Hepatitis: Simsek H

Ozaslan E, Yilmaz R, Simsek H, Tatar G. · Division of Gastroenterology, Hacettepe University Hospital, Ankara, Turkey. · Ann Pharmacother. · Pubmed #12398565 No free full text.

Abstract: OBJECTIVE: Due to their antiproliferative activity, the probable effects of interferons on a fetus are a concern. We report on a pregnant patient who developed acute hepatitis C during pregnancy and was treated with a short course of interferon alfa therapy with a successful outcome. CASE SUMMARY: A 26-year-old woman was diagnosed with acute hepatitis C at the 16th week of pregnancy. She received a total dose of 72 million units of interferon alfa-2b during a 2 1/2 month period. Although the therapy was discontinued due to adverse effects, a complete biochemical and virologic response was obtained. Premature labor occurred and healthy, but growth-restricted, twin infants were born transvaginally. At 18 months of age, they had normal development, with a negative hepatitis C serology. DISCUSSION: The rate of transmission of hepatitis C virus from mother to infant is within the range of 1-5%. Although acute hepatitis C during pregnancy is a very rare occurrence, the mother is at a great risk for chronic infection. There is scarce literature about the probable effects of interferon use during pregnancy due to a lack of controlled studies in this special population. A total of 8 infants, including ours, exposed to interferon alfa and/or ribavirin during pregnancy showed no congenital anomalies or malformations. CONCLUSIONS: Patients with chronic hepatitis whose therapy can be delayed should not be treated with interferon due to a lack of controlled studies. However, women exposed to interferon inadvertently during pregnancy may be encouraged to continue pregnancy. In patients with acute hepatitis C during pregnancy, the use of interferon therapy should be considered with close monitoring.

Schiff E, Simsek H, Lee WM, Chao YC, Sette H, Janssen HL, Han SH, Goodman Z, Yang J, Brett-Smith H, Tamez R. · University of Miami, Miami, Florida, USA. · Am J Gastroenterol. · Pubmed #18721244 No free full text.

Abstract: OBJECTIVE: The efficacy and safety of entecavir in patients with chronic hepatitis B and advanced liver fibrosis/cirrhosis was assessed from three large, randomized, multicenter, phase III studies. PATIENTS AND METHODS: These studies enrolled patients (> or = 16 yr) with chronic hepatitis B, elevated alanine aminotransferase (ALT) levels, and compensated liver disease. Two trials enrolled nucleos(t)ide-naive patients randomized to at least 48 wk of treatment with entecavir 0.5 mg/day or lamivudine 100 mg/day. The third trial randomized lamivudine-refractory patients to 48 wk of entecavir 1 mg/day or lamivudine 100 mg/day. In this post hoc descriptive analysis, the efficacy and safety in patients with advanced liver fibrosis/cirrhosis (Ishak fibrosis stages 4-6) were examined for consistency with those seen in the overall study populations. RESULTS: Of the 1,633 treated patients, 245 had advanced liver fibrosis/cirrhosis (120 entecavir and 125 lamivudine). Among entecavir-treated patients with advanced liver fibrosis, improvement in Ishak fibrosis was observed in 57% of nucleos(t)ide-naive hepatitis B e antigen (HBeAg)-positive patients, 59% of nucleos(t)ide-naive HBeAg-negative patients, and 43% of lamivudine-refractory HBeAg-positive patients versus 49%, 53%, and 33% of lamivudine-treated patients with advanced liver fibrosis. The overall trends in other histologic, virologic, biochemical, and serologic outcomes in entecavir- versus lamivudine-treated patients with advanced liver fibrosis/cirrhosis were consistent with those observed in the overall study populations in each trial. The treatment was well tolerated. CONCLUSION: These data confirm that the performance of entecavir relative to that of lamivudine in patients with advanced liver fibrosis/cirrhosis was consistent with the relationship observed in the overall treated population.

Sherman M, Yurdaydin C, Simsek H, Silva M, Liaw YF, Rustgi VK, Sette H, Tsai N, Tenney DJ, Vaughan J, Kreter B, Hindes R, Anonymous00005. · Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada. · Hepatology. · Pubmed #18537189 No free full text.

Abstract: In hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients who were refractory to current lamivudine therapy, switching to entecavir was superior to continued lamivudine at week 48 for histologic improvement, viral load reduction by polymerase chain reaction and alanine aminotransferase normalization. We assessed the efficacy, safety, and resistance profile of entecavir through 96 weeks of treatment. A total of 286 patients were randomized and treated with entecavir 1 mg (n = 141) or continued lamivudine 100 mg (n = 145). At week 52, 77 entecavir-treated patients who had a protocol-defined virologic response (HBV branched DNA [bDNA] < 0.7 MEq/mL but HBeAg-positive) continued blinded therapy for up to 96 weeks. Patients were assessed for efficacy, safety, and emerging resistance. Cumulative proportions of all treated patients who achieved confirmed efficacy endpoints were also analyzed. Between week 48 and the end of dosing, the proportions of patients with HBV DNA <300 copies/mL by polymerase chain reaction increased from 21% to 40%, and alanine aminotransferase normalization (< or =1x upper limit of normal) increased from 65% to 81%. In the second year, HBeAg seroconversion was achieved by 10% of patients. Of the 77 patients in the second year treatment cohort, entecavir resistance emerged in six patients, and seven experienced virologic breakthrough (five with genotypic resistance acquired before year 2). The safety profile of entecavir in the second year of therapy was consistent with that reported during year 1. CONCLUSION: Through 96 weeks of treatment, 1 mg entecavir resulted in continued clinical benefit in lamivudine-refractory HBeAg-positive chronic hepatitis B patients with a safety profile comparable to lamivudine.

Balaban YH, Korkusuz P, Simsek H, Gokcan H, Gedikoglu G, Pinar A, Hascelik G, Asan E, Hamaloglu E, Tatar G. · Department of Internal Medicine, Division of Gastroenterology, Abant Izzet Baysal University, Bolu - Turkey. · Ann Hepatol. · Pubmed #18007554 No free full text.

Abstract: OBJECTIVE(S): Non-alcoholic steatohepatitis (NASH) is a chronic liver disease with unknown etiology. The insulin resistance, immune mechanisms and oxidative stress are the main factors in its pathogenesis. Dipeptidyl peptidase IV (DPPIV) or CD26 is a protein with endocrine and immune functions. This study aimed to elicudate the changes related to DPPIV in NASH patients. METHODS: Serum and urinary DPPIV activities were measured in 31 NASH patients and 17 healthy controls. The liver biopsies of 29 patients were immunolabeled for CD26. RESULTS: The mean age of patients were 46 +/- 11 years and 14 (45%) of them were female. The serum DPPIV activity was higher in patients (57.3 +/- 7.8 U/L) than controls (43.6 +/- 10.6 U/L) (p < 0.0001), and correlated with the histopathological grade (p = 0.038, r = 0.373) and hepatosteatosis (p = 0.018, r = 0.423) but not with stage (p = 0.286), class (p = 0.286) or CD26 staining (p = 0.743). The urinary DPPIV activity was similar in patients (1.52 +/- 0.94 U/mmol creatinine) and controls (1.37 +/- 0.68 U/mmol creatinine) (p = 0.861). Three acinar zones of liver had equal CD26 expression (p = 0.076). The intensity of CD26 immunostaining was correlated with histopathological grade (p = 0.001) and hepatosteatosis (p = 0.003) but no correlation with stage or class could be detected (p = 0.610 and 0.956, respectively). In CONCLUSIONS: The serum DPPIV activity and the staining intensity of CD26 in liver are correlated with histopathologic grade of NASH and hepatosteatosis. DPPIV can be proposed as a novel candidate with several potential functions in NASH pathogenesis.

Flink HJ, Hansen BE, Heathcote EJ, Feinman SV, Simsek H, Karayalcin S, Mach T, Leemans WF, de Man RA, Verhey E, Schalm SW, Janssen HL, Anonymous00255. · Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. · Am J Gastroenterol. · Pubmed #17029610 No free full text.

Abstract: OBJECTIVES: Antiviral therapy leads to HBeAg seroconversion in 10-40% of the patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in progression of liver disease and increased risk of hepatocellular carcinoma. As part of a global randomized controlled trial we investigated the efficacy (i.e., loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN alpha2b) in patients who failed to respond to previous courses of standard interferon (IFN) or lamivudine. METHODS: We analyzed a total of 76 previous nonresponders: 37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and 22 were nonresponders to both therapies. All patients received a 52-wks course of 100 microg Peg-IFN alpha2b weekly combined with either 100 mg lamivudine daily or a placebo. After therapy patients were followed for 26 wks. RESULTS: Thirteen (35%) nonresponders to previous IFN, five (29%) nonresponders to previous lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to treatment with Peg-IFN alpha2b. No difference in response was found for those treated with Peg-IFN alpha2b alone or in combination with lamivudine. Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase) > 4 x ULN (upper limit of normal) responded better to Peg-IFN alpha2b than those with ALT levels <or= 4 x ULN (53%vs 20%, respectively, p= 0.036). CONCLUSIONS: Peg-IFN alpha2b is effective in approximately one-third of patients who failed to respond to previous treatment with standard IFN or lamivudine. High serum ALT level at baseline of Peg-IFN alpha2b therapy was the best predictor for response in these patients.

Balaban YH, Sumer H, Simsek H, Us D, Tatar G. · Department of Internal Medicine, Unit of Gastroenterology, Hacettepe University, Ankara, Turkey. · Ann Hepatol. · Pubmed #16807517 No free full text.

Abstract: BACKGROUND: Hepatocyte growth factor (HGF) is not only an antiapoptotic and antifibrotic factor of liver, but it is also an adipokine. Serum HGF levels are strongly associated with liver diseases, obesity, insulin resistance (IR), and metabolic syndrome (MS). Non-alcoholic steatohepatitis (NASH) is the hepatic component of MS. To the best of our knowledge, serum HGF levels in patients with NASH have not been previously studied. Our aim was to elucidate the correlation of HGF with the clinical and histopathological parameters of NASH. METHODS: The study group consisted of 26 patients (13 men) who had clinical diagnoses of NASH and underwent liver biopsies. Controls were 13 volunteers (3 men) with negative viral autoimmune markers, and with normal levels of serum lipids and liver enzymes. RESULTS: Among the NASH patients, 14(54%) were overweight and 10 (39%) had grade I-II obesity. All the patients had class 3-4 non-alcoholic fatty liver disease (NAFLD) except for 2 who had class 2 disease. All of the patients had Child's class A liver disease, and MS was present in 5 (19%) patients and 8(31%) patients had Homeostasis Model Assessment of Insulin Resistance (HOMA) > 3. Serum HGF levels were similar in NASH patients (1.24 +/- 1.09 pg/mL) and controls (0.86 +/- 0.22 pg/mL) (p = 0.21). The levels of serum HGF did not differ between the patients with or without MS (1.65 +/- 1.48 pg/mL and 1.04 +/- 0.80 pg/mL, respectively, p=0.65). HGF was not correlated with the laboratory or histopathological parameters. CONCLUSIONS: Serum HGF levels were higher in NASH patients than in the controls, although it was statistically insignificant and a correlation with MS could not be detected in this study.

Simsek H, Shorbagi A, Balaban Y, Tatar G. · No affiliation provided · J Hepatol. · Pubmed #18644652 No free full text.

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Simsek H, Balaban YH, Sümer H, Yilmaz E, Tatar G. · No affiliation provided · Dig Dis Sci. · Pubmed #16964543 No free full text.

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Agca E, Akcay A, Simsek H. · No affiliation provided · Ann Pharmacother. · Pubmed #15122001 No free full text.

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Sanver A, Gurlek A, Simsek H, Tatar G. · No affiliation provided · Diabetes Care. · Pubmed #11375385 links to  free full text

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