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April - June, 2011

Vol. 10 Issue 2

On the cover: Abdominal CT was performed in the early arterial phase images there was a homogenously enhancing lesion in segment 2 and a hypodense lesion in segment 1 for characterization of the lesions, dynamic contrast-enhanced MRI was performed.

HEPATOLOGY HIGHLIGHTS

ORIGINAL ARTICLES

Clinical Studies

  • Non-alcoholic fatty liver disease and the metabolic syndrome in an urban hospital serving an African community Charles Asabamaka Onyekwere, Anthonia O. Ogbera, Babajide O. Balogun Page 119-124

    Background. Liver disease continues to be a major cause of morbidity and mortality in sub-Saharan Africa, including Nigeria, due to the high endemicity of viral hepatitis B. However non-alcoholic fatty liver disease may be an important contributory factor. The impact of fatty liver disease in our region has not been evaluated. AIM. To determine the prevalence of non-alcoholic fatty liver disease (NAFLD) among a population of diabetic (DM) subjects attending the endocrine clinic of LASUTH compared with non-diabetic subjects; ascertain other contributing factors and compare the occurrence of the metabolic syndrome in subjects with and without NAFLD. Methodology. Consecutive patients who satisfy the study criteria were enrolled. An investigator- administered questionnaire was used to determine symptoms of liver disease, followed by physical examination to obtain anthropometric indices as well as signs of liver disease. Abdominal scan was performed to determine radiologic evidence of fatty liver and fasting blood samples were collected from for the measurement of fasting lipid profile, glucose, liver biochemistry and serology for hepatitis B and C markers. Results. One hundred and fifty subjects, mean age 56years (standard deviation = 9, range 20-80 yr) and gender ratio (F: M) of 83:67(55%:45%), were recruited. 106 were diabetics and 44 non-diabetics. The overall prevalence of NAFLD amongst all study subjects was 8.7%. The prevalence rate of NAFLD was higher in the DM cases than in the Control subjects but this difference was not statistically significant (9.5 vs. 4.5%, p = 0.2). Only one of the subjects with fatty liver disease had elevated transaminase levels (steatohepatitis) and also had type 2 DM. Central obesity as measured by waist circumference (WC) and SGPT levels were significantly higher in people with fatty liver. The mean body mass index (BMI) of diabetic and non-diabetic patients was similar (31 vs. 30 kg/m2). The prevalence of the metabolic syndrome was higher in the subjects with NAFLD than in those without fatty liver disease but this difference was not statistically significant (p = 0.8). Conclusion. Non-alcoholic fatty liver disease is present in Africa but is less than what one would expect based on American and European studies.

  • Risk factors and predictors of non-alcoholic fatty liver disease in Taiwan Ying Chin Lin, Shou Chu Chou, Pai Tsang Huang, Hung Yi Chiou Page 125-132

    Background and rationale for the study. Ultrasound assessment of the severity of non-alcoholic fatty liver disease (NAFLD) shows substantial observer variability. The purpose of this retrospective study is to develop a more objective, quantitative, and applicable assessment method for all physicians. Main Results. Male gender, and increases in age, body mass index, alanine aminotransferase (ALT), triglycerides (TG), and total cholesterol (TC) were found to be significantly correlated to higher scores. The following algorithm, derived from a 3,275 member training group, for predicting the extent of fatty liver infiltration was then constructed using these parameters. In (π1/π0) = -8.360-0.065*Gender+0.010*age+0.256*BMI+0.024*ALT+0.03*TG+0.002*TC In (π2/π0)= -19.0.92+0.482*Gender+0.043*age+0.529*BMI+0.046*ALT+0.005*TG+0.005*TC π0: the probability of non fatty liver. π1: the probability of degree 1 fatty liver. π2: the probability of degree 2-3 fatty liver. π0 + π1 + π2 = 1 The resulting algorithm was tested for its predictive power a 1,065 member validation group. The algorithm predicted the actual ultrasound fatty liver score in the validation group with 87.9, 14.2, and 72.6% accuracy for those with no, grade 1, and grade 2-3 fatty liver, respectively. For prediction of grade 2-3 fatty liver, its sensitivity was 70.8%, its specificity 85.2%, its positive predictive power 63.2% and its negative predictive power 88.8%. Conclusions. The algorithm developed here is fast and has substantial predictive power for grade 2-3 fatty liver. No specialized equipment or expertise is needed, and it can be easily used by the general practitioner to predict the extent of fatty infiltration in cases of NAFLD.

  • Molecular and serological characterization of occult hepatitis B infection in blood donors from Mexico Beatriz María García-Montalvo, Laura Patricia Ventura-Zapata Page 133-141

    Occult hepatitis B virus (HBV) infection (OBI) is characterized by presence of HBV DNA in blood or liver tissue without detectable HBV surface antigen (HBsAg), with or without antibodies to hepatitis B core antigen (anti-HBc) or antibodies against HBsAg (anti-HBs). A molecular and serological characterization was done of OBI in blood donors from Yucatan, Mexico. HBV DNA was found in 24 (6.4%) of the 372 evaluated samples. Anti-HBs was present in 15/24 samples (62.5%), and no significant difference was observed between HBV DNA positivity and anti-HBs levels. HBV genotype H was detected in 66.7% of samples, followed by genotypes D (20.8%) and F (8.3%). Amino acid substitutions were identified in the core region of nine samples, and most of these changes were located in immunodominant epitopes. No precore stop codon 28 mutant (W28Stop) was identified among the analyzed HBV isolates. In conclusion, genotype H is the main circulating HBV strain among OBI blood donors from Yucatan, Mexico. Mutations in the core region may contribute to viral persistence.

  • Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding Pavel Drastich, Jan Lata, Jaromir Petrtyl, Radan Bruha, Vlastimil Prochazka, Tomas Vanasek, Petr Zdenek, Jelena Skibova, Tomas Hucl, Julius Spicak Page 142-149

    Administration of nonselective beta-blockers in prophylaxis of first variceal bleeding is not suitable for all patients. Thus, we evaluated endoscopic variceal band ligation (EVBL) in primary prevention of bleeding in patients with cirrhosis and large esophageal varices. A total of 73 consecutive patients with liver cirrhosis and large esophageal varices without a history of gastrointestinal bleeding were randomized to receive either EVBL or propranolol and were followed for up to 18 months. Forty patients underwent EVBL and 33 patients received propranolol. Variceal bleeding occurred in 2 patients in the EVBL (5%) and in 2 patients in the propranolol group (6%, NS). The 18 month actuarial risk for first variceal bleed was 5% in the EVBL (95% CI, 0-12%) and 20% in the propranolol group (95% CI, 0-49%, NS). The actuarial probability of death at 18 months of follow-up was 5% (95% CI, 0-11%) in the EVBL group and 7% (95% CI, 0-17%, NS) in the propranolol arm. In conclusion, EVBL was an effective and safe alternative to propranolol in primary prophylaxis of bleeding in patients with large esophageal varices.

  • Lipid-bound sialic acid (LSA) in liver diseases of different etiologies Lech Chrostek, Bogdan Cylwik, Anatol Panasiuk, Dorota Brodowska-Adamusiak, Ewa Gruszewska Page 150-154

    Objective. There are evidences that the changes in glycosylation and sialylation of proteins and lipids play an important role in the pathogenesis and progression of various liver diseases. The aim of this study was to evaluate the changes in the sialylation of serum lipids measured by the level of lipid-bound sialic acid (LSA) in liver diseases of different etiologies. Materials and methods. Tested group consisted of 303 patients suffering from liver diseases: alcoholic and non-alcoholic cirrhosis, chronic non-viral hepatitis, toxic hepatitis, chronic viral C and B hepatitis, autoimmune hepatitis, primary liver cancer, liver cancer and cirrhosis (mixed group), acute hepatitis B, primary biliary cirrhosis and fatty liver. LSA was determined by the method of Katopodis and co-workers. Results. There were significant differences in the serum LSA concentrations between liver diseases of different etiologies. The level of LSA in liver tumors was higher than that in both types of cirrhosis: alcoholic and non-alcoholic. In turn, LSA level in non-alcoholic cirrhosis was lower than in toxic hepatitis and mixed group. There was no difference in LSA concentration between tumor and mixed group. Similarly to LSA, AFP level in tumor group was also higher than that in both cirrhotic groups, but there was no difference in AFP concentration between tumor and mixed group. Conclusions. The sialylation of serum lipids alters in liver diseases of different etiologies. Given the importance of glycans in biological systems we can speculate that the changes in lipids sialylation play an important role in liver pathology, especially in primary cancer, cirrhosis and toxic hepatitis.

  • Familial hypobetalipoproteinemia in a hospital survey: genetics, metabolism and non-alcoholic fatty liver disease Carlos Gutiérrez-Cirlos, María Luisa Ordóñez-Sánchez, María Teresa Tusié-Luna, Bruce W. Patterson, Gustav Schonfeld, Carlos A. Aguilar-Salinas Page 155-164

    Introduction. Familial hypobetalipoproteinemia (FHBL) is an autosomal dominant disease characterized by abnormally low levels of apolipoprotein-B (apoB) containing lipoproteins. FHBL is caused by APOB, PCSK9 or ANGPTL3 mutations or is associated with loci located in chromosomes 10 and 3p21. However, other genes should be involved. This study describes the kinetic parameters of the apoB containing lipoproteins and sequence abnormalities of the APOB and PCSK9 genes of FHBL patients identified in a large hospital based survey. Material and methods. Cases with primary or secondary causes of hypobetalipoproteinemia were identified. ApoB kinetics were measured in cases with primary forms in whom truncated forms of apoB were not present in VLDL (n = 4). A primed constant infusion of [13C] leucine was administered, VLDL and LDL apoB production and catabolic rates measured by a multicompartmental model and compared to normolipemic controls. In addition, these subjects had an abdominal ultrasound and direct sequencing was carried out for the PCSK9 and apoB genes. Results. Three individuals had normal apoB production with increased catabolic rate; the remaining had reduced synthetic and catabolic rates. Various polymorphisms, some of them previously unreported (*), in the PCSK9 gene (R46L, A53V, I474V, D480N*, E498K*) and in the apoB gene (N441D*, Y1395C, P2712L, D2285E*, I2286V, T3540S*, T3799M*) were found in the FHBL patients. We found hepatic ultrasound changes of hepatic steatosis in only one of the four probands. Conclusion. FHBL without truncated apoB is a heterogeneous disease from a metabolic and a genetic perspective. Hypobetalipoproteinemia is a risk factor but not an obligate cause of steatosis.

  • The efficacy of anti-viral therapy on hepatitis B virus-associated glomerulonephritis: A systematic review and meta-analysis Zhou Yi, Yuan Wei Jie, Zhu Nan Page 165-173

    Objectives. To assess the efficacy of anti-viral therapy on hepatitis B virus associated glomerulonephritis (HBV-GN). Design, setting, participants, & measurements. We searched PubMed, Embase and Cochrane Library for prospective controlled trials which assessed the efficacy of anti-viral therapy on HBV-GN in adult or pediatric patients between January, 1970 and October, 2010. Results were summarized using fixedeffects model because of an absence of heterogeneity among the studies (I2 = 0%). Results. Six trials with a total of 159 patients were included; among them five trials were specified as hepatitis B virus-associated membranous glomerulonephritis (HBV-MN). In adult patients, the incidence of proteinuria remission, not only total remission (complete remission CR + partial remission PR) (2.97 to 109.93, P = 0.002) but also CR (1.18 to 16.11, P = 0.03), significantly increased in the anti-viral treatment. In pediatric patients, only the incidence of total remission (1.77 to 17.75, P = 0.003) was increased significantly; the incidence of CR was not pooled with clinical and statistical heterogeneity (I2 = 81.5%, P = 0.004).Combine the data from adult and pediatric patients with HBV-MN, the same results were found. All the results of proteinuria remission kept with virologic response (VR), including HBeAg conversion (5.68 to 40.04, P < 0.00001) and reduction of HBV-DNA (5.60 to 463.16, P = 0.0005). Conclusions. Antiviral therapy including IFN and lamivudine is effective on remission of proteinuria, HBeAg clearance, and HBV-DNA reduction.

  • Onset of heart failure determines the hepatic cell death pattern Kerstin Herzer, Guntje Kneiseler, Lars Peter Bechmann, Felix Post, Martin Schlattjan, Jan-Peter Sowa, Till Neumann, Günter Marggraf, Raimund Erbel, Guido Gerken, Ali Canbay, Christoph Jochum Page 174-179

    Background and rationale. Acute and chronic heart failure (HF) may affect the liver, but the underlying mechanisms that lead to progressive liver damage are poorly understood. The hepatic cytokeratin-18 (CK18) epitopes M65 and M30 have been reported to distinguish between overall (necrotic) and apoptotic cell death, respectively. We aimed to evaluate the predominant hepatic cell death pattern in acute vs. chronic heart failure and examined if these assays predict the course of the disease. Main results. In a prospective study comprising 21 patients with acute HF (AHF) and 18 patients with chronic HF (CHF) serum levels of M65 and M30 were assessed. Compared with CHF, M65 levels were significantly increased in patients with AHF (CHF: 1,283 ± 591.6U/l vs. AHF: 20,912 ± 15,132U/l, p < 0.001). In addition, M30 levels were significantly increased in AHF (CHF: 642.2 ± 177.4U/l vs. AHF: 3,844 ± 5,293U/l, p < 0.05), but the M30/M65 ratio was significantly higher in CHF (CHF: 0.54 ± 0.15 vs. AHF: 0.20 ± 0.19, p < 0.001), indicating a greater contribution of apoptotic cell death in CHF. AHF patients with higher M30 values had a worse prognosis. Conclusions. The ratio of CK18 M30/M65 is a potential marker to discriminate AHF from CHF induced LF and M30 might be a prognostic marker for survival in AHF induced liver injury.

  • Does pre-liver transplant HBV DNA level affect HBV recurrence or survival in liver transplant recipients receiving HBIg and nucleos(t)ide analogues? Isabel Campos-Varela, Lluís Castells, Maria Buti, Víctor Vargas, Itxarone Bilbao, Francisco Rodríguez-Frías, Rosendo Jardí, Ramón Charco, Jaime Guardia, Rafael Esteban Page 180-187

    Background and Aims. The risk of recurrent hepatitis B virus (HBV) infection and prognosis of liver transplantation in patients with HBV has dramatically changed with the use of prophylaxis including hepatitis B immune globulin (HBIg) and antiviral agents. Methods. This study analyzes the prognostic value of HBV DNA level before orthotopic liver transplantation (OLT) and the effect of HBV prophylaxis on rates of HBV recurrence and survival. Between 1988 and 2008, 859 patients underwent OLT in our center; 60 patients had HBV-related liver disease and in 49, HBV DNA was determined by real time-PCR before OLT. Survival and HBV recurrence were analyzed according to preoperative viral load (HBV DNA <103 IU/mL vs. HBV DNA ≥103) and prophylaxis regimens (HBIg vs HBIg and antivirals). Results. On multivariate analysis, prophylaxis with HBIg alone, but not HBV-DNA levels was independently associated with poor survival, with a relative risk (RR) of death of 6.5 (95% CI 2.1-19.8, P = 0.001). The risk of HBV recurrence, in this small series, was also associated with monoprophylaxis with HBIg (RR 27, 95% CI 5.2-147.2, P < 0.0001), but not with HBV-DNA levels. Conclusions. When prophylaxis with HBIg and antiviral agents was administered, survival and HBV recurrence were not influenced by HBV-DNA levels determined by real time-PCR prior to OLT.

  • Hepatobiliary laboratory abnormalities among patients with chronic or persistent immune thrombocytopenia (ITP) Cheryl Enger, Dimitri Bennett, Katie L. Dawson, Manuel A. Aivado, Dickens Theodore, Andrew T. McAfee Page 188-195

    Therapies for immune thrombocytopenia (ITP) may be associated with abnormal hepatobiliary laboratory (HBL) values, but the epidemiology of these abnormalities is unknown in the ITP population. The study aim was to provide prevalence and incidence rates, as well as risk factors for abnormal HBL values among a cohort of patients with chronic or persistent primary ITP. Health insurance claims data from 3,244 patients with chronic or persistent ITP was examined to estimate the prevalence of abnormal HBL values: elevated levels of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), total bilirubin, and Alkaline Phosphatase (ALP). Incidence of abnormal HBL values was estimated in a sub cohort of 2557 (79%) patients without evidence of comorbidities related to secondary thrombocytopenia, liver disease, or abnormal HBL values during the 12-month baseline period. The baseline prevalence of ALT and AST > 3x the upper limit of normal (ULN) was 4.6 and 3.7%, respectively. The baseline prevalence of total bilirubin and ALP >1.5x ULN was 4.2 and 3.2%, respectively. The incidence rate of new HBL abnormalities (HBLA) was 1.24/1,000 personyears (95% CI: 0.52-2.56) for ALT>3x ULN and 0.41/1,000 person-years (95% CI: 0.08-1.32) for AST>3x ULN. HBLAs were significantly associated with male gender, liver disease, diabetes, congestive heart failure, lupus, hematological cancers, and HIV infection. In conclusion, the prevalence of HBLA, specifically ALT>3x ULN, among the ITP population is relatively high compared with atrial fibrillation, though within the confidence interval for that estimate. HBLAs were significantly associated with male gender, liver disease, and several other comorbidities, thus, distinguishing drug-induced liver injury in this population is clinically challenging.

ORIGINAL ARTICLES

Basic studies

  • Hypothermic preservation of rat liver microorgans (LMOs) in bes-gluconate solution. Protective effects of polyethyleneglycol (PEG) on total water content and functional viability Cecilia Mandolino, Ma. Dolores Pizarro, Alejandra B. Quintana, Joaquín V. Rodríguez, Ma. Eugenia Mamprin Page 196-206

    We have reported of an alternative solution to preserve hepatocytes that have three key components: gluconate, sucrose and an aminosulfonic acid (BGS solution). In order to extend the use of this solution to organs as the liver, we evaluate the effect of the addition of PEG of 8, 20 and 35 kDa to BG Solution on the total water content and functional viability of rat liver microorgans (LMOs). LMOs were preserved (48 h 0 ºC) in the following solutions: ViaSpan®; BGS; BG plus 4% PEG 8000 (BG8); BG plus 4% PEG 20.000 (BG20) and BG plus 4% PEG 35.000 (BG35). LDH Release and Total Water Content showed a marked increase in LMOs preserved in BGS. This indicates that, in the absence of PEG, the tissue showed important cell membrane integrity deterioration and was incapable of regulating cell volume. After the preservation period, all groups were reoxygenated (120 min, 37 ºC, KHR) and Total Water Content, Glycogen Content and Oxygen Consumption were determined. After 120 min LMOs preserved in BG35 showed values of Oxygen Consumption similar to controls. On the other hand, LMOs preserved in BG8, BG20 and ViaSpan® showed oxygen consumption rates and glycogen content significantly smaller than controls. In conclusion, BG35 was the most effective preservation solution to protect LMOs against cold preservation injury due to ischemia and reoxygenation. It is a good alternative to ViaSpan® because of its higher buffer capacity, its best indexes of respiration activity and for being considerably less expensive.

  • Aminoguanidine potentiates the hepatoprotective effect of silymarin in CCL4 treated rats Ahmed Fahmy Ahmed, Mona Fouad Mahmoud, Marwa Arafat Ouf, Eman Abd El-Fathaah Page 207-215

    This study examined the possible hepatoprotective effect of aminoguanidine in comparison with silymarin and investigated the possible beneficial effects of the combination of aminoguanidine and silymarin on CCL4-induced liver fibrosis. Male Wister albino rats were randomly divided into five groups (10 rats/group). Group I included control rats injected only with liquid paraffin and saline; group II represents CCL4 control (injected with CCL4 3 times a week for 6 weeks in a dose of 25μl/100gm.b.w i.p, diluted 1:6 with liquid paraffin); group III treated with aminoguanidine (100 mg/kg); group IV was given silymarin (100 mg/kg); group V was given aminoguanidine (100 mg/kg) and silymarin (100 mg/kg). Fibrosis was depicted histologically and biochemically. CCL4 increased serum liver enzymes (ALT, AST, and ALP), lactate dehydrogenase (LDH), level of nitric oxide (NO), tumor necrosis factor alpha (TNFα) and liver malondialdehyde content (MDA), collagen fiber percent and decreased liver reduced glutathione (GSH) content as endogenous antioxidant. Histopathological changes induced by CCL4 include regenerative nodules, deteriorated parenchyma; the lobules were infiltrated with fat and structurally altered. Aminoguanidine, silymarin and their combination reduced these changes and attenuated the pathological effects of CCL4 induced liver injury. The combination of both drugs was better than each drug alone. It is concluded that aminoguanidine has protective effect against CCL4 induced hepatoxicity via its iNOS inhibition and antioxidant effects. In addition, the combination of AG with silymarin has more potent hepatoprotective effect than each drug alone.

EDITORIAL

IMAGES IN HEPATOLOGY

  • Focal nodular hyperplasia vs. hemangioma: Computed tomography and magnetic resonance imaging findings Ridvan Karahasanoglu, Hafize Otcu, Tuba Selcuk, Adem Ucar, Adem Kiris Page 218-220

    Focal nodular hyperplasia (FNH) and hemangioma are benign and generally asymptomatic hepatic tumors. With distinctive imaging findings on dynamic computed tomography (CT) and magnetic resonance imaging (MRI), differentiation of these benign hepatic tumors from metastases can be made. We described imaging findings of these hepatic lesions in a 57-year-old man who presented with rectal adenocarcinoma for staging.

CASE REPORTS

  • Identification of a novel mutation of MTP gene in a patient with abetalipoproteinemia Mehri Najafi Sani, Mozhgan Sabbaghian, Fatemeh Mahjoob, Angelo B. Cefalù, Maurizio R. Averna, Nima Rezaei Page 221-226

    Abetalipoproteinemia (ABL), or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder of lipoprotein metabolism, characterized by fat malabsorption, hypocholesterolemia retinitis pigmentosa, progressive neuropathy and acanthocytosis from early infancy. We describe the clinical and molecular characterization of a 6-month-old infant born of consanguineous, apparently healthy parents from Iran. The patient was hospitalized because of failure to thrive, greasy stool and vomiting. The patient's serum lipid profile, the clinical phenotype and the duodenal histology suggested the clinical diagnosis of ABL. The MTP gene analysis by direct sequencing revealed a novel homozygous mutation (c.1586 A > G-H529R). The parents were heterozygotes for the same mutation and interestingly the father showed a lipid profile characterized by a slight reduction of total and LDL-cholesterol plasma levels

  • Uncommon localization of amyloidosis in gallbladder: Description of a case and brief literature review Daniela Tirotta, Vittorio Durante Page 227-232

    Amyloidosis is a rare disease that is caused by extracellular deposits of amorphous, insoluble fibrillar protein, which often occur in the kidneys, the heart, the nervous system, the digestive tract, especially the hepatosplenic and intestinal tract, and can be present in bone marrow, though unusual in the gallbladder. The interest of this case lies in the rarity of amyloidosis localisation and in the uncommon clinical presentation as acute cholecystitis. We have reviewed cases of amyloidosis with gallbladder involvement in literature and briefly discussed the predictive value of the main histological diagnostic methods.

  • Chronic HBV with pregnancy: Reactivation flare causing fulminant hepatic failure Ashish Singhal, Rajesh Kanagala, Sajid Jalil, Harlan I. Wright, Vivek Kohli Page 233-236

    Chronic HBV infection is a dynamic state of interaction between HBV, hepatocytes, and the immune system of the host. A series of reactivation flares and remissions may occur due to multiple causes. Among them, spontaneous reactivation and immunosuppressive drugs including steroids or cancer chemotherapy are well known. This is due to immune-mediated destruction of HBV-expressing cells following withdrawal of immunosuppressive effect. Few cases have been reported in females during postpartum period. We report a case of fulminant hepatic failure during pregnancy in a previously unrecognized hepatitis B positive female requiring emergent liver transplantation.

LETTER TO EDITOR

LIVER NEWS ELSEWHERE

  • Changes in insulin sensitivity and body weight during and after peginterferon and ribavirin therapy for hepatitis C Mohammed Eslam, Reyes Aparcero, Manuel Romero Gomez Page 241-243

    Background & aims. Chronic hepatitis C is associated with an increased prevalence of insulin resistance, which might result from liver disease, metabolic factors, or the hepatitis C virus (HCV) itself. The effect of antiviral treatment on insulin sensitivity is not well known. We evaluated changes in insulin resistance and weight in patients with hepatitis C during and after peginterferon and ribavirin therapy. Methods. Virahep-C was a prospective, multi-center study of a 48-week course of combination antiviral therapy in patients infected with HCV genotype 1. Insulin resistance was estimated by the homeostasis model assessment index (HOMA2-IR) based on fasting glucose and insulin levels. Results. Among 341 patients, 40% had insulin resistance (HOMA2-IR > 2.0). The presence of insulin resistance was associated with increasing age, body mass index, (BMI) and fibrosis stage. Among patients with insulin resistance at the start of the trial, median decreases in HOMA2-IR values during treatment were 0.74 at 24 weeks and 0.89 at 48 weeks, whereas BMI decreased by 1.2 and 2.2 kg/m2 at the same timepoints (P < 0.001 for all). At follow-up, HOMA2-IR and BMI levels returned toward baseline values in patients that did not respond or relapsed, but HOMA2IR values remained significantly lower in patients with sustained virological response (SVR) (P < 0.001), despite increases in BMI. Conclusions. In patients with HCV genotype 1 infections, therapy with peginterferon and ribavirin is associated with decreases in body weight and insulin resistance. Among patients with insulin resistance before treatment, resolution of HCV infection results in sustained improvements in the homeostasis model assessment index, so HCV could have a direct role in the pathogenesis of insulin resistance.

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