Psoriasis and the liver: problems, causes and course.

BACKGROUND/OBJECTIVES: Psoriasis patients have a higher risk of liver abnormalities such as non-alcoholic fatty liver disease (NAFLD), drug-induced hepatitis, alcoholic hepatitis and neutrophilic cholangitis, than the general population. Associated liver disease limits therapeutic options and necessitates careful monitoring. The aim of the study was to identify liver problems in psoriasis patients and to investigate the underlying causes as well as their course. METHODS: The files of 518 psoriasis patients were retrospectively reviewed. Among these, 393 patients with relevant laboratory data were analysed for liver enzymes and their relation to the known risk factors for liver disease (obesity, diabetes mellitus, alcohol consumption, hepatotoxic medications, dyslipidemia, psoriatic arthritis and infectious hepatitis). RESULTS: Among 393 patients, 24% and 0.8% developed liver enzyme abnormalities and cirrhosis, respectively. The most common factors associated with pathological liver enzymes were drugs (57%) and NAFLD (22%). Other rare causes were alcoholic hepatitis, viral hepatitis, neutrophilic cholangitis, autoimmune hepatitis and toxic hepatitis due to herbal therapy. Drug-induced liver enzyme abnormalities were reversible whereas in patients with NAFLD transaminases tended to fluctuate. One patient with herbal medicine-related cirrhosis died of sepsis. CONCLUSION: Liver enzyme abnormalities are common in psoriasis patients and are mostly associated with drugs and NAFLD. Although most cases can be managed by avoiding hepatotoxic medications and close follow up, severe consequences like cirrhosis may develop.

Tumor necrosis factor-alpha inhibitors for the treatment of psoriasis patients with liver cirrhosis: A report of four cases with a literature review.

Patients with psoriasis are at an increased risk of developing liver disease due to various factors. The existing data regarding the treatment of psoriasis patients with associated liver cirrhosis is limited. We report four patients of psoriasis with liver cirrhosis who were treated with TNF-alpha inhibitors for a mean duration of 35.4 months. Two patients were treated with etanercept, one with adalimumab and one was treated with both infliximab and etanercept. Three patients tolerated the treatment well without any deterioration of liver disease whereas one died of progressive liver disease. Although large-scale, controlled studies are needed, this case series provides insights regarding the long-term safety of TNF-alpha inhibitors in patients with psoriasis and liver cirrhosis.

A multicenter, randomized, prospective study of 14-day ranitidine bismuth citrate- vs. lansoprazole-based triple therapy for the eradication of Helicobacter pylori in dyspeptic patients.

BACKGROUND/AIMS: Proton-pump inhibitor and ranitidine bismuth citrate-based triple regimens are the two recommended first line treatments for the eradication of Helicobacter pylori. We aimed to compare the effectiveness and tolerability of these two treatments in a prospective, multicentric, randomized study. MATERIALS AND METHODS: Patients with dyspeptic complaints were recruited from 15 study centers. Presence of Helicobacter pylori was investigated by both histology and rapid urease test. The patients were randomized to either ranitidine bismuth citrate 400 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=149) or lansoprazole 30 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=130) treatment arm for 14 days. Adverse events have been recorded during the treatment phase. A 13 C urea breath test was performed 6 weeks after termination of treatment to assess the efficacy of the therapy. Eradication rate was calculated by intention-to-treat and per-protocol analysis. RESULTS: Two hundred seventy-nine patients (123 male, 156 female) were eligible for randomization. In per-protocol analysis (n=247), Helicobacter pylori was eradicated with ranitidine bismuth citrate- and lansoprazole-based regimens in 74,6% and 69,2% of cases, respectively (p>0,05). Intention-to-treat analysis (n=279) revealed that eradication rates were 65,1% and 63,6% in ranitidine bismuth citrate and in lansoprazole-based regimens, respectively (p>0,05). Both regimes were well-tolerated, and no serious adverse event was observed during the study. CONCLUSION: Ranitidine bismuth citrate-based regimen is at least as effective and tolerable as the classical proton-pump inhibitor-based regimen, but none of the therapies could achieve the recommendable eradication rate.

Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. SUBJECTS AND METHODS: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. RESULTS: Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (ß = 0.392; t = 2.226, P < 0.01). CONCLUSIONS: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis.

Circulating levels of vascular endothelial growth factor A and its soluble receptor in patients with biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Vascular endothelial growth factor A (VEGF) is a multifunctional cytokine affecting angiogenesis and vascular function. The biological activity of VEGF is modulated by its soluble receptor VEGFR-1 (sVEGFR-1). We explored the associations of VEGF and sVEGFR-1 concentrations with liver histology in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS: The study was comprised of 99 patients with NAFLD and 75 healthy controls. Serum VEGF and sVEGFR-1 concentrations were measured using commercially available enzyme-linked immunosorbent assays. RESULTS: Serum VEGF levels did not differ in patients with NAFLD (1882 ± 942 pg/mL) compared with healthy controls (1985 ± 945 pg/mL, p = 0.42). However, compared with healthy subjects, levels of sVEGFR-1 were significantly lower in patients with NAFLD (1.59 ± 0.58 ng/mL vs. 1.16 ± 0.34 ng/mL, respectively, p <0.001). After allowance for potential confounders, serum sVEGFR-1 levels retained their independent significance as a predictor of liver fibrosis in patients with NAFLD (ß = -0.19; t = -1.81, p <0.05). CONCLUSIONS: Our results show that patients with biopsy-proven NAFLD have a significant reduction in serum sVEGFR-1 concentrations that predict the degree of liver fibrosis, independent of potential confounders.

Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease.

OBJECTIVE: The novel adipokines omentin, chemerin, and adipsin are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histological phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Serum levels of omentin, chemerin, and adipsin were assayed by enzyme-linked immunosorbent assay in 99 patients with biopsy-proven NAFLD and 75 control subjects. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. RESULTS: Adipsin levels did not differ between patients and controls, whereas both omentin and chemerin levels were significantly higher in patients with biopsy-proven NAFLD than in controls (both p values <0.001). Serum omentin levels were significantly associated with C-reactive protein (r = 0.29, p < 0.01) and the degree of hepatocyte ballooning (r = 0.27, p < 0.01), whereas chemerin showed a modest association with liver fibrosis (r = 0.22, p = 0.04). After stepwise linear regression analysis adjusting for potential confounders, serum omentin levels retained their independent significance as a predictor of hepatocyte ballooning in patients with NAFLD (ß = 1.42; t = 2.79, p < 0.01). CONCLUSIONS: Our results suggest that serum omentin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of hepatocyte ballooning.

Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease.

The novel adipokines vaspin, obestatin, and apelin-36 are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histologic phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). Serum levels of vaspin, obestatin, and apelin-36 were assayed by enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 81 controls. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. Univariable analysis showed that concentrations of vaspin and apelin-36 were significantly higher in patients with NAFLD than in controls, whereas no differences in obestatin levels were found. Serum vaspin levels showed a statistically significant association with C-reactive protein (r = 0.378, P < .001) and liver fibrosis scores (r = 0.401, P < .001), whereas apelin-36 levels showed a modest association with homeostasis model assessment of insulin resistance (r = 0.204, P < .01). After stepwise linear regression analysis, serum vaspin levels were the only independent predictor of liver fibrosis scores in patients with NAFLD (ß = 0.37, t = 3.99, P < .01). Serum vaspin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver fibrosis scores. These findings support further investigation of this novel adipokine in metabolic liver diseases.

Serum zinc-α2-glycoprotein concentrations in patients with non-alcoholic fatty liver disease.

BACKGROUND: Evidence suggests that zinc-α(2)-glycoprotein (ZAG) might serve as a biomarker for human metabolic alterations. We measured serum ZAG in patients with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined its association with clinical, biochemical, and histological phenotypes. METHODS: Serum ZAG was determined using ELISA in 90 patients with biopsy-proven NAFLD and 81 controls. RESULTS: Serum ZAG concentrations did not differ in patients with NAFLD (median 61 µg/mL; interquartile range: 56-73 µg/mL) compared with healthy controls (median 66 µg/mL; interquartile range: 56-78 µg/mL, Mann-Whitney U-test, p=NS). However, among patients with NAFLD serum ZAG concentrations were significantly higher in males and in those with the metabolic syndrome. After stepwise linear regression analysis, serum ZAG concentrations were the only independent predictor of the number of metabolic syndrome components in patients with NAFLD (ß=0.22; t=2.001, p<0.05). CONCLUSIONS: In summary, the hypothesis of an association between NAFLD and serum ZAG concentrations is not supported by the present results. However, ZAG remains an interesting molecule for further research in the field of human metabolic disorders.

Effects of a long-acting somatostatin analogue, lanreotide, on bile duct ligation-induced liver fibrosis in rats.

BACKGROUND/AIMS: Somatostatin receptors have been shown on hepatic stellate cells, and somatostatin infusion has been shown to inhibit hepatic stellate cells activation. We aimed to test the effects of a long-acting somatostatin analogue, lanreotide, on bile duct ligation-induced liver fibrosis in rats. METHODS: Thirty-seven Wistar rats were divided into 5 groups as follows: Group 1, bile duct ligation+lanreotide; Group 2, bile duct ligation; Group 3, sham+lanreotide; Group 4, sham; and Group 5, control group. Lanreotide-autogel (20 mg/kg/month) or saline in intraperitoneal doses was administered. Serum biochemical parameters, liver collagen level, and oxidative stress and histological parameters were determined after 28 days. RESULTS: The tissue collagen level, biochemical parameters (AST, ALT, bilirubins, alkaline phosphatase, γ-glutamyl transpeptidase) and oxidative stress parameters (malondialdehyde, luminal, lucigenin) in the bile duct ligation groups were higher than in the sham-operated and control groups (p<0.001 for all). Lanreotide improved malondialdehyde and glutathione levels in the bile duct ligation+lanreotide group. In histopathological examination, bile duct ligation groups showed stage-3 liver fibrosis, while all the controls were normal. Lanreotide did not improve the liver fibrosis histologically or biochemically. CONCLUSIONS: A monthly active somatostatin analogue, lanreotide, improved malondialdehyde and glutathione; however, it was not able to improve bile duct ligation-induced liver fibrosis in rats. Although lanreotide is a long-acting medication, it did not show anti-fibrotic effects in the model.

Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease.

OBJECTIVE: Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily with pleiotropic effects on inflammation, endocrine function and the immune system. Reduced OPG levels are related to insulin resistance. We tested the hypothesis that serum levels of OPG may be associated with nonalcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Four groups of patients were enrolled in the present study: subjects with definite nonalcoholic steatohepatitis (NASH, n = 56), borderline NASH (n = 26), simple fatty liver (n = 17) and healthy controls without evidence of liver disease (n = 58). Serum levels of OPG were measured by ELISA. RESULTS: Concentrations of OPG were significantly lower in patients with definite NASH (median: 45 pg/mL, p < 0.001) and borderline NASH (57 pg/mL, p < 0.001) than in controls (92 pg/mL). The area under the ROC curve for distinguishing between steatohepatitis (definite NASH plus borderline NASH) and healthy controls using OPG was 0.82. The use of a cut-off level < 74 pg/mL for serum OPG levels yielded sensitivity and specificity values of 75.6% and 75.9%, respectively. CONCLUSIONS: Serum osteoprotegerin concentrations are reduced in patients with the more severe forms of NAFLD and may serve as a noninvasive biomarker to identify patients with NASH.

Serum fetuin A/α2HS-glycoprotein levels in patients with non-alcoholic fatty liver disease: relation with liver fibrosis.

BACKGROUND: Serum concentrations of fetuin A/α2HS-glycoprotein (AHSG) have been linked to human metabolic alterations and can serve as an indicator of liver cell function. We assayed serum levels of AHSG in patients with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined their association with clinical, biochemical and histological phenotypes. METHODS: Serum AHSG levels were determined by enzyme linked immunosorbent assay in 99 patients with biopsy-proven NAFLD and 75 age- and gender-matched controls. RESULTS: Serum AHSG levels were significantly higher in patients with NAFLD (940 ± 120 µg/mL) compared with healthy controls (800 ± 130 µg/mL, Student's t test, P < 0.001). Bivariate analyses (Spearman's rank correlation) in patients with NAFLD showed a statistically significant association between AHSG levels and insulin resistance as assessed by the HOMA (homeostasis model assessment) index (r = 0.31, P < 0.01) and the liver fibrosis score index (r = 0.36, P < 0.001). The association between AHSG and fibrosis remained statistically significant even after adjustment for potential confounders, including the HOMA index ([beta] = 1.65, t = 2.38, P < 0.05). CONCLUSION: Serum AHSG levels are significantly increased in adult patients with biopsy-proven NAFLD and are associated with insulin resistance. Importantly, our pilot data indicate that serum AHSG levels may identify NAFLD patients with higher fibrosis scores.

Caspase-cleaved fragments of cytokeratin 18 in patients with chronic hepatitis B.

BACKGROUND: During hepatocyte apoptosis, intermediate filament protein cytokeratin 18 is cleaved by caspases at Asp396 which can be specifically detected by the monoclonal antibody M30 (M30-antigen). In this study, we sought to determine whether serum M30-antigen levels can serve as a useful biomarker of liver injury in the clinical spectrum of HBV infection. METHODS: Serum M30-antigen levels were measured in inactive HBV carriers (n=54), patients with HBeAg-negative chronic hepatitis B (CHB, n=47), patients with HBeAg-positive CHB (n=42) and healthy controls (n=29). All subjects were treatment-naïve. RESULTS: There were significant differences in serum M30-antigen levels across the study groups (P<0.001; Kruskal-Wallis test). Post hoc analyses revealed that M30-antigen levels did not differ significantly between inactive HBV carriers (median 109.6 U/L) and healthy controls (median 106.1 U/L). However, both patients with HBeAg-negative (CHB, median 182.9 U/L, P<0.001) and HBeAg-positive CHB (median 158.3 U/L, P<0.001) had significantly higher levels of M30-antigen compared with inactive HBV carriers. CONCLUSIONS: Hepatocyte apoptotic activity--as reflected by serum M30-antigen levels--is increased in chronic active hepatitis B, but is not associated with the HBeAg status. In contrast, apoptosis does not appear to be a prominent feature of inactive HBV carriers.

Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease.

BACKGROUND: The fibroblast growth factor 21 (FGF21) hormonal pathway is a metabolic signalling cascade and has been recently identified as the master hormonal regulator of glucose, lipids and overall energy balance. In this observational, case-control study, we assayed serum levels of FGF21 in patients with nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined their association with clinical, biochemical and histological phenotypes. MATERIALS AND METHODS: Serum levels of FGF21 were assayed by ELISA in 82 patients with biopsy-proven NAFLD and 77 controls. We analysed associations between FGF21 and the characteristics of patients with NAFLD by multiple linear regression analysis. RESULTS: Levels of FGF21 were significantly higher in patients with NAFLD (median 200 pg mL(-1) ; interquartile range: 87-410 pg mL(-1)) than in healthy controls (median 93 pg mL(-1) ; interquartile range: 70-180 pg mL(-1) , Mann-Whitney U-test, P<0·001). There was a stepwise increase in serum FGF21 levels according to the liver steatosis score (median level in subjects with score 1: 170 pg mL(-1) ; score 2: 220 pg mL(-1) ; score 3: 280 pg mL(-1) , P for trend <0·01). After stepwise linear regression analysis, serum FGF21 levels were the only independent predictor of hepatic steatosis scores in patients with NAFLD (ß=0·26; t=2·659, P<0·01). CONCLUSIONS: Serum FGF21 levels are increased in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver steatosis. These findings support further investigation of this molecule in metabolic liver diseases.

The prevalence of the mutation in codon 249 of the P53 gene in patients with hepatocellular carcinoma (HCC) in Turkey.

UNLABELLED: Hepatocellular carcinoma (HCC) is one of the most common cancers in the worldwide. Aflotoxins, products of Aspergillus Flavus found in the high humidity environments induce HCC in humans by causing mutations in oncogenes such as codon 249 mutation of p53 in hepatocytes. In turkey, aflatoxins are found to be increased in some foods in certain areas, such as Istanbul which have high humidity. In present study we aimed to look for the prevalence of codon 249 mutation of p53 in patients with HCC, cirrhosis and chronic hepatitis B (CHB). METHODS: DNA was extracted from plasma and mutation was detected by PCR-RFLP method. RESULTS: the codon 249 mutation of p53 is found one out of 50 HCC (2%) patients. In conclusion, although codon 249 mutation of p53 gene has been found very rare but it exists showing the effect of aflatoxins in HCC patients in Turkey.

R72P polymorphism of TP53 in ulcerative colitis patients is associated with the incidence of colectomy, use of steroids and the presence of a positive family history.

P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR = 3.03; 95%CI = 1.91-2.40; p = 0.003), but only modest association with UC (OR = 1.61; 95%CI = 0.98-2.65; p = 0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR = 8.0; 95%CI = 1.68-38.08, p = 0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR = 17.77; 95%CI = 0.98-323.34, p = 0.012) and steroid use (OR = 10.14; 95%CI = 2.63-39.12, p = 0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.

Coronary flow reserve is impaired in patients with nonalcoholic fatty liver disease: association with liver fibrosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. Coronary flow reserve (CFR) is widely used to examine the integrity of coronary microvascular circulation. We evaluated the prevalence of impaired CFR in patients with biopsy-proven NAFLD. We also investigated the independent clinical, biochemical, and liver histology predictors of CFR in the setting of NAFLD. METHODS: Fifty-nine consecutive patients with NAFLD and 77 age- and gender-matched controls were evaluated. CFR recordings were performed by transthoracic Doppler harmonic echocardiography. CFR>or=2.0 was considered normal. RESULTS: CFR was significantly lower in patients with NAFLD than in controls (2.11+/-0.45 vs. 2.52+/-0.62, P<0.001). An impaired CFR (i.e. <2) was found in 25 NAFLD patients (42.4%) whereas all controls had normal CFR values (P<0.001). A stepwise linear regression analysis in NAFLD patients identified liver fibrosis scores as the only independent predictor of CFR values (beta=-0.60; t=-2.44, P=0.021). CONCLUSION: Our findings indicate that in patients with biopsy-proven NAFLD: (a) an abnormal CFR is found in approximately 42.4% of cases, and (b) liver fibrosis scores are an independent predictor of depressed CFR.

Microalbuminuria in nondiabetic patients with nonalcoholic fatty liver disease: association with liver fibrosis.

Recent evidence has suggested an association between microalbuminuria and ultrasound-diagnosed nonalcoholic fatty liver disease (NAFLD) in patients with diabetes and prediabetes. However, few data are available on the occurrence of microalbuminuria in nondiabetic subjects with histologically proven NAFLD. We thus evaluated the relationships between microalbuminuria and liver histology in a hospital-based sample of 87 adults with biopsy-proven NAFLD from Turkey. An albumin excretion rate less than 30 mg/d was considered within the reference range, whereas an albumin excretion rate from 30 to 300 mg/d was considered to indicate microalbuminuria. Compared with those without microalbuminuria (n = 73), NAFLD patients with microalbuminuria (n = 14) had significantly higher homeostasis model assessment of insulin resistance values (3.9 +/- 1.3 vs 5.8 +/- 3.7, P < .001). There were no differences in the prevalence of microalbuminuria in patients with definite nonalcoholic steatohepatitis, borderline nonalcoholic steatohepatitis, and simple fatty liver. In the entire study cohort, mean fibrosis scores were significantly higher in patients with microalbuminuria than in those without (1.27 +/- 0.26 vs 0. 80 +/- 0.11, P < .05). This difference persisted after adjustment for potential confounders. These results indicate the presence of a significant association between the severity of insulin resistance and microalbuminuria in patients with NAFLD. In addition, microalbuminuria may identify NAFLD patients with higher fibrosis scores.

Is HCV genotyping cost-effective even when the prevalences of genotypes 2 and 3 are low?

BACKGROUND/AIMS: The management of chronic hepatitis C virus (HCV) infection is costly. Genotyping determines the indication, probability of response, and duration of treatment and the dose of ribavirin. Although genotyping is accepted cost-effective, the cost of genotyping in all of the patients to find out a minority may offset the gain. The present study aimed; (1) to determine the frequency rate of HCV genotypes and (2) to compare the cost of HCV treatment tailored according to the genotype versus that planned supposing it to be genotype 1. METHODOLOGY: Six centers were included into the study. Name, age, genotype, and serotype of each patient were entered. For genotyping, HCV-RNA was extracted by acid-guanidium-phenol-chloroform method. Cost of genotyping, HCV-RNA studies and the treatment with pegylated interferon and ribavirin was estimated. The cost was determined according to two scenarios: (A) To manage patients as if all had genotypes other than 2-3. (B) To manage them after determining the geno type. The management was assumed to be made by current guidelines. RESULTS: The data of 834 patients were analyzed: Genotypel was predominant: 730 (87.5%). The rest was composed of G2:26 (3.1%), G3:26 (3.1%), G4:14 (1.7%), mixed: 13 (1.6%), undetermined: 25(3%). The cost of approach A (for 100 patients) was 1,718,200 USD; that of approach B (for 100 patients) was 1,671,900 USD. With genotype targeted therapy, every 100 patient would save 46,300 USD. CONCLUSIONS: The prevalent genotype in our country is genotypel. The sum of genotypes 2 and 3 corresponds to 6%. Genotyping HCV and tailoring the treatment thereafter are cost-effective even in the countries where prevalence of these genotypes is low.

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.