Hepatocellular Carcinoma with Distant Metastasis Cured by 20-Day Sorafenib Treatment.

There are only 13 cases of complete remission after sorafenib use in advanced hepatocellular carcinoma (HCC) worldwide. We herein report a rarer case in which the patient was cured after only 20 days of sorafenib use. A 61-year-old male patient was diagnosed with a huge HCC. The mass occupied almost the whole of the right hepatic lobe and a portion of segment 4. We performed extended right hepatectomy for cure. However, 3.5-cm-sized subcarinal lymph node metastasis was detected at 15 months after operation. We prescribed sorafenib 400 mg bid for palliative treatment. The patient had severe fever, pain, and blisters on the hands and feet, so the patient stopped taking it after 20 days. Subcarinal lymph node disappeared on chest computed tomography after 3 months, and there was no evidence of recurrence for a year.

Early Colon Cancer Recurring as Liver Metastasis without Local Recurrence Three Years after Complete Endoscopic Mucosal Resection.

Early colon cancer is defined as colon cancer that invades mucosal or submucosal layer regardless of lymph node invasion. Endoscopic mucosal resection can effectively remove early colon cancer which has no lymph node metastasis. Especially, pedunculated polyp has higher complete resection rate and lower recurrence rate that rarely needs additional surgical treatment than sessile polyp. Hence, it is common to follow up without additional treatment after complete resection of pedunculated polyp. We report a case of early colon cancer recurring as liver metastasis 3 years after complete endoscopic mucosal resection.

Efficacy and Safety of Daclatasvir and Asunaprevir in Patients with Hepatitis C Virus Genotype 1b Infection on Hemodialysis.

Background/Aims: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. Methods;: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. Results: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. Conclusions: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474).

Hepatic Failure by Spontaneous Reactivation of Hepatitis B Virus without a Trigger Factor in a Patient with Anti-HBs.

A patient who has achieved resolution of acute hepatitis B and acquired anti-HBs would get protective immunity against hepatitis B virus (HBV). However, reactivation of HBV could happen if the patient was exposed to an immunocompromised state by using immunosuppressive drugs or chemotherapeutic agents. That is because cccDNA could reside within hepatocytes after recovery of acute hepatitis B. Therefore, guidelines for hepatitis B recommend the use of prophylactic antiviral agents such as entecavir or tenofovir in patients with anti-HBc IgG. The reactivation of hepatitis B without exposure to an immunocompromised state is very rare and only 1 case has been reported in the world to date. An 82-year-old male patient visited Dankook University Hospital because of high aspartate transaminase, alanine aminotransferase, and total bilirubin. He had shown HBsAg negative/anti-HBs positive when he had blood test examinations 1 year previously. However, the present blood test revealed HBsAg positive/anti-HBs negative and a high titer of HBV DNA (814,815 copies/mL). He had undergone vertebroplasty 5 years previously and had no other medical history. Other blood and radiological examinations failed to show other diseases that could affect host immunity. He started antiviral treatment with entecavir. However, he passed away because of deteriorated hepatic function and hepatorenal syndrome 20 days after admission. It is very rare that a patient with anti-HBs would develop hepatic failure and pass away without trigger factors. Here, we report the case with a literature review.

Development of tenofovir disoproxil fumarate resistance after complete viral suppression in a patient with treatment-naïve chronic hepatitis B: A case report and review of the literature.

Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue that is recommended as first-line therapy for patients with chronic hepatitis B. The results of a longitudinal study of TDF treatment demonstrated no development of resistance. We observed one treatment-naïve chronic hepatitis B (CHB) patient who developed TDF resistance after complete viral suppression during long-term TDF treatment. A 37-year-old HBeAg-positive man received TDF 300 mg/d for 43 mo. The hepatitis B virus (HBV) DNA titer was 8 log10 copies/mL at baseline and became undetectable at 16 mo after treatment. However, the HBV DNA titer rebounded to 7.5 log10 copies/mL at 43 mo after treatment. We performed full sequencing to find mutation sites associated with virologic breakthrough. The results showed 9 mutation sites, most of which had not been well-known as mutation sites. We changed the therapy from tenofovir to entecavir with a regimen of 0.5 mg once daily. After 4 mo, the HBV DNA titer decreased to 267 copies/mL, and the liver enzyme levels were normalized.

Efficacy and safety of daclatasvir plus asunaprevir for Korean patients with HCV genotype Ib infection: a retrospective multi-institutional study.

BACKGROUND/AIMS: The combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection. METHODS: We retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area. RESULTS: A total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients. CONCLUSIONS: DCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon.

Tracing hepatitis B virus to the 16th century in a Korean mummy.

UNLABELLED: A rare find of a mummified child from the 16th century AD, in Korea, with relatively preserved organs, enabled a search for ancient hepatitis B virus (aHBV) DNA sequences from laparoscopic-derived liver biopsies. Analysis of the complete aHBV genome (3,215 base pairs) revealed a unique HBV genotype C2 (HBV/C2) sequence commonly spread in Southeast Asia, which probably represents an HBV that infected the Joseon Dynasty population in Korea. Comparison of the aHBV sequences with contemporary HBV/C2 DNA sequences revealed distinctive differences along four open reading frames. Genetic diversity between contemporary and recovered aHBV/C2 DNA may be the result of immunologic, environmental, and/or pharmacologic pressures. The calculated time of most recent common ancestor suggests that the Korean HBV sequence origin dates back at least 3,000 years and possibly as long as 100,000 years. This isolate most likely represents the earliest human HBV sequence that colonized Southeast Asia by human migration. CONCLUSION: This study describes the complete sequence of the oldest HBV isolate and the most ancient full viral genome known so far.

[Clinical aspects of intraabdominal cystic lymphangioma in Korea].

BACKGROUND/AIMS: cystic lymphangioma is an uncommon disease, and rarely develops in the intraabdomen. The aim of this article was to discuss about clinical characteristics of intraabdominal cystic lymphangioma developed in Korea. METHODS: age, sex, symptoms, locations and size of the lesions, diagnostic methods, treatments, complications and recurrence were analyzed in 13 pathologically confirmed cases of intraabdominal cystic lymphangioma and 18 cases of literature consideration reported in Korea. RESULTS: intraabdominal cystic lymphangioma commonly developed in adults compared to the other lymphangioma, and frequently located in the mesentery. Abdominal pain was the most common symptom, but it was a non-specific finding. Tenderness and abdominal mass were not significantly associated. The size of mass was diverse. Abdominal ultrasonography and abdominal CT were diagnostic tools most commonly used, but preoperative diagnosis was possible only in 22.6%. All patients were discharged without any complications, and no recurrence was reported. CONCLUSIONS: preoperative diagnosis of intraabdominal cystic lymphangioma is difficult and symptoms and signs are not specific. Intraabdominal cystic lymphangioma should be suspected in patients with non specific abdominal pain and intraabdominal mass and active diagnostic evaluation is mandatory.

Efficacy of initial treatment with clevudine in naive patients with chronic hepatitis B.

BACKGROUND/AIMS: Clevudine, a pyrimidine nucleoside analogue, has potent antiviral effects in patients with chronic viral hepatitis B (CHB). We report the efficacy of initial treatment with clevudine in naïve patients with CHB living in Daejeon and Chungcheong Province, South Korea. METHODS: One hundred five adults with CHB were administered 30 mg of clevudine per day for an average of 51 weeks. We evaluated viral markers and liver biochemistry retrospectively every 3 months. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatitis B virus (HBV) DNA before the treatment were 184 ± 188 IU/L, 150 ± 138 IU/L, and 7.1 ± 1.2 log copies/mL, respectively. Undetectable rates (< 60 IU/mL) of DNA were 36.2%, 68.9%, 83.6%, 76.2%, and 75.8% at 12, 24, 36, 48, and 60 weeks, respectively. Seroconversion rates were 9.1%, 13.6%, 24.6%, 26.5%, and 26.1% and ALT normalization rates were 64.5%, 78.1%, 87.9%, 90.0% at 12, 24, 36, and 48 weeks, respectively. Six patients (5.7%) had a viral breakthrough. CONCLUSIONS: Clevudine is a useful drug in the initial treatment of patients with CHB, with a potent antiviral effect and low incidence of viral breakthrough.

Chronic 835-MHz radiofrequency exposure to mice hippocampus alters the distribution of calbindin and GFAP immunoreactivity.

Exponential interindividual handling in wireless communication system has raised possible doubts in the biological aspects of radiofrequency (RF) exposure on human brain owing to its close proximity to the mobile phone. In the nervous system, calcium (Ca(2+)) plays a critical role in releasing neurotransmitters, generating action potential and membrane integrity. Alterations in intracellular Ca(2+) concentration trigger aberrant synaptic action or cause neuronal apoptosis, which may exert an influence on the cellular pathology for learning and memory in the hippocampus. Calcium binding proteins like calbindin D28-K (CB) is responsible for the maintaining and controlling Ca(2+) homeostasis. Therefore, in the present study, we investigated the effect of RF exposure on rat hippocampus at 835 MHz with low energy (specific absorption rate: SAR=1.6 W/kg) for 3 months by using both CB and glial fibrillary acidic protein (GFAP) specific antibodies by immunohistochemical method. Decrease in CB immunoreactivity (IR) was noted in exposed (E1.6) group with loss of interneurons and pyramidal cells in CA1 area and loss of granule cells. Also, an overall increase in GFAP IR was observed in the hippocampus of E1.6. By TUNEL assay, apoptotic cells were detected in the CA1, CA3 areas and dentate gyrus of hippocampus, which reflects that chronic RF exposure may affect the cell viability. In addition, the increase of GFAP IR due to RF exposure could be well suited with the feature of reactive astrocytosis, which is an abnormal increase in the number of astrocytes due to the loss of nearby neurons. Chronic RF exposure to the rat brain suggested that the decrease of CB IR accompanying apoptosis and increase of GFAP IR might be morphological parameters in the hippocampus damages.

Effect of 835 MHz radiofrequency radiation exposure on calcium binding proteins in the hippocampus of the mouse brain.

Worldwide expansion of mobile phones and electromagnetic field (EMF) exposure has raised question of their possible biological effects on the brain and nervous system. Radiofrequency (RF) radiation might alter intracellular signaling pathways through changes in calcium (Ca(2+)) permeability across cell membranes. Changes in the expression of calcium binding proteins (CaBP) like calbindin D28-k (CB) and calretinin (CR) could indicate impaired Ca(2+)homeostasis due to EMF exposure. CB and CR expression were measured with immunohistochemistry in the hippocampus of mice after EMF exposure at 835 MHz for different exposure times and absorption rates, 1 h/day for 5 days at a specific absorption rate (SAR)=1.6 W/kg, 1 h/day for 5 days at SAR=4.0 W/kg, 5 h/day for 1 day at SAR=1.6 W/kg, 5 h/day for 1 day at SAR=4.0 W/kg, daily exposure for 1 month at SAR=1.6 W/kg. Body weights did not change significantly. CB immunoreactivity (IR) displayed moderate staining of cells in the cornu ammonis (CA) areas and prominently stained granule cells. CR IR revealed prominently stained pyramidal cells with dendrites running perpendicularly in the CA area. Exposure for 1 month produced almost complete loss of pyramidal cells in the CA1 area. CaBP differences could cause changes in cellular Ca(2+)levels, which could have deleterious effect on normal hippocampal functions concerned with neuronal connectivity and integration.

Scanning electron microscope study of ancient parasite eggs recovered from Korean mummies of the Joseon Dynasty.

We have previously shown that parasite eggs have been identified in the coprolites of Korean mummies. These eggs have shed light on parasitic infection patterns in Korean populations living several hundred years ago. We conducted a scanning electron microscopy (SEM) study on ancient Trichuris trichiura, Ascaris lumbricoides, Metagonimus yokogawai, Paragonimus westermani, and Gymnophalloides seoi eggs recovered from Korean mummies of the Joseon Dynasty. We anticipated that the taphonomic conditions of mummification would alter the eggs of certain species but not of others. Our SEM data show that each species of ancient egg exhibited different degrees of preservation. Thus, some of them, for example, M. yokogawai, exhibited a better preservation status than others, suggesting that they should be the first candidates considered when choosing subjects for future paleoparasitological studies.

[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].

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 microg/week, n=48) or peginterferon alpha-2b (1.5 microg/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.

[A case of malignant gastrointestinal stromal tumor of ileum with liver abscess].

Gastrointestinal stromal tumor (GIST) is an uncommon mesenchymal tumor of the gastrointestinal tract and is generally located in the stomach and small intestine. They usually present with abdominal pain, gastrointestinal bleeding, and palpable mass. Some patients present with rare symptoms that are more common in malignant GIST. Malignant GIST combined with a liver abscess has not been reported yet in the literatures. We report a case of 67-year-old woman who suffered from liver abscess combined by malignant GIST with central necrosis and fistula in the ileum. She complained of fever, chills, and abdominal pain. Abdominal CT scan showed huge liver abscess and ileal mass with air pocket. Small bowel series showed contrast material filling into the ileal GIST mass. An operation was performed and the final diagnosis was malignant GIST of the ileum with invasion into the sigmoid colon and urinary bladder.

Endoscopic investigation of the internal organs of a 15th-century child mummy from Yangju, Korea.

Our previous reports on medieval mummies in Korea have provided information on their preservation status. Because invasive techniques cannot easily be applied when investigating such mummies, the need for non-invasive techniques incurring minimal damage has increased among researchers. Therefore, we wished to confirm whether endoscopy, which has been used in non-invasive and minimally invasive studies of mummies around the world, is an effective tool for study of Korean mummies as well. In conducting an endoscopic investigation on a 15th-century child mummy, we found that well-preserved internal organs remained within the thoracic, abdominal and cranial cavities. The internal organs - including the brain, spinal cord, lung, muscles, liver, heart, intestine, diaphragm and mesentery - were easily investigated by endoscopy. Even the stool of the mummy, which accidentally leaked into the abdominal cavity during an endoscopic biopsy, was clearly observed. In addition, unusual nodules were found on the surface of the intestines and liver. Our current study therefore showed that endoscopic observation could provide an invaluable tool for the palaeo-pathological study of Korean mummies. This technique will continue to be used in the study of medieval mummy cases in the future.

[A case of severe skin eruption caused by lamivudine in a patient with chronic hepatitis B].

Lamivudine is widely used for the treatment of chronic hepatitis B infection because of it's remarkable antiviral efficacy and safety. We report a case of severe skin eruption caused by lamivudine. A 47-year-old female was admitted because of jaundice and itching sensation. She was diagnosed as chronic hepatitis B infection a few years ago but did not receive any specific treatment. Laboratory data showed acute deterioration of chronic hepatitis B infection. We prescribed lamivudine as a rescue therapy. Her general condition improved and lab data showed improvement in liver function test thereafter. However, she complained of severe skin eruption and itching sensation a few days after the discharge. We stopped lamivudine because the symptoms did not improve despite the use of anti-histamine. Skin biopsy showed interface dermatitis. After stopping lamivudine, her symptoms improved. However, the skin eruption developed again after lamivudine was restarted. Adefovir was used instead, and the patient did not experience any further skin problems since then.