Hepatitis: Sohn JH

Kim TY, Sohn JH. · Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea. · Korean J Gastroenterol. · Pubmed #17641552 links to  free full text

Abstract: Clinical management of chronic hepatitis B is rapidly evolving after the recent development of new antiviral drugs. These agents have been shown to be effective in improving virological, biochemical, and histological features in high proportion of the patients with chronic hepatitis B. However, these drugs can not eliminate hepatitis B virus (HBV) directly. It can only suppress HBV replication. Furthermore, the emergence of drug resistant HBV has become problematic according to the long-term use of oral antiviral drugs. Therefore, physicians should be careful in selecting whom to treat, when to start treatment, how long to treat, how to monitor patients before, during and after the treatment, which drug to choose, and how to manage patients with drug resistance. This review will focus on the monitoring and treatment strategy for chronic hepatitis B and drug resistant hepatitis B, quoting some clinical data of recently introduced or promising future drugs.

Choi HJ, Cho BC, Sohn JH, Shin SJ, Kim SH, Kim JH, Yoo NC. · Division of Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu shinchon-dong 134, Seoul, Korea. · J Neurooncol. · Pubmed #18949445 No free full text.

Abstract: Brain metastases from hepatocellular carcinoma are extremely rare. The objectives of the current study were to assess the natural history, outcome, and possible prognostic factors in patients with brain metastases from hepatocellular carcinoma. Between 1995 and 2006, 6,919 patients with hepatocellular carcinoma were treated at Yonsei University Health System. Of those, 62 (0.9%) had a diagnosis of brain metastasis. We carried out a retrospective review of these 62 patients and performed a statistical analysis. The median age at the time patients were diagnosed with brain metastasis was 54 years. Forty-seven patients (76%) were male, and 53 patients had hepatitis B. Median time from diagnosis of hepatocellular carcinoma to brain metastasis was 18.2 months, and 5 patients had brain involvement as their initial presentation. Intracranial hemorrhage was frequently associated (54.8%) with brain metastasis. The most common presenting symptoms were motor weakness, mental change, and headache. Metastases were treated with whole-brain radiation therapy (WBRT) alone in 17 patients and gamma knife surgery alone in 10 patients. Six patients underwent surgical resection and 5 patients were treated with surgical resection followed by WBRT. Twenty-four patients (39%) received steroids only. Median survival after diagnosis of brain metastasis was 6.8 weeks (95% confidence interval: 3.8-9.8 weeks). Univariate analysis showed that treatment modality, number of brain lesions, alpha-fetoprotein, ECOG performance score, recursive partitioning analysis (RPA) class, and Child-Pugh classification had a statistically significant impact on survival. In multivariate analysis, treatment modality, number of brain lesions, and Child-Pugh classification were statistically significant prognostic factors for survival. The overall prognosis of patients with brain metastases from hepatocellular carcinoma is extremely poor. Nevertheless, some subsets of patients manifested the most favorable survival criteria (single brain metastasis and good liver function); thus, for at least these patients, treatment may result in an improved survival time.

Sohn JH, Han KL, Kim JH, Rukayadi Y, Hwang JK. · Department of Biotechnology, Yonsei University, Seodaemun-gu, Seoul, Korea. · Biol Pharm Bull. · Pubmed #18239286 links to  free full text

Abstract: Cisplatin is one of the most effective antineoplastic drugs, but it has undesirable side effects such as hepatotoxicity at high doses. This study investigated the protective effect of macelignan, isolated from Myristica fragrans HOUTT. (nutmeg), against cisplatin-induced hepatotoxicity and the possible mechanisms involved in these effects in mice. Pretreatment with macelignan for 4 d significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. The results also showed that the protective effects of macelignan on cisplatin-induced hepatotoxicity may be associated with the mitogen activated protein kinase (MAPK) signaling pathway. Cisplatin-induced phosphorylation of c-Jun N-terminal kinase1/2 (JNK1/2) and extracellular signal-regulated kinase1/2 (ERK1/2) was abrogated by pretreatment with macelignan, however, that of p38 was not significantly affected. It was also found that macelignan attenuated the expression of phosphorylated c-Jun in cisplatin-treated mice. Accordingly, it is suggested that the hepatoprotective effects of macelignan could be related to activation of the MAPK signaling pathway, especially JNK and c-Jun, its substrate. The present findings suggest that co-treatment of cisplatin with macelignan may provide more advantage than cisplatin treatment alone in cancer therapy.

Yoon J, Lee JI, Baik SK, Lee KH, Sohn JH, Lee HW, Namkung J, Chang SJ, Choi JW, Kim HW, Yeh BI. · Department of Biochemistry and Institute of Basic Medical Sciences, Wonju College of Medicine, Yonsei University, 162 Ilsandong, Wonju, Gangwondo 220-701, Republic of Korea. · World J Gastroenterol. · Pubmed #18069766 links to  free full text

Abstract: AIM: To confirm the predictive factors for interferon (IFN)-alpha and ribavirin combination therapy for chronic hepatitis patients with hepatitis C virus (HCV) genotype 1b. METHODS: HCV RNA from 50 patients infected with HCV genotype 1b was studied by cloning and sequencing of interferon sensitivity determining region (ISDR), PKR-eIF2alpha phosphorylation homology domain (PePHD). Patients were treated with IFN-alpha and ribavirin for 6 mo and grouped by effectiveness of the therapy. A variety of factors were analyzed. RESULTS: Our data showed that age, HCV RNA titer, and ISDR type could be used as the predictive factors for combined IFN-alpha and ribavirin efficacy. Characteristically, mutations in PePHD appeared only when the combination therapy was effective. Other factors, such as sex and alanine aminotransferase (ALT) level, were not related to its efficacy. Adjusting for age and HCV RNA titer indicated that the ISDR type was the most potent predictive factor. CONCLUSION: HCV RNA ISDR type is an important factor for predicting efficacy of IFN-alpha and ribavirin combination therapy in Korean patients.

Kim TY, Sohn JH, Ahn SB, Son BK, Lee HL, Eun CS, Jeon YC, Han DS. · Department of Internal Medicine, Hanyang University, Guri, Korea. · Korean J Hepatol. · Pubmed #17898552 links to  free full text

Abstract: BACKGROUND/AIMS: Recently, the incidence of acute hepatitis A has increased nationwide and is related to the low rate of IgG anti-HAV. This study compared the prevalence of IgG anti-HAV in two university hospitals located in a large city and in a small city including a rural region according to age, gender, and the year of diagnosis. METHODS: IgG anti-HAV was measured in a total of 4299 patients, who visited Seoul or Guri Hanyang University Hospital between January 2002 and December 2006. RESULTS: The positive rates of the antibody in Seoul and Guri hospitals were 52.7% vs 57.1% in under the age of 1, 40.7% vs 42.2% in age of 1 to 4, 31.8% vs 30.3% in age of 5 to 9, 24.8% vs 27.1% in age of 10 to 14, 11.6% vs 18.2% in age of 15 to 19, 23.0% vs 20.3% in age of 20 to 24, 40.5% vs 42.9% in age of 25 to 29, 67.5% vs 75.0% in age of 30 to 34, 86.5% vs 88.1% in age of 35 to 39, 95.3% vs 93.6% in age of 40 to 44, 97.0% vs 98.7% in age of 45 to 49, and 98.5% vs 98.6% in patients who were more than 50, respectively. The positive rates of the antibody were not significantly different between two sites according to each age group and gender. CONCLUSIONS: The results confirmed the low rates of IgG anti-HAV, particularly in the ages of 10-24 that match the age group of recently increased incidence of acute hepatitis A nationwide. Therefore, measurement of the antibody and vaccination should be considered in this age group.

Chang MH, Sohn JH, Kim TY, Son BK, Kim JP, Jeon YC, Han DS. · Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea. · Korean J Gastroenterol. · Pubmed #17641556 links to  free full text

Abstract: BACKGROUND/AIMS: The aim of this study was to identify non-endoscopic predictors for the presence of large esophageal varices in Korean patients with liver cirrhosis. METHODS: Among 736 patients with liver cirrhosis newly diagnosed between the year 2001 and 2005, 245 patients (171 men and 74 women, mean age of 51.9 years) fulfilled the inclusion criteria and underwent EGD as screening tests for esophageal varices. Fifteen variables were analysed to identify the presence of large esophageal varices. RESULTS: Esophageal varices were noted in 186 patients (75.9%) and large varices in 55 patients (22.4%), while 59 patients (24.1%) had no varices at the time of initial diagnosis of cirrhosis. The causes of liver cirrhosis were viral hepatitis (41.2%), chronic alcoholism (42.4%), viral hepatitis/alcoholism (9.8%), and others (6.6%). Fifty-one percent, 35.1% and 13.9% of the patients belonged to Child-Pugh class A, B, and C, respectively. Variables associated with the presence of large esophageal varices on univariate analysis were the presence of ascites, splenomegaly (long-axis >or= 12 cm by ultrasound measure), alcoholism, Child-Pugh class, platelet count, prothrombin time, and albumin. On multivariate analysis, alcohol, splenomegaly, and ascites were significantly associated with the presence of large esophageal varices. If the patients have two of them, sensitivity and negative predictive value were 80% and 91.7%, respectively. Patients without all three factors had no large esophageal varices. CONCLUSIONS: These results suggest that patients who have at least two among ascites, splenomegaly, and alcoholism would have an increased risk of having large esophageal varices.

Son BK, Sohn JH, Kim TY, Park YK, Jeon YC, Han DS. · Department of internal medicine, Hanyang University College of medicine, Guri, Korea. · Korean J Hepatol. · Pubmed #17380081 links to  free full text

Abstract: The combination therapy with pegylated interferon alpha and ribavirin has increasingly prescribed for chronic hepatitis C. Although many side effects of interferon such as flu-like symptoms, gastrointestinal and neuropsychiatric symptoms are well known, only several cases of interferon-induced pulmonary toxicity have been reported. Interferon-induced pulmonary toxicity usually develops from 2 weeks to 12 weeks after treatment for HCV infection. Diagnosis is commonly based on clinical findings such as a dry cough, dyspnea, hypoxemia, and a restrictive pattern in pulmonary function testing, bilateral diffuse parenchymal infiltrations, histopathological findings of interstitial pneumonitis, and exclusion of any other causative agents. Prompt withdrawal of the drug is the cornerstone of treatment. We report a case of PEG-IFN alpha-2a induced pulmonary toxicity in a 50-year-old male patient with hepatitis C. To our knowledge, this is the first case of pegylated interferon alpha-2a induced pulmonary toxicity in Korea.

Jeong JY, Sohn JH, Son BK, Paik CH, Kim SH, Han DS, Jeon YC, Lee MH, Lee DH, Kee CS. · Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea. · Korean J Gastroenterol. · Pubmed #17322788 links to  free full text

Abstract: BACKGROUND/AIMS: Alcoholic hepatitis is an acute or acute-on-chronic inflammatory syndrome associated with significant morbidity and mortality. Traditionally, Maddrey discriminant function (DF) score and Child-Turcott-Pugh (CTP) score have been used for stratifying the prognosis of alcoholic hepatitis. Recently, the model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator for severe alcoholic hepatitis. Therefore, this analysis was aimed to compare MELD score with DF and CTP scores for predicting the short-term mortality in Korean patients with alcoholic hepatitis. METHODS: The medical records of patients hospitalized with alcoholic hepatitis between January 1, 1999 and December 31, 2004 at Hanyang University Guri-Hospital were analyzed retrospectively. RESULTS: Of the 138 medical records reviewed, 74 cases fulfilled the inclusion criteria (61 males and 13 females; mean age 47.1 years). Twelve patients (16.2%) died within 90 days after admission. Univariate analysis demonstrated that variables such as ascites, hepatic encephalopathy, splenomegaly, international normalized ratio, CTP, and DF scores were significantly correlated with increased 90-day mortality while MELD score was not. According to the multivariate analysis, only CTP score was statistically significant (p=0.012) while DF and MELD scores were not significant for predicting 90-day mortality. The survival analysis with Cox regression test showed higher DF and CTP scores, but not MELD score, significantly increased the risk of in-hospital mortality. CONCLUSIONS: This study demonstrates that DF and CTP scores are independent predictors of short-term mortality in patients with alcoholic hepatitis.

Chung YW, Sohn JH, Baek CH, Kim JP, Jeon YC, Han DS, Lee DH, Kee CS, Park IK. · Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea. · Korean J Gastroenterol. · Pubmed #16554678 links to  free full text

Abstract: Macroenzymes are normal enzymes complexed with an immunoglobulin (usually IgG, rarely IgA or IgM). A number of macroenzymes have been reported in the literature. Among them, macro-AST has been detected in diseases such as acute and chronic hepatitis, various malignancies and autoimmune diseases, but usually not associated with any specific disease. We report a case of elevated AST activity in serum due to marco-AST formation in a female with chronic hepatitis C which was confirmed by AST isoenzyme electrophoresis. To our knowledge, this is the first report of macro-AST occurred in chronic hepatitis patient in Korea.

Kim JB, Sohn JH, Lee HL, Kim JP, Han DS, Hahm JS, Lee DH, Kee CS. · Department of Internal Medicine, Hanyang University Guri Hospital Kyunggi, Korea. · Korean J Hepatol. · Pubmed #15218346 links to  free full text

Abstract: BACKGROUND/AIMS: Recently, acute toxic liver injury has been reported to be the most common cause of acute hepatitis. The frequency and clinical manifestations of acute toxic liver injury was evaluated. METHODS: The medical records of 68 patients demonstrating clinically significant acute toxic liver injury were retrospectively reviewed. Patients with mild biochemical abnormalities were excluded. RESULTS: The annual percentage of toxic liver injury ranged from 50% to 90% among acute hepatitis groups. Among the causes, prescribed drugs (group D) accounted for 55%, herbs or plant products (group H) for 42% and both accounted for 3%. Antibiotics and anti-inflammatory drugs were the most common agents (78%) among group D. The mean age of the patients was 43 and 70% of patients were female. Of the population, common symptoms were jaundice, weakness, fatigue, and nausea. Initial ALT and AST levels were 847 +/- 879 and 664 +/- 625 IU/L, and initial total bilirubin was 7.5 +/- 8.1 mg/dL. Acute toxic liver injury occurred after a mean of 32 days after first exposure. Liver injury resolved within a mean of 32 days. Hepatocellular, mixed, and cholestatic type was 45.2%, 32.3%, 22.5%, respectively. CONCLUSIONS: Recently, acute toxic liver injury has been the most common cause of acute hepatitis in Korea. Prescribed drugs and herbs or plant products are equally important etiologic agents of toxic liver injury. However, etiologic difference may not affect clinical courses or outcomes. A nationwide investigation of the hepatotoxicity of drugs, herbs or other plant products is required.

Lee HL, Han DS, Kim JB, Jeon YC, Sohn JH, Hahm JS. · Department of Internal Medicine, Hanyang University Kuri Hospital, Guri, Korea. · J Korean Med Sci. · Pubmed #15201518 links to  free full text

Abstract: A 47-yr-old man with hepatitis B virus associated liver cirrhosis was admitted to our hospital with diarrhea and generalized edema and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia by intestinal biopsy and 99m Tc albumin scan. During hospitalization, he received subcutaneous octreotide therapy. After 2 weeks of octreotide therapy, follow-up albumin scan showed no albumin leakage, and the serum albumin level was sustained. We speculate that liver cirrhosis can be a cause of intestinal lymphangiectasia and administration of octreotide should be considered for patients with intestinal lymphangiectasia whose clinical and bio-chemical abnormalities do not respond to a low-fat diet.

Kim TY, Lee SH, Kim TJ, Cho KR, Cho SC, Han SH, Yang SY, Chung YW, Sohn JH, Baik SH, Bae SC, Lee DH, Kee CS. · Institute of Digestive Disease, The Hospital for Rheumatic Diseases, Hanyang University College of Medicine, Seoul, Korea. · Taehan Kan Hakhoe Chi. · Pubmed #12499822 links to  free full text

Abstract: Patients with systemic lupus erythematosus (SLE) have a chance of developing liver involvement in their lifetime. The main cause of liver involvement in SLE patients is previous treatment with hepatotoxic drugs or hepatotropic viral hepatitis. Wilson's disease is a hereditary disorder and is usually diagnosed in patients presenting either neuropsychiatric disorders or manifestations related to chronic liver disease. Fulminant hepatic failure as the initial manifestation of Wilson's disease is rare. The relationship between systemic lupus erythematosus and Wilson's disease has not been established. We report a case of a 12-year-old girl with SLE who presented fulminant hepatic failure as an initial manifestation of Wilson's disease. The diagnosis was established with decreased serum ceruloplasmin level and the presence of Kayser-Fleischer ring. We treated with repeated plasma exchange. Despite repeated plasma exchange she died of multi-organ failure on the 16th hospital day. Considering this case, Wilson's disease should be considered as a cause of fulminant hepatic failure, especially in juvenile age cases.

Cho SC, Lee SH, Shinn JJ, Han SH, Roh BJ, Sohn JH, Lee DH, Kee CS. · Department of Internal Medicine, College of Medicine, Hanyang University Institute of Digestive Diseases, Seoul, Korea. · Taehan Kan Hakhoe Chi. · Pubmed #12499816 links to  free full text

Abstract: BACKGROUND/AIMS: A significant correlation between HBV DNA and liver damage was found in precore mutant strains but there was no significant association between viral replication and liver damage in HBeAg positive patients. Laboratory tests are often requested to predict hepatitis activity (grade) and fibrosis (stage) in HBeAg positive chronic hepatitis B. We assessed ALT, AST, and HBV-branched DNA to find which is the best for predicting hepatitis activity and fibrosis. METHODS: Routine biochemical liver function tests and HBV DNA in sera were assessed in 119 young patients positive with HBsAg and HBeAg. The mean age of patients was 21+/-2 years. All patients were male. By logistic regression analysis the relationships between laboratory data, hepatitis activity, fibrosis, or risk of chronic active hepatitis were analyzed. RESULTS: There was a significant correlation between aminotransferase (AST, ALT) and hepatitis activity/ fibrosis. A significant inverse relationship between the HBV bDNA and hepatitis activity was demonstrated (Pearson's correlation coefficient: lobular activity,-0.305; porto-periportal activity, -0.410). But HBV bDNA was not correlated with severity of fibrosis. AST and HBV bDNA was the important test for predicting the more severe hepatitis activity (lobular activity and porto-periportal activity: score>/=3, respectively) CONCLUSION: The higher AST, but the lower HBV bDNA, in sera shows the more severe hepatitis activity. AST and HBV bDNA could be helpful for assessing the hepatitis activity in young male patients with HBeAg positive chronic hepatitis B if proper reference values are used.

Yeh BI, Han KH, Lee HW, Sohn JH, Ryu WS, Yoon DJ, Yoon J, Kim HW, Kong ID, Chang SJ, Choi JW. · Department of Biochemistry and Institute of Basic Medical Science, Wonju School of Medicine, Yonsei University, Wonju, Republic of Korea. · J Med Virol. · Pubmed #11857525 No free full text.

Abstract: Interferon-alpha (IFN-alpha) has been used to treat hepatitis C Virus (HCV)-induced infection but has been effective in only about half of all patients. It is suggested that the different responses to IFN-alpha treatment in HCV infection may be influenced by HCV genotypes, HCV RNA titer at the beginning of IFN-alpha therapy, and the sequences of the interferon sensitivity determining region (ISDR). However, there have also been reports showing that these have no relation to an IFN-alpha effect. In a previous study, it was found that the nucleotide sequence variation in the hypervariable region (HVR) 1 of the HCV could predict the effect of IFN-alpha. In the present investigation, an attempt was made to determine the predictive factors of IFN-alpha therapy. Twenty-six patients with HCV infection were treated with IFN-alpha. Among these, 13 patients recovered after 3 to 6 months of IFN-alpha treatment, although the other 13 patients showed no response after 6 months of treatment with IFN-alpha. In order to determine the predictive factors of IFN-alpha therapy, the ALT levels, HCV genotypes, HCV serum titer, and the quasispecies of HVR 1 were compared between responders and non-responders. It is suggested that the variation in the HVR 1 and HCV serum titer can be used to predict the effect of IFN-alpha.