The incidence of severe hepatitis A virus (HAV) infection has been increasing. However, clinicopathologic features of severe HAV infection that lead to liver transplantation (LT) have not been reported in Korea. We retrieved 16 LT cases with HAV infection during the last 3 years at Asan Medical Center, Seoul, Korea. Fifteen cases progressed to hepatic encephalopathy. Thirteen cases survived with or without complications, and three patients died of sepsis. The explanted liver showed massive or zonal necrosis with moderate to severe cholestasis. The zonal distribution of necrosis was frequently associated with endothelialitis of portal and/or central veins. Degenerative changes of hepatocytes were various in degree and distribution. Viral inclusions were suspected in two cases. Although HAV infection is usually confirmed by serological tests, significant venulitis of central and/or portal veins and viral inclusions, which are rarely observed, can suggest an HAV infection as a cause of massive hepatic necrosis of unknown mechanism.
Cholestasis ; Fluconazole ; Hepatic Encephalopathy ; Hepatitis ; Hepatitis A ; Hepatitis A virus ; Hepatocytes ; Humans ; Incidence ; Korea ; Liver ; Liver Transplantation ; Massive Hepatic Necrosis ; Necrosis ; Portal Vein ; Sepsis ; Serologic Tests ; Veins

BACKGROUND: We summarize our experience in the pathological diagnosis of late complications of liver transplantation (LT) to better understand the causes of late allograft dysfunction in a population mostly composed of patients with hepatitis B virus (HBV) infection. METHODS: We reviewed 361 post-transplant liver biopsies from 174 patients who underwent LT and first presented with liver function abnormalities 3 months post-procedure. The underlying diseases included HBV-associated liver disease (77%), toxic or alcoholic liver disease (10.3%), hepatitis C virus (HCV)-associated liver disease (8.6%), primary biliary cirrhosis (1.2%), primary sclerosing cholangitis (1.2%), and metabolic disease (1.7%). RESULTS: The three most common late complications were acute rejection (32.5%), recurrent disease (19.1%), and biliary complication (17.1%). Patients who underwent LT for HBV infection or for drug- or alcohol-related liver disease had a lower incidence of recurring disease than those who underwent transplantation for HCV infection. During post-transplantation months 3-12, acute rejection was the most common cause of allograft dysfunction and recurring disease was the leading cause for allograft dysfunction (p=0.039). The two primary causes of late allograft dysfunction have overlapping histological features, although acute rejection more frequently showed bile duct damage and vascular endothelialitis than recurring HBV infection, and recurring HBV infection had more frequent lobular activity and piecemeal necrosis. CONCLUSIONS: The causes of late liver allograft dysfunction are closely associated with the original liver diseases and the period after LT. Careful attention is required for differential diagnosis between acute rejection and recurrent HBV.
Bile Ducts ; Biopsy ; Cholangitis, Sclerosing ; Diagnosis, Differential ; Hepacivirus ; Hepatitis B virus ; Humans ; Incidence ; Liver ; Liver Cirrhosis, Biliary ; Liver Diseases ; Liver Diseases, Alcoholic ; Liver Transplantation ; Metabolic Diseases ; Rejection (Psychology) ; Transplantation, Homologous ; Transplants

BACKGROUND: Surgical resection is the treatment of choice of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. However, the benefit of clearing resection margin is still controversial. METHODS: We reviewed 281 surgically resected cases of IPMN. The recurrences were compared according to the histologic grade (benign or borderline IPMN, malignant noninvasive IPMN, invasive carcinoma) and size (pancreatic intraepithelial neoplasia, PanIN, less than 0.5 cm in the long axis; and IPMN, greater than or equal to 0.5 cm) of the residual lesions at the resection margin. RESULTS: Sixty cases (21.4%) were invasive carcinoma, and 221 (78.6%) noninvasive cases included 87 (31.0%) benign, 107 (38.1%) borderline and 11 (3.9%) malignant noninvasive IPMN cases. In noninvasive IPMN, increased recurrence in patients with five or more years of follow-up was only related to the involvement of resection margin by severe dysplasia. The recurrence of invasive carcinoma was high (27.3%) even when the resection margin was clear, and was not related to the grade or size of residual tumors at the resection margin. CONCLUSIONS: Invasiveness is a strong risk factor for recurrence in IPMN regardless of the status of the resection margin. However, in noninvasive IPMN, histologic grading of residual lesions at the resection margin predicts local recurrence.
Carcinoma, Intraductal, Noninfiltrating ; Follow-Up Studies ; Humans ; Mucins ; Neoplasm, Residual ; Pancreas ; Recurrence ; Risk Factors

Understanding the important alterations during hepatocarcinogenesis as well as the characteristic magnetic resonance imaging (MRI) and histopathological features will be helpful for managing patients with chronic liver disease and hepatocellular carcinoma. Recent advances in MRI techniques, such as fat/iron quantification, diffusion-weighted images, and gadoxetic acid-enhanced MRI, have greatly enhanced our understanding of hepatocarcinogenesis.
Carcinoma, Hepatocellular ; Humans ; Liver Diseases ; Magnetic Resonance Imaging ; Pathology

BACKGROUND: Idiopathic portal hypertension (IPH) is a rare clinicopathologic entity that shows clinical evidences of portal hypertension with no pathologic features of cirrhosis. METHODS: The clinical and pathologic features of 8 cases with IPH were analyzed via the medical records along with the biopsy or resected liver specimens. RESULTS: Six patients were male and two were female. The chief complaints were sudden variceal bleeding in seven patients and abdominal pain in one patient. Six patients were treated with varix ligation and one was treated with splenectomy after the failure of bleeding control. One patient underwent a liver transplantation due to severe symptoms of portal hypertension. The prognosis of all the patients was excellent. Microscopically, the portal tracts were variably fibrotic, and the portal veins in them were sclerotic, obliterated or dilated in 7 cases; pathologic abnormalities were absent in 1 case. Cirrhosis was absent in all cases, while septal fibrosis was present in one resected liver. CONCLUSIONS: IPH is a minor cause of portal hypertension. However, a liver biopsy to show the subtle portal vascular changes and fibrosis in patients who have the clinical symptoms of portal hypertension is important for making the diagnosis of IPH.
Abdominal Pain ; Biopsy ; Diagnosis ; Esophageal and Gastric Varices ; Female ; Fibrosis ; Hemorrhage ; Humans ; Hypertension, Portal* ; Ligation ; Liver ; Liver Transplantation ; Male ; Medical Records ; Portal Vein ; Prognosis ; Splenectomy ; Varicose Veins

BACKGROUND: The resurgence of tuberculosis and the widespread emergence of multidrug-resistant M. tuberculosis have emphasized the importance of rapid and accurate diagnostic procedures. Recently, the oligonucleotide chip has proven to be a useful tool in the rapid diagnosis of infectious diseases. The purpose of this study was to rapidly and accurately detect specific mutations in the rpoB, katG and rpsL genes associated with rifampin, isoniazid and streptomycin resistance in M. tuberculosis, respectively, using a single oligonucleotide chip. METHOD: For detection of drug-resistance, 7 wild-type and 13 mutant-type probes for rifampin, 2 wild-type and 3 mutant-type probes for isoniazid, and 2 wild-type and 2 mutant-type probes for streptomycin were designed and spotted onto glass slides. Fifty-five cultured samples of M. tuberculosis were amplified by PCR, and then underwent hybridization and scanning. Direct sequencing was done to verify the results from the oligonucleotide chip and to analyze the types of mutations. RESULT: Thirty-five cases out of 40 rifampin-resistant strains(~88%) had mutations in the rpoB gene. One case had a new mutation(D516F, GAC R TTC) and another known mutation together. Twenty cases out of 42 isoniazid-resistant strains(~50%) had mutations in the katG gene, while 7 cases out of 9 streptomycin-resistant strains(~78%) had mutations in the rpsL gene. From these results, the oligonucleotide chip was confirmed to be able to detect the most frequent mutations from the genes associated with rifampin, isoniazid and streptomycin resistance. The results proved that the drug-resistance detection probes were specific. When the results from the oligonucleotide chip and DNA sequencing were compared, the types of mutations were exactly matched. CONCLUSION: The diagnostic oligonucleotide chip with mutation specific probes for drug resistance is a very reliable and useful tool for the rapid and accurate diagnosis of drug resistance against rifampin, isoniazid and streptomycin in M. tuberculosis infections.
Communicable Diseases ; Diagnosis ; Drug Resistance ; Drug Resistance, Multiple ; Glass ; Isoniazid ; Mycobacterium tuberculosis* ; Mycobacterium* ; Polymerase Chain Reaction ; Rifampin ; Sequence Analysis, DNA ; Streptomycin ; Tuberculosis

BACKGROUND/AIMS: Mucin-hypersecreting bile duct tumor is rare, and has an unusual histologic characteristic of having various degrees of cellular atypia ranging from dysplasia to invasive carcinoma in the same specimen. To gain insight into the role of p16, p14 and p53 in the carcinogenic process of bile duct tumor, we analyzed the expression status of these proteins in mucin-hypersecreting bile duct tumor. METHODS: Immunohistochemical staining of p16, p14 and p53 were performed in 34 paraffin embedded tissues obtained from 22 patients of mucin-hypersecreting bile duct tumor. RESULTS: Thirty-four specimens were categorized into low-grade dysplasia (9), high-grade dysplasia (4), carcinoma in situ (CIS, 11) and invasive carcinoma (10) based on the degree of cytologic and structural atypia. p53 overexpressions were found in 6 (17.6%, 3 in CIS, 3 in invasive carcinoma) and more frequently observed in the advanced histologic stages (p<0.05). Loss of p16 staining was found only in 2 (6%) of low-grade dysplasia specimen. Loss of p14 staining was found in 21 (61.7%, 7 in low-grade dysplasia, 2 in high-grade dysplasia, 8 in CIS, and 4 in invasive carcinoma) and was frequently observed in low-grade and high-grade dysplasia compared to p53 (p<0.05). CONCLUSIONS: In mucin-hypersecreting bile duct tumor, p14 and p53 may play a role in the early and advanced stage of carcinogenesis, respectively. Further study regarding genetic and epigenetic alterations in p14 and p53 gene may be needed.
Adult ; Aged ; Bile Duct Neoplasms/*genetics/secretion ; Carcinoma/*genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/secretion ; English Abstract ; Female ; *Genes, p16 ; *Genes, p53 ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mucins/*secretion ; *Mutation ; Tumor Suppressor Protein p14ARF/*genetics

Purpose: We aimed to investigate clinical outcomes between top-down (TD) and conventional step-up (SU) therapies in pediatric patients with moderate to severe ulcerative colitis (UC). Materials and Methods: All patients underwent clinical and endoscopic evaluation at diagnosis and 4 months and 1 year after treatment. Patients who started treatment with corticosteroid were grouped in the SU group, while those that initiated early infliximab (IFX) were grouped in the TD group. Among the SU group, patients who eventually changed to IFX treatment due to steroid resistance or dependency were included in the SU(R) group. Results: In total, 44 children with moderate to severe UC were included for analysis. Twenty-one patients were included in the SU group, 23 were included in the TD group, and 10 were enrolled in the SU(R) group. Relapse rates were 47.6% (10/21) in the SU group and 17.4% (4/23) in the TD group (p=0.033). Among relapsed patients, the durations from remission to relapse were 17.3 months (0.9–46.9) in the SU group and 24.3 months (1.8–44.9) in the TD group. There was no statistically significant difference in the sustained durations of remission after IFX administration between the SU(R) and TD groups [3.9 (1.4–6.3) and 2.3 (0.3–5.2) years, respectively (p>0.05)]. Conclusion According to our study, early use of IFX without corticosteroid treatment for children with moderate to severe UC helps to lower relapse rates. We also found that IFX was a very effective treatment for pediatric UC, with a sustained duration of remission similar between TD and SU(R) groups.

Background/Aims: We evaluated whether anti-Saccharomyces cerevisiae antibody (ASCA) titers are associated with diagnostic findings, disease activity, Paris classification phenotypes, and persistence after infliximab (IFX) treatment in children with Crohn’s disease (CD). We also investigated the role of ASCA as a predictor of mucosal healing (MH) and clinical remission (CR). Methods: This study included 61 CD patients aged 19 years or younger who were diagnosed and treated between September 2010 and January 2019 and followed for at least 1 year. ASCA was regularly measured at the diagnosis of CD and at least 1 year after IFX therapy. Results: The average follow-up period was 3.8±3.4 years (range, 1.0 to 7.2 years). Regression analysis showed that the ASCA titer was the only factor associated with Simple Endoscopic Score for Crohn's Disease (SES-CD) or CR among all the parameters. In patients who had achieved MH (SES-CD=0), ASCA immunoglobulin G (IgG) was not associated with MH, but in patients without MH, ASCA IgG was associated with SES-CD (p=0.005) and CR (p<0.001). The cutoff value of ASCA IgG in patients with CR was 21.8 units. However, there was no difference in the relapse rate between the ASCA IgG-positive and -negative groups during the follow-up period. Conclusions In patients who have not achieved MH, ASCA IgG is closely related to mucosal damage and CR. Unlike Western studies, ASCA IgG may be more helpful in predicting prognosis than immunoglobulin A in Korean patients, but it is not an appropriate indicator to predict the relapse of CD.

Purpose: We aimed to investigate clinical outcomes between top-down (TD) and conventional step-up (SU) therapies in pediatric patients with moderate to severe ulcerative colitis (UC). Materials and Methods: All patients underwent clinical and endoscopic evaluation at diagnosis and 4 months and 1 year after treatment. Patients who started treatment with corticosteroid were grouped in the SU group, while those that initiated early infliximab (IFX) were grouped in the TD group. Among the SU group, patients who eventually changed to IFX treatment due to steroid resistance or dependency were included in the SU(R) group. Results: In total, 44 children with moderate to severe UC were included for analysis. Twenty-one patients were included in the SU group, 23 were included in the TD group, and 10 were enrolled in the SU(R) group. Relapse rates were 47.6% (10/21) in the SU group and 17.4% (4/23) in the TD group (p=0.033). Among relapsed patients, the durations from remission to relapse were 17.3 months (0.9–46.9) in the SU group and 24.3 months (1.8–44.9) in the TD group. There was no statistically significant difference in the sustained durations of remission after IFX administration between the SU(R) and TD groups [3.9 (1.4–6.3) and 2.3 (0.3–5.2) years, respectively (p>0.05)]. Conclusion According to our study, early use of IFX without corticosteroid treatment for children with moderate to severe UC helps to lower relapse rates. We also found that IFX was a very effective treatment for pediatric UC, with a sustained duration of remission similar between TD and SU(R) groups.