BACKGROUND/AIMS: Oxidative stress is known to play a role in the pathogenesis of a certain liver diseases such as alcoholic liver disease, metal storage disease, and ischemia/reperfusion injury. Recently oxidative stress(lipid peroxidation) has also been implicated in hepatic fibrosis, which is now regarded as a common response to chronic liver injury regardless of its nature. Development of fibrosis and cirrhosis are the major complications of chronic hepatitits B. So we aimed to detect lipid peroxidation in chronic hepatitis B and to investigate its potential role in the pathophysiology of the disease. METHODS: The subjects were histologically-proven 56 patients, including fatty liver(FL, n=8), healthy HBsAg carrier(n=6), chronic persistent hepatitis(CPH, n=8), mild chronic active hepatitis(CAH-m, n=10), severe CAH(CAH-s, n=16), and liver cirrhosis(LC, n=8). All patients were serologically HBsAg-positive except those with FL. Lipid peroxidation was detected in serum and liver specimen with TBARS(thiobarbituric acid-reacting substances) assay. Western blot and immunohistochemical stain of liver specimen were also performed, using polyclonal antibody against malondialdehyde (MDA). RESULTS: 1. There were no significant differences in serum TBARS levels among groups(p= 0.24). 2. The mean tissue TBARS level(nmol/g) was significantly higher in CAH-s group(175.4+ 41.5) than in other groups(FL 54.0+ 6.4, Carrier 51.1+ 15.9, CPH 63.9+ 2.9, CAH-m 68.9+ 7.9, LC 22.6+ 5.1) (p<0.05). 3. Tissue TBARS levels correlated with serum ALT levels(r=0.5934, p<0.05). 4. Western blot showed MDA bands only in CAH-s group. 5. Immunohistochemistry showed a strong MDA stain around portal and periportal area in CAH-s group, but weak or no stain in other groups. CONCLUSIONS: This study shows that lipid peroxidation can be detected in situ and commonly occurs in severe chronic hepatitis B. Oxidative stress may be related to active necroinflammatory change of the liver and contribute to the progression of the disease in chronic hepatitis B.
Blotting, Western ; Fibrosis ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic ; Humans ; Immunohistochemistry ; Lipid Peroxidation* ; Liver Diseases* ; Liver Diseases, Alcoholic ; Liver* ; Malondialdehyde ; Oxidative Stress ; Thiobarbituric Acid Reactive Substances

Asymptomatic chronic HBsAg carriers with normal liver function tests are, in general regarded as having no liver pathology. Most of the histologic findings in asymptomatic chronic carriers have been reported from areas with low incidence of Hepatitis B virus (HBV) infection, such as North America and Western Europe. It is well known that there are many differences in HBV infection between low and high endemic areas, but there have been few reports on the histologic findings of asymptomatic chronic HBsAg carriers from endemic areas. The present study was undertaken in Korea which is one of the endemic areas for HBV infection and was designed to assess the prevalence of chronic liver disease by peritoneoscopic liver biopsy among asymptomatic chronic HBsAg carriers and to make a basis for the follow-up of asymptomatic chronic HBsAg carriers according to the results obtained. One hundred and ten asymptomatic HBsAg-positive carriers with normal liver function tests and no hepatomegaly were included in the study. Final diagnosis by peritoneoscopic liver biopsy revealed that of the 110 asymptomatic carriers only 27 (24.5%) had a histologically normal liver, while 51 (46.4%) had chronic liver diseases, and the remaining 32 (29.1%) had nonspecific histologic abnormalities (nonspecific reactive changes in 18 cases, cholestasis in 6 cases, and fatty change in 8 cases). Of the 51 patients with chronic liver diseases, 3 had liver cirrhosis, 4 chronic active hepatitis with cirrhosis, 11 chronic active hepatitis and 33 chronic persistent hepatitis. The frequency of liver cirrhosis and chronic active hepatitis with cirrhosis was significantly high in the over 30 years of age group (12.1%) than in the under 30 years of age group (0%; p = 0.011 by Fisher's exact test). In conclusion, 46.4% of the Korean asymptomatic chronic HBsAg carriers with normal liver function tests and no hepatomegaly had chronic liver disease. This finding contrasted with reports from low incidence areas of HBV infection. Our results suggest that in endemic areas, a liver biopsy should be considered to assess the status of liver disease in asymptomatic chronic HBsAg carriers even if liver function tests are normal and hepatomegaly is absent, and the result can be used as a basis for the follow-up of each asymptomatic chronic HBsAg carriers.
Adolescent ; Adult ; Biopsy ; Carrier State/*pathology ; Chronic Disease ; Female ; Hepatitis B/*pathology/physiopathology ; Hepatitis B Surface Antigens/*analysis ; Human ; Laparoscopy ; Liver/*pathology/physiopathology ; Male ; Middle Age

BACKGROUND: Protease-activated receptor 2 (PAR2) belongs to a family of G protein- coupled receptors activated by proteolytic cleavage. Trypsin-like serine proteases interact with PAR2 expressed by a variety of tissues and immune cells. The aim of our study was to investigate whether PAR2 stimulation can lead to the activation of human macrophages. METHODS: PAR2-mediated proliferation of human macrophage cell line THP-1 was measured with MTT assay. We also examined the extracellular regulated kinase (ERK) phosphorylation and cytokine production induced by trypsin and PAR2-agonist using western blot and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Treatment of trypsin or PAR2-activating peptide increased cell proliferation in a dose-dependent manner, and induced the activation of ERK1/2 in THP-1 cells. In addition, trypsin-induced cell proliferation was inhibited by pretreatment of an ERK inhibitor (PD98059) or trypsin inhibitor (SBTI). Moreover, PAR2 activation by trypsin increased the secretion of TNF-alpha in THP-1 cells. CONCLUSION: There results suggest that PAR2 activation by trypsin-like serine proteases can induce cell proliferation through the activation of ERK in human macrophage and that PAR2 may play a crucial role in the cell proliferation and cytokine secretion induced by trypsin-like serine proteases.
Blotting, Western ; Cell Line* ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Humans* ; Macrophages* ; Phosphorylation ; Phosphotransferases ; Receptor, PAR-2* ; Serine Proteases ; Trypsin ; Tumor Necrosis Factor-alpha

Antigen delivery systems play critical roles in determining the quality and quantity of Ab responses in vivo. Induction of protective antibodies by B cells is essential in the development of vaccines against infectious pathogens, whereas production of IgE antibodies is prerequisite for investigation of allergic responses, or type 1 hypersensitivity reactions. Viruslike particles (VLPs) are efficient platforms for expression of proteins of interest in highly repetitive manners, which grants strong Ab responses to target antigens. Here, we report that delivery of hen egg lysozyme (HEL), a model allergen, through VLP could provoke strong HEL specific IgE Ab responses in mice. Moreover, acute allergic responses were robustly induced in the mice sensitized with VLPs that express HEL, when challenged with recombinant HEL protein. Our data show that antigen delivery in the context of VLPs could function as a platform for sensitization of mice and for subsequent examination of allergic reactions to molecules of interest.

Mirizzi syndrome with a biliobiliary fistula (Mirizzi syndrome type II) is a rare complication of a long-standing gallbladder stone disease. It is even rarer for a gallbladder stone to migrate through a biliobiliary fistula into the common duct. We encountered this interesting complication of Mirizzi syndrome type II in an 86 year-old female patient. A large gallbladder stone migrated into, and impacted into the distal common bile duct through a cholecystohepaticodochal fistula. The stone was resistant to mechanical lithotripsy and was treated with biliary endoprosthesis and oral bile acids.
Aged ; Aged, 80 and over ; Biliary Fistula/*complications ; Case Report ; Cholelithiasis/*complications ; Common Bile Duct Calculi/*etiology ; Common Bile Duct Diseases/*complications ; Female ; Fistula/*complications ; Human ; Liver Diseases/*complications ; Syndrome

We experienced a case of primary sclerosing cholangitis(PSC) in a 40-year-old female who complained of jaundice and pruritus. Marked elevation of serum alkaline phophatase level, typical beaded appearance and pruned-tree appearance on endoscopic retrograde cholangiography, together with a finding of chronic obliterative fibrosing cholangitis on sono-guided gun biopsy specimen of the liver led to a confirmative diagnosis of PSC. The patient responded to ursodeoxycholic acid (UDCA), but was reluctant to treatment and died of hepatic failure 7 months later. PSC is a very rare disease in Korea. So far, only 5 cases including our present case have been reported in the Korean literature. Male-to-female ratio was 2:3 and the median age was 40(27-80 years old). Ulcerative colitis was associated in one case. Four cases involved both intra, and extrahepatic bile ducts and one case was reported to be confined in the intrahepatic bile ducts. Fatality was in 3 cases, 20 days, 36 days, and 7 months after the initial presentaion, respectively. The causes of death were acute cholangitis and sepsis in two, and hepatic failure in one. We herein report a case of PSC and clinical charateristics of the reported cases in Korea, and review the literature with an emphasis on UDCA treatment in PSC.
Adult ; Bile Ducts, Extrahepatic ; Bile Ducts, Intrahepatic ; Biopsy ; Cause of Death ; Cholangiography ; Cholangitis ; Cholangitis, Sclerosing* ; Colitis, Ulcerative ; Diagnosis ; Female ; Humans ; Jaundice ; Korea ; Liver ; Liver Failure ; Pruritus ; Rare Diseases ; Sepsis ; Ursodeoxycholic Acid

BACKGROUND: Local anesthetics combined with an opiate are frequently used as a postoperative epidural PCA regimen. Ropivacaine is known to have a selective blockade of the sensory nerve without motor blockade. This study is designed to show advantages of ropivacaine over bupivacaine. METHODS: Patients undergoing elective abdominal and orthopedic surgeries were randomly selected and divided into two groups, B and R. The patients in group B and R received 0.2% bupivacaine and 0.2% ropivacaine respectively through an epidural catheter using a PCA pump. Both local anesthetic solutions were mixed with 4 microgram/ml of fentanyl. The PCA pumps of both groups were set in the same manner. A basal rate of 2 ml/hr was infused from 1hour after the onset of surgery. This basal rate was continued postoperatively. A bolus dose and lock out time were set at 2 ml and 20 minutes respectively. The Visual analogue pain scale (VAS), demand dose, complication and additional intramuscular analgesic requirements were checked up to 24 hours after surgery in 6-hour interval. RESULTS: The VAS was significantly lower in group R than in group B at 6, 12, 18 and 24 hours after the surgery (P < 0.05). Total additional bolus doses of the PCA pump were not significantly different in either group at 6, 12, 18 and 24 hours after surgery. The patients in group R showed more satisfaction and less additional intramuscular injections. CONCLUSIONS: 0.2% Ropivacaine, mixed with 4microgram/ml of fentanyl, was more effective than bupivacaine, mixed with the same concentration of fentanyl, in controlling postoperative pain using an epidural PCA pump.
Analgesia ; Analgesia, Patient-Controlled* ; Anesthetics, Local ; Bupivacaine* ; Catheters ; Fentanyl ; Humans ; Injections, Intramuscular ; Orthopedics ; Pain Measurement ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis

Primary gastric T-cell lymphoma is very rare. Only a few cases have been reported in the literature. Moreover, Epstein-Barr virus-associated primary gastric T-cell lymphoma is extremely rare. We report a case of Epstein-Barr virus-associated primary gastric T-cell lymphoma, which showed rapidly progressive endoscopic features. Three esophagogastroduodenoscopic examinations in a 26-day period revealed different findings at different locations. The lymphoma cells were positive for UCHL-1, but negative for L26 and Ki-1 in immunohistochemical staining.
Herpesvirus 4, Human ; Lymphoma ; Lymphoma, T-Cell* ; T-Lymphocytes*

We recently experienced a case of spontaneous perforation of infected necrosis into the colon and duodenum during the course of acute pancreatitis in a 63 year-old male patient. Enteric perforations or fistulas in the setting of acute pancreatitis implicate severe underlying pathology and have substantial morbidity and mortality. In the meantime it has generally been accepted that infected pancreatic or peripancreatic necrosis should be managed surgically as soon as possible. Enteric perforations in the present case contributed to transient improvement of the patient's infection sign and condition, and thus an early operation was able to be avoided. Delayed surgical management resulted in complete recovery of the patient without postoperative morbidity. Herein we report an unusual complication of acute pancreatitis.
Acute Disease ; Case Report ; Human ; Intestinal Perforation/*etiology ; Male ; Middle Age ; Pancreatitis/*complications

Background/Aims: Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods: This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results: This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups. Conclusions In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.