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Hepatocellular carcinoma (HCC) is a highly aggressive disease that is usually diagnosed at an advanced stage. Advanced HCC has limited treatment options and often has a poor prognosis. For the past decade, tyrosine kinase inhibitors have been the only treatments approved for advanced HCC that have shown overall survival (OS) benefits; however, but their clinical efficacy has been limited. Recent trials have demonstrated promising advancements in survival outcomes through immunotherapy-based treatments, such as combinations of immune checkpoint inhibitors (ICIs) with other ICIs, antiangiogenic drugs, and locoregional therapies. The atezolizumab-bevacizumab and durvalumab-tremelimumab (STRIDE) regimen has significantly improved survival rates as a first-line treatment and has become the new standard of care. Therefore, combined treatments for advanced HCC can result in better treatment outcomes owing to their synergistic effects, which requires a multidisciplinary approach. Ongoing studies are examining other therapeutic innovations that can improve disease control and OS rates. Despite improvements in the treatment of advanced HCC, further studies on the optimal treatment selection and sequences, biomarker identification, combination approaches with other therapies, and development of novel immunotherapy agents are required. This review presents the current treatment options and clinical data of the ICI-based combination immunotherapies for advanced HCC from a multidisciplinary perspective.
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Background/Aims@#The histologic status of the immune-tolerant (IT) phase of chronic hepatitis B relative to long-term outcomes is unclear. This study aimed to discover how the serological criteria currently in use correspond to histologic criteria in determining the IT phase and indication for liver biopsy. @*Methods@#Patients in the serological IT phase determined by positive hepatitis B e antigen, hepatitis B virus (HBV) DNA ≥106 IU/mL, and normal or minimally elevated alanine aminotransferase (ALT) ≤60 IU/L, who underwent liver biopsy at three different hospitals were included. The distribution of the histologic IT phase, defined as fibrosis of stage 1 or less and inflammation of grade 1 or less, was compared with that of the serological IT phase. The risk factors for the incidence of liver-related events, such as hepatocellular carcinoma, liver cirrhosis, liver transplantation, and death, were also analyzed. @*Results@#Eighty-two (31.7%) out of 259 clinically suspected IT phase patients belonged to the histologic IT phase. Age over 35, high AST, and low albumin were useful for ruling out the histologic IT phase. Risk factors predicting liver-related events were age and significant fibrosis stage. There was no significant difference in the proportion of histologic IT phase and clinical prognosis between normal ALT and mildly elevated ALT groups. However, even in patients with normal ALT, age was an important factor in predicting the presence of the histologic IT phase. @*Conclusions@#A significant number of patients who belonged to the serological IT phase were not in the histologic IT phase. Patients over 35 years and those with high AST, low albumin, and low HBV DNA levels were more likely to experience poor long-term clinical outcomes. Therefore, additional histologic assessment should be considered.
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Objectives@#This study aimed to identify the socioeconomic factors related to tooth brushing behavior among adults in Korea. @*Methods@#This cross-sectional study used data from the Korea Community Health Survey (KCHS) in 2019. Respondents aged 19 years and older (n=299,099) comprised the study sample. The dependent variable was tooth brushing behavior, whereas the independent variables were demographic and socioeconomic factors. The data were processed using chi-squared test, independent t-test, ANOVA, and adjusted multiple logistic regression analysis were performed. Statistical analysis was performed using the STATA 17.0 program, with significance set at the 5% level. @*Results@#About half (55%) of the respondents brushed their teeth at least twice a day. The findings also revealed significant differences according to socioeconomic status (P<.01). Those who brushed their teeth less than twice a day had the following characteristics: men, aged 45 years or older, low income, working outside, less educated, without a spouse, and living in rural areas. Adjusted multiple logistic regression analysis showed that the area of residence contributed to tooth brushing behavior. @*Conclusions@#The area of residence, as well as socioeconomic status, should be considered in oral health education and intervention strategies.
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Pandemic of coronavirus disease 2019 (COVID-19) has caused many changes in the healthcare system and patients with preexisting advanced liver disease, notably cirrhosis, are associated with a severe course and a high mortality rate of COVID-19. In patients with liver disease, the underlying liver disease severity is closely related to the prognosis, so appropriate management of liver disease will be one of the most important strategies to protect the patient from COVID-19 infection that may occur in the future. The approach to patient care should be individualized and flexible according to the type and severity of patient’s underlying liver disease, the prevalence of COVID-19, and availability of medical resource. If possible, standard of care for patients with liver disease should be resumed In addition, it is necessary to predict and prepare for the wave of liver disease yet to come after the COVID-19 pandemic.
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Background@#Mac-2 binding protein glycosylation isomer (M2BPGi) has been established as a non-invasive biomarker for liver fibrosis. We evaluated the diagnostic efficacy of M2BPGi compared with those of other liver fibrosis markers in liver fibrosis in non-alcoholic fatty liver disease (NAFLD). @*Methods@#We analyzed serum M2BPGi levels in 113 NAFLD patients. A pathologist graded liver fibrosis histopathologically. The diagnostic efficacies of serum M2BPGi and other liver fibrosis markers (aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors, and NAFLD fibrosis score [NFS]) were evaluated using correlation, area under the ROC curve (AUC), logistic regression, and C-statistics. @*Results@#Serum M2BPGi level and other liver fibrosis markers showed a moderate correlation with fibrosis grade. The AUC values of M2BPGi were 0.761, 0.819, 0.866, and 0.900 for diagnosing fibrosis (F) > 0, F > 1, F > 2, and F > 3, respectively. Logistic regression analysis showed M2BPGi as the only independent factor associated with F > 2 and F > 3. Although C-statistics showed that NFS was the best diagnostic factor for F > 2 and F > 3, M2BPGi with NFS had an increased C-statistics value, indicating that it is a better diagnostic model. @*Conclusions@#The serum M2BPGi level increased with liver fibrosis severity and could be a good biomarker for diagnosing advanced fibrosis and cirrhosis in NAFLD patients. A well-controlled, prospective study with a larger sample size is needed to validate the diagnostic power of M2BPGi and other fibrosis markers in NAFLD.
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Background@#Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea. @*Methods@#A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]). @*Results@#Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test). @*Conclusion@#The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.
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Background/Aims@#Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. @*Methods@#We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. @*Results@#Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. @*Conclusions@#Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.
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Pandemic of coronavirus disease 2019 (COVID-19) has caused many changes in the healthcare system and patients with preexisting advanced liver disease, notably cirrhosis, are associated with a severe course and a high mortality rate of COVID-19. In patients with liver disease, the underlying liver disease severity is closely related to the prognosis, so appropriate management of liver disease will be one of the most important strategies to protect the patient from COVID-19 infection that may occur in the future. The approach to patient care should be individualized and flexible according to the type and severity of patient’s underlying liver disease, the prevalence of COVID-19, and availability of medical resource. If possible, standard of care for patients with liver disease should be resumed In addition, it is necessary to predict and prepare for the wave of liver disease yet to come after the COVID-19 pandemic.
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Background@#Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea. @*Methods@#A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]). @*Results@#Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test). @*Conclusion@#The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.
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Background/Aims@#Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. @*Methods@#We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. @*Results@#Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. @*Conclusions@#Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.
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Background/Aims@#The treatment outcomes and prognostic markers of acute variceal bleeding (AVB) in hepatocellular carcinoma (HCC) patients remain unclear. Therefore, we evaluated the clinical outcomes and prognostic factors of AVB in HCC patients. @*Methods@#Cirrhotic patients with endoscopically confirmed AVB between 2007 and 2013 were enrolled in this prospective study. Prognostic factors were identified by multivariate Cox proportional hazards regression analysis. @*Results@#Among the 329 enrolled patients, 125 patients (38.0%) were diagnosed with HCC. The 6-week mortality rates of all enrolled AVB patients and the HCC subgroup were 14.9% and 26.4%. The 5-day treatment failure, 6-week mortality, cirrhosis-related complications, and duration of hospitalization were greater in HCC patients than in non-HCC patients (all p<0.05). In the HCC subgroup, the Model for End-Stage Liver Disease (MELD) score (hazard ratio [HR], 1.145; p=0.001) and Barcelona Clinic Liver Cancer (BCLC) stage (C–D vs 0–B) (HR, 3.096; p=0.019) were independent predictors of 6-week mortality. Our study revealed that 85% of HCC patients with both a MELD score ≥15.5 and BCLC stage C–D died within 6 weeks, and the 6-week mortality risk was 21-fold higher in this group than in the group with a lower MELD score and earlier HCC stage (p<0.001). @*Conclusions@#The 5-day treatment failure and 6-week mortality rates were significantly higher among AVB patients with HCC than those without HCC. The MELD score and the presence and stage of HCC are strong predictors of 6-week mortality in patients with AVB.
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Background/Aims@#Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved. @*Methods@#A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed. @*Results@#Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P @*Conclusions@#This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.
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BACKGROUND/AIMS: Limited information is available regarding patient survival after sorafenib discontinuation in patients with hepatocellular carcinoma (HCC). Thus, we developed and validated a novel survival prediction model. METHODS: Clinical data from 409 patients with HCC who stopped taking sorafenib between September 2008 and February 2015 were reviewed. RESULTS: In the training cohort, four factors were independent negative predictors of survival (p400 ng/mL. Area under the receiver operating characteristic curve values to predict 1-, 3-, and 6-month survival rates were 0.805, 0.809, and 0.774, respectively, in the training cohort and 0.783, 0.728, and 0.673, respectively, in the validation cohort (n=137). When the training and validation cohorts were stratified into three risk groups (NEXT score 0 [low-risk] vs 1 to 2 [intermediate-risk] vs 3 to 4 [high-risk]), survival differed significantly between the groups (p<0.05, log-rank test). CONCLUSIONS: In patients with HCC, survival after stopping sorafenib is poor. However, risk estimates based on a new “NEXT score” may help predict survival and prognosis even in patients who discontinue sorafenib treatment.
Subject(s)
Humans , Carcinoma, Hepatocellular , Cohort Studies , Prognosis , ROC Curve , Sodium , Survival RateABSTRACT
PURPOSE: Our previous study demonstrated the hypoglycemic effects of mulberry (Morus alba L.) leaf and the underlying mechanisms. Here we explored the potency of mulberry twigs (TW) and root barks (RB) in postprandial hypoglycemic effects in vitro and in vivo. METHODS: The major components of TW and RB were determined by high performance liquid chromatography (HPLC). Alpha-glucosidase inhibition and glucose/fructose uptake inhibition in Caco-2 cells were determined for TW, RB, and their major components, followed by an oral sugar tolerance test (OSTT) in streptozotocin-induced diabetic rats. Male Wistar rats were fed a high-fat diet for 2 weeks and then a single dose of streptozotocin (35 mg/kg B.W) was administered by intraperitoneal injection. Rats with fasting blood glucose levels above 126 mg/dL were randomly divided into 5 groups (n = 8/group) for the following treatments by gavage for 4 weeks: vehicle (normal control and diabetic control), 200 mg/kg B.W of TW or RB or 100 mg/kg B.W of oxyresveratrol (OXY). RESULTS: OXY and mulberroside A were identified as the major components of TW and OXY, mongolicin, and kuwanon H for RB. A significant inhibitory activity on alpha-glucosidase was found for TW, RB, and OXY (p = 0.0099). There was a dose-dependent inhibition of TW and RB on the intestinal sugar uptakes in Caco-2 cells, showing a greater impact on fructose compared to glucose. The OSTT showed that TW and RB significantly delayed time to maximal concentration (p = 0.0088) and decreased maximal concentration (p = 0.0043) compared to the control group. CONCLUSION: These results suggest that TW and RB may have a postprandial hypoglycemic effect, particularly in the case of high fructose or sucrose intake. OXY was suggested as a contributor to the hypoglycemic effect of TW and RB. Further studies are needed for the systemic effect of TW and RB in circulation.
Subject(s)
Animals , Humans , Male , Rats , alpha-Glucosidases , Blood Glucose , Caco-2 Cells , Chromatography, Liquid , Diet, High-Fat , Fasting , Fructose , Glucose , Hypoglycemic Agents , Injections, Intraperitoneal , Morus , Rats, Wistar , Streptozocin , SucroseABSTRACT
Endoscopic submucosal dissection (ESD) is widely accepted as an alternative treatment to surgical resection for gastric neoplastic lesions. Among the complications of gastric ESD, perforation is usually manifested as a pneumoperitoneum. Here, we report a patient with a right-sided pneumothorax, pneumoperitoneum, and pneumoretroperitoneum as complications of gastric ESD. The patient recovered without further complications using conservative treatment, including endoscopic clipping, nasogastric drainage, and insertion of a chest tube.
Subject(s)
Humans , Chest Tubes , Drainage , Endoscopy , Pneumoperitoneum , Pneumothorax , RetropneumoperitoneumABSTRACT
BACKGROUND/AIMS: Argon plasma coagulation (APC) has some merits in the treatment of gastric neoplasms including a shorter operative time and fewer complications compared with endoscopic mucosal resection or endoscopic submucosal dissection. However, there are few reports on the outcomes of gastric neoplasms treated using APC. The aim of this study was to evaluate APC in the treatment of early gastric neoplasms in terms of clinical efficacy, safety, and local recurrence. METHODS: We enrolled 28 patients who received APC therapy at the Kyungpook National University Hospital between May 2007 and April 2013. Clinical outcomes were analyzed. RESULTS: The median follow-up period was 24.8 months (range, 2 to 78). Among the 28 lesions treated using the APC procedure, tumor recurrence was encountered in seven lesions (25.0%). Recurrence was found in 50% (5/10) of single APC cases and 11% (2/18) of rescue APC cases. The mean time to recurrence was 16.1 months (range, 2 to 78). There were no serious APC-related complications such as perforation, bleeding, or infection. CONCLUSIONS: APC therapy can be a useful treatment with a favorable safety profile for patients with early gastric neoplasms. However, further studies are necessary to determine the long-term prognosis of patients undergoing this treatment.
Subject(s)
Humans , Argon Plasma Coagulation , Follow-Up Studies , Hemorrhage , Operative Time , Prognosis , Recurrence , Stomach NeoplasmsABSTRACT
No abstract available.
Subject(s)
Humans , Apoptosis/radiation effects , Gamma Rays , Tumor Suppressor Protein p53/metabolismABSTRACT
The legend of Figure 2 was given incorrectly.
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Acute gastric variceal bleeding is one of the most serious complications in portal hypertension, and is associated with high mortality and morbidity. Endoscopic variceal obturation (EVO) using Histoacryl(R) (n-butyl-2-cyanoacrylate) has been accepted as an effective hemostatic procedure in acute gastric variceal bleeding. However, EVO is not a widely performed because of technical difficulties and complications such as mucosal ulceration, perforation, and systemic embolism. Herein, we report a patient who developed hepatic failure caused by portal vein occlusion by Histoacryl(R) injection for management of gastric variceal bleeding.
Subject(s)
Humans , Embolism , Esophageal and Gastric Varices , Hypertension, Portal , Liver Failure , Mortality , Portal Vein , Splenic Vein , UlcerABSTRACT
BACKGROUND/AIMS: Proton pump inhibitor (PPI) and two types of antimicrobial agents, amoxicillin, and clarithromycin have been widely used for the eradication of Helicobacter pylori. However, antibiotic resistant strains has rapidly increased and has emerged as an important factor for eraducation failure. MATERIALS AND METHODS: Patients diagnosed with chronic gastritis, peptic ulcer disease or gastric epithelial neoplasm was examined by H. pylori PCR for mutation at 23S rRNA. Positive H. pylori PCR without 23S rRNA mutation was eradicated by standard triple therapy. Patients with 23S rRNA mutation was eradicated by standard triple therapy or concomittent therapy with amoxicillin, PPI, clarithromycin and metronidazol or quadruple therapy with bismuth, PPI, tetracycline and metronidazol. We evaluated the predictors of eradication failure with regards to 23S rRNA mutation and initial eradication regimen. RESULTS: Nine hundred sixty-one patients were studied. H. pylori PCR was positive in 35.0% of the patients and 23S rRNA mutatation was found in 22.2% of the patients. The eradication rate of H. pylori for the A2143G point mutated group with standard triple therapy was 28.5% and significantly lower than 93.1% of the wild type group and 100% of the concomitant therapy group, 66.6% of one week quadruple group and 100% of two week quadruple group (P<0.005). CONCLUSIONS: When 23S rRNA point mutation was positive, the standard triple therapy was not effective and the eradication rates was only 22.2%. Alternative regimens should be considered when 23S rRNA point mutation is detected, especially when A2143G point mutation is detected because A2143G point mutation is highly related to eradication failure.