Large-scale surveillance study of the safety and effectiveness of entecavir in Korean patients with chronic hepatitis B

BACKGROUND/AIMS@#Entecavir (ETV) is effective and safe antiviral agent against hepatitis B virus (HBV) in clinical and real-world setting but, most studies were performed in single institute or have limitation in patient's number. A large-scale nation-wide real-world surveillance study was carried out to investigate safety, efficacy and clinical effectiveness of ETV in Korean patients with chronic hepatitis B (CHB).@*METHODS@#Between 2006 and 2012, 3,444 patients were enrolled from 132 Korean institutions. For the safety assessment, investigators recorded the occurrence of observed and patient-reported adverse events (AEs), as well as laboratory abnormalities. Efficacy, which consisted of change in HBV DNA and alanine aminotransferase (ALT), was evaluated in patients who had received at least 16 weeks of ETV treatment. Overall clinical effectiveness, based on improvement of ALT, HBV DNA and patient's symptoms, was evaluated by physicians.@*RESULTS@#Of the patients, 3,367 were evaluated for safety and 3,115 for efficacy and clinical effectiveness. Three hundred and eighty AEs were reported in 255 cases (7.57%), and 67 adverse drug reactions in 54 cases (1.6%). Serious AEs (SAE) were 19 events in nine cases (0.27%). Serious adverse drug reactions (SADR) were three events in two cases (0.06%), and unexpected SAE/SADR were three events in two cases (0.06%). Medical history and concomitant medications were factors inf luencing incidence rates of AEs. Overall clinical effectiveness rate was 96.53%, which was clinically assessed as marked improved or improved state.@*CONCLUSIONS@#This study showed that ETV was well tolerated and clinically effective in Korean patients with CHB in a real-world nation-wide setting.

A Decade-old Change in the Screening Rate for Hepatocellular Carcinoma Among a Hepatitis B Virus-infected Population in Korea / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Evaluating a change in the screening rate for hepatocellular carcinoma (HCC) is critical for understanding screening implementation, and whether targeted population groups are receiving proper screening. This study examined recent nationwide changes in HCC screening use among hepatitis B virus (HBV)-infected populations after the introduction of the Korean National Cancer Screening Program and predictors of screening adherence.</p><p><b>METHODS</b>We analyzed 165 and 276 participants ≥40 years of age who were hepatitis B surface antigen-positive from 2001 (14,936 participants) to 2010-2011 (9159 participants) Korea National Health and Nutrition Examination Surveys, respectively. Demographic data, socioeconomic factors, and HCC screening use were collected by means of self-reported questionnaires.</p><p><b>RESULTS</b>The rate of HCC screening within the previous 2 years increased significantly from 17.5% in 2001 to 40.3% in 2010-2011 (P < 0.0001). The rate of HCC screening use increased from 2001 to 2010-2011 in all study populations. Subjects who had a higher income status and were aware of their infection were more likely to have undergone recent HCC screening.</p><p><b>CONCLUSIONS</b>This study showed a substantial increase in HCC screening in high-risk HBV-infected subjects from 2001 to 2010-2011. However, the HCC screening participation rate remained suboptimal despite the introduction of the nationwide screening program. Efforts should be made to identify high-risk individuals and increase attendance at HCC screening events among high-risk groups.</p>

Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A

BACKGROUND/AIMS: The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). METHODS: Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. RESULTS: PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1: 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4: 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. CONCLUSIONS: Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.

Complications Requiring Hospital Admission and Causes of In-Hospital Death over Time in Alcoholic and Nonalcoholic Cirrhosis Patients

BACKGROUND/AIMS: Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade. METHODS: We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis. RESULTS: Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods. CONCLUSIONS: The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.

Massive Bleeding Hemobilia Occurred in Patient with Hepatocellular Carcinoma / 대한소화기학회지

Massive bleeding hemobilia occurs rarely in patients with hepatocellular carcinoma (HCC) without any invasive procedure. Upper gastrointestinal bleeding in patient with cirrhosis and abdominal pain with progressive jaundice in patient with HCC were usually thought as variceal bleeding and HCC progression respectively. We experienced recently massive bleeding hemobilia in patient with HCC who was a 73-year old man and showed sudden abdominal pain, jaundice and hematochezia. He had alcoholic cirrhosis and history of variceal bleeding. One year ago, he was diagnosed as HCC and treated with transarterial chemoembolization periodically. Sudden right upper abdominal pain occurred then subsided with onset of hemotochezia. Computed tomography showed bile duct thrombosis spreading in the intrahepatic and extrahepatic ducts, while an ampulla of vater bleeding was observed during duodenoscopy. Hemobilia could be one of the causes of massive bleeding in patients with cirrhosis and HCC especially when they had sudden abdominal pain and abrupt elevation of bilirubin.

A Case of Spontaneous Hemoperitoneum without Spleen Injury after a Diagnostic Colonoscopy / 대한내과학회지

Colonoscopy is a widely used diagnostic and therapeutic intervention with an excellent safety profile. Although an intraperitoneal hemorrhage is a rare complication after colonoscopy, and usually associated with splenic injury or solid organ pathology, it is potentially serious and can be life-threatening. We report a rare case of spontaneous intraperitoneal hemorrhage after diagnostic colonoscopy without splenic injury or intra-abdominal abnormality, known as idiopathic spontaneous intraperitoneal hemorrhage. This case emphasizes that physicians should be aware of the emergence of acute abdomen after colonoscopy.

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

BACKGROUND/AIMS: The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH. METHODS: One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8+/-13.5 years, mean+/-SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea. RESULTS: According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis > or =2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH. CONCLUSIONS: Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.

Rhabdomyolysis and Mild Kidney Injury in a Patient with Acute Hepatitis A / 영남의대학술지

A 48-year-old male visited the emergency room of the authors' hospital due to nausea, vomiting, and myalgia for four days. Acute hepatitis A was identified from the serologic marker of the hepatitis A virus. Mild elevation of the serum creatinine and creatinine phosphokinase (CPK) suggested rhabomyolysis, which was confirmed with the serum aldolase, myoglobin, and urine myoglobin. With supportive care, both the liver and renal functions were recovered gradually and fully. This case shows that rhabdomyolysis can be one of the mechanisms of renal complication in cases of acute symptomatic hepatitis A.

Apoptosis and diagnosis of nonalcoholic steatohepatitis / 대한간학회지

No abstract available.

Gastric Outlet Obstruction by Impacted Phytobezoar at the Normal Duodenal Bulb

Phytobezoars are the most common bezoars composed of non-digestible food materials, such as fiber, seeds, skin of fruits. The predisposing factors of bezoars are altered gastrointestinal motility and anatomy. It is uncommon for bezoars occurring in patient with normal gastric anatomy to cause impaction on the duodenal bulb. We experienced a phytobezoar at the duodenal bulb causing gastric outlet obstruction in a patient who had no predisposing factors. The patient was treated by endoscopic removal.

Autoimmune hemolytic anemia during PEG-interferon and ribavirin treatment for hepatitis C / 대한내과학회지

The current best treatment for HCV infection is combination therapy with PEG-interferon and ribavirin. This combination therapy has markedly increased the number of sustained virologic responders but is associated with various side effects, especially hematological abnormalities. We recently experienced a 45-year-old man who developed PEG-interferon induced autoimmune hemolytic anemia (AIHA) and retinal premacular hemorrhage. The worsening hemolysis after ribavirin withdrawal and exclusion of other causes implicated PEG-interferon as the cause of the AIHA. To the best of our knowledge, this is the first case reported from Korea. Treatment with PEG-interferon requires careful follow-up, as it can induce or exacerbate autoimmune diseases.

A Case of Bleeding on the Ampulla of Vater Due to Angiodysplasia in a Patient with End Stage Renal Disease / 대한소화기내시경학회지

Gastrointestinal angiodysplasia is one of the causes of acute and chronic gastrointestinal bleeding, and gastrointestinal angiodysplasia makes up 2~6% of all the cases of upper gastrointestinal bleeding. Bleeding from the ampulla of Vater is very rare. We report here on an unusual case of bleeding from angiodysplasia at the ampulla of Vater in a 58-aged woman with end stage renal failure. This lesion was successfully treated with endoscopic argon plasma coagulation.

Myxedema Ascites: Case Report and Literature Review

Myxedema ascites caused by hypothyroidism is rare, so its diagnosis is often delayed and patients frequently receive unnecessary procedures such as liver biopsies and exploratory laparotomies. We report a 71-yr-old man with clinical ascites that was the first manifestation of hypothyroidism, and which resolved completely in response to thyroid hormone replacement therapy. To our knowledge, this is the first report of myxedema ascites in Korea. A review of the literature revealed 51 well-documented cases of myxedema ascites. Analyses of ascites from patients in this condition usually show high protein (>2.5 g/dL) and low white blood cell counts, with a high proportion of lymphocytes. A consistent feature is the good response to thyroid hormone replacement therapy, which has always led to resolution of the ascites. Myxedema ascites is thus rare but easy to treat; it should be borne in mind, especially if the ascites fluid has a high protein content.

A Case of Acute Pancreatitis Associated with Fasciola Hepatica / 대한소화기내시경학회지

Fascioliasis is a zoonotic helminthiasis caused by the trematode Fasciola hepatica, which is a parasite that infects the hepatobiliary system of herbivorous animals such as cattle and sheep. Humans are accidentally infected after ingestion of the water, raw aquatic plants and raw liver of herbivorous animals that are all contaminated by metacercaria. Fascioliasis produces no symptoms in most patients, but adult Fasciola hepatica occasionally gives rise to intestinal obstruction or pancreatobiliary disease. The metacercaria can migrate along the vessels or lymphatic ducts, and they can induce disease of the liver, lung and heart. We report here on a rare case of a 68-year-old male who presented with acute abdominal pain. He was diagnosed as acute pancreatitis associated with Fasciola hepatica.

A Case of Pulmonary Thromboembolism in Active Ulcerative Colitis / 대한소화기학회지

Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease. The reported incidence is 1-6%. The most common thromboembolic complications are deep venous thrombosis of legs and pulmonary thromboembolism. Cerebral thrombosis, portal vein thrombosis, retinal venous thrombosis and arterial thrombosis were also reported. We experienced a case of ulcerative colitis complicated with pulmonary thromboembolism. The patient was a 70-year-old woman who was diagnosed as ulcerative colitis on colonoscopy. We used prednisolone and sulfasalazine for the treatment of ulcerative colitis. Twenty five days later, she complained of abrupt dyspnea and chest pain. Chest CT and ventilation-perfusion scan revealed a thromboembolism in both lung. After the treatment of heparin & warfarin therapy, follow-up chest CT showed much regressed pulmonary thromboembolism. We report a 70-year-old woman with ulcerative colitis complicated with pulmonary thromboembolism and treated with heparin & warfarin therapy successfully.

A Case of Lower GI Bleeding from Portal Hypertensive Colopathy Successfully Treated with Octreotide Administration and Endoscopic Hemoclipping / 대한소화기내시경학회지

Cirrhotic patients with portal hypertension are often found to have changes in their colonic mucosa. Such mucosal changes are termed portal hypertensive colopathy. Most patients with portal hypertension remained asymptomatic but some may show massive bleeding. The mainstay of treatment for portal hypertensive gastropathy include non-surgical methods such as octreotide injection, endoscopic hemostasis, and interventional methods such as TIPS. However, treatment for portal hypertensive colopathy remained unresolved. The authors here report a case of a 41 year old male with liver cirrhosis admitted for fever and abdominal pain, who reported an episode of hematochezia in the course of admisssion period. Subsequent colonoscopy revealed angiodysplasia-like lesions throughout the entire colon. We observed that such lesions were the source of hematochezia and that direct clipping with octreotide injection was successful in controlling the bleeding.

A Case of Hemorrhagic Colitis Complicated by Thrombotic Thrombocytopenic Purpura / 대한소화기내시경학회지

Hemorrhagic colitis may be seen as a complication of inflammatory bowel disease, as well as infectious colitis related to several pathogens, including enterohemorrhagic E. coli, Shigella, Yersinia and Campylobacter. Also, it is seen in the form of antibiotic-associated hemorrhagic colitis. However, Escherichia coli serotype O157:H7 is now recognized as an important identifiable cause of hemorrhagic colitis. Occasionally, patients with E. coli serotype O157:H7 infection are diagnosed as having thrombotic thrombocytopenic purpura (TTP), a condition similar to hemolytic uremic syndrome (HUS) but with more prominent neurological findings and less renal involvement. We report a case in a 47-year-old woman who developed hemorrhagic colitis complicated by TTP, responded to steroid and antibiotic treatment.

Spontaneously Reduced Invaginated Appendiceal Intussusception after Colonoscopic Examination / 대한소화기내시경학회지

Appendiceal intussusception is an uncommon type of intussusception with the incidence of 0.01% in children and adults. In many cases it was developed by secondary conditions, such as polyps, carcinoma or lymphoma. But some other cases was reduced after barium enema study and had none of initiating causes. Therefore, making an accurate diagnosis is important in providing the optimal treatment for the patient. We present an appendiceal intussusception spontaneously reduced after colonoscpic examination. A 61-year-old woman with indigestion, nausea and right lower quadrant abdominal tenderness was admitted for further evaluation and treatment. Colonoscopic exam revealed a invaginated appendix with normal appearing covring mucosa intraluminaly. Blind mucosal biopsies on the appendiceal orifice yielded mild inflammatory cell infiltration. Two days after the colonoscopic procedure, patient's abdominal symptoms and sign were disappeared. Abdominal CT scan revealed that appendiceal intussusception was spontaneously reduced and a few several reactive mesenteric lymphadenopathy was observed. The ultrasound scan revealed the appendiceal wall swelling. The patient was discharged after the relief of abdominal symptom without further treatment.

A Case of Successful Treatment of a Bleeding Duodenal Ulcer with Endoscopic Hemoclipping in a Child / 대한소화기내시경학회지

Upper gastrointestinal bleeding in infant and children is much less common than that in adults. Upper gastrointestinal bleeding in infants and young children is most often acssociated with stress ulcer or erosions, but in older children it may also be caused by duodenal ulcer, esophagitis, and esophageal varices. Because the total blood volume of a child is relatively small and can deplete rapidly, gastrointestinal bleeding is a catastrophic event. However, it is not associated with significant mortality except in those with a severe primary illness. Data on therapeutic endoscopy for pediatric gastrointestinal bleeding are limited to case reports. The hemoclip has recently been added to armamentaria of endoscopic devices. This method has several advantages, including fewer complication and the fact that less expertise is needed to achieve permanent hemostasis. We report a case of successful endoscopic control of a bleeding duodenal ulcer using with a hemoclip in a 22-month-old boy. Endoscopic hemoclipping would be a safe and efficacious treatment for control of bleeding from peptic ulcers in children.

A Case of Gastrointestinal Bleeding Caused by Dieulafoy-like Lesions of the Stomach and Rectum in a Patient with Chronic Renal Failure / 대한소화기내시경학회지

Dieulafoy's lesion is a very rare cause of gastrointestinal bleeding that occurs after rupture of an exposed submucosal artery. The majority of lesions are found in the stomach, but rarely it has also been identified in the duodenum, small bowel, colon and rectum. We describe a 78-year-old female with chronic renal failure who presented with melena and was subsequently found to have a Dieufaloy-like lesion in the stomach. The bleeding was successfully managed by endoscopic hemoclipping. During the follow-up, massive gastrointestinal bleeding was developed by a Dieulafoy-like lesion in the rectum. This lesion was managed by endoscopic band ligation, but there was recurrent bleeding from the ulcer site. The ulcer site was locally excised and primary closure was carried out.