Galip Ersoz

Intestinal permeability in liver cirrhosis.

OBJECTIVE To determine the changes in intestinal permeability in liver cirrhosis and to investigate whether intestinal permeability relates to the stage and aetiology of cirrhosis or existence of spontaneous bacterial peritonitis (SBP). DESIGN A prospective study of intestinal permeability in patients with cirrhosis. SETTING Gastroenterology and Nuclear Medicine Departments of Ege University Hospital. PARTICIPANTS Intestinal permeability was assessed in 44 consecutive patients with cirrhosis and 10 healthy volunteers by measuring 24 h urine excretion of (99m)technetium diethyl triamine penta-acetic acid (99mTc DTPA). Cases with an associated disease, impaired renal function, continuing alcohol consumption and drug intake which is known to have an effect on intestinal permeability were excluded. MAIN OUTCOME MEASURES Comparisons of 24 h urine excretion of 99mTc DTPA were made between the groups of cirrhotics and controls, different grades of cirrhosis (according to Child-Pugh criteria), alcoholic and non-alcoholic cirrhotics and cirrhotic patients with and without SBP. RESULTS Patients with cirrhosis excreted 99mTc DTPA significantly more than controls (11.56 +/- 8.96% in cirrhotics and 4.30 +/- 1.49% in controls, P < 0.0001). There was no relationship of 24 h urine excretion of the tracer with the grade and aetiology of cirrhosis (12.20 +/- 9.47%, 11.41 +/- 9.84%, and 11.09 +/- 8.42%, in Child A, B, and C groups and 8.45 +/- 6.57% and 12.05 +/- 9.25% in alcoholic and non-alcoholic cirrhotics, respectively). No significant difference was found between cirrhotic patients with and without SBP in terms of excretion of the administered dose of 99mTc DTPA (9.98 +/- 9.47% and 12.20 +/- 8.82%, respectively). CONCLUSIONS This study shows that intestinal permeability increased in cirrhotic patients regardless of the grade and aetiology of disease. The presence of SBP does not seem to be due to increased intestinal permeability.

Safety, tolerability, and efficacy of pegylated-interferon alfa-2a plus ribavirin in HCV-related decompensated cirrhotics.

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.

Liver Fibrosis Is Associated with Decreased Peripheral Platelet Count in Patients with Chronic Hepatitis B and C

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.

Pegylated interferon alfa-2b monotherapy and pegylated interferon alfa-2b plus lamivudine combination therapy for patients with hepatitis b virus e antigen-negative chronic hepatitis b

ABSTRACT Forty-eight hepatitis B virus (HBV) E antigen-negative chronic hepatitis B patients received pegylated interferon alfa-2b either alone or with lamivudine for 48 weeks and were followed for an additional 24 weeks. At the end of follow-up, virological response rates (HBV DNA levels of <400 copies/ml) were similar in the monotherapy (24%) and combination therapy (26%) groups.

Serum procalcitonin and CRP levels in non-alcoholic fatty liver disease: a case control study

BackgroundBoth C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD.MethodsFifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system.ResultsSerum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 ± 0.01, 0.04 ± 0.01 versus 0.06 ± 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 ± 1.6 and 5.2 ± 2.5 versus 2.9 ± 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels.ConclusionSerum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.

Garlic oil and Helicobacter pylori infection

PBC. In 1989, a 45-yr-old woman was admitted to the hospital because of right upper quadrant abdominal pain, asthenia, anorexia, and weight loss in the previous 3 months. On physical examination, irregular hepatomegaly was noticed. There were no palpable adenopathy or splenomegaly. Laboratory data showed elevation of alkaline phosphatase and were otherwise within normal limits. Abdominal ultrasonography and CT scan disclosed several space-occupying lesions in right and left hepatic lobes. Fine-needle aspiration of one of these lesions was informed as metastases of poorly differentiated carcinoma. An extensive search of a primary tumor was unsuccessful. An exploratory laparotomy was performed; liver nodules and hilar adenopathy were noticed. Pathological examination of adenopathy showed a large B-cell lymphoma (centroblastic lymphoma). Extent of disease was evaluated with a chest CT scan and a bone marrow biopsy that were normal. The patient was treated with eight cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone); a complete remission of liver lesions was observed. Six years later, she complained of arthralgia, pruritus, and Raynaud’s phenomenon. Antimitochondrial antibodies were positive (1/1280), and a percutaneous liver biopsy showed an inflammatory process of the portal triads with focal ductal injury, compatible with stage I PBC. Signs of malignant infiltration were not appreciated. In our patient, the diagnosis of PHL in assumable in the absence of liver histology, in view of the clinical and radiological presentation, the response to therapy with long lasting remission, and the evidence of lymphomatous involvement of the hilar lymph nodes. Unfortunately, we cannot elucidate whether PBC was present when the patient was first seen, for liver biopsy and antimitochondrial antibodies were not performed. We believe that, although our case does not fulfill the strict criteria proposed by Caccamo et al. (2), it should be considered as a PHL, because extension to affected lymph nodes probably reflects local dissemination.

Long-Term Efficacy of Interferon-alpha and Ursodeoxycholic Acid in Treatment of Chronic Type C Hepatitis

Interferon-alpha (IFN) and ursodeoxycholic acid(UDCA) combined have a controversial role in thetreatment of chronic type C hepatitis. We studied thelong-term efficacy of both drugs alone or incombination. In a three-year period, 108 patients wererandomized into three treatment arms: (1) IFN alone 3 MUthree times a week (N = 49), (2) IFN 3 MU three times aweek + UDCA 250 mg twice a day (N = 45), and (3) UDCA alone 250 mg twice a day (N = 14). Response wasdefined as complete normalization of serum ALT. For theresponders at the end of six months, the treatment wasrun to 12 months. Nonresponders (NRs) of the first group were crossed over to combinationand NRs of the combination received 6 MU three times aweek IFN + UDCA for the next six months. The enrollmentto the UDCA alone arm was stopped early, since only 1/14 normalized serum ALT at the end of thirdmonth. However, 12/14 completed six months and 11 NRsreceived IFN 3 MU three times a week alone for the nextsix months. Twelve discontinued treatment due to side effects. Responders were followed-upuntreated for 18 months. Sustained response (SR) wasdefined as persistence of normal serum ALT levels inthis period. At the end of six months, 22/45 (48%) from the IFN-alone and 23/39 (58%) from thecombination group responded. Twenty NRs from former and15 of latter group were crossed over. While none of the20 from the IFN-alone group responded to thecombination, 1/15 NRs of the combination group responded todose escalation. SR was achieved in 9/45 (20%) of theIFN alone and 7/39 (18%) of the combination group. Themean time form the end of the treatment to the relapse was not different between the groups.Five of 11 UDCA NRs responded to IFN with SR in 2. Itwas concluded that UDCA as a single agent is ineffectivein achieving response in the treatment of chronic type C hepatitis. Combined with IFN, itincreases response rate insignificantly although this isnot sustained.

Macrophage migration inhibitory factor expression and MIF gene -173 G/C polymorphism in nonalcoholic fatty liver disease.

Aim To investigate the macrophage migration inhibitory factor (MIF) expression and −173 G/C polymorphism of the MIF gene in nonalcoholic fatty liver disease (NAFLD). Method Ninety-one patients with diagnosis of NAFLD and 104 healthy controls were included in the study. MIF −173 G/C polymorphism was detected using the PCR–restriction fragment length polymorphism based method. NAFLD was stratified as nonalcoholic steatohepatitis (NASH), probable NASH and steatosis, respectively in groups 1, 2 and 3, according to NAFLD Activity Score. MIF expression was detected by immunohistochemistry staining. Results Mean age of the patients was 50.1±9.6 years, and 54 of them were male. Serum alanine aminotransferase and aspartate aminotransferase were 50/83, 42/63 and 31/32, respectively in groups 1, 2 and 3, (P<0.05). Both the MIF expression of hepatocytes and mononuclear cells were more prominent in groups 1 and 2 than group 3. There was no correlation between MIF expression of hepatocytes and fibrosis stage. However, MIF expression of mononuclear cells significantly increased according to fibrosis stage (P<0.05, R : 0.2). There was no significant correlation between MIF genotype and MIF expression in the liver. Conclusion MIF expression is significantly increased especially by mononuclear cells in liver tissue of patients with NASH secondary to inflammation. Thus, it should be considered as a consequence not a causal factor.

hydatid acute pancreatitis: a rare complication of hydatid liver disease. Report of two cases

Acute pancreatitis (AP) is known to be a rare complication of hydatid disease. We present two cases of AP due to intrabiliary ruptured hydatid cysts of the liver. High serum and urine amylase levels and ultrasonographic findings, compatible with AP, were detected. On ultrasonography and computed tomography dilated bile ducts and cystic masses in the liver were seen. A communication between the bile ducts and a cyst in one case, and a total common bile duct obstruction with hydatid material in the other case, were seen on endoscopic retrograde cholangiopancreatograms. The patients were treated surgically with mainly omentoplasty. Recovery was uneventful. A diagnosis of AP should be kept in mind in patients with hydatid liver disease presenting with upper abdominal pain.

Living donor liver transplantation for hepatitis B cirrhosis

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 institutions experience with LDLT in patients with chronic HBV infection.