Hepatitis: Bolukbas C

Bolukbas C, Bolukbas FF, Kebdir T, Canayaz L, Dalay AR, Kilic G, Ovunc O. · Department of Internal Medicine, Harran University, Sanliurfa, Turkey. · Acta Gastroenterol Belg. · Pubmed #16432996 No free full text.

Abstract: Sarcoidosis is a chronic granulomatous multisystemic disorder of unknown aetiology. Although interferon gamma has been implicated in the pathogenesis of sarcoidosis, only a few cases of sarcoidosis associated with interferon alpha therapy have been reported. We report a case with chronic hepatitis C (CHC) who developed sarcoidosis after the treatment by interferon alpha and ribavirin. The combination therapy of interferon alpha and ribavirin was given to a 50-year-old female with CHC who had not responded to a previous treatment by interferon alpha. She has been admitted with non-productive cough, dyspnoea and fever 11 months after the initiation of combination therapy. Chest x-ray and thorax computed tomography revealed bilateral hilar masses and nodular infiltrations in the lung parenchyma. Pulmonary function test showed a mild restriction. Biopsy of mediastinal lymphadenopathy revealed noncaseating granuloma. She was diagnosed to have pulmonary sarcoidosis at stage II, and the combination treatment was discontinued. Her symptoms regressed after inhaler steroid treatment. Six months after the diagnosis of sarcoidosis, the patient was asymptomatic and a complete sustained response to hepatitis C was achieved. During the three years of follow-up, both pulmonary sarcoidosis and hepatitis C have not recurred. We suggest that sarcoidosis may develop in chronic hepatitis C patients during interferon alpha and/or ribavirin treatment, and diagnostic tests for this adverse effect should be performed during the follow-ups.

Bolukbas C, Bolukbas FF, Kendir T, Akbayir N, Ince AT, Abut E, Horoz M, Dalay AR, Sokmen MH, Ovunc O. · Department of Internal Medicine, Division of Gastroenterology, Harran University, Sanliurfa, and Gastroenterology Clinic, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey. · Dig Dis Sci. · Pubmed #16944009 No free full text.

Abstract: In this study, the effect of lamivudine therapy on viral suppression, Child-Pugh score, and survival was assessed in patients with decompensated cirrhosis due to precore mutant hepatitis B virus and the results were compared with those for nonreplicative cirrhotic patients. Twenty-three replicative patients who received lamivudine and 15 nonreplicative patients were included and followed up for an average of 23.7+/-13.4 months. At baseline, there were no significant differences between the groups with regard to clinical and biochemical parameters or Child-Pugh scores, except for serum alanine aminotransferase levels (P<0.05) and quantitative hepatitis B virus DNA measurements (P<0.001). Compared to baseline, there was no significant difference in Child-Pugh score in the lamivudine group at the last visit (P=0.202), whereas a marked increase was observed in nonreplicative patients (P=0.002). Mortality rates in the lamivudine and nonreplicative groups were 17.43% and 13.3%, respectively (P=0.556), and there was no difference in survival analysis (P=0.809). Lamivudine therapy stabilizing clinical situation in decompensated cirrhotics with precore mutation makes the natural history of the disease equal with nonreplicative decompensated cirrhotics or even provides some advantages over them.

Aslan M, Horoz M, Nazligul Y, Bolukbas C, Bolukbas FF, Selek S, Aksoy N, Erel O. · Department of Internal Medicine, School of Medicine, Harran University, Sanliurfa, Turkey. · Int J Clin Pract. · Pubmed #17887991 No free full text.

Abstract: The sensitivity of standard biochemical tests for liver function is low and insufficient for a reliable determination of the presence or absence of liver disease. The aim of the present study was to investigate serum paraoxonase and arylesterase activities and lipid hydroperoxide (LOOH) levels, and to find out that whether the measurement of serum paraoxonase and arylesterase activities would be useful as an index of liver function status in chronic hepatitis (CH). Fourty-four patients with CH (24 CHB and 20 CHC) and 38 controls were enrolled. Serum paraoxonase and arylesterase activities were detected spectrophotometrically. LOOH levels were measured by the FOX-2 assay. Serum paraoxonase and arylesterase activities were significantly lower in patients with CH than controls (p < 0.001 for both), while LOOH levels were significantly higher (p < 0.001). Paraoxonase and arylesterase activities were inversely correlated with LOOH levels (r = -0.394, p < 0.05; r =-0.362, p < 0.05, respectively). Fibrosis scores of CH patients were significantly correlated with paraoxonase and arylesterase activities and LOOH levels (r =-0.276, p < 0.05; r = -0.583, p < 0.001 and r = 0.562, p < 0.001, respectively). Our results indicated that decrease in the activities paraoxonase and arylesterase may play a role in the pathogenesis of CH. In addition, serum paraoxonase and arylesterase activities measurement may add a significant contribution to the liver function tests.

Horoz M, Aslan M, Selek S, Koylu AO, Bolukbas C, Bolukbas FF, Celik H, Erel O. · Harran University School of Medicine, Department of Internal Medicine, Sanliurfa, Turkey. · Clin Biochem. · Pubmed #17335792 No free full text.

Abstract: OBJECTIVES: Paraoxonase-1 (PON1) activity has been reported to decrease in both haemodialysis patients and patients with HCV infection. We aimed to investigate paraoxonase and arylesterase activities, and lipid hydroperoxide levels (LOOH) in haemodialysis patients with or without hepatitis C infection, and to find out whether PON1 activity is affected further by the presence of HCV infection in HD patients. DESIGN AND METHODS: Twenty HCV (+) haemodialysis patients, 26 HCV (-) haemodialysis patients, and 26 controls were enrolled. Paraoxonase and arylesterase activities were measured spectrophotometrically. LOOH levels were measured by ferrous oxidation with xylenol orange assay. RESULTS: Haemodialysis patients with or without HCV infection had lower paraoxonase and arylesterase activities than controls (all p<0.001), while higher LOOH levels (both p<0.001). Paraoxonase and arylesterase activities, and LOOH levels were comparable between haemodialysis patients with or without HCV infection (p>0.05). Significant inverse correlation was observed between paraoxonase or arylesterase activities, and LOOH levels (p<0.05, beta=-0.319 and p<0.05, beta=-0.348, respectively). CONCLUSION: We concluded that PON1 activity significantly decreases in both haemodialysis patients with or without HCV infection. Nevertheless, PON1 activity is not affected further by the presence of HCV infection in haemodialysis patients.

Horoz M, Bolukbas C, Bolukbas FF, Aslan M, Koylu AO, Selek S, Erel O. · Harran University, School of Medicine, Department of Internal Medicine, Sanliurfa, Turkey. · BMC Infect Dis. · Pubmed #16842626 links to  free full text

Abstract: BACKGROUND: Both uremia and hepatitis C infection is associated with increased oxidative stress. In the present study, we aimed to find out whether hepatitis C infection has any impact on oxidative stress in hemodialysis subjects. METHODS: Sixteen hepatitis C (+) hemodialysis subjects, 24 hepatitis C negative hemodialysis subjects and 24 healthy subjects were included. Total antioxidant capacity, total peroxide level and oxidative stress index were determined in all subjects. RESULTS: Total antioxidant capacity was significantly higher in controls than hemodialysis subjects with or without hepatitis C infection (all p < 0.05/3), while total peroxide level and oxidative stress index were significantly lower (all p < 0.05/3). Hepatitis C (-) hemodialysis subjects had higher total antioxidant capacity compared to hepatitis C (+) hemodialysis subjects (all p < 0.05/3). Total peroxide level and oxidative stress index was comparable between hemodialysis subjects with or without hepatitis C infection (p > 0.05/3). CONCLUSION: Oxidative stress is increased in both hepatitis C (+) and hepatitis C (-) hemodialysis subjects. However, hepatitis C infection seems to not cause any additional increase in oxidative stress in hemodialysis subjects and it may be partly due to protective effect of dialysis treatment on hepatitis C infection.

Bolukbas C, Bolukbas FF, Kocyigit A, Aslan M, Selek S, Bitiren M, Ulukanligil M. · Department of Internal Medicine, Gastroenterology Division, Harran University, Medical Faculty, Sanliurfa, Turkey. · J Gastroenterol Hepatol. · Pubmed #16638108 No free full text.

Abstract: BACKGROUND AND AIM: A significant proportion of cancer is attributable to DNA damage caused by chronic infection and inflammation. Because both hepatitis B and C viruses (HBV and HCV, respectively) cause chronic infection and inflammatory disease, the aim of the present study was to investigate whether there is a difference in peripheral DNA damage in patients with chronic HCV compared with patients with chronic HBV; and whether there is an association in the level of peripheral DNA damage with a natural history of HBV infection. METHODS: Twenty patients with chronic hepatitis C, 20 patients with chronic hepatitis B, 11 patients with cirrhosis secondary to hepatitis B, 12 inactive hepatitis B s antigen (HBsAg) carriers and 21 healthy subjects were included in the study. The DNA damage in lymphocytes was determined using the alkaline comet assay. RESULTS: Although the chronic hepatitis C group had similar levels of DNA damage compared with patients with cirrhosis due to hepatitis B (P > 0.05) and non-cirrhotic patients with chronic hepatitis B (P > 0.05), they had higher levels of DNA damage compared with inactive HBsAg carriers (P = 0.021) and controls (P = 0.001). Hepatitis B cirrhotic patients and patients with chronic hepatitis B had significantly higher levels of DNA damage than inactive HBsAg carriers (P = 0.002 and P = 0.012, respectively) and controls (both P = 0.001). Linear logistic regression analysis showed that chronic hepatitis C and HBV-related cirrhosis were discriminators in determining DNA damage in lymphocytes (beta 0.424 and P = 0.013, beta 0.393 and P = 0.016, respectively). CONCLUSIONS: Chronic hepatitis C, based on the severity of liver disease, or cirrhosis as an advanced form of HBV infection increase DNA damage in lymphocytes independently of confounding factors such as age, gender, body mass index and smoking habits.

Horoz M, Bolukbas C, Bolukbas FF, Kocyigit A, Aslan M, Koylu AO, Gumus M, Celik H, Koksal M. · Harran University, School of Medicine, Department of Internal Medicine, Sanliurfa, Turkey. · Mutat Res. · Pubmed #16458331 No free full text.

Abstract: Despite the high prevalence of hepatitis C infection among hemodialysis subjects, there is no information concerning the DNA damage of hepatitis C (+) hemodialysis subjects. We aimed to find out if there is any additional effect of hepatitis C infection on peripheral DNA damage in maintenance hemodialysis subjects. Fifteen hepatitis C (+) and 22 hepatitis C (-) hemodialysis subjects, 21 hepatitis C subjects without renal disease, and 22 healthy controls were enrolled. Peripheral DNA damage was assayed using alkaline comet assay. Median DNA damage levels of the study groups were as follows: hepatitis C (+) maintenance hemodialysis subjects, 88 (0-232); hepatitis C (-) maintenance hemodialysis subjects, 58 (0-228); hepatitis C (+) subjects without renal disease, 112 (44-252); controls, 26 (0-72). DNA damage level was significantly higher among hepatitis C (+) subjects without renal disease than hepatitis C (-) maintenance hemodialysis subjects and healthy controls (both p<0.05/6). Both maintenance hemodialysis subjects with and without HCV infection had significantly higher DNA damage level than healthy controls (both p<0.05/6). DNA damage level was comparable between hepatitis C (+) subjects without renal disease and HCV (+) hemodialysis subjects, and between hemodialysis subjects with and without hepatitis C infection (all p>0.05/6). Linear regression analysis revealed that hepatitis C infection was the only independent factor in predicting the peripheral DNA damage (p<0.05, beta=0.395). Each one of end-stage renal disease and hepatitis C infection significantly increases DNA damage level. However, in hemodialysis subjects, hepatitis C infection does not cause significant additional increase in DNA damage level, and it may be partly due to protective effect of hemodialysis on hepatitis C infection.

Bolukbas C, Bolukbas FF, Horoz M, Aslan M, Celik H, Erel O. · Gastroenterology Division, Department of Internal Medicine, Harran University, Medical Faculty, Sanliurfa, Turkey. · BMC Infect Dis. · Pubmed #16262897 links to  free full text

Abstract: BACKGROUND: Oxidative stress can be defined as an increase in oxidants and/or a decrease in antioxidant capacity. There is limited information about the oxidative status in subjects with hepatitis B virus infection. We aimed to evaluate the oxidative status in patients with various clinical forms of chronic hepatitis B infection. METHODS: Seventy-six patients with hepatitis B virus infection, in whom 33 with chronic hepatitis, 31 inactive carriers and 12 with cirrhosis, and 16 healthy subjects were enrolled. Total antioxidant response and total peroxide level measurement, and calculation of oxidative stress index were performed in all participants. RESULTS: Total antioxidant response was significantly lower in cirrhotics than inactive HbsAg carriers and controls (p = 0.008 and p = 0.008, respectively). Total peroxide level and oxidative stress index was significantly higher in cirrhotic (p < 0.001, both) and chronic hepatitis B subjects (p < 0.001, both) than inactive HbsAg carriers and controls. Total antioxidant response was comparable in chronic hepatitis B subjects, inactive HbsAg carriers and controls (both, p > 0.05/6). Total peroxide level and oxidative stress index were also comparable in inactive HBsAg carriers and controls (both, p > 0.05/6). Serum alanine amino transferase level was positively correlated with total peroxide level and oxidative stress index only in chronic hepatitis B subjects (p = 0.002, r = 0.519 and p = 0.008, r = 0.453, respectively). CONCLUSION: Oxidative stress occurs secondarily to increased total lipid peroxidation and inadequate total antioxidant response and is related to severity of the disease and replication status of virus in hepatitis B infection.

Bolukbas FF, Bolukbas C, Horoz M, Gumus M, Erdogan M, Zeyrek F, Yayla A, Ovunc O. · Department of Internal Medicine, Gastroenterology Division, Harran University, Medical Faculty, Sanliurfa, Turkey. · BMC Gastroenterol. · Pubmed #15387890 links to  free full text

Abstract: BACKGROUND: As anorexia and hypermetabolism are common in cirrhosis, leptin levels may be increased in this disease. In this study, we investigated the relation between the severity of disease and serum leptin levels in post-hepatitis cirrhosis and the role of body composition, gender and viral aetiology of cirrhosis in this association. METHODS: Thirty-five cases with post-hepatitis cirrhosis and 15 healthy controls were enrolled in this study. Body composition including body mass index, body fat percentage and body fat mass were determined. Serum leptin levels were assayed. RESULTS: Leptin levels were significantly higher among cirrhotic patients independent of sex compared to controls (p = 0.001). Female patients in both groups have had higher leptin levels than males (in cirrhotics p = 0.029, in controls p = 0.02).Cirrhotic patients in each of A, B and C subgroups according to the Child- Pugh classification revealed significantly different levels compared to controls (p = 0.046, p = 0.004, p = 0.0001, respectively). Male cirrhotics in Child-Pugh Class B and C subgroups had significantly higher leptin levels compared to male controls (p = 0.006, p = 0.008). On the other hand, female patients only in Child Pugh class C subgroup have had higher levels of serum leptin compared to controls (p = 0.022).Child-Pugh classification has been found to be the sole discriminator in determination of leptin levels in cirrhotics by linear regression (beta: 0.435 p = 0.015). CONCLUSION: Serum leptin levels increase in advanced liver disease independently of gender, body composition in posthepatitic cirrhosis. The increase is more abundant among patients that belong to C subgroup according to the Child- Pugh classification.