The Prevalence of Minimal Hepatic Encephalopathy in an Outpatient Hepatology Clinic.

BACKGROUND: Minimal hepatic encephalopathy can only be detected by specific psychometric or neuropsychological tests. We aimed to determine the prevalence of minimal hepatic encephalopathy in a hepatology outpatient clinic of a tertiary center. METHODS: A total of 82 patients with chronic liver disease were involved prospectively in this study. Control groups consisted of healthy volunteers (n = 123) and chronic renal failure patients (n = 28). We used 2 different methods to detect minimal hepatic encephalopathy. First method was a battery of 5 psychometric tests (number connection tests A and B, digit symbol test, serial dot test, line tracing test) which was filled by all patients. The second method was critical flicker frequency test. Both methods were used in the whole group (n = 233). We applied linear regression analysis to the results of psychometric tests of healthy volunteers to establish equations to calculate the expected values of each test. Test results of the patients were evaluated according to the expected results obtained from these equations. RESULTS: The prevalence of minimal hepatic encephalopathy detected by psychometric tests and critical flicker frequency test was 13% and 14%, respectively. When the positivity of both tests was deemed necessary to diagnose minimal hepatic encephalopathy, the rate of minimal hepatic encephalopathy was 3.6% (n = 3) in a chronic liver disease patient group. CONCLUSION: Minimal hepatic encephalopathy is a difficult clinical condition to diagnose, and it is more appropriate to use psychometric tests and critical flicker frequency test together.

The liver-kidney axis: Is serum leptin a potential link in non-alcoholic fatty liver disease-associated chronic kidney disease?

BACKGROUND AND STUDY AIMS: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for chronic kidney disease (CKD). Previous studies argued that leptin levels increase significantly with the progression of CKD. But the association between leptin and CKD has not been investigated in patients with NAFLD. Therefore, we conducted this study to establish whether increased leptin level is associated with CKD in NAFLD patients. PATIENTS AND METHODS: In our prospective study with a follow up period of six months thirty-five teetotaller biopsy-proven NAFLD patients were divided as groups with mild, versus advanced, fibrosis. Liver fibrosis was also assessed with Fibroscan. Serum leptin levels were measured by radioimmunoassay. For insulin resistance we used the homeostasis model assessment method (HOMA-IR). For the kidney function, we used the abbreviated formula Modification of Diet in Renal Disease (MDRD) formula, which estimates GFR. For statistical analysis, Student's-t test, Mann-Whitney test, linear regression-binary logistic regression analyses and the ROC curve analysis were used. RESULTS: Advanced fibrosis and increased HOMA-IR were risk factors for decreased eGFR. Leptin correlated inversely with advanced fibrosis (p: 0.03) and low leptin was a risk factor for CKD (p: 0.02). In ROC curve analysis, advanced fibrosis and low leptin were risk factors for decreased eGFR (p: 0.007 and 0.004, respectively). Low leptin level was dependently associated with decreased eGFR. CONCLUSION: Advanced fibrosis in NAFLD patients is a risk factor for CKD. Leptin correlated inversely with advanced fibrosis. Unlike the previous studies, which were not performed in NAFLD patients, we found decreased leptin in NAFLD patients with decreased eGFR. Low leptin level was found to be a dependent predictor for differentiating NAFLD patients with high risk for CKD.

Efficacy and Safety of Ombitasvir/Paritaprevir/ Ritonavir + Dasabuvir ± Ribavirin Combinations in Patients with Genotype 1 Hepatitis C and Inherited Bleeding Disorders.

BACKGROUND: Hepatitis C is one of the leading causes of death in patients with inherited bleeding disorders. Currently, direct-acting antiviral drugs used for the treatment of hepatitis C have become an effective and a reliable option for people with inherited bleeding disorders. The aim of this study is to report the efficacy and safety of ombitasvir + paritaprevir/ritonavir and dasabuvir combination in the treatment of hepatitis C in patients with inherited bleeding disorders. METHODS: In this retrospective study, we evaluated the efficacy and safety of the combination of ombitasvir + paritaprevir/ritonavir and dasabuvir in 10 adult patients with hemophilia A, 4 patients with hemophilia B, and 1 patient with von Willebrand disease who were infected with hepatitis C genotype 1. RESULTS: Five patients had genotype 1a and 10 patients had genotype 1b chronic hepatitis C. One patient had Child A cirrhosis, 14 patients had chronic hepatitis C without cirrhosis. Hepatitis C virus ribonucleic acid was negative in all patients at week 4 and at the end of the treatment. Sustained virologic response was obtained in all patients. Serious side effects were detected in 3 patients, which were intra- muscular bleeding, erosive gastritis-related gastrointestinal bleeding, and pneumonia. CONCLUSION: Ombitasvir + paritaprevir combined with ritonavir and dasabuvir ± ribavirin is an effective treatment for patients infected with genotype 1 hepatitis C who have coagulation disorders. Tolerance and side effects are similar to other treatment options.

The effect of direct antiviral treatment on the depression, anxiety, fatigue and quality-of-life in chronic hepatitis C patients.

OBJECTIVE: In this study, we aimed to investigate the effects of direct antiviral treatment on depression, anxiety, fatigue and quality of life in patients with chronic hepatitis C. METHODS: Subjects included in study were treatment experienced and treatment naive chronic hepatitis C patients admitted to the hepatology outpatient clinic between December 2016 and June 2017. Before and after the treatment, Beck depression, Beck anxiety, liver-specific quality of life and fatigue severity-impact scales were administered. Descriptive statistical methods, Kolmogorov-Smirnov distribution test Wilcoxon sign and kappa coefficient tests were used to evaluate the study data. RESULTS: Forty-four patients were included in the study; however, it was completed with 35 patients only, as some of the patients were excluded for various reasons. There was no significant difference between depression and anxiety scores of the patients before and after the treatment, but depression and anxiety were found to be recovered in 28.5% (4/14) and 23.5% (4/17) of the subjects, respectively. At the end of the treatment, fatigue severity-impact scales and liver-specific quality of life were not significantly different from those before the treatment. CONCLUSION: In this study, we found that direct antivirals did not lead to depression, anxiety or fatigue and did not decrease liver-specific quality of life. In some cases, depression and anxiety decreased after the treatment.

Apoptosis and Disease Severity is Associated with Insulin Resistance in Non-alcoholic Fatty Liver Disease.

BACKGROUNDS AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). We evaluated whether IR contributes to hepatocyte apoptosis, inflammation, and fibrosis in NAFLD. METHODS: Forty-four teetotaller patients with biopsy-proven diagnosis of NAFLD were enrolled. Twenty-eight NAFLD patients with IR were compared with 16 subjects without IR. For apoptotic activity caspase 3 and 8, transcription nuclear factor kB (NF-kB), and anti-apoptotic Bcl-2 protein were determined through immunohistochemical methods. RESULTS: HOMA-IR index was significantly correlated with the stage and caspase 3- and 8 levels (p= 0.001, 0.02, and 0.01, respectively). HOMA-IR index was independently associated with the severity of fibrosis ( = 5.9, p = 0.001), caspase-3 ( = 0.16, p = 0.001), and caspase-8 (b =0.032, p = 0.018) levels. TNF-sRp55 level was positively correlated with HOMA-IR index (p = 0.024). Patients with IR had significantly higher necroinflammatory grade, stage, caspase-3, and caspase-8 levels than those without IR (p = 0.022, 0.007, 0.031, and p = 0.011, respectively). HOMA-IR index had statistically significant values for distinguishing of severe necroinflammatory grade, stage and for differentiating NASH from simple fatty liver (AUC = 0.78, 0.76, and 0.82, respectively). CONCLUSION: This study demonstrates that IR in NAFLD is associated with enhanced hepatocyte apoptosis and histopathologic disease severity. These data indicate that NAFLD patients with IR may have increased risk for disease progression.

Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease.

BACKGROUND/AIMS: Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to find the relation between oxidative stress parameters and histopathological findings in NAFLD patients with and without insulin resistance (IR). MATERIALS AND METHODS: Thirty-two patients with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied (M/F: 17/15; mean age 46.5±11.4 years). Twenty-one NAFLD patients with IR were compared with 11 patients without IR. The fasting insulin level was measured, and the insulin resistance index was calculated using the homeostasis model assessment (HOMA) method. Malondialdehyde (MDA) and superoxide dismutase (SOD) activities were measured in tissue and serum specimens. Glutathione (GH) was measured in tissue homogenates. Nitric oxide (NO), vitamin E and C levels were measured in serum. RESULTS: Patients with IR had significantly higher tissue MDA levels (p=0.001) and significantly decreased tissue SOD and GH levels (p=0.001 and 0.002, respectively) than those without IR. The steatosis grade, necroinflammatory grade and stage were significantly higher in patients with IR (p=0.035, 0.003 and 0.001, respectively). HOMA IR significantly correlated with the necroinflammatory grade, stage, tissue MDA, SOD and GH (p=0.013, 0.001, 0.008, 0.001 and 0.001, respectively). Serum MDA (ß=1.88, p=0.002), serum SOD (ß=0.57, p=0.006), tissue MDA (ß=0.22, p=0.006), tissue SOD (ß=1.48, p=0.071) and stage (ß=2.81, p=0.003) were independently associated with increased HOMA IR. Increased MDA [OR: 1.51; 95% CI: (1.03-2.22); p=0.034] was a risk factor for non-alcoholic steatohepatitis (NASH), and increased SOD activity had a preventive effect against NASH [OR: 0.008; 95% CI: (0.001-0.98); p=0.04]. CONCLUSION: This study shows that insulin resistance in NAFLD correlates with enhanced oxidative stress. Histopathological disease severity significantly correlated with oxidative stress parameters. These data show that NAFLD patients with IR may have increased risk for disease progression.

Five-year results of oral antiviral therapy in HBeAg-negative chronic Hepatitis B.

BACKGROUND/AIMS: Several guidelines recommend the use of tenofovir or entecavir as the first-line treatment for hepatitis B due to the lower resistance rates of these drugs than lamivudine, although lamivudine may still be preferred because of its low adverse effect profile and cost. It is important to know which patients might benefit from lamivudine as the first-line treatment. We aimed to assess the success rates of lamivudine, entecavir, and tenofovir, as well as the resistance rates, frequencies of HBsAg clearance, and risk factors for lamivudine resistance. MATERIALS AND METHODS: A total of 191 patients with chronic HBeAg-negative hepatitis who were treated with lamivudine, entecavir, or tenofovir were included. Predictors of resistance to lamivudine were analyzed. RESULTS: The cumulative first-, second-, third-, fourth-, and fifth-year rates of virologic breakthrough during extended lamivudine therapy were 24%, 30%, 38%, 46%, and 54%, respectively. The rate of undetectable DNA at the 60th month of those who took lamivudine was 51%. Cox regression analysis revealed that positive HBV DNA at the sixth month (HR=15; 95% CI: [7.1-33], p=0.001), being aged 41 years or more (HR=3.4; 95% CI: [1.8-6.4], p=0.001), and baseline HBV DNA of 170,500 IU/mL or higher (HR=2.1; 95% CI: [1.2-3.7], p=0.01) were independently associated with the development of resistance to lamivudine. CONCLUSION: In HBeAg-negative chronic hepatitis B, baseline serum hepatitis B virus DNA levels exceeding 170,500 IU/mL, partial virologic response in the sixth month, and age of 41 years or more were independent predictors for virologic breakthrough. Moreover, 2% of these patients cleared HBsAg.

Nonalcoholic fatty liver may increase the risk of operation in patients with fatty liver and the frequency of cancer in their first-degree relatives.

BACKGROUND: Fatty liver is a common disease in developed countries. We investigated the frequency of operation in patients with fatty liver and the frequency of cancer in their first-degree relatives. METHODS: In this study, we evaluated 105 patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD), 121 patients with hepatitis C (61 patients with fatty liver and 60 patients without fatty liver), 50 patients with inflammatory bowel disease (IBD), and 109 patients with dyspepsia as a control group. RESULTS: There was no difference for sex, mean age, and marital status among the groups, except that patients with IBD were younger than others (p < 0.001). The frequency of cancer in family was as follows: 18 % in IBD, 9 % in dyspepsia, 28 % in hepatitis C with hepatic steatosis, 21.5 % in hepatitis C without steatosis, and 27 % in NAFLD (p = 0.006). Then, we divided the study group into two groups-group 1: IBD + dyspepsia + hepatitis C without hepatic steatosis, and group 2: hepatitis C with hepatic steatosis + NAFLD-and performed the same analysis. We found that the frequency of cancer in family was 16 % in group 1 (the patients without fatty liver) vs. 24.4 % in group 2 (those with fatty liver; p = 0.037). We also investigated the rate of operation in patients. The results were as follows: 33 % in group 1 vs. 43 % in group 2 (p = 0.043). CONCLUSIONS: Independently of the underlying chronic diseases, occurrence of fat in the liver increased the frequency of operation in patients with fatty liver and the rate of cancer in their first-degree relatives. Understanding the underlying causes of fatty liver forms might decrease the cancer frequency in the population and number of operation in patients with fatty liver.

Fatty liver disease might increase the risk of abdominal operation in patients with fatty liver and the prevalence of cancer in first-degree relatives.

BACKGROUND/AIMS: We investigated the risk of abdominal operation in patients with fatty liver and the risk of any cancer in first-degree relatives of patients with fatty liver. MATERIALS AND METHODS: We evaluated 105 patients with nonalcoholic fatty liver disease (NAFLD), 121 patients with biopsy-proven hepatitis C (61 patients with fatty liver and 60 patients without fatty liver), 50 patients with inflammatory bowel disease (IBD), and 109 patients with dyspepsia. RESULTS: There was no difference in sex, mean age, and marital status among the groups except that patients with IBD were younger than the others (p<0.001). The frequency of cancer among family members was 18% in IBD, 9% in dyspepsia, 28% in hepatitis C with steatosis, 21.5% in hepatitis C without steatosis, and 27% in NAFLD (p=0.006). Then, we divided the study group into two groups as follows: group 1: (IBD+dyspepsia+hepatitis C without steatosis) and group 2: (hepatitis C with steatosis+NAFLD). We found that the frequency of cancer was 16% in group 1 versus 24.4 % in group 2 (p=0.037). We also investigated the risk of abdominal operation in patients with fatty liver. The results were as follows: 33% in group without fatty liver versus 43% in group with fatty liver (p=0.043). CONCLUSION: Understanding the underlying causes of fatty liver forms might decrease the cancer frequency in the population and number of operations in patients with fatty liver.

The role of EUS and EUS-FNA in the management of pancreatic masses: five-year experience.

BACKGROUND/AIMS: The efficacy of endoscopic ultrasound with fine-needle aspiration (EUS-FNA) in the diagnosis and staging of pancreatic malignancy is quite well established. The aim of this study is to describe a single-centre's experience. METHODOLOGY: Data were collected retrospectively on all patients with solid pancreatic masses undergoing EUS-FNA from January 2006 to March 2011. In tumor cases, TNM staging using EUS was compared with the results of histopathological staging. RESULTS: EUS-FNA of pancreatic lesions was performed in 125 patients. Of these patients, data of 75 were available (69% men, mean age 59.97±11.12 (SD) years); 58 (76%) of the lesions were ductal adenocarcinoma, 11 (14.5%) were chronic pancreatitis, 4 (%5) were intraductal papillary mucinous carcinoma (IPMN) and 2 (%3) were insulinoma. Diagnostic yield of the EUS-FNA procedure was 74.7% (56/75). Specimens from six patients were inadequate. In multivariate analysis, lesion diameter below 2cm was an independent predictor for the inadequacy of material (p=0.04). CONCLUSIONS: In patients with pancreatic mass with suspected malignancy, EUS-FNA provided a diagnosis with accuracy rate of 75%. Inadequate material with EUS-FNA was significantly more frequent in lesions below 2cm.

Carbamazepine-induced hypogammaglobulinemia.

Carbamazepine is used to control seizures. Its common side effects are sleep disorders, anorexia, nausea, vomiting, polydipsia, irritability, ataxia, and diplopia. Involvement of the immune system is rare, and few cases of decreased immunoglobulin levels have been reported. We describe a patient with low immunoglobulin levels due to carbamazepine use who presented with recurrent urinary tract infection. Intravenous immunoglobulin was administered, and immunoglobulin levels increased to safer levels after discontinuation of carbamazepine. Previous reports describe severe infection after carbamazepine-induced hypogammaglobulinemia. Therefore, in patients using antiepileptics, particularly carbamazepine, serum immunoglobulin levels should be checked in those with recurrent infections.

Validation of biochemical markers for the prediction of liver fibrosis and necroinflammatory activity in hemodialysis patients with chronic hepatitis C.

BACKGROUND: Liver biopsy is an imperfect gold standard for assessing the disease severity in hemodialysis patients with chronic hepatitis C. Our purpose was to compare the accuracy of the FibroTest (FT) and ActiTest (AT) with liver biopsy and the AST-to-platelet ratio index (APRI) in determining hepatic fibrosis and necroinflammatory activity in hemodialysis patients with hepatitis C virus (HCV). METHODS: The FT-AT index combining 6 biochemical markers was assessed in 33 hemodialysis patients with HCV. Liver fibrosis and necroinflammatory activity was staged and graded according to the METAVIR scoring system. RESULTS: The accuracy of FT-AT versus biopsy was 0.46 for significant fibrosis and 0.36 for severe necroinflammatory activity. The FT index had a positive predictive value of 20% for scores greater than 0.6 and a negative predictive value of 45% for scores less than 0.2. Eleven of the 33 patients had scores ≤0.2, 6 had significant fibrosis on biopsy. Four out of 5 patients with FT scores >0.6 had mild fibrosis. APRI correlated well with the biopsy. CONCLUSION: The FT-AT test does not seem to be a reliable noninvasive marker for the prediction of necroinflammatory activity and fibrosis in hemodialysis patients with HCV and cannot be used as an alternative to either liver biopsy or APRI.

Long-term effect of interferon therapy in patients with HBeAg positive chronic hepatitis B infection.

INTRODUCTION: Several studies have reported that interferon therapy increases elimination rate of HBeAg and anti-HBe seroconversion in chronic hepatitis B (CHB) patients. We aimed to evaluate long-term results of interferon-α treatment in HBeAg positive CHB patients in a country with exclusively D genotype. METHODS: Seventy-one naive CHB patients (M/F 61/10, mean age 29±12 years, range 16-62) treated with 6 months of interferon-α 2b, 10 MU tiw and had a consequent untreated follow-up period of at least 10 years with positive response were identified and their data were reviewed. The therapy response was defined as HBeAg seroconversion with undetectable HBV-DNA. The responders were followed-up at 3-6-month intervals. RESULTS: Twenty-eight (39%) patients achieved HBeAg seroconversion (25 within the therapy, 3 within the consequent 12 months off-treatment follow-up). The responders were followed-up with a mean period of 152 months (range 123-181). In the follow-up period, 21/25 (84%) initial responders relapsed. On the other hand, 3 patients who did not respond at the end of therapy sustained the response during follow-up. Hence 21/28 total responders relapsed (75%), either with HBeAg reversion (3, 14.3%) or HBV-DNA elevation over 2000 IU/ml (or its equivalent in other types of definitions) and ALT elevation (18, 85.7%). The sustained response was present in 7 patients (9.8%). Serious side effects precluding completion of treatment occurred in three patients (4.2%). In multivariate analysis none of the pre-treatment parameters appeared to be significant in predicting response. CONCLUSION: Sustained response to interferon treatment is low in HBeAg positive CHB patients with genotype D.

Is alanine aminotransferase level a surrogate biomarker of hepatic apoptosis in nonalcoholic fatty liver disease?

AIM: To evaluate the serum alanine aminotransferase (ALT) variabilities in nonalcoholic fatty liver disease (NAFLD) and correlate it with hepatocyte apoptosis and oxidative stress parameters. METHODS: 24 patients with NAFLD and normal ALT were compared with 26 subjects with NAFLD and elevated ALT. Liver oxidative stress was estimated on the basis of malondialdehyde, superoxide dismutase and glutathione. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor-kappaB, antiapoptotic Bcl-2 protein and serum TNF receptor levels were measured. RESULTS: The mean caspase 3 and 8 activity scores, oxidative stress parameters, necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Patients with nonalcoholic steatohepatitis had significantly higher caspase 3 and 8 activity (percentage of cells with positive staining per high power field), and serum malondialdehyde (mmol/l) levels than those with simple steatosis. ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis. A receiver operating characteristic curve did not demonstrate sensitivity and specificity for discriminative power of ALT. CONCLUSION: Apoptosis and oxidative stress are the main processes contributing to disease progression in NAFLD. ALT values do not correlate with the parameters of apoptosis and oxidative stress. The disease severity can only be determined by liver biopsy.

The effects of pegylated interferon alpha 2b on bile-duct ligation induced liver fibrosis in rats.

OBJECTIVE: To test the effects of peginterferon in an unrecoverable model of bile-duct ligation (BDL) induced liver fibrosis. MATERIAL AND METHODS: Thirty-seven Wistar rats were divided into five groups: group 1, BDL + peginterferon (n = 8); group 2, BDL (n = 8); group 3, sham + peginterferon (n = 7); group 4, sham (n = 7); and group 5, control group (n = 7). Peginterferon-alpha 2b (50 microgr/kg) or saline (1 mL/kg) was administered intraperitonealy every week for four weeks. Serum biochemical markers, liver tissue oxidative stress, collagen and transforming growth factor-beta (TGF-beta) levels were examined after four weeks. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining. RESULTS: The levels of tissue collagen, TGF-beta, biochemical markers (AST, ALT, bilirubins, alkaline phosphates, gamma-glutamyl transpeptidase) and oxidative stress markers (Malondialdehyde, luminal, lucigenin) of the BDL group were higher than the sham operated and control groups (all-p < 0.001). Peginterferon improved malondialdehyde, luminal and glutathione levels in the BDL + peginterferon group (p < 0.05). Histopathological examination of the BDL groups showed stage-3 fibrosis, while all the control groups were normal. Peginterferon showed no improvement in fibrosis either histologically, or biochemically. CONCLUSIONS: Peginterferon improved levels of malondialdehyde, glutathione and luminal in the rat model of BDL induced liver fibrosis. Peginterferon however,showed no anti-fibrotic effects in this model and therefore may not be a useful treatment for liver fibrosis.

Efficacy of pre-S-containing HBV vaccine combined with lamivudine in the treatment of chronic HBV infection.

Treatment of chronic hepatitis B (CHB) is difficult. The response rate to interferon (IFN) as well as nucleoside analogs is not more than 30% in general. While interferon has many side effects, development of resistance in most of the nucleoside analogs precludes long-term use. Both groups of drugs are most efficacious in patients who already had or develop strong cellular immunity with treatment. A pre-S2-containing vaccine was shown to enhance cellular immunity and suppress hepatitis B virus (HBV)-DNA in subjects with chronic hepatitis B. We aimed to test the efficacy of short-term use of a nucleoside analog in combination with a pre-S2-containing vaccine in patients with CHB. In this open study, 48 consecutive patients (32 males and 16 females, mean age +/- SD: 33 +/- 12 years) with CHB without cirrhosis were treated with 100 mg/day lamivudine and four weekly intramuscular injections of Genhevac B 20 mcg (six doses) for 24 weeks. While 19 patients were hepatitis B e antigen (HBeAg) positive (+ve), 29 patients were Anti-HBe/HBV-DNA +ve at the outset. Response was defined as seroconversion to anti-HBe in HBeAg +ve subjects and normalization of alanine aminotransferase (ALT) with loss of HBV-DNA in anti-HBe/HBV-DNA +ve subjects. HBeAg seroconversion occurred in 5/19 subjects (26%). Eighteen of 29 anti-HBe/HBV-DNA +ves responded. In the follow-up, while relapse was not observed in any of the patients who seroconverted, 11/18 from the anti-HBe/HBV-DNA +ve group relapsed, resulting in a sustained response (SR) rate of 24% in this group. All the relapses happened in the first 48 weeks of follow-up, with no relapse thereafter. Pretreatment high serum HBV-DNA was a strong negative predictor of sustained response (SR) in HBeAg +ve group. Pretreatment serum ALT over 2 x upper limit of normal and HBV-DNA less than 200 pg/ml appeared positive predictors. None of HBeAg +ve previous interferon failures responded. Twenty-four weeks of lamivudine and hepatitis B vaccine treatment induces SR in around 1/4 of the patients with CHB. Most of the responders had high ALT and relatively low DNA.

Serum gamma-glutamyltranspeptidase distinguishes non-alcoholic fatty liver disease at high risk.

BACKGROUND/AIMS: Hepatocyte apoptosis is an important and invasive predictor of liver injury and fibrosis in non-alcoholic fatty liver disease (NAFLD). Increased gamma-glutamyltranspeptidase (GGT) level is frequently observed in NAFLD. Hepatocyte growth factor (HGF) stimulates fibrogenesis and is correlated with GGT. The study aimed to determine whether GGT can distinguish NAFLD patients at high risk. METHODOLOGY: Fifty biopsy-proven NAFLD patients (M/F: 24/26) were divided as the normal GGT group (n = 25) and the high GGT group (n = 25) (each patients' GGT > two fold of upper-limit of normal). Liver histology was graded according to Brunt et al. TNF-sRp55, caspase-3 and 8, NFkappaB and Bcl-2 were measured by immunohistochemical methods. For statistical analysis, Student's t test, chi-square test, multivariate regression analysis and the area under receiver operating characteristic (ROC) curve were used. RESULTS: The high GGT group had significantly higher NFkappaB, caspase-3 and 8, and Bcl-2 levels (54.52 +/- 26.02, p = 0.002; 55.95 +/- 27.18, p = 0.002; 47.85 +/- 28.04, p = 0.001; 11.19 +/- 12.33, p = 0.016, respectively). Serum TNF-sRp55 levels of both groups were similar (2922.93 +/- 307.26, and 2885 +/- 194.47; p = 0.78). Differences in reference to histological steatosis grade and inflammation were not significant. However, fibrosis stage was higher in the high GGT group (p = 0.048). CONCLUSION: Multinominal logistic regression analysis showed that increased GGT level was a risk factor for advanced fibrosis in NAFLD (OR: 1.0, CI: 0.98-1.01; p =0.032). Using serum GGT levels the area under the ROC curve for the prediction of advanced fibrosis was 0.74 (95% CI: 0.54-0.94). The serum GGT cut-off value for the prediction of advanced fibrosis was 96.5 U/L; with 83% sensitivity and 69% specificity.

Leptin in nonalcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD. METHODS: Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student's t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH. RESULTS: We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively). CONCLUSION: Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.