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In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment.3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020. Clinical history and sustained viral response (SVR) were obtained from medical records and data linkage to the Australian Pharmaceutical Benefits Scheme. Factors associated with SVR were assessed by multivariable logistic regression (MVR).At recruitment, 32.2% had cirrhosis (72.9% Child Pugh class B/C), and 19.9% were treatment experienced. Of the 2,939 with data, 93.3% confirmed SVR. 137 patients received second-line therapy. Patients with cirrhosis had lower SVR rate (88.4 vs. 95.8%; p 0.001). On MVR, failure to achieve SVR was associated with Genotype 3 (adj-OR = 0.42, 95%CI 0.29-0.61), male gender (adj-OR = 0.49, 95%CI 0.31-0.77), fair/poor adherence (adj-OR = 0.52, 95%CI 0.28-0.94), cirrhosis (adj-OR = 0.57, 95%CI 0.36-0.88), FIB-4 3.25 (adj-OR = 0.52, 95%CI 0.33-0.83) and MELD score ≥ 20 (adj-OR = 0.25, 95%CI 0.08-0.80). Consistent results were seen in cirrhotic sub-analysis.Excellent SVR rates were achieved with DAAs in this real-world cohort of patients with chronic HCV infection. More advanced liver disease and clinician impression of poor adherence were associated with HCV treatment failure. Supports to improve liver fibrosis assessment skills for non-specialist DAA prescribers in the community and to optimize patient adherence are likely to enable more effective pursuit of HCV elimination in Australia.

Background and Aim Surveillance and early detection and curative treatment of hepatocellular carcinoma (HCC) are the mainstay of improving survival for patients, but there are several barriers to achieving this goal. We reported the impact of remoteness of residence on receipt of treatment, tumor stage, and survival in patients with HCC in Queensland. Methods We conducted a retrospective cohort study of 1651 HCC patients (147 migrants) from 1 January 2007 to 31 December 2016. We used Wilcoxon rank‐sum test to compare the median age at the time of diagnosis and Bayesian Weibull accelerated failure time regression to identify independent predictors of time to death. Results The median survival time after HCC diagnosis was 9.0 months (interquartile range 2.0–24.0). Metropolitan residence (P = 0.02), non‐English language (P, In a cohort study of 1651 patients with hepatocellular carcinoma, we found patients living in rural and remote areas were more likely to present with late stage of tumor, less likely to receive curative treatment such as surgical resection, and experience 25% shorter survival time. In a multivariate analysis, remote residence, preferred language, older age at presentation, poorly differentiated tumor, and presence of medical comorbidity were associated with poorer HCC survival, possibly because of limited access to surveillance and curative treatment.

Background and aim End-stage liver disease is a leading cause of mortality. Fewer than 60% of patients with decompensated cirrhosis survive after two years, with patients often experiencing distressing symptoms impairing quality of life. Early advanced care planning and timely palliative care referral can improve quality of life and the end of life experience. We aimed to determine palliative care referral rates and patterns for patients admitted with decompensated cirrhosis, and to identify the factors associated with referral. Methods This was a retrospective, single-centre study undertaken at a metropolitan tertiary referral hospital. Patients admitted between the 1st June 2016 to 31st January 2019 with a Child-Pugh score of B or C, and a Model for End-Stage Liver Disease score ≥15 were included. We assessed survival and compared those referred and not referred to palliative care, adjusting for lag-time to referral (Kaplan-Meier analysis). Results One-hundred-and-sixteen admissions met eligibility criteria for referral. The median age at admission was 59 years, with 76% male. Only a fifth of eligible patients (25/116) were referred to palliative care. The median survival (from referral) for those referred to palliative care was 20 days, versus 148 days for those not referred. Conclusions Despite benefits from timely referral, less than one-quarter of palliative care eligible patients were referred. Referral appears reserved for those facing imminent death - surviving just under three weeks post-referral, yet mortality in non-referred patients remained high (148-day median). Low rates and late referral are a missed opportunity to improve the end of life care for patients with end-stage liver disease.

Background First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection. Methods Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016–2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU. Results Compared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p p = 0.002) and in regional/remote areas (p p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p = 0.51) and ‘good’ adherence (90.0% vs. 86.9%, respectively; p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p Conclusions Our data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.

Background and Aim Health‐related quality‐of‐life measurements are important to understand lived experiences of patients who have cirrhosis. These measures also inform economic evaluations by modelling quality‐adjusted life years (QALYs). We aimed to describe health‐related quality of life, specifically multiattribute utility (scale anchors of death = 0.00 and full health = 1.00), across various stages and etiologies of cirrhosis. Methods Face‐to‐face interviews were used to collect Short Form 36 (SF‐36) questionnaire responses from CirCare study participants with cirrhosis (June 2017 to December 2018). The severity of cirrhosis was assessed using the Child‐Pugh score classified as class A (5–6 points), B (7–9), or C (10–15) and by the absence (“compensated”) versus presence (“decompensated”) of cirrhosis‐related complications. Results Patients (n = 562, average 59.8 years [SD = 11.0], male 69.9%) had a range of primary etiologies (alcohol‐related 35.2%, chronic hepatitis C 25.4%, non‐alcoholic fatty liver disease (NAFLD) 25.1%, chronic hepatitis B 5.9%, “other” 8.4%). Significantly lower (all P, Measuring health‐related quality of life is important for understanding patients' experiences living with cirrhosis. Multiattribute utility is a summary measure commonly derived from health‐related quality‐of‐life questionnaires by applying population‐based preference weights with anchors of death (0.00) and perfect health (1.00) and is used in health state modelling, including economic evaluations that incorporate quality‐adjusted life years (known as QALYs). Here, we report health‐related quality‐of‐life and multiattribute utility values for a range of cirrhosis disease stages. These values will inform both clinical and economic research, including cost‐effectiveness modelling that captures benefits to both the quantity and quality of people's lives through the better prevention and management of cirrhosis.

Summary Background Liver-related mortality varies across developed nations. Aim To assess the relative role of various risk factors in relation to liver-related mortality in an ecological study approach. Methods Data for liver-related mortality, prevalence data for hepatitis B and C, human immunodeficiency virus (HIV), alcohol consumption per capita, Type 2 Diabetes mellitus (T2DM), overweight and obesity were extracted from peer-reviewed publications or WHO databases for different developed countries. As potential other risk-modifying factors, purchase power parity (PPP)-adjusted gross domestic product (GDP) per capita and health expenditure per capita were assessed. As an environmental ‘hygiene factor’, we also assessed the effect of the prevalence of Helicobacter pylori. Only countries with a PPP-adjusted GDP greater than $20 000 and valid information for at least 8 risk modifiers were included. Univariate and multivariate analyses were utilised to quantify the contribution to the variability in liver-related mortality. Results The proportion of chronic liver diseases (CLD)-related mortality ranged from 0.73–2.40% [mean 1.56%, 95% CI (1.43–1.69)] of all deaths. Univariately, CLD-related mortality was significantly associated with Hepatitis B prevalence, alcohol consumption, PPP-adjusted GDP (all P < 0.05) and potentially H. pylori prevalence (P = 0.055). Other investigated factors, including hepatitis C, did not yield significance. Backward elimination suggested hepatitis B, alcohol consumption and PPP-adjusted GDP as risk factors (explaining 66.3% of the variability). Conclusion Hepatitis B infection, alcohol consumption and GDP, but not hepatitis C or other factors, explain most of the variance of liver-related mortality.

Determining risk for recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) is an important clinical need. We assessed consecutive patients who underwent LT for HCC following sequential transarterial chemoembolization (TACE). Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) categories: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Cox proportional hazard models were used to predict HCC recurrence. One hundred seventy-three patients underwent TACE and imaging to assess response prior to LT. TACE responses were: CR = 23.7%, PR = 24.3%, SD = 27.7% and PD = 24.3%. Five-year HCC recurrence rate was 5.3% in patients responding to TACE (CR/PR), versus 17.6%, among patients who did not respond (SD/PD, p = 0.014). In multivariate analysis, independent pre-LT predictors of recurrence were response to TACE and largest radiologic size of tumor (>3 cm vs. ≤3 cm). HCC recurrence rate for patients with tumor size >3 cm and no response to TACE was 35.8%, compared with 1.9% for patients with tumor size ≤3 cm and response to TACE (p = 0.0007). We conclude that mRECIST criteria and tumor size differentiate patients with high or low likelihood of HCC recurrence after LT. These findings raise the possibility of incorporating response to TACE and largest tumor size to identify patients at highest risk for HCC recurrence.

The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients. Materials and Methods: Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems, steatosis was dichotomized as &lt, 5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in 151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs. CT/TT: 86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs. CT/TT: 44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients (CC vs. CT/TT: 72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3-F4 (CC vs. CT/TT: 74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23–8.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.

Low-density lipoprotein cholesterol (LDL-C) levels and interleukin 28B (IL28B) polymorphism are associated with sustained viral response (SVR) to peginterferon/ribavirin (pegIFN/RBV) for chronic hepatitis C (CHC) infection. IL28B has been linked with LDL-C levels using a candidate gene approach, but it is not known whether other genetic variants are associated with LDL-C, nor how these factors definitively affect SVR. We assessed genetic predictors of serum lipid and triglyceride levels in 1604 patients with genotype 1 (G1) chronic hepatitis C virus (HCV) infection by genome-wide association study and developed multivariable predictive models of SVR. IL28B polymorphisms were the only common genetic variants associated with pretreatment LDL-C level in Caucasians (rs12980275, P = 4.7 × 10−17, poor response IL28B variants associated with lower LDL-C). The association was dependent on HCV infection, IL28B genotype was no longer associated with LDL-C in SVR patients after treatment, while the association remained significant in non-SVR patients (P < 0.001). LDL-C was significantly associated with SVR for heterozygous IL28B genotype patients (P < 0.001) but not for homozygous genotypes. SVR modelling suggested that IL28B heterozygotes with LDL-C > 130 mg/dL and HCV RNA ≤600 000 IU/mL may anticipate cure rates >80%, while the absence of these two criteria was associated with an SVR rate of

In 2009, an association between the interleukin-28B (IL28B) polymorphism and treatment outcome for genotype 1 (G1) hepatitis C virus (HCV) infection, as well as spontaneous clearance of HCV, was reported. Since the initial publications, over 100 articles have appeared in the peer-reviewed literature, with many more manuscripts in press and abstracts presented at scientific meetings. Despite the proliferation of data concerning the IL28B polymorphism and HCV infection, there remain many critical unanswered questions about clinical implications and the underlying biological mechanisms. In this review, we discuss the basic principles of genome-wide association study methodologies that are important for interpreting the results of genetic association studies. We then review the current literature concerning the association between IL28B variants and interferon (IFN) treatment response in patients with chronic HCV infection, as well as spontaneous HCV clearance. We consider the relevance of the IL28B polymorphism to non-G1 HCV, as well as the special treatment populations of HIV/HCV co-infection and recurrent HCV post-liver transplantation. We review current knowledge of the biological mechanisms underlying this genetic association, including the link to liver IFN-stimulated gene expression, and identify continuing gaps in our knowledge and key research priorities. Finally, pegylated-IFN and ribavirin is no longer the standard of care for the treatment of G1 HCV, and we conclude by considering the relevance of IL28B polymorphisms in the era of direct-acting antivirals.

Cytokeratin-18 (CK-18) is a major intermediate filament protein in liver cells. The M30 fragment of CK-18 has been identified as a useful marker of apoptosis associated with fibrosis and steatosis in nonalcoholic steatohepatitis (NASH). We sought to assess the relationship of this marker and steatosis in a cohort of adult patients with chronic hepatitis C. The study cohort included sera from 267 treatment-naive chronic hepatitis C (CHC) patients and 100 healthy controls with normal alanine aminotransferase (ALT). Biopsies from CHC patients were assessed for METAVIR fibrosis stage, Histology Activity Index (HAI) inflammation score and steatosis grade by expert histopathologists. The M30 fragment of CK-18 was quantified by ELISA. Wilcoxon Rank Sum, Spearman Correlation and Linear Regression tests were performed for statistical analysis. Median CK-18 levels were higher in CHC patients compared to controls (411 vs 196 U/L, P < 0.0001). Fibrosis stage was associated with increasing serum CK-18 levels (P = 0.015) and CK-18 levels were higher for F2-F4 vs F0-F1 (500 vs 344 U/L; P = 0.001). There was no association between CK-18 and increasing steatosis grade 1, 2 or 3 (460.7 vs 416.8 vs 508.3 U/L; P = 0.35) and presence or absence of steatosis (445.3 vs 365.8 U/L; P = 0.075). Fibrosis stage was independently associated with serum M30 in a multivariable linear regression model (P = 0.03). CK-18 levels were higher in CHC compared to healthy controls and associated with hepatic fibrosis. There was no difference in CK-18 M30 levels between CHC patients with and without steatosis. Although apoptosis may still contribute to hepatitis C virus (HCV)-mediated steatosis, our results suggest that serum CK-18 will not be a clinically useful test for identifying significant steatosis in CHC.

Background and Aim: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients.

Purpose of review: To improve understanding of recent developments in the noninvasive assessment of fibrosis and their potential clinical application to a range of chronic liver diseases. Recent findings: Many noninvasive tests have evolved from their primary validation in chronic hepatitis C virus (HCV) infection to integration into clinical management algorithms for chronic liver disease of varying cause. Recent studies consider the use of these techniques in sequence or in combination, and compare the performance of serum and imaging-based noninvasive techniques to identify patients with significant fibrosis, or those at most risk of clinical sequelae from advanced-stage disease. Methods developed in chronic hepatitis C have now been applied in different chronic liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, HIV/HCV co-infection and primary biliary cirrhosis. A number of new management algorithms have been developed to facilitate the integration of noninvasive techniques into clinical practice. Summary: Noninvasive tools to assess liver diseases continue to evolve. New imaging technologies have been developed. Existing biomarkers and imaging modalities have been better integrated into clinical practice algorithms, and applied to different chronic liver diseases. Noninvasive techniques will likely continue to be refined and play an important role in the future management of patients with chronic liver disease.

Anaemia frequently complicates peginterferon/ribavirin therapy for chronic hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase (ITPA) genetic variants are associated with ribavirin-induced anaemia and dose reduction; however, their impact in real-life clinic patient cohorts remains to be defined. We studied 193 clinic patients with chronic hepatitis C infection of mixed viral genotype (genotype 1/4 n = 123, genotype 2/3, n = 70) treated with peginterferon/ribavirin. Patients were genotyped for ITPA polymorphisms rs1127354 and rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present. Estimated ITPA deficiency was graded on severity (0-3, no deficiency/mild/moderate/severe, n = 126/40/24/3, respectively). Multivariable models tested the association with anaemia at 4 weeks of treatment [including decline in haemoglobin (g/dL); haemoglobin10 g/dL and haemoglobin decline3 g/dL]; ribavirin dose reduction and EPO use and explored sustained viral response (SVR) to peginterferon/ribavirin. More severe ITPA deficiency was associated with less reduction in haemoglobin level (P0.001; R(2) = 0.34), less ribavirin dose reduction (OR 0.42; (95% CI = 0.23-0.77); P = 0.005) and less EPO use [OR 0.53; (0.30-0.94); P = 0.029]. ITPA deficiency was associated with SVR [OR: 1.70; (1.02-2.83); P = 0.041] independently of clinical covariates (adjusted R(2) = 0.31). In this clinical cohort, ITPA deficiency helped predict the risk of on-treatment anaemia, ribavirin dose reduction, need for EPO support and was associated with SVR. For patients on HCV regimens including peginterferon/ribavirin, testing for ITPA deficiency may have clinical utility.

Single-nucleotide polymorphisms (SNPs) in the IL28B and PNPLA3 gene regions have been associated with hepatic steatosis in genotype 1 (G1) chronic HCV infection but their clinical impacts remain to be determined.We sought to validate these associations and to explore their impact on treatment response to peginterferon and ribavirin therapy.A total of 972 G1 HCV-infected Caucasian patients were genotyped for the SNPs rs12979860 (IL28B) and rs2896019 (PNPLA3). Multivariable analysis tested IL28B and PNPLA3 for association with the presence of any steatosis (0 %); clinically significant steatosis (5 %); steatosis severity (grade 0-3/4); and the interacting associations of the SNPs and hepatic steatosis to sustained viral response (SVR).IL28B and PNPLA3 polymorphisms were associated with the presence of any steatosis (rs12979860, p = 1.87 × 10(-7); rs2896019, p = 7.56 × 10(-4)); clinically significant steatosis (rs12979860, p = 1.82 × 10(-3); rs2896019, p = 1.27 × 10(-4)); and steatosis severity (rs12979860, p = 2.05 × 10(-8); rs2896019, p = 2.62 × 10(-6)). Obesity, hypertriglyceridemia, hyperglycemia, liver fibrosis, and liver inflammation were all independently associated with worse steatosis. Hepatic steatosis was associated with lower SVR, and this effect was attenuated by IL28B. PNPLA3 had no independent association with SVR.IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis. IL28B attenuates the association between steatosis and SVR. Remediable metabolic risk factors remain important, independently of these polymorphisms, and remain key therapeutic goals to achieve better outcomes for patients with HCV-associated hepatic steatosis.

Background & Aims IL28B polymorphisms have been associated with both treatment induced and spontaneous clearance of hepatitis C virus (HCV). We previously found that LDL cholesterol levels were higher in chronic hepatitis C (CHC) patients with the CC genotype at the rs12979860 polymorphism, located proximal to the IL28 gene. Here we analyzed the association of steatosis with IL28B genotype in treatment naive patients with CHC. Methods Two independent cohorts of 145 genotype 1 infected patients from an antifibrotic study and 180 genotype 1 patients from Duke were analyzed for the presence and severity of steatosis in relation to the rs12979860 polymorphism at the IL28B locus. TaqMan assay based genotyping classified three groups CC, CT, and TT. Results CC genotype was associated with a lower prevalence of steatosis. In the antifibrotic study, steatosis was found in 47.6% (50/105) of IL28B non-CC vs . 22.5% (9/40; p =0.008) in CC patients. Similarly, steatosis was found in 67.4% (89/132) of non-CC patients compared to only 39.6% (19/48; p =0.001) of CC patients in the Duke cohort. Conclusions IL28B CC genotype is associated with less pronounced disturbances of lipid metabolism, as reflected both in serum lipoprotein levels and hepatic steatosis, in HCV infection.

Genome-wide association studies (GWAS) have recently identified host genetic variation to be critical for predicting treatment response and spontaneous clearance in patients infected with hepatitis C virus (HCV). These important new studies are reviewed and their future clinical implications discussed. Single-nucleotide polymorphisms in the region of the IL28B gene on chromosome 19, coding for the interferon (IFN)-λ-3 or IL28B gene, are strongly associated with treatment response to pegylated IFN and ribavirin in patients infected with genotype 1 HCV. The good response variant is associated with a twofold increase in the rate of cure. Allele frequencies differ between ethnic groups, largely explaining the observed differences in response rates between Caucasians, African Americans and Asians. IL28B polymorphism is also strongly associated with spontaneous clearance of HCV. The biological mechanisms responsible for these genetic associations remain unknown and are the focus of ongoing research. Knowledge of a patient's IL28B genotype is likely to aid in clinical decision making with standard of care regimens. Future studies will investigate the possibility of individualizing treatment duration and novel regimens according to IL28B type.

Note: Letter / Comment on: Hepatology. 2010 Aug;52(2):421-9 Reference EPFL-ARTICLE-165071doi:10.1002/hep.23826 Record created on 2011-04-15, modified on 2016-08-09

Two functional variants in the inosine triphosphatase (ITPA) gene causing inosine triphosphatase (ITPase) deficiency protect against ribavirin (RBV)-induced hemolytic anemia and the need for RBV dose reduction in patients with genotype 1 hepatitis C virus (HCV). No data are available for genotype 2/3 HCV. We evaluated the association between the casual ITPA variants and on-treatment anemia in a well-characterized cohort of genotype 2/3 patients treated with variable-duration pegylated interferon alfa-2b (PEG-IFN-α2b) and RBV. Two hundred thirty-eight Caucasian patients were included in this retrospective study [185 (78%) with genotype 2 and 53 (22%) with genotype 3]. Patients were treated with PEG-IFN-α2b plus weight-based RBV (1000/1200 mg) for 12 (n = 109) or 24 weeks (n = 129). The ITPA polymorphisms rs1127354 and rs7270101 were genotyped, and an ITPase deficiency variable was defined that combined both ITPA variants according to their effect on ITPase activity. The primary endpoint was hemoglobin (Hb) reduction in week 4. We also considered Hb reduction over the course of therapy, the need for RBV dose modification, and the rate of sustained virological response (SVR). The ITPA variants were strongly and independently associated with protection from week 4 anemia (P = 10-6 for rs1127354 and P = 10-7 for rs7270101). Combining the variants into the ITPase deficiency variable increased the strength of association (P = 10-11). ITPase deficiency protected against anemia throughout treatment. ITPase deficiency was associated with a delayed time to an Hb level < 10 g/dL (hazard ratio = 0.25, 95% confidence interval = 0.08-0.84, P = 0.025) but not with the rate of RBV dose modification (required per protocol at Hb < 9.5 g/dL). There was no association between the ITPA variants and SVR. Conclusion: Two ITPA variants were strongly associated with protection against treatment-related anemia in patients with genotype 2/3 HCV, but they did not decrease the need for RBV dose reduction or increase the rate of SVR.

20 G2) were included. SVR was defined as undetectable HCVRNA at 24 weeks of follow up. The SNP analysis of rs12979860 variant was determined in 50ng of DNA by RT-PCR using specific oligonucleotide primers and probes to amplify the sequence target in DNA (Tib MoLBIOL GmbH, Berlin Germany). All HCV patients were genotyped as CC, CT or TT. Results: CT and TT variants were present in 45 and 18 subjects (56% and 23%, respectively) of the studied population. CC polymorphism had the lowest frequency in our cohort (21%, CI 95%: 12.89–31.83%) and it was strongly associated with response to standard treatment (OR 2.95); 76% of CC carriers achieved SVR compared with 55.5% and 44.4% of SVR in patients with CT and TT variants.