Hepatitis: Karasu Z

Akay S, Karasu Z. · Ege University Medical School Department of Gastroenterology, Izmir, Turkey. · Expert Opin Biol Ther. · Pubmed #18847315 No free full text.

Abstract: Post-transplant hepatitis B virus (HBV) recurrence prophylaxis is a sine qua non of liver transplantation for HBV-related liver disease because of high rate and aggressive course of HBV recurrence. Hepatitis B immune globulin (HBIG) is a polyclonal immune globulin solution obtained from plasma, donated by individuals with high titres of anti-HBs (hepatitis B antibody). Although it was being used for postexposure prophylaxis against HBV since 1974, its use in post-transplant prophylaxis of HBV infection was not until 1987. Long-term prophylaxis with HBIG alone had been the standard treatment in post-transplant HBV prophylaxis until the introduction of lamivudine. Combining HBIG with oral nucleotide/nucleoside analogues in post-transplant prophylaxis of recurrent HBV resulted in lower recurrence rates of infection. However, high cost and emergence of immune escape mutations are still the problems to be solved regarding HBIG therapy in post-transplant prophylaxis of HBV recurrence.

Gunsar F, Akarca US, Ersoz G, Kobak AC, Karasu Z, Yuce G, Ilter T, Batur Y. · Ege University Medical School Gastroenterology, Izmir, Turkey. · Antivir Ther. · Pubmed #16218171 No free full text.

Abstract: The only beneficial agent for the treatment of chronic delta hepatitis (CDH) is interferon (IFN). However, there is no consensus on the best dosage or duration of IFN therapy. As ribavirin (RBV) increases the sustained response when added to IFN in chronic hepatitis C, probably because of its immunomodulatory effect, we aimed to investigate the efficacy of 2-year IFN treatment and whether RBV had any additive effect to IFN in CDH. METHODS: Patients (n = 31) with CDH were randomized with a 1:2 ratio as 10 patients (3 females/7 males, age 39 +/- 9) receiving IFN monotherapy (9 MU IFN-alpha2a three times weekly) and 21 patients (8 females/13 males, age 38 +/- 11) receiving IFN plus RBV for 2 years (IFN at the same dosage and RBV at 1000-1200 mg/day). Alanine transferase normalization and hepatitis delta virus (HDV) RNA negativity at the end of treatment and at the end of the follow-up period (at least 6 months following 2-year treatment) were primary endpoints of the study. In addition, virological response and biochemical response were determined separately. RESULTS: Eight of 31 patients (25%) had cirrhosis in liver biopsies. Six patients from the IFN monotherapy group and 12 patients from the combination group had biochemical response. Five patients from the IFN monotherapy group and 11 patients from the combination group had virological response at the end of therapy. Two patients from the IFN group and five patients from the combination group had sustained biochemical response at the end of the follow-up period. Hepatitis B virus (HBV) activations with HBV DNA positivity were observed in two patients (one from the IFN monotherapy group, one from the combination group). Two patients (20%) in the IFN group and five patients (23.5%) in IFN plus RBV group remained as virological responders at the end of the follow-up period (P > 0.05). None of the patients with liver cirrhosis were responsive at the end of the follow-up period. CONCLUSION: Almost 20% of the patients with CDH were responsive to 2-year IFN treatment at the end of the follow-up period and no additional effect of RBV was observed. Patients with advanced liver disease failed to respond to treatment.

Karasu Z, Ozacar T, Akyildiz M, Demirbas T, Arikan C, Kobat A, Akarca U, Ersoz G, Gunsar F, Batur Y, Kilic M, Tokat Y. · Department of Gastroenterology, Ege University Medical School, Bornova, Izmir, Turkey. · Antivir Ther. · Pubmed #15651751 No free full text.

Abstract: Post-transplant prevention of hepatitis B virus (HBV) infection is based on treatment with lamivudine and/or hepatitis B immune globulin (HBIG). However, optimum doses and duration for these drugs are not yet clear. We tested high doses of lamivudine (300 mg/day) in combination with low doses of HBIG (200-400 IU/2-4 weeks). Eighty patients who had post-transplant prophylaxis of lamivudine and HBIG were included in the study. Of those, 20 had hepatitis D virus co-infection and eight were HBV DNA-positive at the time of transplantation. Ten HBV DNA-positive patients were treated with lamivudine (150 mg/day) before transplantation; all were HBV DNA-negative after lamivudine treatment. All patients in the anhepatic phase were given 4000 IU of HBIG. Following this, 400 or 800 IU HBIG was administered intramuscularly daily for 5-10 days post-transplantation and 2-4 times weekly thereafter, according to serum titre of antibodies to hepatitis B surface antigen (anti-HBs). Lamivudine was maintained or initiated at the time of transplantation and was continued indefinitely. Median follow-up was 21 months (range 3-73 months). Recurrence of hepatitis B surface antigen (HBsAg)-positivity occurred in only three out of 78 (4%) patients; two of these three were HBV DNA-positive. Median anti-HBs titre at the final follow-up was 68 IU. Patient and graft survival was 85% at 1 year. In conclusion, a combination of lamivudine 300 mg/day and low-dose HBIG prevents post-transplantation recurrence of hepatitis B, even in the presence of viral replication in the pre-transplant period.

Akarca US, Ersoz G, Gunsar F, Karasu Z, Saritas E, Yuce G, Batur Y. · Division of Gastroenterology, Ege University Faculty of Medicine, Izmir, Turkey. · Antivir Ther. · Pubmed #15259895 No free full text.

Abstract: BACKGROUND AND AIMS: Results of studies using lamivudine and interferon combination in the treatment of chronic hepatitis B are not consistent or conclusive. This study aimed to evaluate the efficacy of interferon plus lamivudine use versus single lamivudine in anti-HBe-positive chronic hepatitis B. METHODS: Eighty patients were treated with either lamivudine or lamivudine plus simultaneously started interferon. Patients were assigned in groups according to random allocation rule. Lamivudine was given 150 mg/day for 96 weeks in each group; interferon was administered 10 MU three times a week for 24 weeks in the combination therapy group. RESULTS: Alanine aminotransferase (ALT) normalization was achieved earlier in patients treated with lamivudine alone. At the end of treatment, there was no difference between the groups with respect to HBV DNA negativity, ALT normalization and breakthrough rate. Histological improvement was remarkable in each group, but fibrosis score and necro-inflammatory activity were much lower in lamivudine-treated patients. CONCLUSIONS: Addition of interferon to the lamivudine regimen does not increase the effectiveness of the treatment. Considering the side effects of interferon treatment, this combination seems not to be convenient for anti-HBe-positive chronic hepatitis B.

Kiyici M, Yilmaz M, Akyildiz M, Arikan C, Aydin U, Sigirli D, Nart D, Yilmaz F, Ozacar T, Karasu Z, Kilic M. · Ege University, Organ Transplantation Center, Izmir, Turkey. · Transplant Proc. · Pubmed #18589140 No free full text.

Abstract: BACKGROUND/AIMS: Hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrences affect both patient and graft survivals post-orthotopic liver transplantation (OLT) in HBV patients with HCC. We analyzed the relationship between HBV and HCC recurrence in a large cohort of HBV-OLT patients with versus without HCC. METHODS: Two hundred eighty-seven HBV patients with OLT (72 also with HCC) were included in the study. Mean follow-up in the post-OLT period was 31.7 +/- 24.7 (range, 3-119) months. RESULTS: Post-OLT HBV recurrence observed in 10.1% of patients was more prevalent among the HCC group; 23.6% versus 5.5% in patients with and without HCC, respectively. The mean interval for the development of HBV recurrence was 39.5 +/- 28.5 (range, 2-99) months. Among 72 HCC patients, 8 patients (11.1%) had recurrent HCC, and 7 of them also had HBV recurrence. The mean interval for the development of HCC recurrence was 11.2 +/- 7.85 (range, 2-23) months after OLT. OLT patients with HCC with tumors exceeding the Milan criteria had worse 1-, 3-, and 5-year survival rates than patients with HCC meeting the Milan criteria. HBV and HCC recurrence-free survivals were significantly lower in patients with HCC and HBV recurrence, respectively. In the 7 patients with both HCC and HBV recurrence, mean HBV recurrence time was 9.42 +/- 6.75 months and mean HCC recurrence time was 9.57 +/- 6.75 months. There was a strong correlation between HBV and HCC recurrence times. Cox proportional hazards regression analysis showed that only HCC recurrence was a significant independent predictor of HBV recurrence (P < .001; hazard ratio [HR] = 26.94; 95% confidence interval [CI] = 10.81-67.11). On the other hand, HBV recurrence (P = .013; HR = 5.80; 95% CI = 1.45-23.17) and nodule count (P = .014; HR = 13.08; 95% CI = 1.70-100.83) were significant predictors of HCC recurrence. CONCLUSIONS: HBV and HCC recurrences demonstrate a close relationship in patients with OLT.

Tekin F, Gunsar F, Karasu Z, Akarca U, Ersoz G. · Department of Gastroenterology, Ege University Medical School, Izmir, Turkey. · Aliment Pharmacol Ther. · Pubmed #18346186 No free full text.

Abstract: BACKGROUND: Pretransplantation clearance of hepatitis C virus (HCV)-RNA reduces the risk of HCV recurrence after transplantation. Furthermore, a sustained virological response could reduce disease progression and slow clinical deterioration in nontransplanted patients. AIM: To evaluate the safety, tolerability and efficacy of pegylated-interferon (PEG-IFN) alfa-2a plus ribavirin therapy in HCV-related decompensated cirrhotics. METHODS: Twenty HCV-related decompensated cirrhotics (44-67 years, 12 males, six Child-Pugh score A, 14 Child-Pugh score B, all with genotype 1b) were enrolled into the study. Treatment with PEG-IFN alfa-2a (135 microg, once a week) plus ribavirin (1000-1200 mg/day) was commenced. A 48-week treatment was planned in patients who had early virological response. RESULTS: Treatment was stopped in 8 (40%) patients. The remaining 12 (60%) patients completed 48 weeks of therapy; nine (45%) of them obtained end-of-therapy virological response and six (30%) of them obtained sustained virological response. Living donor liver transplantation was performed in three (15%) patients. Eight (40%) and six (30%) patients needed to reduce PEG-IFN alfa-2a and ribavirin dosages, respectively. No patient died during the follow-up period. CONCLUSION: PEG-IFN alfa-2a plus ribavirin therapy is safe, tolerable and efficacious in selected HCV-related decompensated cirrhotics.

Akyildiz M, Karasu Z, Zeytunlu M, Aydin U, Ozacar T, Kilic M. · Department of Gastroenterology, Ege University Medical School, Bornova, Izmir, Turkey. · J Gastroenterol Hepatol. · Pubmed #18031370 No free full text.

Abstract: BACKGROUND: Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. METHOD: Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. RESULTS: In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6-48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. CONCLUSION: Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.

Karasu Z, Akyildiz M, Kilic M, Zeytunlu M, Aydin U, Tekin F, Yilmaz F, Ozacar T, Akarca U, Ersoz G, Gunsar F, Ilter T, Lucey MR. · Department of Gastroenterology, Ege University Medical School, Bornova, Izmir, Turkey. · J Gastroenterol Hepatol. · Pubmed #18031369 No free full text.

Abstract: BACKGROUND AND AIM: Living donor liver transplantation (LDLT) has particular advantages for Turkey where hepatitis B virus (HBV) infection is the most common cause of cirrhosis, both because LDLT circumvents the difficulties encountered in the emerging world in providing deceased donor organs, and because it allows preemptive antiviral therapy. The aim of this study was to review one institution's experience with LDLT in patients with chronic HBV infection. METHODS: A total of 109 patients with chronic HBV infection underwent LDLT between September 1999 and June 2005, of whom 40 were coinfected with hepatitis D virus and 23 had hepatocellular carcinoma. Antiviral prophylaxis was attempted in all, beginning prior to transplantation with lamivudine or adefovir, and continuing after transplantation with low dose intramuscular hyperimmune B immunoglobulin (HBIg) plus lamivudine or adefovir. RESULTS: In a median follow up of 20 months (range 1-66 months), there was no donor mortality. One-year recipient survival was 90%, and in total 16 recipients died. None of the deaths was related to HBV. Recurrence of HBV infection was detected by reappearance of serum hepatitis B surface antigen in six patients (5.5%) at 5, 8, 12, 17, 34 and 46 months after transplantation, respectively. There was no influence of donor hepatitis B core antibody status on the likelihood of recurrence of HBV in the allograft. CONCLUSION: The results indicate that LDLT with antiviral treatment and low dose HBIg provides excellent results for donors and recipients.

Basturk B, Karasu Z, Kilic M, Ulukaya S, Boyacioglu S, Oral B. · Department of Immunology, Gazi University Faculty of Medicine, Besevler 06500, Ankara, Turkey. · Infect Genet Evol. · Pubmed #17974504 No free full text.

Abstract: BACKGROUND AND AIM: Cytokines play important roles in the regulation of immune response. The aim of the study was to investigate the association of the cytokine gene polymorphisms with persistence of hepatitis B virus (HBV) infection and the development of end-stage liver disease (ESLD) due to HBV infection. METHODS: The study involved 27 patients with end-stage liver disease due to HBV infection, 23 HBV carriers and 60 healthy controls. All genotyping (TNF-alpha, TGF-beta, IL-10, IFN-gamma) experiments were performed using sequence specific primers (PCR-SSP) by using commercial kit according to manufacturers' instructions. RESULTS: The frequencies of TNF-alpha -308 G/G and TGF-beta1 codon 10-25 T/C-G/G polymorphisms were significantly higher in HBV-infected individuals (patients+carriers) when compared with those of healthy controls (p: 0.02 and p: 0.004, respectively). The frequency of TNF-alpha -308 G/G polymorphism was significantly higher in the patients than those of the healthy controls (p: 0.02), whereas the frequency of TGF-beta1 codon 10-25 T/T-G/G polymorphism was lower (p: 0.028). On the other hand, TNF-alpha -308 G/G and TGF-beta codon 10-25 T/C-G/G polymorphisms were significantly more common in HBV carriers than the control group (p: 0.017 and p: 0.018, respectively). In addition, TNF-alpha -308 G allele frequency was significantly more common in HBV-infected individuals (patients+carriers) than those of healthy controls (p: 0.0007). TNF-alpha -308 G allele frequency was also found to be higher in patients or carriers when compared with those of healthy controls (p: 0.01 and p: 0.01, respectively). Statistically significant differences were still kept after Bonferroni correction of the p-values for only TNF-alpha -308 G allele frequency in patients or carriers (Pc). CONCLUSION: Our study suggests that TNF-alpha gene polymorphism in patients infected with HBV would result in relatively inefficient inhibition of HBV and development of ESLD, and therefore, may be valuable predictor determinants for the development of ESLD in patients with chronic HBV infection.

Kilic M, Aydin U, Noyan A, Arikan C, Aydogdu S, Akyildiz M, Karasu Z, Zeytunlu M, Alper M, Batur Y. · Department of Surgery, Ege University Hospital, Izmir, Turkey. · Transplantation. · Pubmed #17713430 No free full text.

Abstract: BACKGROUND: Acute liver failure (ALF) carries a high mortality unless urgent orthotopic liver transplantation (OLT) is performed on time. Live donors are utilized to treat this irreversible condition first in pediatric cases and then in adults. Herein, we aimed to report our experience with live donors for ALF in a country of a deceased donor organ donation rate is only 1.5 per million people. METHODS: Among the 245 live donor liver transplantations (LDLT) performed from June 1999 to December 2005, 14 of them (6%) were performed for ALF in 8 pediatric and 6 adult cases. Right lobes were harvested for the adult cases whereas left lateral segments were harvested for pediatric cases, except one child transplanted with a right lobe graft. The etiology of the disease was; acute hepatitis B in four cases, hepatitis A in three cases, Wilson disease two cases, autoimmune hepatitis in two cases, and was unknown in three cases. RESULTS: Three-year graft and patient survival is 79% for these series. Five of the six adult patients and six of the eight pediatric cases survived after transplantation. There was not any donor mortality or major morbidity. CONCLUSIONS: LDLT offers a safe and effective modality of treatment for ALF for both pediatric and adult patients to overcome the problem of organ shortage especially in countries where the chance of receiving an organ from a deceased donor is low.

Karasu Z, Akyildiz M, Zeytunlu M, Noyan A, Yuzer Y, Tokat Y, Kilic M. · Department of Gastroenterology, Ege University Medical School, Bornova, Izmir, Turkey. · Hepatogastroenterology. · Pubmed #17591069 No free full text.

Abstract: BACKGROUND/AIMS: Acute liver failure is a fatal condition unless an urgent liver transplantation is performed. In countries like Turkey, because of limited availability of cadaveric allografts, living donors could be used as an organ source for acute liver failure. We report our single center experience. METHODOLOGY: Six adult-to-adult right lobe living donor liver transplantations have been performed for those patients admitted with fulminant liver failure between September 2000 and April 2004. RESULTS: The age of the patients ranged between 19 and 54 years. Etiology was fulminant hepatitis B in 4 patients, Wilson's disease in 1 patient, and unknown in 1 patient. Five of 6 patients survived and are currently alive and well with a mean 30 (2-46) months follow-up. None of the survivors had neurological sequela. One patient died because of sepsis 2 months after transplantation. There was no donor mortality. CONCLUSIONS: Adult-to-adult right lobe living donor liver transplantation seems to be an effective and safe option for patients with fulminant liver failure, especially in countries with a limited number of available cadaveric donors.

Celebi Kobak A, Karasu Z, Kilic M, Ozacar T, Tekin F, Gunsar F, Ersoz G, Yuzer Y, Tokat Y. · Department of Gastroenterology, General Surgery, and Microbiology, Ege University Faculty of Medicine, Izmir, Turkey. · Transplant Proc. · Pubmed #17580169 No free full text.

Abstract: Liver allografts from donors previously exposed to hepatitis B virus (HBV) carry the risk of transmission of HBV infection to immunosuppressed recipients. However, exclusion of donor candidates with the serologic evidence of resolved hepatitis B-HBV surface antigen (HbsAg) negative and HBV core antibody (anti-HBc) positive-is not feasible in countries endemic for HBV. AIM: Our aim was to assess the safety of living donor liver transplantation from anti-HBc positive donors. MATERIALS AND METHODS: In our institution, 152 transplants were performed between June 1999 and April 2004. Fifty-six (37%) of the living donors were anti-HBc positive. Twenty of these liver grafts were transplanted to HbsAg-negative recipients. We excluded four HBsAg negative recipients who died because of early complications after transplantation. Lamivudine (100 mg/day) was given for prophylaxis of de novo HBV infection. RESULTS: The mean follow-up time for 16 HBsAg-negative recipients was 21.7 (7-48) months. None of them experienced de novo HBV infection. CONCLUSION: The use of liver allografts from anti-HBc-positive living donors is reasonably safe in HBsAg-negative recipients under lamivudine prophylaxis.

Karasu Z, Tekin F, Ersoz G, Gunsar F, Batur Y, Ilter T, Akarca US. · Department of Gastroenterology, Ege University Medical School, Izmir, Turkey. · Dig Dis Sci. · Pubmed #17464564 No free full text.

Abstract: Thrombocytopenia is a common complication of chronic liver diseases, but its pathogenesis is not clear. Although generally attributed to hypersplenism, other factors should also be considered. We investigated the relationship between the peripheral platelet count and the degree of fibrosis in patients with chronic viral hepatitis. In an effort to avoid the effects of hypersplenism, we excluded patients with splenomegaly and/or bi- or pan-cytopenia. Seven hundred eighty-four patients (265 chronic viral hepatitis C and 519 chronic viral hepatitis B) were included in the study. Univariate analysis showed that the peripheral platelet count had a negative correlation with fibrosis score, necroinflammatory activity, and age in both groups. In multivariate analysis, the peripheral platelet count had a similar correlation with the fibrosis score and age, but not with necroinflammatory activity, in both groups. The peripheral platelet count decreased more significantly in females with chronic hepatitis C but not in the chronic hepatitis B group. In conclusion, a decrease in peripheral platelet count may be a sign of an increase in the degree of fibrosis during the course of chronic viral hepatitis B and C and factors other than hypersplenism may play a role in this decrease in the peripheral platelet count.

Akyildiz M, Gunsar F, Ersoz G, Karasu Z, Ilter T, Batur Y, Akarca U. · Department of Gastroenterology, Ege University Medical School, Bornova, Izmir, Turkey. · Dig Dis Sci. · Pubmed #17431777 No free full text.

Abstract: We studied clinical and laboratory effects of 3 months of lamivudine with adefovir combination and adefovir dipivoxil (AD) alone in the treatment of patients with lamivudine-resistant hepatitis B virus (HBV) infection. Eligible patients were hepatitis B surface antigen-positive men and women with compensated liver disease who were given lamivudine at least more than 6 months and had HBV polymerase gene mutation. Patients were assigned to receive adefovir 10 mg/day (Group 1) or adefovir 10 mg once daily and lamivudine 100 mg once daily combination during first 3 months, and then stopped lamivudine and continued adefovir (Group 2).Median age was 48 years (34 males and 20 females, and 35 were HBeAg-negative). Baseline median ALT, AST, and HBV DNA levels were 66 IU/l, 49 IU/l, and 6.7 log(10) copy/ml, respectively. Median adefovir therapy time and ALT normalization time were 9 and 3.5 months, respectively. There was no significant difference between groups according to the baseline HBV DNA, ALT, HBe Ag status, age, gender, and lamivudine resistance time. Virological and biochemical responses were similar in both groups during therapy. Two patients (8%) had ALT flare more than five times upper limit of normal without any clinical decompensation in Group 1. Mild ALT elevation according to baseline levels were found in 8 (27.6%) and 4 (17.4%) patients, respectively, in Group 2 and Group 1, and no statistically significance between two groups.In conclusion, this study showed that it is not necessary to continue lamivudine therapy while switching to AD therapy. Adefovir alone is effective in the treatment of patients with lamivudine resistant HBV infection and compensated liver disease, without significant clinical and laboratory flares. However, it is not easy to say that switching to AD with cessation of lamivudine is safe, because the study population is not enough for precise conclusion and resistance may be a considerable problem against AD in patients using long-term treatment.

Aladağ M, Karasu Z, Wright H, Gürakar A. · Department of Gastroenterology, Inönü University School of Medicine, Malatya, Turkey. · Turk J Gastroenterol. · Pubmed #16830275 links to  free full text

Abstract: BACKGROUND/AIMS: Data suggests on the basis of thrice a week therapy, efficacy of mono consensus interferon is comparable to other alpha interferons. One-year follow-up after 12-month daily consensus interferon monotherapy for chronic hepatitis C among non-responders or relapsers to previous consensus interferon monotherapy is investigated. METHODS: Between February and August 1998, 11 non-cirrhotic patients with previous consensus interferon failure were treated. Six were relapsers and five non-responders. Serum HCV-RNA was tested at the 12th and 48th weeks of treatment and followed for one year thereafter. RESULTS: Eight (72%) were HCV-RNA negative at both 12th and 48th weeks. Of these, 60% (3/5) were among previous non-responders and 83% (5/6) were among previous relapsers. One year sustained virological response was 55%. Of this, 40% (2/5) were among non-responders and 66% (4/6) previous relapsers. CONCLUSIONS: These findings suggest that daily consensus interferon needs to be further investigated as an alternative to pegylated formulations, especially with the addition of ribavirin.

Akyildiz M, Karasu Z, Arikan C, Nart D, Kilic M. · Department of Gastroenterology and Hepatology, Ege University Organ Transplant and Research Center, Izmir, Turkey. · Pediatr Transplant. · Pubmed #16176422 No free full text.

Abstract: Giant cell hepatitis (GCH) with autoimmune hemolytic anemia (AHA) is a distinct entity with an aggressive course. Drugs, autoimmunity, and viruses have been implicated in its etiology. Without treatment, liver dysfunction is progressive and fatal. Although successful immunosuppressive treatment has been reported, a few patients have undergone liver transplantation with recurrence of the primary disease in the allograft. We report, an 18-year-old boy with progressive GCH with AHA without recurrence in the allograft following deceased donor (DD) liver transplantation.

Akay S, Karasu Z, Akyildiz M, Tokat Y, Goker E. · Department of Gastroenterology, Ege University, Izmir 35040, Turkey. · Transplant Proc. · Pubmed #15964375 No free full text.

Abstract: Kaposi's sarcoma has a higher incidence in organ transplant recipients. We report on a 41-year-old Turkish man with liver transplantation-associated Kaposi's sarcoma that involved the skin and the gut. Immediately after discontinuation of immunosuppressive medication, there was an acute rejection episode. After controlling the acute rejection with steroids, the immunosuppressive treatment was continued together with vincristine, which resulted in disease remission. After 6 months, withdrawal of vincristine lead to relapse of the disease, prompting commencement of vincristine again, which has maintained the patient in remission for more than 3 years without any significant side effects. In conclusion, long-term vincristine may be an effective, safe treatment option for Kaposi's sarcoma.

Karasu Z, Ozacar T, Akarca U, Ersoz G, Erensoy S, Gunsar F, Kobat A, Tokat Y, Batur Y. · Department of Gastroenterology, Ege University Medical School, Izmir, Turkey. · J Viral Hepat. · Pubmed #15720538 No free full text.

Abstract: Anti-HBs immunoglobulins (HBIG) and lamivudine are main options to prevent hepatitis B virus (HBV) reinfection after liver transplantation. Although they are very effective, development of mutant viruses and high cost of treatment are main limitations for their application. Additionally there is an uncertainity for the duration of that prophylaxis regimen and its mostly applied indefinitely. Recently, post-transplant HBV vaccination is reported to be a cheaper alternative prophylaksis strategy, that enables discontinuation of HBIG. To investigate the efficacy of HBV vaccination in patients transplanted for HBV cirrhosis, we administered double course of double dose recombinant HBV vaccine (Genhavac B; containing HBV pre-S1, pre-S2, and S gene products). Vaccination has been started 1 month after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. The first cycle consisted of 0, 1- and 6-month schedule, and, in nonresponders, second cycle 0, 1-, 2-month schedule. Fourteen patients included into the study. Only one patient seroconverted (an anti-HBs titre of 37 IU/L) after the first cycle. No other patient responded to second cycle. HBV vaccination in the post-transplantation setting does not seems like an effective strategy in the prophylaxis of HBV recurrence.

Akay S, Karasu Z, Akyildiz M, Tokat Y. · Department of Gastroenterology, Ege University, Izmir 35040, Turkey. · Transplant Proc. · Pubmed #15621144 No free full text.

Abstract: Failure of prophylaxis for hepatitis B virus (HBV) recurrence in liver transplant patients with HBV immunoglobulin (HBIG) or lamivudine or both can be associated with rapid development of liver failure. Some of these patients develop a devastating clinicopathological state characterized by jaundice and rapidly progressive liver failure or fibrosing cholestatic hepatitis. We present two liver transplant recipients who experienced HBV recurrence while they were under lamivudine and HBIG prophylaxis. One of them had finding of severe HBV infection; the other, fibrosing cholestatic hepatitis. After commencing adefovir dipivoxil both patients showed improvements in clinical status and laboratory data. At month 4 of treatment, HBV DNA values became negative and liver function tests almost normalized. In addition, in one case showed HBs ag/anti-HBs seroconversion. When failure of prophylaxis with lamivudine and HBIG occurs, adefovir dipivoxil should be considered to be a safe and effective choice for recurrent HBV infections in liver transplant patients.

Akyildiz M, Karasu Z, Arikan C, Kilic M, Zeytunlu M, Gunsar F, Ersoz G, Akarca U, Batur Y, Tokat Y. · Edge University Medical School, Izmir, Turkey. · Transplant Proc. · Pubmed #15251354 No free full text.

Abstract: It is not clear whether pretransplantation MELD (model for End-Stage Liver Disease) score can foresee posttransplant outcome. We retrospectively evaluated 80 adult patients (55 men, 25 women) who underwent living donor liver transplantation between September 1998 and March 2003. Five other patients with fulminant hepatitis were excluded. The UNOS-modified MELD scores were calculated to stratify patients into three groups: group 1) MELD score less than 15 (n = 13); group 2) MELD score 15 to 24 (n = 36); and group 3) MELD score 25 and higher (n = 26). The patients were predominantly men (n = 52, 69.3%) with overall mean age of 43.9 years (range, 17-62 years). The mean follow-up was 15.7 months (range, 1-47; median = 14 months). The mean MELD score was 22.7 (range, 9-50; median = 21). The overall 1- and 2-year patient survivals were 87% and 78.7%, respectively. The 1-year patient survivals for groups 1, 2, and 3 were 100%, 87%, and 79%; respectively. 2-year survivals, 100%, 79%, and 61%, respectively. Survivals stratified by MELD showed no statistically remarkable differences in 1-year and 2-year patient survival (P = .08). In contrast, 1-year and 2-year patient survival rates for UNOS status 2A, 2B, and 3 were 73%-50%, 95%-91%, and 91%-91%, statistically significant difference (P = .002). Finally, to date preoperative MELD score showed no significant impact on 1- and 2-year posttransplant outcomes in adult-to-adult living donor liver transplantation recipients, but we await longer-term follow-up with greater numbers of patients.

Ersöz G, Akarca US, Günşar F, Karasu Z, Batur Y. · Ege University Faculty of Medicine, Department of Gastroenterology, Izmir, Turkey. · Turk J Gastroenterol. · Pubmed #15048595 links to  free full text

Abstract: BACKGROUND/AIMS: The most important problem of the lamivudine therapy is the frequent development of drug resistance. Treatment of chronic hepatitis B patients resistant to lamivudin remains to be established. We investigated in this study the efficacy of interferon therapy for breakthrough infection to combination therapy with interferon and lamivudine. METHODS: Interferon therapy was applied to nine patients who experienced HBV DNA breakthrough with ALT elevation for at least three months during the lamivudine treatment, which was given in combination with interferon for the first six months. These patients were compared with 10 patients who developed breakthrough but were not given interferon. All the patients continued to receive lamivudine. RESULTS: Of the nine patients who were given interferon, two lost HBV DNA and had normal ALT after six months of treatment. ALT levels returned to normal in two patients who had no virological response. Of those patients not given interferon, none lost HBV DNA, but three had normal ALT at the end of the same duration of follow-up. CONCLUSIONS: The patients with breakthrough infection during lamivudine treatment, which was combined with interferon at the beginning, may benefit from another cycle of interferon treatment.

Günsar F, Akarca US, Ersöz G, Karasu Z, Yüce G, Batur Y. · Department of Gastroenterology, Ege University Hospital Izmir, Turkey. · Hepatogastroenterology. · Pubmed #12239904 No free full text.

Abstract: BACKGROUND/AIMS: Primary biliary cirrhosis and autoimmune hepatitis are two main immune-mediated liver diseases. Some patients display characteristics of both diseases, so called overlap syndrome. The aims of this study were to investigate and to compare the clinical and laboratory features and responses to therapy in primary biliary cirrhosis and overlap syndrome. METHODOLOGY: Twenty-three patients with primary biliary cirrhosis (21 females, 2 males; median age: 50 years) and 20 with primary biliary cirrhosis-autoimmune hepatitis overlap syndrome (18 females, 2 males; median age: 44 years) were included in the study. All patients with primary biliary cirrhosis were treated with ursodeoxycholic acid. Of patients with overlap syndrome, 16 were treated with ursodeoxycholic acid and 4 with ursodeoxycholic acid plus prednisolone. Histological findings laboratory and clinical data were compared at the baseline and at the 2nd year of treatment. RESULTS: Fatigue and pruritus were the most frequent and comparable symptoms in each group. Serum ALT, AST, gamma-glutamyl transpeptidase, total protein, globulin and gammaglobulin levels were higher in patients with overlap syndrome than those in patients with primary biliary cirrhosis. At the end of the 2nd year of the treatment, ALT normalization was achieved in 12 (52%), alkaline phosphatase in 7 (30%) patients with primary biliary cirrhosis. One of the non-responders to ursodeoxycholic acid therapy had the histological findings of overlap syndrome in her control biopsy. Fibrosis score deteriorated in 50% of the patients. Of ursodeoxycholic acid-treated overlap syndrome patients, 11 completed 2 years of treatment. Three patients were biochemically non-responsive and prednisolone was added to their regimen. Of the remaining 8 patients, 7 (64% of total patients) had normal ALT. Three patients had worse fibrosis score comparing the onset of the treatment. Six of 7 (86%) patients who were given ursodeoxycholic acid plus prednisolone including ursodeoxycholic acid-non-responsives had normal ALT and 2 of 6 biopsy-controlled patients display deterioration of their fibrosis score. CONCLUSIONS: Biochemical tests tended to be higher in patients with overlap syndrome comparing to those with primary biliary cirrhosis. Response to ursodeoxycholic acid treatment in patients with overlap syndrome was comparable with that obtained in primary biliary cirrhosis. Therefore it should be the first-line treatment. Non-responsive patients may benefit from the use of ursodeoxycholic acid plus prednisolone combination.

Töz H, Ok E, Yilmaz F, Akarca US, Erensoy S, Zeytinoğlu A, Ozkahya M, Karasu Z, Yüce G, Başçi A. · Department of Nephrology, Ege University Medical School, Izmir, Turkey. · J Nephrol. · Pubmed #12116989 No free full text.

Abstract: BACKGROUND: Liver biopsy (LB) gives an accurate picture of the severity of hepatitis C virus (HCV) infection in end-stage renal disease. The aim of this study was to find out whether clinical and histopathological course of HCV infection in renal transplant (RT) patients (pts) is different from dialysis (Dx) pts. METHODS: Forty Dx and 46 RT pts underwent LB. Clinical and biochemical data were retrospectively collected from medical charts. ALT level above the upper limit was described as elevated. LB was done regardless of the ALT level. LB specimens were examined using a semiquantitative scoring system locally modified from Scheuer. Histological activity (grade) and fibrosis (stage) were scored separately. RESULTS: ALT was elevated in 65% of Dx pts. At the time of LB 30% of Dx pts had elevated ALT and 95% were viremic. Normal/minimal inflammation was detected in 25% of LBs, chronic hepatitis in 72.5%, cirrhosis in 2.5%. Stage and grade were respectively 1.08 +/- 1.02 and 4.30 +/- 2.98. Normal/minimal inflammation was detected in 9% of the 46 RT pts, chronic hepatitis in 84%, cirrhosis in 7%. Stage and grade were respectively 1.74 +/- 1.1 and 5.39 +/- 2.21. Although there was no significant difference in the histological grade between Dx and RT pts, histological stage was significantly higher in RT pts than Dx. The frequency of cirrhosis, hepatitis and normal inflammation was similar in the two groups. CONCLUSION: Histopathological liver injury due to HCV infection seems to be more severe in RT than Dx pts but this does not seem to be clear at the clinical and biochemical level. Sequential histopathological assessment and longer follow-up will be required to clarify this issue.

Ersoz G, Karasu Z, Akarca US, Gunsar F, Yuce G, Batur Y. · Ege University Medical School, Department of Gastroenterology, Izmir, Turkey. · Eur J Gastroenterol Hepatol. · Pubmed #11507363 No free full text.

Abstract: Drug-induced chronic hepatitis is a rare pathological condition. There is no reported case with chronic hepatitis secondary to nitroimidazole use. We report a patient who developed nitroimidazole-induced chronic hepatitis following acute exacerbation of hepatitis three times after nitroimidazole use.

Ersoz G, Karasu Z, Yildiz C, Akarca US, Yuce G, Batur Y. · Department of Gastroenterology, Ege University Medical School, Bornova, 35100 Izmir, Turkey. · J Clin Pharm Ther. · Pubmed #11422607 No free full text.

Abstract: Toxic hepatitis secondary to amoxycillin-clavulanic acid is an infrequent clinical picture. Most of the cases are reported to have a benign course. We report two cases of severe hepatic failure following amoxycillin-clavulanic acid use. One of the cases had cholestatic features primarily, and the other had hepatocellular injury prominently. The first case had also findings of trombotic trombositic purpura and had a fatal course.