ABSTRACT
Background/Aims@#Metabolic dysfunction-associated fatty liver disease (MAFLD) is categorized into three subtypes: overweight/obese (OW), leanormal weight with metabolic abnormalities, and diabetes mellitus (DM). We investigated whether fibrotic burden in liver differs across subtypes of MAFLD patients. @*Methods@#This cross-sectional multicenter study was done in cohorts of subjects who underwent a comprehensive medical health checkup between January 2014 and December 2020. A total of 42,651 patients with ultrasound-diagnosed fatty liver were included. Patients were classified as no MAFLD, OW-MAFLD, lean-MAFLD, and DM-MAFLD. Advanced liver fibrosis was defined based on the nonalcoholic fatty liver disease fibrosis score (NFS) or fibrosis-4 (FIB-4) index. @*Results@#The mean age of the patients was 50.0 years, and 74.1% were male. The proportion of patients with NFS-defined advanced liver fibrosis was the highest in DM-MAFLD (6.6%), followed by OW-MAFLD (2.0%), lean-MAFLD (1.3%), and no MAFLD (0.2%). The proportion of patients with FIB-4-defined advanced liver fibrosis was the highest in DM-MAFLD (8.6%), followed by lean-MAFLD (3.9%), OW-MAFLD (3.0%), and no MAFLD (2.0%). With the no MAFLD group as reference, the adjusted odds ratios (95% confidence intervals) for NFS-defined advanced liver fibrosis were 4.46 (2.09 to 9.51), 2.81 (1.12 to 6.39), and 9.52 (4.46 to 20.36) in OW-MAFLD, leanMAFLD, and DM-MAFLD, respectively, and the adjusted odds ratios for FIB-4-defined advanced liver fibrosis were 1.03 (0.78 to 1.36), 1.14 (0.82 to 1.57), and 1.97 (1.48 to 2.62) in OW-MAFLD, lean-MAFLD, and DM-MAFLD. @*Conclusions@#Fibrotic burden in the liver differs across MAFLD subtypes. Optimized surveillance strategies and therapeutic options might be needed for different MAFLD subtypes.
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Hepatitis B virus (HBV) affects approximately 250 million patients worldwide, resulting in the progression to cirrhosis and hepatocellular carcinoma, which are serious public health problems. Although universal vaccination programs exist, they are only prophylactic and not curative. In the HBV life cycle, HBV forms covalently closed circular DNA (cccDNA), which is the viral minichromosome, in the nuclei of human hepatocytes and makes it difficult to achieve a complete cure with the current nucleos(t)ide analogs and interferon therapies. Current antiviral therapies rarely eliminate cccDNA; therefore, lifelong antiviral treatment is necessary. Recent trials for antiviral treatment of chronic hepatitis B have been focused on establishing a functional cure, defined by either the loss of hepatitis B surface antigen, undetectable serum HBV DNA levels, and/or seroconversion to hepatitis B surface antibody. Novel therapeutic targets and molecules are in the pipeline for early clinical trials aiming to cure HBV infection. The ideal strategy for achieving a long-lasting functional or complete cure might be using combination therapies targeting different steps of the HBV life cycle and immunomodulators. This review summarizes the current knowledge about novel treatments and combination treatments for a complete HBV cure.
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Background/Aims@#Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections. @*Methods@#A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated. @*Results@#The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78–0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72–0.77, P10%; this is the cutoff point for the definition of sepsis. @*Conclusions@#Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.
ABSTRACT
Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.
ABSTRACT
Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.
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Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = −0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.
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In the Barcelona Clinic Liver Cancer staging system, intermediate stage hepatocellular carcinoma (HCC) is defined as large multinodular tumors without vascular invasion or extrahepatic spread in an asymptomatic patient with good performance status. Intermediate stage HCC includes various subgroups and it is characterized by extensive heterogeneity. Current guidelines recommend transarterial chemoembolization (TACE) as the standard treatment modality for patients with intermediate stage HCC. Although TACE provides improved survival benefits compared with supportive care for patients with intermediate stage HCC, all of them are not good candidates for TACE. TACE refractoriness is another obstacle to effective treatment of patients with intermediate stage HCC. Given that many studies recently reported improved survival in patients treated with hepatic resection over TACE, we reviewed the survival outcomes of TACE and hepatic resection as a treatment strategy of intermediate stage HCC.
ABSTRACT
Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = −0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.
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BACKGROUND/AIMS: Guidelines recommend surveillance for hepatocellular carcinoma (HCC) recurrence at 3-month intervals during the first year after curative treatment and 6-month intervals thereafter in all patients. This strategy does not reflect individual risk of recurrence. We aimed to stratify risk of recurrence to optimize surveillance intervals 1 year after treatment. METHODS: We retrospectively analyzed 1,316 HCC patients treated with resection/radiofrequency ablation at Barcelona Clinic Liver Cancer stage 0/ A. In patients without 1-year recurrence under 3-monthly surveillance, a new model for recurrence was developed using backward elimination methods: training (n=582)/ validation cohorts (n=291). Overall survival (OS) according to risk stratified by the new model was compared according to surveillance intervals: 3-monthly versus 6-monthly (n=401) after lead time bias correction and propensity-score matching analyses. RESULTS: Among patients without 1-year recurrence, age and international normalized ratio values were significant factors for recurrence (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00 to 1.03; p=0.009 and HR, 5.63; 95% CI, 2.24 to 14.18; p < 0.001; respectively). High-risk patients stratified by the new model showed significantly higher recurrence rates than low-risk patients in the validation cohort (HR, 1.73; 95% CI, 1.18 to 2.53; p=0.005). After propensity-score matching between the 3-monthly and 6-monthly surveillance groups, OS in high-risk patients under 3-monthly surveillance was significantly higher than that under 6-monthly surveillance (p=0.04); however, OS in low-risk patients under 3-monthly surveillance was not significantly different from that under 6-monthly surveillance (p=0.17). CONCLUSIONS: In high-risk patients, 3-monthly surveillance can prolong survival compared to 6-monthly surveillance. However, in low-risk patients, 3-monthly surveillance might not be beneficial for survival compared to 6-monthly surveillance.
Subject(s)
Humans , Bias , Carcinoma, Hepatocellular , Cohort Studies , International Normalized Ratio , Liver Neoplasms , Recurrence , Retrospective StudiesABSTRACT
BACKGROUND/AIMS: Liver transplantation offers the only definite cure for cirrhosis but lacking donors is problem. Stem cell therapy is attractive in this setting. In this study, we aimed to explore the safety and efficacy of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell (PBMC) in cirrhotic patients. METHODS: A total of nine decompensated cirrhotic patients were randomized into three groups: group 1 (n = 3) was control group, group 2 (n = 3) received granulocyte-colony stimulating factor (G-CSF) mobilization for 3 days, and group 3 (n = 3) received G-CSF mobilized PBMCs by leukapheresis and PBMC transplantation through ultrasound-guided percutaneous portal vein puncture. Liver function and clinical features were evaluated. RESULTS: At baseline, the Child-Turcotte-Pugh and the model for end-stage liver disease scores were comparable in study groups. Compared with group 1, there was a tendency to improve liver function in group 3 at 6 months after treatment. Treatment was tolerable and no complications were encountered related to the G-CSF mobilization or percutaneous portal administration of PBMCs. Imaging studies showed patent portal veins at the end of the study period. CONCLUSIONS: Autologous PBMC transplantation through ultrasound-guided percutaneous portal vein puncture could be considered as a safe alternative treatment for decompensated cirrhotic patients.
Subject(s)
Humans , Fibrosis , Granulocyte Colony-Stimulating Factor , Leukapheresis , Leukocytes, Mononuclear , Liver Cirrhosis , Liver Diseases , Liver Transplantation , Liver , Monocytes , Portal Vein , Punctures , Stem Cells , Tissue DonorsABSTRACT
BACKGROUND/AIMS: A recent study reported that entecavir had inferior efficacy in nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients compared to NA-naïve patients. We sought to compare the efficacy of tenofovir disoproxil fumarate (TDF) in NA-experienced and NA-naïve CHB patients. METHODS: We retrospectively enrolled 252 consecutive patients who had a serum hepatitis B virus (HBV) DNA level greater than 2,000 IU/mL at the initiation of TDF treatment and who received TDF for at least 6 months. Complete virologic suppression (CVS) was defined as undetectable serum HBV DNA. We generated a multivariate Cox proportional-hazard model to examine predictive factors that were independently associated with time to CVS. RESULTS: The mean age of patients was 48.2 years, and the cohort included 181 NA-naïve patients and 71 NA-experienced patients. The median duration of TDF treatment was 14.4 (interquartile range, 9.5-17.8) months. A total of 167 (92.3%) of 181 NA-naïve patients achieved CVS, and 60 (84.5%) of 71 NA-exposed patients achieved CVS. Forty-nine (89.1%) of 55 patients who previously took an NA aside from adefovir and 11 (68.8%) of 16 adefovir-experienced patients achieved CVS. In multivariable analysis, previous adefovir exposure significantly influenced time to CVS (hazard ratio, 0.37; 95% confidence interval, 0.19-0.72; P=0.003), after adjusting for HBeAg positivity, baseline HBV DNA level and cirrhosis. CONCLUSIONS: Tenofovir had inferior efficacy in adefovir-experienced CHB patients compared to NA-naïve patients. The response of patients with previous adefovir exposure to TDF monotherapy should be monitored closely.
Subject(s)
Humans , Cohort Studies , DNA , Fibrosis , Hepatitis B , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic , Hepatitis, Chronic , Retrospective Studies , TenofovirABSTRACT
Fucoidan is a traditional Chinese medicine suggested to possess anti-tumor effects. In this study the anti-metastatic effects of fucoidan were investigated in vitro in human hepatocellular carcinoma (HCC) cells (Huh-7 and SNU-761) under normoxic and hypoxic conditions and in vivo using a distant liver metastasis model involving injection of MH134 cells into spleen via the portal vein. Its ability to protect hepatocytes against bile acid (BA)-induced apoptosis was investigated in primary hepatocytes. Fucoidan was found to suppress the invasion of HCC cells through up-regulation of p42/44 MAPK-dependent NDRG-1/CAP43 and partly, under normoxic conditions, through up-regulation of p42/44 MAPK-dependent VMP-1 expression. It also significantly decreased liver metastasis in vivo. As regards its hepatoprotective effect, fucoidan decreased BA-induced hepatocyte apoptosis as shown by the attenuation of caspase-8, and -7 cleavages and suppression of the mobilization of caspase-8 and Fas associated death domain (FADD) into the death-inducing signaling complex. In summary, fucoidan displays inhibitory effects on proliferation of HCC cells and protective effects on hepatocytes. The results suggest fucoidan is a potent suppressor of tumor invasion with hepatoprotective effects.
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BACKGROUND/AIMS: The aim of this study was to evaluate the influence of recent chemotherapy on the patterns of the maximum-standardized uptake value (M-SUV) and sensitivity of 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in colorectal cancer. METHODS: We retrospectively analyzed the FDG-PET/CT of 509 patients who underwent surgery for colorectal cancer. Subgroup analysis was performed according to chemotherapy status; 401 patients were not treated with chemotherapy and 108 patients were treated with chemotherapy within 6 months prior to surgery. Pathologic analysis of the surgical specimen was used as the gold standard. RESULTS: The M-SUV was significantly lower in patients treated with chemotherapy than in those not treated with chemotherapy in pathologically confirmed same stages of disease. The difference in the sensitivity of the M-SUV according to chemotherapy status was greatest using a cutoff M-SUV value of 6.4 (p<0.001). The longest diameter of the primary tumor was the most important factor that correlated with M-SUV of the primary tumor irrespective of the chemotherapy effect (p<0.001). The M-SUV of the primary tumor was not an independent predictor of lymph node metastasis in colorectal cancer. CONCLUSIONS: The results indicate that the M-SUV of FDG-PET/CT should be interpreted in the context of concurrent chemotherapy.
Subject(s)
Aged , Female , Humans , Male , Antineoplastic Agents/adverse effects , Chemoradiotherapy, Adjuvant/adverse effects , Chemotherapy, Adjuvant/adverse effects , Colorectal Neoplasms/drug therapy , Fluorodeoxyglucose F18 , Neoplasm Invasiveness , Neoplasm Metastasis , Positron-Emission Tomography/methods , Radiopharmaceuticals , Retrospective StudiesABSTRACT
Spontaneous regression of hepatocellular carcinoma (HCC) is extremely rare, and dozens of cases have been reported in the literature. In this report, we present a case of pathologically confirmed HCC that partially regressed without medical intervention. A 54-year-old Korean male with chronic hepatitis B had a hepatic mass detected by abdominal ultrasonography during a routine visit. A clinical diagnosis of HCC was made after measuring serum alpha-fetoprotein levels followed by dynamic computed tomography and magnetic resonance imaging. The patient delayed surgical resection; however, after 5 months, the size of the HCC decreased from 3.2 to 1.0 cm in diameter without any treatment. At that time the mass was surgically resected. Histopathology confirmed that the hepatic mass was consistent with partially regressed HCC and showed more intra- and peri-tumoral lymphocytes consisting of greater CD4+ T cell infiltration than what is normally seen in resected HCC.
Subject(s)
Humans , Male , Middle Aged , alpha-Fetoproteins , Carcinoma, Hepatocellular , Diagnosis , Hepatitis B, Chronic , Lymphocytes , Magnetic Resonance Imaging , Neoplasm Regression, Spontaneous , UltrasonographyABSTRACT
Spontaneous regression of hepatocellular carcinoma (HCC) is extremely rare, and dozens of cases have been reported in the literature. In this report, we present a case of pathologically confirmed HCC that partially regressed without medical intervention. A 54-year-old Korean male with chronic hepatitis B had a hepatic mass detected by abdominal ultrasonography during a routine visit. A clinical diagnosis of HCC was made after measuring serum alpha-fetoprotein levels followed by dynamic computed tomography and magnetic resonance imaging. The patient delayed surgical resection; however, after 5 months, the size of the HCC decreased from 3.2 to 1.0 cm in diameter without any treatment. At that time the mass was surgically resected. Histopathology confirmed that the hepatic mass was consistent with partially regressed HCC and showed more intra- and peri-tumoral lymphocytes consisting of greater CD4+ T cell infiltration than what is normally seen in resected HCC.
Subject(s)
Humans , Male , Middle Aged , alpha-Fetoproteins , Carcinoma, Hepatocellular , Diagnosis , Hepatitis B, Chronic , Lymphocytes , Magnetic Resonance Imaging , Neoplasm Regression, Spontaneous , UltrasonographyABSTRACT
Pancreatic neuroendocrine tumors (PNET) are rare, with approximately 2.2 in 1,000,000 people affected annually. In the classification of neuroendocrine tumors, glucagonomas are a functional PNET and comprise 1.6% of PNET. Glucagonoma syndrome is a paraneoplastic syndrome that is characterized by necrolytic migratory erythema, weight loss, anemia, and diabetes mellitus. Metastatic disease at presentation is common, but is often limited to the liver and regional lymph nodes. Sunitinib malate improves the progression-free and overall survival of PNET. This report presents a 45-year-old Asian woman with prolonged neutropenia after sunitinib treatment of a glucagonoma with multiple hepatic metastases. The severity of the neutropenia after the sunitinib treatment fluctuated from grade 1 to 4 repeatedly, with a non-febrile pattern. Ultimately, the patient did not recover from the neutropenia, even after stopping the sunitinib.
Subject(s)
Female , Humans , Anemia , Asian People , Diabetes Mellitus , Glucagonoma , Indoles , Liver , Lymph Nodes , Necrolytic Migratory Erythema , Neoplasm Metastasis , Neuroectodermal Tumors, Primitive , Neuroendocrine Tumors , Neutropenia , Pancreas , Paraneoplastic Syndromes , Pyrroles , Weight LossABSTRACT
Crohn's disease is a chronic inflammatory disease that can involve the entire gastrointestinal tract. Several studies indicate that Crohn's patients with long disease duration have an increased risk of small bowel or colorectal cancer. In Korea, only a few cases of Crohn's disease-related small bowel or colorectal cancer have been reported. Here, we described 3 cases of colorectal cancer and 2 cases of small bowel cancer in patients with Crohn's disease. Among 5 patients, 3 had Crohn's disease-related lower gastrointestinal malignancy and the other 2 had sporadic lower gastrointestinal malignancies. Since the diagnosis of Crohn's disease-related lower gastrointestinal malignancy tends to be delayed, the development of malignancy should be considered in patients with long duration of Crohn's disease if patients have refractory symptoms despite intensive medical treatment. Surgical consultation should not be delayed.