• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.4
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• pp.201-212
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• 2023

Purpose: The gastrointestinal system is the most commonly affected organ, followed by the lungs, in patients with primary immunodeficiency disease (PID). Hence, it is common for children with PIDs to present with gastrointestinal symptoms. We aimed to analyze the clinical and histopathological findings of patients who were initially admitted to pediatric gastroenterology/hepatology clinics and subsequently diagnosed with PIDs to identify the clinical clues for PIDs. Methods: The demographic, laboratory, and histopathological findings, treatment modality, and outcomes of patients initially admitted to the pediatric gastroenterology/hepatology unit and subsequently diagnosed with PIDs were recorded. Results: The study included 24 patients (58.3% male; median age [range]: 29 [0.5-204] months). Common clinical presentations included chronic diarrhea (n=8), colitis (n=6), acute hepatitis (n=4), and acute liver failure (n=2). The association of autoimmune diseases, development of malignant diseases, and severe progression of viral diseases was observed in 20.8%, 8.3%, and 16.6% of the patients, respectively. Antibody deficiency was predominantly diagnosed in 29.2% of patients, combined immunodeficiency in 20.8%, immune dysregulation in 12.5%, defects in intrinsic and innate immunity in 4.2%, autoinflammatory disorders in 8.3%, and congenital defects of phagocytes in 4.2%. Five patients remained unclassified (20.8%). Conclusion: Patients with PIDs may initially experience gastrointestinal or liver problems. It is recommended that the association of autoimmune or malignant diseases or severe progression of viral diseases provide pediatric gastroenterologists some suspicion of PIDs. After screening using basic laboratory tests, genetic analysis is mandatory for a definitive diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3555-3559
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• 2013

Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factors for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variation and the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infected with HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249S mutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP) in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basal core promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group. R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was not significantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations was independently associated with the risk of HCC in Thai patients.

• Korean Journal of Veterinary Research
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• v.27 no.2
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• pp.277-290
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• 1987

This paper dealt with etiological studies on the acute fatal disease of Angora rabbits occurring as a group in Korea. The disease was confirmed as an acute infectious disease caused by virus. The results obtained were summarized as follows: The disease produced a high morbidity in the rearing Angora rabbits and a high mortality in the infected rabbits, and was acute. The infected rabbits died soon without premonitory signs after inappetence. The body temperature of the affected rabbits rose to $40^{\circ}C$ and nearly all deaths occurred within 48 hours after inoculation. In many cases a bloody foam was visible from the nostrils after death. According to the progress of the disease the nervous signs, such as ataxia, paralysis of the legs, and torticollis could be recognized in the some cases. Rabbits that had recovered from the disease were severe emaciation, and bristly and sparse hairs. In macroscopical findings, there were hemorrhage and edema of the lung, hemorrhage or hyperemia of the tracheal and broncheal mucosae, appearance of blood-tinged effusion in the respiratory tract. The principal lesions were found in the liver. Usually the lobular necrosis of the liver cells was progressed, and focal necrosis and hemorrhagic spots of various sizes were often observed in the liver. Liver was as a whole pale. In chronic cases, however, there was a slight liver cirrhosis with the atrophy of the parenchymal cells. The other lesions encountered grossly consisted of swelling and petechiae of the kidney, hyperemia and hemorrhage of the spleen, catarrh of the small intestine, and hyperemia of the brain. The urinary bladder contained a lot of turbid urine or bloody urine and urinary cast, and was distended with the urine. In microscopical findings, the most striking lesions occurred in the liver and may be classified as viral hepatitis. The hepatic lesions were initially characterized by progression from periportal to peripheral necrosis of the lobules with the infiltration of mononuclear cells. Focal necrosis of various sizes, hemorrhage and hyperemia were often observed in the hepatic lobules. In chronic cases, there were intensive infiltration of lymphocytes, proliferation of fibroblasts, appearance of plasmal cells, and atrophy of parenchymal cells in the hepatic tissue. Perivascular lymphocytic infiltration and meningitis were seen in the brain and spinal cord. In the kidney, there were acute glomerulonephritis, hemorrhage, necrosis of the uriniferous tubules, and retention of eosinophilic substance within the renal tubules. Proliferation of fibroblasts and infiltration of mono-nuclear cells were found in the interstitial stroma of the kidney in chronic case. There were also hemorrhage and edema in the lung, hyperemia and hemorrhage in the trachea and bronchus, perivascular lymphocytic infiltration and focal myocardial necrosis in the heart, hyperemia and hemorrhage in the spleen, vacuolization and desquamation of mucous epithelia in the urinary bladder, catarrhal inflammation of the small intestine, hemorrhage in the adrenal cortex and hyperemia in the other organs. In the electron microscopical findings of the hepatic tissue, crystals of viral particles appeared in the cytoplasm of the hepatocytes and the sinusoidal endothelial cells, and the viral particles, were small in size and polygonal. The authors suppose the virus may belong to picornaviridae family of RNA viruses. Also immature virus-like particles, dilated rough endoplasmic reticulum and destruction of nuclear membrane were seen in the hepatocytes. From these results, it is concluded that the sudden death is an acute viral disease characterized by hepatitis and the affected rabbits may be died of viremia.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.13 no.1
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• pp.44-50
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• 2010

Purpose: To estimate the viral suppressive effect of entecavir monotherapy in Korean children and adolescents with lamivudine-resistant chronic hepatitis B (CHB). Methods: One milligram of entecavir was administered once daily to 6 patients (4 boys; mean age, 17.5 years; range, 15.10~24.6 years) with lamivudine-resistant CHB for a mean duration of therapy of 13.4 months (range, 1~21.1 months). The therapeutic results were compared with 11 patients who received adefovir (0.3 mg/kg/day [maximal dose 10 mg]) for at least 12 months (mean, 33.4 months; range, 12.4~58.3 months). The serum HBV DNA level and serologic markers were measured every 2 months. Results: The interval to a HBV DNA titer decrement (>1 $log_{10}$) was 1.2${\pm}$0.2 and 4.4${\pm}$5.2 months (p=0.185) for the entecavir and adefovir groups, respectively. The interval to a HBV DNA titer decrement (>2 $log_{10}$) was 2.4${\pm}$2.3 and 9.2${\pm}$7.3 months (p=0.025), for the entecavir and adefovir groups, respectively. Conclusion: The therapeutic efficacy of entecavir was favorable in children and adolescents, especially in shortening the interval to a >2 $log_{10}$ decrement in the HBV DNA titer. Long-term follow up is needed to determine the therapeutic efficacy of entecavir for lamivudine-resistant CHB in children and adolescents.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.56-78
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• 1998

Objective: Chronic hepatitis B infection (CHB) occurs in 6% to 10% of population in Korea. In ethinic communities where prevalence of chronic infection is high such as Korea, transmission of hepatitis B infection is either vertical (ie, by perinatal infection) or by close family contact (usually from mothers or siblings) during the first 5 years of life. The development of chronic hepatitis B infection is increasingly more common the earlier a person is exposed to the virus, particularly in fetal and neonatal life. And it progress to cirrhosis and hepatocellular carcinoma, especially in severe liver damage and perinatal infection. Histopathology of CHB is important when evaluating the final outcomes. A numerical scoring system which is a semiquantitatively assessed objective reproducible classification of chronic viral hepatitis, is a valuable tool for statistical analysis when predicting the outcome and evaluating antiviral and other therapies. In this study, a numerical scoring system (Ludwig system) was applied and compared with the conventional histological classification of De Groute. And the comparative analysis of cinical findings, family history, serology, and liver function test by histopathological findings in chronic hepatitis B of children was done. Methods: Ninety nine patients [mean age=9 years (range=17 months to 16 years)] with clinical, biochemical, serological and histological patterns of chronic HBV infection included in this study. Five of these children had hepatocelluar carcinoma. They were 83 male and 16 female children. They all underwent liver biopsies and histologic evaluation was performed by one pathologist. The biopsy specimens were classified, according to the standard criteria of De Groute as follows: normal, chronic lobular hepatitis (CLH), chronic persistent hepatitis (CPH), mild to severe chronic active hepatitis (CAH), or active cirrhosis, inactive cirrhosis, hepatocellular carcinoma (HCC). And the biopsy specimens were also assessed and scored semiquantitatively by the numerical scoring Ludwig system. Serum HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc (IgG, IgM), and HDV were measured by radioimunoassays. Results: Male predominated in a proportion of 5.2:1 for all patients. Of 99 patients, 2 cases had normal, 2 cases had CLH, 22 cases had CPH, 40 cases had mild CAH, 19 cases had moderate CAH, 1 case had severe CAH, 7 cases had active cirrhosis, 1 case had inactive cirrhosis, and 5 cases had HCC. The mean age, sex distribution, symptoms, signs, and family history did not differ statistically among the different histologic groups. The numerical scoring system was correlated well with the conventional histological classification. The histological activity evaluated by both the conventional classification and the scoring system was more severe as the levels of serum aminotransferases were higher. In contrast, the levels of serum aminotransferases were not useful for predicting the degree of histologic activity because of its wide range overlapping. When the histological activity was more severe and especially the cirrhosis more progressing, the prothrombin time was more prolonged. The histological severity was inversely related with the duration of seroconversion of HBeAg. Conclusions: The histological activity could not be accurately predicted by clinical and biochemical findings, but by the proper histological classification of the numerical scoring system for the biopsy specimen. The numerical scoring system was correlated well with the conventional histological classification, and it seems to be a valuable tool for the statistical analysis when predicting the outcome and evaluating effects of antiviral and other therapies in chronic hepatitis B in children.

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.307-311
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• 1992

Anorexia, nausea, and vomiting are one of the most frequent symptoms in viral hepatits patients. These may be due to poorly detoxified substances by dysfunctioned hepatocytes or by gastritis, but the pathophysiology is not totally understood. The symptoms interfere with adequate nutrient intake and are managed by metoclopramide, which accelerates gastric emptying. Thus delayed gastric emptying may well be a contributing factor to such symptoms. To determine such a relationship, we measured gastric emptying time in 11 normal subjects,9 acute (AVH), and 12 chronic B viral hepatitis (CVH) patients. All were males with a mean age of 23 years. An egg was labeled with 0.5 mCi of $^{99m}Tc-sulfur$ colloid, fried, then eaten between 2 slices of bread with 100 cc of water. Anterior and posterior images were taken at 20 minute intervals over a 2 hour period. A geometric mean of activity pertaining to the gastric region was measured, and $T_{1/2}$ was calculated from the time activity curve. $T_{1/2}$ for normal the group was $57.8{\pm}6.3$ minutes while that for the AVH and CVH group was $58.2{\pm}8.2$ (p=0.40) and $64.1{\pm}10.5$ (p=0.09), respectively. There was 1 AVH Patient and 4 CVH patients with prolonged $T_{1/2}$. Anorexia and nausea was seen in 71% and 46% of the patients, respectively. 80% and 60% of the patients with prolonged $T_{1/2}$ had anorexia and nausea, respectively.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.79-89
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• 1998

Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

• Journal of Yeungnam Medical Science
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• v.14 no.1
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• pp.155-167
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• 1997

The identification of serum HBV DNA is very important for the assessment of the disease activity in persistent infection, for the evaluation of the infectivity of an individuals blood. The dot blot, however, has limited sensitivity and sometimes inconsistent with other serological markers and clinical settings. Using the most important recent advance in molecular biology, the polymerase chain reaction(PCR), specific DNA sequences can be amplified more than a million-fold in a few hours and with this technique the detection of the extreme low level of DNA is possible. This study was to determine sensitivity of the PCR for the detection of serum HBV DNA in comparison with dot blot analysis and to investigate the serum HBV DNA status and clinical significance of PCR in patients with chronic HBsAg positive liver disease. The subjects of this study were 17 patients with asymptomatic HBsAg carriers(9 HBeAg positive patients, 8 anti-HBe positive patients), 91 chronic hepatitis B(50 HBeAg positive patients, 41 anti-HBe positive patients), 57 liver cirrhosis(21 HBeAg positive patients, 36 anti-HBe positive patients), 27 hepatocellular carcinoma(10 HBeAg positive patients, 17 anti-HBe positive patients). The results were summerized as following; The detection rates of HBV DNA by dot blot, PCR were 58.9%, 72.2% in HBeAg positive patients, 34.3%, 53.9% in anti-HBe positive patients. The detection rates of HBV DNA by PCR in HBeAg negative patients were 25.0% in asymptomatic HBsAg carriers, 61.0% in chronic hepatitis B, 52.8% in liver cirrhosis, 52.9% in hepatocellular carcinoma. The positive rate for HBV DNA is a significant difference between HBeAg positive and negative asymptomatic HBsAg carriers, but not significantly difference in other groups. In conclusions, this study confirmed that the PCR is much more sensitive than the dot blot analysis in detecting the HBV DNA in the sera of patients with chronic liver disease. The presence of HBV DNA in the serum was detected by PCR with higher sensitivity and it suggested that active viral replication is still going on in most patients with chronic HBsAg positive liver disease irrespective of HBeAg/anti-HBe status, and PCR may be used as a prognostic factor in asymptomatic HBsAg carriers.

• Journal of Chest Surgery
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• v.31 no.4
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• pp.393-397
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• 1998

A 25-year-old man with viral cardiomyopathy and chronic active hepatitis successfully underwent dynamic cardiomyoplasty for the first time in Korea on July 30, 1996. The patient had been intermittently dyspneic for 5 years and was admitted to our center twice because of heart failure. For the past 2 years, he was NYHA functional class III status with a left ventricular ejection fraction(LVEF) of around 30%. The patient was born with scoliosis and showed a short stature. The liver function showed elevated liver enzymes, and hepatitis B antigen was positive. The liver biopsy revealed chronic active hepatitis. The preoperative echocardiogram showed decreased left ventricular function with grade II mitral and grade II tricuspid regurgitation with dilated left and right atrium. Recently his symptoms worsened and we decided to perform a dynamic cardiomyoplasty. The left latissmus dorsi muscle(LDM) was mobilized and tested with lead placement on his right lateral decubitus position. The patient was positioned into supine and, after median sternotomy, the heart was wrapped with the mobilized muscle. The Russian made cardiomyostimulator(EKS-445) and leads (Myocardial PEMB for heart and PEMP-1 for LDM) were used. The total operation time was 8 hours and there were no perioperative episodes. Postoperatively the LDM had been trained for a 10 week period and currently the stimulation ratio is maintained at 1:4. The postoperative LVEF did not increase with the value of 30-35%. However, the patient feels better postoperatively with slightly increased activity.

• Molecules and Cells
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• v.37 no.1
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• pp.66-73
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• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.