preserving pancreaticoduodenectomy (PPPD) in Korea between 2012 and 2018. De novo NAFLD was determined based on hepatic attenuation in nonenhanced computed tomography during follow-up. RESULTS: Of the 786 patients, 216 (27.5%) had a newly developed NAFLD at 2 years after PD. The incidences of newly developed NAFLD at 0.5, 1, 1.5, and 2 years were 13 (1.7%), 41 (5.2%), 48 (6.1%), and 114 (14.5%), respectively. The Whipple group showed a significantly higher incidence of NAFLD than the PPPD group (40.3% vs 24.5%, P < .001). Seventeen patients (2.2%) had severe fatty liver with abnormal liver enzymes. Multivariable analysis revealed that Whipple operation (vs PPPD; adjusted odds ratio [AOR]: 1.92, P < .001) and high preoperative body mass index (vs normal; AOR: 1.71, P = .001) were independently associated with a higher risk of NAFLD. CONCLUSION: The incidence of NAFLD was 27.5% at 2 years after PD. Undergoing Whipple operation and high preoperative body mass index were significantly associated with de novo NAFLD development.

Serum Sorbitol Dehydrogenase as a Novel Prognostic Factor for Hepatocellular Carcinoma after Surgical Resection.

The majority of patients with hepatocellular carcinoma (HCC) undergoing curative resection experience tumor recurrence. To examine the association between preoperative serum sorbitol dehydrogenase (SORD), a liver-derived enzyme that reflects liver damage, and recurrence of HCC after curative resection, 92 patients were randomly selected who underwent curative resection for HCC between 2011 and 2012 from a prospective registry. Recurrence-free survival (RFS) was compared based on serum SORD levels. Cox proportional hazard models were used to investigate prognostic factors for RFS. During a median follow-up duration of 57.1 months, 43 patients experienced HCC recurrence. Patients with serum SORD ≥15 ng/mL (HR, 3.46; 95% CI, 1.76-6.81; p < 0.001) had worse RFS compared with patients with serum SORD <15 ng/mL. Serum AFP and SORD levels were two independent prognostic factors for RFS. When patients were stratified by baseline serum SORD and AFP levels, patients with serum AFP levels ≥400 ng/mL and serum SORD levels ≥15 ng/mL had a distinctly poor prognosis with the lowest RFS rates (HR, 22.08; 95% CI, 6.91-70.50; p < 0.001). Baseline serum SORD is an effective prognostic factor for HCC after resection. It may help guide patient selection for surgery, especially when combined with serum AFP levels.

Impact of liver cirrhosis on the clinical outcomes of patients with COVID-19: a nationwide cohort study of Korea.

BACKGROUND/AIMS: The impact of liver cirrhosis (LC) on the clinical outcomes of patients with coronavirus disease 2019 (COVID-19) remains elusive. This study evaluated the association between LC and the development of severe complications from COVID-19. METHODS: We used the National Health Insurance claims data of Korea. We included 234,427 patients older than 19 years who tested for severe acute respiratory syndrome coronavirus 2. Patients with LC who were infected with COVID-19 (n = 67, LC+ COVID+) were matched with those with cirrhosis only (n = 332, LC+ COVID-) and those with COVID-19 only (n = 333, LC- COVID+) using a propensity score in a 1:5 ratio. The primary outcome was the development of severe complications. RESULTS: Of the matched patients, the mean age was 60 years and 59.7% were male. Severe complications occurred in 18, 54, and 60 patients in the LC+ COVID+, LC+ COVID-, and LC- COVID+ groups, respectively. After adjusting for comorbidities, there was no significant difference in the risk of developing severe complications from COVID-19 between the LC+ COVID+ and LC- COVID+ groups but significant difference exists between the LC+ COVID+ and LC+ COVID-. Older age, hypertension, cancer, chronic obstructive pulmonary disease, and a higher Charlson comorbidity index were associated with a higher risk of severe complications in patients with cirrhosis and COVID-19. CONCLUSION: Our study suggests that LC was not independently associated with the development of severe complications, including mortality, in patients with COVID-19. Our results need to be evaluated through a large, prospective study.

Dynamics of Serum Retinol and Alpha-Tocopherol Levels According to Non-Alcoholic Fatty Liver Disease Status.

The available data on the association between micronutrients in the blood and non-alcoholic fatty liver disease (NAFLD) are limited. To investigate the clinical implications of this relationship, we sought to identify the difference in the serum levels of vitamins A and E according to NAFLD status using data from the seventh Korea National Health and Nutrition Examination Survey. In this cross-sectional study of the Korean population, NAFLD and its severity were defined using prediction models. Differences in the prevalence and severity of NAFLD were analyzed according to serum retinol (vitamin A) and alpha (α)-tocopherol (vitamin E) levels. Serum levels of retinol and α-tocopherol were positively correlated with the prevalence of NAFLD. In most prediction models of the NAFLD subjects, serum retinol deficiency was significantly correlated with advanced fibrosis, while serum α-tocopherol levels did not differ between individuals with or without advanced fibrosis. Similar trends were also noted with cholesterol-adjusted levels of α-tocopherol. In summary, while circulating concentrations of retinol and α-tocopherol were positively associated with the presence of NAFLD, advanced liver fibrosis was only correlated with serum retinol levels. Our findings could provide insight into NAFLD patient care at a micronutrient level.

Effect of Spironolactone on COVID-19 in Patients With Underlying Liver Cirrhosis: A Nationwide Case-Control Study in South Korea.

Purpose: On the basis that spironolactone is involved in ACE2 expression and TMPRSS2 activity, previous studies have suggested that spironolactone may influence the infectivity of COVID-19. Research has suggested that cell entry of SARS-CoV-2, the virus that induces COVID-19, is associated with the ACE2 receptor and TMPRSS2. The purpose of this study was to investigate whether spironolactone has a protective effect against COVID-19 and the development of associated complications in patients with liver cirrhosis. Methods: We conducted a nationwide case-control study on liver cirrhosis patients with or without COVID-19 from the population-based data acquired from the National Health Insurance Systems of Republic of Korea. After 1:5 case-control matching, multivariable adjusted conditional logistic regression analysis was performed. Results: Among the patients with liver cirrhosis, the case group with COVID-19 was found to be significantly less exposed to spironolactone compared with the control group without COVID-19. The adjusted odds ratio (OR) and 95% confidence interval (CI) between the two groups was 0.20 (0.07-0.54). In addition, regardless of cumulative dose of spironolactone, exposure to spironolactone was associated with lower COVID-19 infection. In terms of the development of complications due to COVID-19, spironolactone did not show any significant association between the patients with and without complications (P = 0.43). The adjusted OR and 95% CI between the two groups was 1.714 (0.246-11.938). Conclusion: We conclude that spironolactone may reduce susceptibility to COVID-19 but does not affect the development of its associated complications; however, further studies are needed to confirm the exact association between spironolactone and COVID-19 infection.