Favorable effect of corticosteroids in treating acute-on-chronic liver failure underlying chronic hepatitis B

Acute-on-chronic liver failure (ACLF) occurs in the presence of a chronic liver disease or cirrhosis, and often results from exacerbation of chronic hepatitis B (CHB). The efficacy of corticosteroid treatment in ACLF patients with underlying CHB remains unclear. We report the case of a 50-year-old woman who experienced ACLF due to CHB exacerbation and was treated with a combination of corticosteroids and nucleot(s)ide analogue (NUC). The patient showed rapid decompensation due to CHB exacerbation. Three months of antiviral therapy produced no improvement in liver function. Combination therapy with corticosteroids and NUC was started, which did result in improvement of liver function. This case shows that the combined therapy of corticosteroids and NUC can be effective in treating ACLF due to CHB exacerbation.

The PERFECT Study (PEnnel Real liFe Efficacy Clinical Trial), a Double-Blind, Randomized, Multicenter Trial Examining the Efficacy of Biphenyl Dimethyl Dicarboxylate Combined with Garlic Oil in Patients with Transaminase Elevated Chronic Liver Disease / 대한내과학회지

BACKGROUND/AIMS: Biphenyl dimethyl dicarboxylate (DDB) combined with garlic oil (pennel) has been used to treat chronic liver disease. A randomized, double-blind, active- and placebo-controlled clinical trial was conducted to investigate the efficacy, safety and quality of life in chronic liver disease patients. METHODS: A total of 237 patients with chronic liver disease were randomized into three groups; 100 patients were administered pennel, 102 patients Legalon as an active-control and 35 patients placebo for 12 weeks. The primary endpoint was the rate of alanine aminotransferase (ALT) normalization. We assessed differences in ALT levels and malondialdehyde (MDA) as an oxidative biomarker between 0 and 12 weeks, the improvement in quality of life using a chronic liver disease questionnaire (CLDQ) and the incidence of adverse events. RESULTS: Among 237 patients, there were 157 patients with non-alcoholic fatty liver disease, 36 patients with alcoholic liver disease, and 28 patients with chronic hepatitis B and C. The incidence of ALT normalization at 12 weeks was 89% for the pennel group, 18.6% for the active-control group, and 22.9% for the placebo-control group (p < 0.001). The difference in serum ALT level between 0 and 12 weeks was significantly higher in the pennel group (p < 0.001) and the level of MDA was decreased in the pennel group, statistically (p < 0.001). There was no difference in incidence of adverse events among groups. The pennel group showed significant improvement based on the CLDQ (p < 0.001). CONCLUSIONS: Pennel can effectively improve the rate of ALT normalization and the quality of life with a safety profile in chronic liver disease.

The PERFECT Study (PEnnel Real liFe Efficacy Clinical Trial), a Double-Blind, Randomized, Multicenter Trial Examining the Efficacy of Biphenyl Dimethyl Dicarboxylate Combined with Garlic Oil in Patients with Transaminase Elevated Chronic Liver Disease / 대한내과학회지

BACKGROUND/AIMS: Biphenyl dimethyl dicarboxylate (DDB) combined with garlic oil (pennel) has been used to treat chronic liver disease. A randomized, double-blind, active- and placebo-controlled clinical trial was conducted to investigate the efficacy, safety and quality of life in chronic liver disease patients. METHODS: A total of 237 patients with chronic liver disease were randomized into three groups; 100 patients were administered pennel, 102 patients Legalon as an active-control and 35 patients placebo for 12 weeks. The primary endpoint was the rate of alanine aminotransferase (ALT) normalization. We assessed differences in ALT levels and malondialdehyde (MDA) as an oxidative biomarker between 0 and 12 weeks, the improvement in quality of life using a chronic liver disease questionnaire (CLDQ) and the incidence of adverse events. RESULTS: Among 237 patients, there were 157 patients with non-alcoholic fatty liver disease, 36 patients with alcoholic liver disease, and 28 patients with chronic hepatitis B and C. The incidence of ALT normalization at 12 weeks was 89% for the pennel group, 18.6% for the active-control group, and 22.9% for the placebo-control group (p < 0.001). The difference in serum ALT level between 0 and 12 weeks was significantly higher in the pennel group (p < 0.001) and the level of MDA was decreased in the pennel group, statistically (p < 0.001). There was no difference in incidence of adverse events among groups. The pennel group showed significant improvement based on the CLDQ (p < 0.001). CONCLUSIONS: Pennel can effectively improve the rate of ALT normalization and the quality of life with a safety profile in chronic liver disease.

Unusual Treatment of Gastric Mucosa Associated Lymphoid Tissue Lymphoma Unresponsive to Helicobacter pylori Eradication

The connection between Helicobacter pylori and mucosa-associated lymphoid tissue (MALT) lymphoma is well established. H. pylori eradication is the initial treatment for MALT lymphoma. However, in H. pylori negative cases or unresponsive patients after successful eradication, radiation, systemic therapies, and surgical resection should be considered. Also local treatment modalities such as endoscopic mucosal resection (EMR) may be a therapeutic option in cases of low grade, localized MALT lymphoma. Herein, we report a case of a 53-year-old man who had a persistent endoscopic mass and tumor cells on histology for 5 months despite H. pylori eradication. Because of no early response to H. pylori eradication, the possibility of the presence of a high-grade lymphoma component, the proximal location of the tumor, and the exophytic nature of the tumor, we decided to perform EMR for complete resection. After EMR, the patient remained in complete remission throughout the 15-month follow up. In our case, endoscopic resection could lead to a more rapid complete remission. Therefore, we suggest that endoscopic resection may be a useful option for low-grade exophytic-type gastric MALT lymphoma treatment with no response to H. pylori eradication.

The Immunohistochemical Expression of STAT3, Bcl-xL, and MMP-2 Proteins in Colon Adenoma and Adenocarcinoma

BACKGROUND/AIMS: Signal transducers and activators of transcription (STATs) are a family of transcription factors that are activated in response to cytokines and growth factors. STAT3 activation has been implicated in modulating the activity of downstream mediators, such as Bcl-xL and matrix metalloproteinase-2 (MMP-2). The aim of this study was to investigate the immunohistochemical expression of STAT3, B-cell lymphoma-extra large (Bcl-xL), and MMP-2 proteins according to histopathological parameters in colon adenocarcinomas, including lymph node metastasis, tumor differentiation, the TNM stage and the tumor size. METHODS: Immunohistochemical staining with monoclonal STAT3, Bcl-xL, and MMP-2 antibodies was performed on paraffin-embedded specimens from 20 colon adenomas and 39 adenocarcinomas. RESULTS: The expression of STAT3, Bcl-xL, and MMP-2 was increased in the adenocarcinomas as compared with the adenomas (p<0.001). STAT3 expression was stronger in tumors with a distant metastasis than in tumors without a distant metastasis (p=0.012). A larger tumor size was related to an increase in STAT3 expression (p=0.035). CONCLUSIONS: STAT3, Bcl-xL, and MMP-2 may play important roles in the tumorigenesis of colorectal carcinoma. STAT3 may be indicative of a poor prognosis due to its correlation with distant metastases and a larger tumor size.

A Case of a Colon Perforation Due to a Soft Rectal Foreign Body / 대한소화기내시경학회지

Numerous foreign bodies in the rectum have been reported in the literature. Their removal can be challenging depending on the size and shape of the objects and their anatomical location in the rectum. A 64-year-old man presented to the emergency department after inserting a sausage into his rectum. He had some rectal discomfort and lower abdominal pain. There were no signs of bowel perforation. We attempted to extract the sausage impacted in the recto-sigmoid junction by colonoscopy using a snare and grasping forceps but failed to extract the foreign body. Unfortunately, a colon perforation had occurred, and the sausage was eventually extracted by performing a colostomy at the recto-sigmoid junction with primary repair. We report this case of a soft rectal foreign body impacted in the recto-sigmoid colon complicated by a colon perforation with a literature review.

A Case of H. pylori-associated Granulomatous Gastritis with Hypertrophic Gastropathy

A 46-year-old man had chronic granulomatous gastritis characterized by giant gastric folds with noncaseating epithelioid granulomas including giant cells in the corpus. No definite etiologic factors were detected. Histology and the rapid urease test indicated that H. pylori was present in both the antrum and corpus. The granulomatous gastritis with giant gastric folds improved after H. pylori eradication. This case suggests an association between isolated granulomatous gastritis and H. pylori infection.

Two cases of massive duodenal variceal bleeding successfully controlled with endoscopic injection sclerotherapy / 대한내과학회지

Duodenal variceal bleeding is rare and difficult to diagnose. The rupture of duodenal varices leads to massive and often fatal bleeding. However, there is currently no definitive conservative therapy for duodenal varices, such as the methods used for treating esophageal and gastric varices. Endoscopic treatment of variceal hemorrhage has been implemented as an initial single, minimally invasive method for treatment. However, this approach has limited success in the treatment of duodenal variceal hemorrhage. We report two cases of massive duodenal variceal bleeding successfully controlled with endoscopic injection sclerotherapy.

Minute-depressed Type of Submucosal Colon Cancer / 대한소화기내시경학회지

The development of colorectal cancer has been known as the adenoma-carcinoma sequence. Yet another route for cancer development has recently been proposed, which is call the de novo pathway based on the reports of the depressed-type early colorectal cancers. Early colorectal cancer is defined as invasive tumor limited to the colorectal mucosa or submucosa, regardless of the presence or absence of lymph node metastasis. Especially, depressed type colorectal cancers have a much higher rate of submucosal invasion and rapid progression despite of their relatively small sizes. Our case displayed a depressed type tumor that was only 5mm in diameter and it had invaded the deep submucosal layer (SM3); this was resected by operation with no predictive endoscopic finding. So, the depressed type tumor can show deep invasion or lymph node metastasis despite of its small size.

Efficacy of initial treatment with peginterferon alpha-2a versus peginterferon alpha-2b in combination with ribavirin in naive chronic hepatitis C patients living in Daejeon and Chungcheong Province in Korea: A comparative study / 대한간학회지

BACKGROUNDS/AIMS: Peginterferon alpha-2a or -2b is the standard treatment regimen in chronic hepatitis C. However, there have been few comparative studies of the efficacies of these two types of peginterferon. We evaluated their efficacies in combination with ribavirin as a initial treatment for chronic hepatitis C. METHODS: Ninety-seven patients were treated with peginterferon alpha-2a (180 microgram/week, n=48) or peginterferon alpha-2b (1.5 microgram/kg/week, n=49) plus ribavirin (800 mg/day for 24 weeks in genotype non-1 or 1,000-1,200 mg/day for 48 weeks in genotype 1). Virologic responses including the early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and adverse effects were analyzed retrospectively. RESULTS: The virologic response rates did not differ significantly between peginterferon alpha-2a and -2b: 89.6% and 89.7% for EVR, 79.2% and 79.5% for ETR, 72.9% and 73.5% for SVR, respectively. Analysis of the virologic responses according to genotype also revealed no significant differences in SVR between peginterferon alpha-2a and -2b (59.3% vs. 59.7% for genotype 1 and 90.5% vs. 83.3% for genotype non-1, respectively), or in adverse effects including flu-like symptom, rash, itching, neutropenia, and thrombocytopenia. CONCLUSIONS: We found no significant differences in therapeutic efficacies and adverse effects between the alpha-2a and -2b types of peginterferon as the initial treatment regimen in naive chronic hepatitis C patients.

Esophageal Perforation and Empyema after Fish Bone Swallowing / 대한소화기내시경학회지

Most foreign bodies accidentally ingested are eliminated naturally but 10~20% of cases require endoscopic treatment. Esophageal perforation due to the indigestion of a foreign body is rare and might be followed by mediastinitis, broncho-esophageal fistula, pneumomediastinum, peritonitis, and empyema. Rapid surgery is important because the morbidity and mortality depend on the duration from perforation to treatment. A 64 year-old woman sustained odynophagea after swallowing a fish bone. Empyema due to an esophageal perforation developed, and she died despite aggressive treatment. This case highlights the need for an early diagnosis and treatment to reduce the morbidity and mortality

Expression of c-erbB-2 and c-met Proteins in Gastric Adenoma and Adenocarcinoma / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study was to investigate the immunohistochemical overexpression of c-erbB-2 and c-met proteins according to the histopathological parameters such as grade of dysplasia, histological type, depth of invasion, lymph node metastasis, and TNM stage in gastric adenoma and gastric adenocarcinoma. METHODS: Immunohistochemical staining using monoclonal c-erbB-2 and c-met antibodies was performed on paraffin embedded specimens in 43 adenomas and 44 adenocarcinomas. RESULTS: The expression rate of c-erbB-2 was higher in adenomas (91%) than adenocarcinomas (30%). The expression rate of c-met was higher in adenocarcinomas (77%) than adenomas (49%). In adenoma, the expression rate of c-met was higher in high grade dysplasia (94%) than in low grade dysplasia (22%). In adenocarcinoma, c-met expression was significantly related with lymph node metastasis. CONCLUSIONS: c-erbB-2 would be involved in the development of relatively early stage gastric carcinogenesis. c-erbB-2 is related with histologic type and c-met with lymph node metastasis in gastric carcinomas. Although meaning for the experession of these proteins in gastric carcinomas would be different, these proteins may play as important oncogenes in gastric carcinogenesis.

Expression of TGF-beta1, TGF-beta Receptor Type II and VEGF in Colorectal Adenomas and Adenocarcinomas / 대한소화기내시경학회지

BACKGROUND/AIMS: The aim of study was to investigate the expression of TGF-beta, TGF-RII and VEGF determined by immunohistochemical analysis with a comparison of the clinicopathological parameters such as tumor size, grade of dysplasia, lymph node metastasis and Dukes' stage in colorectal adenomas and adenocarcinomas, by use of a tissue microarray method. METHODS: The expression of TGF-beta1, TGF-betaRII, and VEGF was determined by immunohistochemistry in 20 adenomas and 40 adenocarcinomas. Tissue microarrays consisting of 2 mm cores from corresponding blocks were constructed and stained. RESULTS: In adenomas, the staining intensity of TGF-beta, TGF-betaRII and VEGF was increased in a high-grade dysplasia group of patients as compared a with low-grade dysplasia group of patients, respectively. The staining intensity of TGF-betaRII was significantly increased in a high-grade dysplasia group of patients than a low-grade dysplasia group of patients (p =0.021). For the adenocarcinomas, the expression and staining intensity of TGF-beta1, TGF-betaRII and VEGF were increased as compared with the adenomas (p<0.001). However, no significant correlation was observed between the staining intensity of TGF-beta, TGF-betaRII and VEGF and the clinicopathological parameters. CONCLUSIONS: The increased expression of TGF-beta1, TGF-betaRII and VEGF in colorectal adenocarcinoma suggests a role for these proteins in colorectal carcinogenesis. Loss of the growth-inhibitory effect of TGF-beta may commence in the early stage of colorectal carcinogenesis.

Decreased Hepatic Nerve Fiber Innervation in Patients with Liver Cirrhosis

BACKGROUND/AIMS: Hepatic nerve innervation plays important roles in hepatic metabolism and hemodynamic mechanisms. We compared the distribution patterns of hepatic nerves between normal livers and two liver diseases to elucidate the effects of liver disease on the distribution of hepatic nerves. METHODS: Tissue specimens were obtained by ultrasonography-guided needle biopsies from 10 normal controls, 74 patients with chronic hepatitis (CH), and 35 patients with liver cirrhosis (LC). The obtained specimens were immunohistochemically stained using antibodies for S-100 protein and alpha-smooth-muscle actin (alpha-SMA). The degree of the expression in liver tissues was quantified by manual counting of positively stained nerve fibers under light microscopy. The serum hyaluronic acid level was assayed in all subjects to evaluate hepatic fibrosis. Electron microscopy examinations were also performed. RESULTS: The hepatic nerve innervation was significantly lower in LC than in normal controls, as indicated by S-100 protein staining. alpha-SMA and hyaluronic acid levels were higher in LC and CH than in normal controls. Electron microscopy revealed that unmyelinated nerve fiber bundles in the intralobar connective tissue coursed in the vicinity of hepatic triads. CONCLUSIONS: These results suggest that hepatic nerve innervation can be decreased by hepatic inflammatory responses and/or fibrotic changes in LC patients. Further study is needed to clarify this observation.

Clinical Outcomes of Delayed Clearance of Serum HBsAg in Patients with Chronic HBV Infection

BACKGROUND: Spontaneous delayed clearance of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection is a rare event. The aim of this study was to investigate the incidence of delayed clearance of serum HBsAg in chronic HBV infection and to determine the characteristics and clinical outcomes of HBsAg delayed clearance in Korean patients. METHODS: From April 1981 to June 2003, 4,061 patients who were positive for HBsAg were evaluated retrospectively. The following assessments were undertaken in 47 patients who had spontaneous delayed clearance: liver biochemistry, viral markers, alpha-fetoprotein levels, and radiographic examinations including ultrasonography every three to six months for 6-264 months (median 87.9 months). RESULTS: Twenty-four of 47 patients were asymptomatic carriers. The others included seven patients with chronic hepatitis, seven with liver cirrhosis and nine with hepatocellular carcinoma. The estimated annual incidence of HBsAg seroclearance was 0.4%. The time span from positive HBsAg to HBsAg seroclearance in the AHC, CH, LC, and HCC was 62.9, 141, 63, and 95.3 months during follow up. Twenty-four of 24 AHC remained normal, 5 of 7 CH remained as CH and 2 patients remained normal, 1 of 7 with LC developed HCC and 6 of the LC remained as LC, and 4 of 9 HCC patients died. CONCLUSION: The clinical course following delayed clearance of HBsAg had diverse outcomes from AHC to HCC. Therefore, these patients require close follow up for the possible development of hepatocellular carcinoma following HBsAg clearance.

Apoptosis and Cell Proliferation in Gastric Adenoma and Adenocarcinoma

PURPOSE: Cancer is a genetic disease caused by alterations in key regulators of cell growth and cell turnover. We investigated apoptotic cell death and cell proliferation in gastric adenomas and adenocarcinomas. MATERIALS AND METHODS: The TdT-mediated dUTP-biotin nick end labelling (TUNEL) method and immunohistochemistry for Ki-67 were performed, using paraffin-embedded tissues of 41 gastric adenomas and 100 gastric adenocarcinomas. These results were compared with histopathologic parameters. RESULTS: The Ki-67 labelling index was higher in adenocarcinomas than in adenomas and the apoptotic index was higher in adenomas than in adenocarcinomas. There were no significant difference between the apoptotic index/Ki-67 labelling index and clinicopathological parameters. CONCLUSION: We propose that cell proliferation is more closely associated with gastric adenocarcinomas than apoptosis is, but that neither has any clinical significance as a prognostic factor in gastric adenocarcinomas.

Toxic Hepatitis Associated with Carp Juice Ingestion / 대한간학회지

The potential hepatotoxicity of herbal remedies and/or health foods is usually ignored in daily life. There have been cases showing the toxic hepatitis and renal failure associated with the ingestion of raw carp bile. We experienced a case of toxic hepatitis without any evidence of renal failure that was associated with carp juice ingestion. The clinical manifestations were characterized by nausea and vomiting after the ingestion of carp juice for 3 months. The diagnosis of toxic hepatitis was made on the basis of the patient's history, laboratory data, RUCAM (Russel Uclaf Causality Assessment) and the results of ultrasonography guided liver biopsy. The patient showed rapid improvement after instituting supportive therapy.

A Case of Rectal Anisakiasis / 대한소화기내시경학회지

Anisakiasis refers to the infestation of humans by a species of marine nematode larvae belonging to the subfamily Anisakidae, and this condition is seen in people who eat inadequately prepared or raw salt-water fish and squid. Because Koreans like to eat raw fish, anisakiasis of the stomach has been reported occasionally, but involvement of the small bowel or colon is relatively rare. In the case of the colon, anisakiasis of the ascending colon or the transverse colon has been only infrequently reported, and the incidence of rectal anisakiasis is very rare. The present case is a 58-year-old man with no definite abdominal symptoms who visited our hospital for a medical checkup. A 2 cm sized whitish linear live larva was revealed in the rectum and it was removed by colonoscopy.

A Case of Gastric Syphilis Manifested by Upper Gastrointestinal Bleeding / 대한소화기내시경학회지

Syphilis is a chronic systemic infection caused by Treponema pallidum; it is sexually transmitted and characterized by episodes of active disease interrupted by periods of latency. Syphilitic involvement of the stomach can occur via the blood flow in the primary or secondary period of syphilis, but its incidence is very rare. Because gastric syphilis has no pathognomic clinical findings and it shows variable gastroscopic findings, it's not so easy to diagnose. After gastric syphilis is correctly diagnosed, it can be easily cured by appropriate antibiotic therapy. The clinicians need to be aware of this disease entity when the patient has mucosal inflammation and ulceration of stomach with the past history of syphilis, or if the patient has lived in edemic areas of syphilis. We report on a case of gastric syphilis that manifested with upper gastrointestinal bleeding. It was initially thought to be stomach cancer, but it was correctly diagnosed by serologic testing and the histopathologic findings.

A Randomized, Prospective, Comparative, Multicenter Study of Rabeprazole and Ranitidine in the Treatment of Reflux Esophagitis / 대한소화기학회지

BACKGROUND/AIMS: This study was done to evaluate the efficacy of rabeprazole (proton-pump-inhibitor) and ranitidine (H2-receptor antagonist) in the symptom relief and treatment of erosive esophagitis diagnosed by endoscopy. METHODS: A total of 110 patients with typical gastroesophageal reflux disease (GERD) symptoms were enrolled in this multicenter study. They were randomized into rabeprazole group (53 patients) and ranitidine group (57 patients) respectively. The patients in rabeprazole group were given 10 mg of rabeprazole and ranitidine group received 300 mg of ranitidine before breakfast and dinner for 8 weeks. After the end of treatment, we evaluated the endoscopic healing rate of reflux esophagitis and symptomatic improvement. RESULTS: After 8 weeks of treatment, rabeprazole group showed significantly higher complete endoscopic cure rate than ranitidine group (86.8% [46/53] vs. 57.9% [33/57], p=0.001) and higher symptomatic improvement of heartburn (91.2% [31/34] vs. 76.2% [32/42], p=0.085), especially in the first 7 days (76.7% vs. 45.3%, p=0.008). Also, rabeprazole group showed significantly higher improvement of regurgitation symptom than ranitidine group (100% [35/35] vs. 83% [39/47], p=0.009). Both group showed no differences in the improvement of chest pain and globus sensation. All the adverse events (rabeprazole group 4 events vs. ranitidine group 3 events) were mild and there was no abnormality in laboratory test. CONCLUSIONS: In patients with GERD, rabeprazole 10 mg b.i.d. is superior to ranitidine 300 mg b.i.d. in healing of reflux esophagitis and resolving typical GERD symptoms. Rabeprazole is an effective and well-tolerated drug for GERD treatment.