Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Intrahepatic Cholangiocarcinoma Arising from Biliary Hamartomas in Patients with Recurrent Acute Cholangitis: A Case Report and Literature Review.

Biliary hamartomas are tumor-like malformations of the liver. Biliary hamartomas are a type of fibrocystic disorder originating from ductal plate malformation and are typically considered benign, but with the risk of malignant transformation. In this case report, we present a rare occurrence of intrahepatic cholangiocarcinoma (ICC) that developed from biliary hamartomas, along with a literature review. A 76-year-old man with a diagnosis of biliary hamartomas had a history of recurrent cholangitis for 12 years, necessitating cholecystectomy, ERCP, and repeated antibiotic treatments. During his last episode, imaging studies revealed a hypervascular infiltrative mass in the right posterior liver segment. A liver biopsy confirmed adenocarcinoma and subsequent surgical pathology revealed ICC originating from biliary hamartomas. Chronic inflammation in the bile duct associated with biliary hamartomas may serve as a potential trigger for malignant transformation, as observed in this case. Therefore, close surveillance is essential for patients with biliary hamartomas presenting with infectious complications.

Clinicopathological Characteristics of Autoimmune-Like Hepatitis Induced by COVID-19 mRNA Vaccine (Pfizer-BioNTech, BNT162b2): A Case Report and Literature Review.

Widespread use of vaccinations worldwide in the coronavirus disease (COVID-19) pandemic has resulted in various side effects. Here, we presented a 27-year-old man with autoimmune-like hepatitis after the first dose of the BNT162b2 (mRNA) COVID-19 vaccine and reviewed previous reports. He presented with sweating, febrile sensations, and general weakness. He did not have any medical histories. Although he was treated with biphenyl dimethyl dicarboxylate and ursodeoxycholic acid, the elevated liver enzyme levels persisted for 2 months. Liver biopsy demonstrated portal inflammation with rosette formation, interface hepatitis, and infiltration of lymphocytes, histiocytes, plasma cells, and eosinophils. Especially, centrilobular edema and necrosis were found. The symptoms and liver enzymes improved with prednisolone treatment. If persistently elevated liver enzymes are found after COVID-19 mRNA vaccination, the possibility of autoimmune-like hepatitis induced by the vaccine should be considered and a careful pathologic evaluation is required.

Optimal procedure-related hospitalization using clinical pathway protocols following gastric endoscopic submucosal dissection.

BACKGROUND: The clinical pathway (CP) protocols simplified a systematic process from hospitalization to discharge, and were conducted to achieve standardization of the treatment process as well as improve outcomes. Thus, we investigated the optimal procedure-related hospitalization period following gastric endoscopic submucosal dissection (ESD) by comparing the rate of delayed bleeding (DB) and perforation according to CP protocols. METHODS: We retrospectively enrolled 630 patients who underwent ESD for gastric dysplasia or early gastric cancer (EGC); Group A (368 patients) followed Protocol A for a hospital stay of a single night; Group B (262 patients) followed Protocol B for a hospital stay of two nights. RESULTS: The patient characteristics were comparable between the two groups, except for pathologic diagnosis (42.1% in Group A vs. 32.1% in Group B for EGC). DB occurred in 21 patients, and there was no significant difference in the overall DB rates between Group A (12/368 = 3.3%) and Group B (9/262 = 3.4%) (P = 0.904). The DB rates were 2.5% (8/315) and 7.5% (4/53) in Group A, and 2.7% (6/223) and 7.7% (3/39) in Group B, without and with the use of antiplatelets, respectively, and 33.3% (1/3) in Group A and 50.0% (1/2) in Group B with the use of dual antiplatelets. DB developed at various intervals post-discharge from 2 to 17 days, and was successfully controlled by endoscopic hemostasis in most cases. There were no deaths or surgeries required as a result of uncontrolled DB and no postoperative delayed perforation occurred. CONCLUSIONS: The CP protocols with a one-night hospitalization following gastric ESD decreased the hospital stay and did not influence postoperative complications compared to those with two-night hospitalizations.

Exosomal miR-181b-5p Downregulation in Ascites Serves as a Potential Diagnostic Biomarker for Gastric Cancer-associated Malignant Ascites.

PURPOSE: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. MATERIALS AND METHODS: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. RESULTS: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). CONCLUSIONS: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.

Identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is one the most potent nucleot(s)ide analogues for treating chronic hepatitis B virus (HBV) infection. Phenotypic resistance caused by genotypic resistance to TDF has not been reported. This study aimed to characterize HBV mutations that confer tenofovir resistance. METHODS: Two patients with viral breakthrough during treatment with TDF-containing regimens were prospectively enrolled. The gene encoding HBV reverse transcriptase was sequenced. Eleven HBV clones harboring a series of mutations in the reverse transcriptase gene were constructed by site-directed mutagenesis. Drug susceptibility of each clone was determined by Southern blot analysis and real-time PCR. The relative frequency of mutants was evaluated by ultra-deep sequencing and clonal analysis. RESULTS: Five mutations (rtS106C [C], rtH126Y [Y], rtD134E [E], rtM204I/V, and rtL269I [I]) were commonly found in viral isolates from 2 patients. The novel mutations C, Y, and E were associated with drug resistance. In assays for drug susceptibility, the IC50 value for wild-type HBV was 3.8 ±â€¯0.6 µM, whereas the IC50 values for CYE and CYEI mutants were 14.1 ±â€¯1.8 and 58.1 ±â€¯0.9 µM, respectively. The IC90 value for wild-type HBV was 30 ±â€¯0.5 µM, whereas the IC90 values for CYE and CYEI mutants were 185 ±â€¯0.5 and 790 ±â€¯0.2 µM, respectively. Both tenofovir-resistant mutants and wild-type HBV had similar susceptibility to the capsid assembly modulator NVR 3-778 (IC50 <0.4 µM vs. IC50 = 0.4 µM, respectively). CONCLUSIONS: Our study reveals that the quadruple (CYEI) mutation increases the amount of tenofovir required to inhibit HBV by 15.3-fold in IC50 and 26.3-fold in IC90. These results demonstrate that tenofovir-resistant HBV mutants can emerge, although the genetic barrier is high. LAY SUMMARY: Tenofovir is the most potent nucleotide analogue for the treatment of chronic hepatitis B virus infection and there has been no hepatitis B virus mutation that confers >10-fold resistance to tenofovir up to 8 years. Herein, we identified, for the first time, a quadruple mutation that conferred 15.3-fold (IC50) and 26.3-fold (IC90) resistance to tenofovir in 2 patients who experienced viral breakthrough during tenofovir treatment.

Predictors of Malignancies in Patients with Inconclusive or Negative Results of Endoscopic Ultrasound-guided Fine-needle Aspiration for Solid Pancreatic Masses.

Background/Aims: This study analyzed the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic solid masses in patients with or without chronic pancreatitis as well as the clinical parameters relevant to a malignancy when EUS-FNA was negative or inconclusive. Methods: A total of 97 patients, who underwent EUS-FNA for solid pancreatic masses over 2 years at a single institution, were evaluated. All patients underwent EUS-FNA for 3-5 passes with 22 or 25 G needles without an on-site cytopathologist. The final diagnosis was obtained by surgery or compatible clinical outcomes for a more than 12 month follow-up. The diagnostic yields in the patients with or without chronic pancreatitis were compared and the histories and laboratory data relevant to pancreatic ductal adenocarcinoma (PDAC) or pseudo-tumor were analyzed. Results: The final diagnoses were adenocarcinoma in 88 patients (90.7%) and inflammatory pseudo-tumor in 9 (9.3%). The results of EUS-FNA were adenocarcinoma (74), suspicious (7), atypical (5), negative (10), and inadequate specimen (1). The diagnostic accuracies were 76.9% and 91.6% in patients with or without chronic pancreatitis, respectively. Among the 23 cases with non-diagnostic results of EUS-FNA, PDAC was finally diagnosed in 5 out of 7 suspicious, 3 out of 5 atypical, and 5 out of 10 negative cytology cases. The clinical parameters related to a pseudo-tumor were a history of alcohol consumption and pancreatitis, and normal alkaline phosphatase levels. Conclusions: The diagnostic accuracy of pancreatic masses in the background of chronic pancreatitis was low. When EUS-FNA produced inconclusive results, the histories of alcohol consumption, pancreatitis, and serum levels of alkaline phosphatase are useful for making a final diagnosis.

Comparison of liquid-based cytology (CellPrepPlus) and conventional smears in pancreaticobiliary disease.

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUSFNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. METHODS: This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. RESULTS: In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. CONCLUSION: Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.

Diagnostic and prognostic value of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography for colorectal cancer: comparison with conventional computed tomography.

BACKGROUND/AIMS: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been used for preoperative staging of colorectal cancer (CRC). However, the diagnostic accuracy of FDG-PET/CT for detection of lymph node or distant metastasis and its prognostic role have not been well established. We therefore evaluated the diagnostic and prognostic value of FDG-PET/CT in comparison with conventional CT for CRC. METHODS: We investigated 220 patients who underwent preoperative FDG-PET/CT and CT, followed by curative surgery for CRC. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG-PET/CT and CT for detection of lymph node metastasis and distant metastasis were evaluated. In addition, we assessed the findings of FDG-PET/CT and CT according to outcomes, including cancer recurrence and cancer-related death, for evaluation of prognostic value. RESULTS: For detection of lymph node metastasis, FDG-PET/CT had a sensitivity of 44%, a specificity of 84%, and an accuracy of 67%, compared with 59%, 65%, and 62%, respectively, for CT (P=0.029, P=0.000, and P=0.022). For distant metastasis, FDG-PET/CT had a sensitivity of 79%, a specificity of 94%, and an accuracy of 93%, compared with 79%, 87%, and 86%, respectively, for CT (P=1.000, P=0.004, and P=0.037). In addition, positive findings of lymph node metastasis and distant metastasis on FDG-PET/CT were associated significantly with cancer recurrence or cancer-related death (P=0.009, P=0.001, respectively). CONCLUSIONS: Preoperative FDG-PET/CT had a higher specificity and accuracy compared to CT for detection of lymph node metastasis and distant metastasis of CRC. In addition, FDG-PET/CT could be a valuable prognostic tool for CRC.

Efficacy and Safety of Endoscopic Papillary Balloon Dilation Using Cap-Fitted Forward-Viewing Endoscope in Patients Who Underwent Billroth II Gastrectomy.

BACKGROUND/AIMS: Endoscopic exploration of the common bile duct (CBD) is difficult and dangerous in patients with Billroth II gastrectomy (B-II). Endoscopic papillary balloon dilation (EPBD) via a cap-fitted forward-viewing endoscope has been reported to be an effective and safe procedure. We analyzed the technical success and complications of EPBD in patients who underwent B-II. METHODS: Thirty-six consecutive patients with B-II were enrolled from among 2,378 patients who had undergone endoscopic retrograde cholangiopancreatography in a single institute in the last 4 years. The EPBD procedure was carried out using a cap-fitted forward-viewing endoscope with 8-mm balloon catheters for 60 seconds. We analyzed the rates of CBD exploration, technical success, and complications. RESULTS: Afferent loop intubation was performed in all patients and selective cannulation of the bile duct was performed in 32 patients (88.9%). Complications such as transient hypoxia were observed in two patients (5.6%) and perforation, in three patients (9.7%). The perforation sites were ductal injury in two patients and one patient showed retroperitoneal air alone without symptoms. Three patients manifested different clinical courses of severe acute pancreatitis and peritonitis, transient abdominal pain, and retroperitoneal air alone. The condition of one patient improved with surgery and that of the other two patients, with conservative management. CONCLUSIONS: Patients with perforation during EPBD in B-II showed different clinical courses. Tailored treatment strategies are necessary for improving the clinical outcomes.

Clinical outcomes of patients with advanced hepatocellular carcinoma treated with sorafenib: a retrospective study of routine clinical practice in multi-institutions.

BACKGROUND: Sorafenib is an orally administered multikinase inhibitor with antiangiogenic and antiproliferative properties. The results of large clinical trials demonstrate that sorafenib prolongs survival and the time to progression of patients with advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine the outcomes of such patients who were routinely treated with sorafenib at multi-institutions in Korea, in contrast to formal clinical trials. METHODS: Between August 2007 and March 2012, patients with advanced HCC in seven referral medical centers in Daejeon-Chungcheong Province of Korea were retrospectively enrolled to evaluate treatment response, survival, and tolerability following administration of sorafenib. The treatment response was assessed in accordance with the Response Evaluation Criteria in Solid Tumor 1.1 guidelines. RESULTS: Among 116 patients, 66 (57%) had undergone treatment for HCC, and 77 (66%) were accompanied with Child-Pugh A cirrhosis. The median duration of sorafenib treatment was 67 days (range 14-452 days). Median overall survival and median time to progression were 141 days and 90 days, respectively. Complete response, partial response, and stable disease were achieved for 0%, 2%, and 29% of patients, respectively. Overall median survival, but not the median time to progression, was significantly shorter for patients with Child-Pugh B cirrhosis compared with those with Child-Pugh A cirrhosis (64 days vs 168 days, P = 0.004). Child-Pugh B cirrhosis (P = 0.024) and a high level of serum alpha-fetoprotein (P = 0.039) were independent risk factors for poor overall survival. Thirty-nine (34%) patients experienced grade 3/4 adverse events such as hand-foot skin reactions and diarrhea that required dose adjustment. CONCLUSIONS: The clinical outcomes of sorafenib-treated patients with advanced HCC were comparable to those reported by formal clinical trial conducted in the Asia-Pacific region. Underlying hepatic dysfunction was the most important risk factor for shorter survival.

Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B.

Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.

A novel germline mutation in exon 10 of the SMAD4 gene in a familial juvenile polyposis.

Familial juvenile polyposis (FJP) is a rare autosomal dominant hereditary disorder that is characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of cancer. Recently, germline mutations, including mutations in the SMAD4, BMPR1A, PTEN and, possibly, ENG genes, have been found in patients with juvenile polyps. We herein report a family with juvenile polyposis syndrome (JPS) with a novel germline mutation in the SMAD4 gene. A 21-year-old man presented with rectal bleeding and was found to have multiple polyps in his stomach, small bowel, and colon. His mother had a history of gastrectomy for multiple gastric polyps with anemia and a history of colectomy for colon cancer. A review of the histology of the polyps revealed juvenile polyps in both patients. Subsequently, mutation screening in DNA samples from the patients revealed a germline mutation in the SMAD4 gene. The pair had a novel mutation in exon 10 (stop codon at tyrosine 413). To our knowledge, this mutation has not been previously described. Careful family history collection and genetic screening in JPS patients are needed to identify FJP, and regular surveillance is recommended.

Clinical, pathological, and immunohistochemical features of adenomyoma in the ampulla of vater.

BACKGROUND/AIMS: Ampullary adenomyoma is a benign lesion whose malignant potential has yet to be confirmed. Despite its benign nature, adenomyoma is frequently misdiagnosed as a carcinoma or adenoma and is overtreated by extensive surgery. This study was performed to analyze the clinical, pathological, and immunohistochemical features of adenomyomas in the ampulla of Vater. METHODS: Nine cases of adenomyoma in the ampulla of Vater, diagnosed in Chungbuk National University Hospital between 2008 and 2011, were enrolled in this study. We reviewed the clinical data on the symptoms, laboratory data, and radiologic findings of the abdominal computed tomography and endoscopic retrograde cholangiopancreatography. For pathological analysis, all the slides were reviewed by one pathologist, and immunohistochemical stainings with antibodies against cytokeratin 7 (CK7), cytokeratin 20 (CK20), α-smooth muscle actin (α-SMA), and Ki-67 antigen were performed. RESULTS: All the cases were CK7 positive and CK20 negative. A strong cytoplasmic expression of α-SMA was confirmed in all cases. The Ki-67 index was less than 1% in eight cases and 5% in one case. Four cases underwent endoscopic papillectomy, and one case received surgical ampullectomy during colorectal cancer surgery. Five cases that underwent endoscopic or surgical treatment remained symptom-free for three years. Four cases that were closely observed with repeated endoscopic examinations exhibited no interval changes in the papillary lesions. CONCLUSIONS: Endoscopic biopsy and immunohistochemistry can aid in the diagnosis of ampullary adenomyomas. Endoscopic papillectomy or surgical ampullectomy is adequate for the treatment of symptomatic ampullary adenomyomas.

Podoplanin, α-smooth muscle actin or S100A4 expressing cancer-associated fibroblasts are associated with different prognosis in colorectal cancers.

The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), α-smooth muscle actin (α-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or α-SMA CAFs were detected in all the cases. PDPN/S100A4 and α-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN(+) CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN(-)/α-SMA(high) CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN(-)/S100A4(high) CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN(+) CAF phenotype is distinct from the α-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN(-)/α-SMA(high) or PDPN(-)/S100A4(high) CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.

[A case of simultaneously occurred amiodarone-induced hepatitis and hypothyroidism].

Amiodarone is a di-iodated benzofuran derivative that is commonly used to treat patients with various cardiac arrhythmias. It is associated with side effects that involve the liver, thyroid, and other organs. Approximately 1-3% of patients treated with amiodarone suffer from symptomatic liver disease. Thyroid dysfunction occurs in 10% of patients treated with amiodarone. A 65-year-old woman with coronary heart disease and atrial fibrillation was administered with amiodarone. She developed nausea, vomiting, dyspepsia, and sweating within 9 months of amiodarone administration (200 mg orally once a day). Results of the laboratory finding showed increased hepatic enzymes, and low thyroid hormone levels. A liver biopsy showed irregular arrangement of hepatocytes and diffuse micro- and macrovesicular fatty changes. Electron microscopy findings showed pleomorphic mitochondria with crystalloid inclusions and membrane-bound lysosomal structures. The liver and thyroid functions returned to normal, after the amiodarone was stopped. We describe an unusual case in which amiodarone induced hepatitis and hypothyroidism simultaneously. Physicians should take a close look to the adverse event when using amiodarone which can cause adverse effects in multiple organs.

[A case of primary aortoenteric fistula mimicking ulcer bleeding].

Primary aortoenteric fistula (PAEF) is a rare disease with a high mortality rate due to massive hemorrhaging and diagnostic difficulties. Although hemorrhagic regions can be identified by endoscopy, it is difficult to diagnose PAEF by this method. If PAEF is suspected, endoscopic procedure should be terminated and abdominal CT should be performed. Overlooking the herald bleeding of PAEF can lead to massive bleeding and death. An 85-year-old previously healthy male presented with a complaint of melena. Gastrointestinal endoscopy identified a hemorrhagic site in the third portion of the duodenum and endoscopic hemostasis was performed. However, during the procedure, it became apparent that the hemorrhage was probably not the result of a simple duodenal ulceration and abdominal CT was performed immediately. An aortic aneurysm connected to the duodenum was identified, confirming the diagnosis of PAEF. However, the patient died of massive hemorrhaging before an operation could be performed.

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 ≥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.