Hepatitis: Tan J

Tan J, Lok AS. · No affiliation provided · Liver Transpl. · Pubmed #17318864 links to  free full text

This publication has no abstract.

Tan J, Surti B, Saab S. · Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA. · Liver Transpl. · Pubmed #18668664 links to  free full text

Abstract: As the treatment of cirrhosis improves, pregnancy in patients with cirrhosis is likely to become more common. Although maternal and fetal mortality is expected to similarly improve, pregnant patients with cirrhosis face unique risks. These include higher rates of spontaneous abortion and prematurity and a potential for life-threatening variceal hemorrhage, hepatic decompensation, splenic artery aneurysm rupture, and postpartum hemorrhage. Pregnancy outcome may be influenced by the underlying etiology of liver disease, as in viral and autoimmune hepatitis. Medications also impact the course of pregnancy, and must be tailored appropriately during this time.

Tan J, Lok AS. · Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0362, USA. · Curr Opin Gastroenterol. · Pubmed #17414841 No free full text.

Abstract: PURPOSE OF REVIEW: This is a concise review of recent developments in the field of viral hepatitis, based on publications between December 2005 and November 2006. RECENT FINDINGS: Elevated hepatitis B virus DNA levels in patients in their 40s with perinatally acquired hepatitis B virus infection increases the risk for cirrhosis and hepatocellular carcinoma. Six approved therapies are available for chronic hepatitis B. Entecavir is a potent antiviral for nucleoside-naïve patients. For lamivudine resistant hepatitis B virus infection, adefovir should be added to lamivudine to reduce the risk of adefovir-resistant mutations; however, tenofovir may be a more promising alternative to adefovir. A shorter duration of treatment wth pegylated interferon and ribavirin is sufficient for genotype 2 hepatitis C infection but the benefits of extending treatment to 72 weeks for genotype 1 needs to be confirmed. Pegylated interferon monotherapy was shown to be effective in patients with hepatitis D and ribavirin provides no additional benefit. SUMMARY: New developments in the past year will help us fine tune the treatment of viral hepatitis. Even as new treatments are approved, the potential benefits of treatment should be weighed against the risk of drug-resistant mutations with long-term therapy.

Tan J, Degertekin B, Wong SN, Husain M, Oberhelman K, Lok AS. · Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI 48109-0362, USA. · J Hepatol. · Pubmed #18199519 No free full text.

Abstract: BACKGROUND/AIMS: We sought to identify mutations associated with treatment failure to adefovir (ADV) and to determine virologic response to tenofovir (TDF) alone and in combination with emtricitabine (FTC) in these patients. METHODS: Serum samples prior to and after the change in treatment to TDF/TDF+FTC from 13 patients were analyzed by direct sequencing and clonal analysis. RESULTS: ADV-resistant mutations, rtA181V and rtN236T, were detected on direct sequencing in 3 of 8 patients who had virologic breakthrough. Among patients with suboptimal virologic response, rtA181T, rtI233V, and rtN236T were present on clonal analysis in 3 patients. Ten patients received TDF, 8 achieved virologic response. One had ADV-resistance at baseline and persistence of ADV-resistant mutations during TDF treatment, addition of FTC resulted in a further decrease in HBV DNA. Another patient had no ADV-resistance at baseline, and selection of ADV-resistant mutations during TDF treatment. All 3 patients who received TDF+FTC had undetectable HBV DNA within 3-12 months including 2 who had ADV-resistance at baseline. CONCLUSIONS: TDF monotherapy is effective for patients with virologic breakthrough or suboptimal response to ADV, but combination therapy with a nucleoside analogue should be considered in patients with ADV-resistance. No novel mutations were detected.

Giunta B, Somboonwit C, Nikolic WV, Rrapo E, Tan J, Shapshak P, Fernandez F. · Department of Psychiatry and Behavioral Medicine, Institute for Research in Psychiatry Neuroimmunology Laboratory, University of South Florida College of Medicine, Tampa, FL 33613. · Crit Rev Neurobiol. · Pubmed #19409058 No free full text.

Abstract: Hepatitis-C virus (HCV) has infected an estimated 130 million people worldwide, most of whom are chronically infected. Infection is marked by both treatment- and non-treatment-related psychiatric symptoms. Symptoms associated with antiretroviral therapy, interferon-alpha (IFN-alpha), include acute confusional states, delirium, depression, irritability, and even mania. These psychiatric symptoms are further complicated by the high rate of substance abuse and comorbid HIV infection inherent to this population. Even in the absence of IFN-alpha therapy, comorbid depression, cognitive decline, and especially fatigue are common in patients suffering HCV. These comorbidities have significant effects on both treatments and outcomes, and thus are reviewed herein.

Degertekin B, Hussain M, Tan J, Oberhelman K, Lok AS. · Division of Gastroenterology, University of Michigan Medical Center, 3912 Taubman Center, SPC 5362, Ann Arbor, MI 48109, USA. · J Hepatol. · Pubmed #19019484 No free full text.

Abstract: BACKGROUND/AIMS: Early detection of antiviral drug-resistant mutations enables prompt initiation of rescue therapy. The aim of this study was to determine the accuracy and sensitivity of a new line probe assay in the detection of antiviral drug-resistant HBV mutations. METHODS: One-hundred samples from 54 patients with virologic breakthrough during entecavir, lamivudine or adefovir treatment and 21 samples from 21 nucleoside-naïve patients were tested by direct sequencing and an updated line probe assay (Innogenetics, HBV DR v.3) which incorporates probes that can detect mutations at 11 positions of the reverse transcriptase region of the HBV polymerase gene. RESULTS: Complete concordance between line probe and sequencing results was observed for 90/121 samples (74.3%) and 1291/1331 amino acid positions (96.9%). Testing of follow-up samples and clonal analysis of discordant samples confirmed the presence of mutations where line probe assay but not direct sequencing detected mutations. HBV DR v.3 assay consistently detected mutations present in > or = 5% of the virus population when HBV DNA concentration was > or = 4 log10copies/mL. CONCLUSIONS: The updated version of the line probe assay (HBV DR v.3) has high concordance with direct sequencing in detecting antiviral drug-resistant mutations but its sensitivity in detecting mutations at some positions needs to be improved.

Chen H, Yuan L, Tan J, Liu Y, Zhang J. · Obstetrics and Gynecology Department, The Second Affiliated Hospital of Sun Yat-Sen University, Guangdong, China. · Int J Gynaecol Obstet. · Pubmed #18321514 No free full text.

Abstract: OBJECTIVE: To determine the clinical characteristics of patients with fulminant hepatitis of pregnancy (FHP) and acute fatty liver of pregnancy (AFLP) and analyze their correlation with pregnancy outcome. METHODS: Of 55 pregnant women with severe liver disease, 41 had FHP and 14 had AFLP. RESULTS: Jaundice was the primary manifestation for both FHP and AFLP and hepatic encephalopathy was the most significant complication for both. Disseminated intravascular coagulation, albuminuria, and prothrombin activity were found to be independent risk factors of maternal mortality for both. However, the rates of preterm labor, fetal demise, and neonatal asphyxia were lower in the FHP group. CONCLUSION: Women with FHP or AFLP are at risk for severe complications and adverse pregnancy outcome. Since the 2 conditions are managed differently, early diagnosis is essential.

Yee NK, Farina V, Houpis IN, Haddad N, Frutos RP, Gallou F, Wang XJ, Wei X, Simpson RD, Feng X, Fuchs V, Xu Y, Tan J, Zhang L, Xu J, Smith-Keenan LL, Vitous J, Ridges MD, Spinelli EM, Johnson M, Donsbach K, Nicola T, Brenner M, Winter E, Kreye P, Samstag W. · Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877, USA. · J Org Chem. · Pubmed #16958506 links to  free full text

Abstract: A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce >400 kg of cyclized product.

Tan J, Hytiroglou P, Wieczorek R, Park YN, Thung SN, Arias B, Theise ND. · Department of Pathology, New York University Medical Center, New York, NY 10016, USA. · Liver. · Pubmed #12390471 No free full text.

Abstract: BACKGROUND/AIM: Proliferative bile ductular reactions occur in a variety of liver diseases in humans. It is a matter of debate whether such reactions result from progenitor cell proliferation with biliary and hepatocytic differentiation, versus biliary metaplasia of damaged hepatocytes. We investigated bile ductular reactions in liver diseases, paying particular attention to the presence of cells with intermediate (hepatocytic/biliary) features (oval-like cells). METHODS: Five specimens each were selected of submassive hepatic necrosis and cirrhosis due to hepatitis B, hepatitis C, autoimmune hepatitis, alcohol injury, primary biliary cirrhosis and primary sclerosing cholangitis. Immunohistochemical stains were performed for biliary markers (cytokeratins [CKs] 7 and 19), as well as hepatocytic markers (HepParl and alpha-fetoprotein[AFP]) in sequential sections. The degree of staining of each cell type (biliary, hepatocytic, intermediate) was graded semiquantitatively. RESULTS: Hepatocytes always stained diffusely for HepParl, occasionally for CK7, and rarely for CK19. Biliary cells were always diffusely positive for CK7 and CK19, and rarely for HepParl. Intermediate cells were identified in all cases and showed widespread staining for both HepParl and CK7, and less commonly for CK19. AFP was not expressed in any cell type. The morphologic and immunohistochemical features of bile ductular reactions were similar in the different diseases. CONCLUSIONS: Proliferating hepatic parenchymal cells with intermediate (hepatocytic/biliary) morphologic features and combined immunophenotype can be identified in a variety of acute and chronic liver diseases. The similarity of bile ductular reactions among chronic hepatitic, alcoholic and biliary diseases suggests that they result from proliferation of oval-like progenitor cells.

Lian Y, Tan J, Deng Z. · Guangzhou Municipal Eighth People's Hospital, Institute of Infectious Diseases, Guangzhou (510060). · Zhongguo Zhong Xi Yi Jie He Za Zhi. · Pubmed #11789214 No free full text.

Abstract: OBJECTIVE: To study the in vivo anti-viral effect of a Chinese drug, composite Shuangcao Anti-Jaundice Granule No. 1(SCG-1), on duck hepatitis B virus (DHBV). METHODS: Guangzhou brown spot ducklings infected with DHBV were used as the hepatitis B animal model, for which, 1-day old ducklings were infected with DHBV. Positive DHBV-DNA in ducklings sera were detected 13 days after the infection, and then SCG-1 was given for 14 days and DHBV-DNA was detected by dot-blot hybridization test. RESULTS: After medicated with SCG-1 [10 g/(kg.day) and 5 g/(kg.day)] 7 days and 14 days, optic density value (OD value) of DHBV-DNA in ducklings' sera were obviously lower than that before treatment, there was significant difference. But rebound phenomenon appeared in both groups 3 days after stopping medication (P < 0.05). CONCLUSION: SCG-1 could inhibit the replication of DHBV-DNA in Guangzhou ducklings.