[68Ga]/[90Y]FAPI-46: Automated production and analytical validation of a theranostic pair.

INTRODUCTION: With respect to the broad application of FAPI-46 in therapy and diagnostics, there is a need for an efficient as well as convenient way for routine production and quality control of the theranostic pair [90Y]Y/[68Ga]Ga-FAPI-46, since no monograph is currently available for radiolabelled FAPI derivatives. The aim of the current work is to create a GMP compliant theranostic set up for the production and quality control of the diagnostic [68Ga]Ga-FAPI-46 as well as the therapeutic drug [90 Y]Y-FAPI-46, which can be the basis for future monographic standards. METHODS: Sterile [90Y]yttrium chloride solution and a pharmaceutical grade 68Ge/68Ga generator were applied for the labelling of FAPI-46 using the cassette based synthesis module Trasis EASYONE. All chemicals were GMP-grade and excipients were with marketing authorisation. The quality control included test procedures according to Ph. Eur. RESULTS: Fully automated synthesis of the theranostic pair [90Y]Y/[68Ga]Ga-FAPI-46 was achieved on the Trasis EasyOne synthesizer with a radiochemical yield of 88 ± 7% and 56 ± 5% with a radiochemical purity of >99%. Stability experiments showed a durability for [68Ga]Ga-FAPI-46 within 4 h and for [90Y]Y-FAPI-46 within 24 h. All obtained specifications and validations were compliant with the European Pharmacopoeia and regulatory guidelines. Both products were successfully applied in cancer patients. CONCLUSION: In the present work, efficient and robust procedures for the automated production and quality control of the theranostic pair [68Ga]/[90Y]FAPI 46 were developed and validated using the same synthetic platform. The described methods were evaluated in accordance with existing guidelines and toxicological limits, which can be a valuable basis for future monographic standards.

Combined treatment of refractory ascites with an alfapump® plus hernia repair in the same surgical session: A retrospective, multicentre, European pilot study in cirrhotic patients.

INTRODUCTION: The treatment of symptomatic hernia in cirrhotic patients with refractory ascites is critical but challenging. The objective of this study was to assess the feasibility and safety of the implantation of alfapump® combined with concomitant hernia repair in cirrhotic patients with refractory ascites. METHODS: Using data from six European centres, we retrospectively compared patients treated with alfapump® system implantation and concomitant hernia repair [the combined treatment group (CT group, n=12)] or with intermittent paracentesis hernia repair [the standard treatment group (ST group, n=26)]. Some patients of the ST group had hernia repair in an elective setting (STel group) and others in emergency (STem group). The endpoints were requirement of peritoneal drainage, the rate of infectious complications, the in-hospital mortality, the length of stay, paracentesis-free survival. RESULTS: Postoperatively, none of the patients in the CT group and 21 patients (80%) in the ST group underwent peritoneal drainage for the evacuation of ascites fluid (P<0.0001). The overall incidence of infectious complications was not different between groups but there were fewer infections in the CT group than in the STem group (33% vs. 81%; P=0.01). There was no difference for in-hospital mortality. The length of stay was shorter in the CT group (P=0.03). Paracentesis-free survival was significantly better (P=0.0003) in the CT group than in the ST group. CONCLUSION: Implantation of alfapump combined with concomitant hernia repair seems feasible and safe in cirrhotic patients; however, larger and randomized study are required.

Highly variable upper and abyssal overturning cells in the South Atlantic.

The Meridional Overturning Circulation (MOC) is a primary mechanism driving oceanic heat redistribution on Earth, thereby affecting Earth's climate and weather. However, the full-depth structure and variability of the MOC are still poorly understood, particularly in the South Atlantic. This study presents unique multiyear records of the oceanic volume transport of both the upper (<~3100 meters) and abyssal (>~3100 meters) overturning cells based on daily moored measurements in the South Atlantic at 34.5°S. The vertical structure of the time-mean flows is consistent with the limited historical observations. Both the upper and abyssal cells exhibit a high degree of variability relative to the temporal means at time scales, ranging from a few days to a few weeks. Observed variations in the abyssal flow appear to be largely independent of the flow in the overlying upper cell. No meaningful trends are detected in either cell.

Non-invasive evaluation of portal hypertension using shear-wave elastography: analysis of two algorithms combining liver and spleen stiffness in 191 patients with cirrhosis.

BACKGROUND: Two algorithms based on sequential measurements of liver and spleen stiffness using two-dimensional shearwave elastography (2D-SWE) have been recently proposed to estimate clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] ≥10 mm Hg) in patients with cirrhosis, with excellent diagnostic accuracy. AIM: To validate externally these algorithms in a large cohort of patients with cirrhosis. METHODS: One hundred and ninety-one patients with stable cirrhosis (Child-Pugh class A 39%, B 29% and C 31%) who underwent liver and spleen stiffness measurements using 2D-SWE at the time of HVPG measurement were included. Diagnostic accuracy of the 2 algorithms was assessed by calculating sensitivity, specificity, positive and negative predictive values. RESULTS: The first algorithm, using liver stiffness <16.0 kilopascals (kPa) and then spleen stiffness <26.6 kPa, was used to rule-out HVPG ≥10 mm Hg. In our population, its sensitivity and negative predictive value were 95% and 63% respectively. The second algorithm, using liver stiffness >38.0 kPa, or liver stiffness ≤38.0 kPa but spleen stiffness >27.9 kPa, was used to rule-in HVPG ≥10 mm Hg. In our population, its specificity and positive predictive value were 52% and 83% respectively. Restricting the analyses to the 74 patients without any history of decompensation of cirrhosis or to the 65 patients with highly reliable liver stiffness measurement did not improve the results. CONCLUSION: In our population, diagnostic accuracies of non-invasive algorithms based on sequential measurements of liver and spleen stiffness using 2D-SWE were acceptable, but not good enough to replace HVPG measurement or to base clinical decisions.

Cholangiopathy in critically ill patients surviving beyond the intensive care period: a multicentre survey in liver units.

BACKGROUND: The outcome of cholangiopathy developing in intensive care unit (ICU) is not known in patients surviving their ICU stay. AIM: To perform a survey in liver units, in order to clarify the course of cholangiopathy after surviving ICU stay. METHODS: The files of the liver units affiliated to the French network for vascular liver disease were screened for cases of ICU cholangiopathy developing in patients with normal liver function tests on ICU admission, and no prior history of liver disease. RESULTS: Between 2005 and 2015, 16 cases were retrieved. Extensive burns were the cause for admission to ICU in 11 patients. Serum alkaline phosphatase levels increased from day 11 (2-46) to a peak of 15 (4-32) × ULN on day 81 (12-511). Magnetic resonance cholangiography showed irregularities or frank stenosis of the intrahepatic ducts, and proximal extrahepatic ducts contrasting with a normal aspect of the distal common bile duct. Follow-up duration was 20.6 (4.7-71.8) months. Three patients were lost to follow-up; 2 patients died from liver failure and no patient was transplanted. One patient had worsening strictures of the intrahepatic bile ducts with jaundice. Nine patients had persistent but minor strictures of the intrahepatic bile ducts on MR cholangiography, and persistent cholestasis without jaundice. One patient had normal liver function tests. CONCLUSIONS: In patients surviving their ICU stay, ICU cholangiopathy is not uniformly fatal in the short term or clinically symptomatic in the medium term. Preservation of the distal common bile duct appears to be a finding differentiating ICU cholangiopathy from other diffuse cholangiopathies.

1.15 PW-850 J compressed beam demonstration using the PETAL facility.

The Petawatt Aquitaine Laser (PETAL) facility was designed and constructed by the French Commissariat à l'énergie atomique et aux énergies alternatives (CEA) as an additional PW beamline to the Laser MegaJoule (LMJ) facility. PETAL energy is limited to 1 kJ at the beginning due to the damage threshold of the final optics. In this paper, we present the commissioning of the PW PETAL beamline. The first kJ shots in the amplifier section with a large spectrum front end, the alignment of the synthetic aperture compression stage and the initial demonstration of the 1.15 PW @ 850 J operations in the compression stage are detailed. Issues encountered relating to damage to optics are also addressed.

Review article: the aetiology of primary Budd-Chiari syndrome - differences between the West and China.

BACKGROUND: China may have the largest number of Budd-Chiari syndrome (BCS) cases in the world (at least 1914 original papers were published, and at least 20 191 BCS patients were reported). Considering the discrepancy in the clinical profiles and preferred treatment selection of primary BCS between the West and China, understanding its aetiology in these two different regions is very important. AIM: To review the data from large cohort studies and meta-analyses to illustrate the epidemiology of risk factors for BCS in the West and China. METHODS: Relevant papers were identified by major English- and Chinese-language databases, conference abstracts, and by manual search. RESULTS: Risk factors reviewed include myeloproliferative neoplasms (MPNs) and their related gene mutations, anti-phospholipid syndrome, paroxysmal nocturnal haemoglobinuria (PNH), hyperhomocysteinaemia and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation, factor V Leiden (FVL) and prothrombin G20210A mutations, inherited anti-thrombin, protein C and protein S deficiencies, pregnancy and puerperium, poverty, and family history. CONCLUSIONS: We examined the differences in the aetiological distribution of BCS between the West and China. Several recommendations should be considered in Chinese BCS patients: (i) screening for hyperhomocysteinaemia and MTHFR mutation should be regularly performed; (ii) screening for MPNs, PNH, and anti-phospholipid syndrome should be selectively performed; (iii) inherited anti-thrombin, protein C, and protein S deficiencies should be actively explored; (iv) screening for FVL and prothrombin G20210A mutations may be unnecessary; and (v) the clinical significance of pregnancy and puerperium, poverty with bacterial infections and unsanitary environments, and family history as possible risk factors should never be neglected.

Lack of clinical or haemodynamic rebound after abrupt interruption of beta-blockers in patients with cirrhosis.

BACKGROUND: Beta-blockers may have to be interrupted in patients with cirrhosis. The concept of a rebound after interruption of beta-blockers is based on an animal study and on isolated case reports of variceal bleeding. AIM: To determine if a rebound occurs in patients with cirrhosis following abrupt interruption of beta-blockers. METHODS: We prospectively included all consecutive patients with cirrhosis undergoing right heart and hepatic vein catheterisation. Four groups were defined: 'no beta-blockers' including patients not receiving beta-blockers; '≤1 day', '2-3 days' and '≥4 days' classified according to the time patients had interrupted beta-blockers before catheterisation. Results were expressed as median (interquartile range). RESULTS: A total of 150 patients were included. Among the 25 patients in the groups '2-3 days' and '≥4 days', median duration of beta-blockers interruption was 4 (3-6) days. No gastrointestinal bleeding occurred during that period, nor during the following month. Hepatic venous pressure gradient was not different among patients in usually treated with beta-blockers. After adjustment, beta-blockers interruption was not associated with hepatic venous pressure gradient. Cardiac index was higher in the '≥4 days' group [4.6 L/min/m(2) (3.5-5.1)] than in the '≤1 day' group [3.4 (2.6-4.0); P = 0.001] or in the '2-3 days' group [3.1 (2.7-3.7); P = 0.007], but not different from the 'no beta-blockers' group. CONCLUSIONS: Abrupt interruption of beta-blockers is associated neither with an apparent increase in the risk of variceal bleeding nor with a haemodynamic rebound. Thus, interruption of beta-blockers in patients with cirrhosis may not require particular dosing or surveillance.

Faecal carriage of extended-spectrum ß-lactamase (ESBL)-producing enterobacteria in liver disease patients from two hospitals in Egypt and France: a comparative epidemiological study.

This study aimed to assess and compare the epidemiology of faecal carriage of extended spectrum ß-lactamase-producing enterobacteria (ESBL-E) in Hepatology departments of two hospitals specializing in liver diseases, Theodor Bilharz Research Institute (TBRI) in Cairo (Egypt) and Beaujon Hospital (Bj) in Clichy (France). CTX-M groups were identified by PCR, and TEM and SHV derivatives with the check-point system. Phylogenetic groups of E. coli were determined by multiplex PCR, and clone ST131 by PCR of gene pabB. Prevalence of ESBL-E was 77·6% (45/58) in TBRI and 6·5% (13/199) in Bj (P < 10-7). Previous hospitalization was more common (P = 0·003) in Bj patients (93%) than in TBRI patients (45%) suggesting high prevalence of ESBL-E in the Egyptian community. The presence of E. coli B2 ST131 among ESBL-E faecal E. coli in Egypt confirms its pervasiveness in the community and raises concern regarding this highly virulent and resistant clone.

Congenital portosystemic shunts associated with liver tumours.

AIM: To evaluate the diagnosis and presentation of liver tumours in patients with congenital portosystemic shunts (CPS). MATERIALS AND METHODS: Eight patients were diagnosed in Hôpital Beaujon as having CPS. All patients underwent Doppler ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and histological examination of liver tumours. CPS were classified according to anatomy and the amount of portal flow deviated to the systemic circulation as: total, subtotal, or partial. Liver tumours were diagnosed by needle core biopsy (n = 5) or surgery (n = 3). Clinical follow-up was available in all patients but one (mean follow-up 36 months; range 1-5 years). RESULTS: Six patients had total CPS, one patient had a subtotal CPS, and the last had a partial CPS. All patients presented with multiple liver nodules (range four to >15). The tumours were characterized as focal nodular hyperplasia (FNH; n = 4), FNH with hepatocellular adenoma (n = 2), and regenerative nodular hyperplasia (n = 2). In four of seven patients (57%) that had follow-up, tumours showed enlargement or new lesions appeared. CONCLUSION: In this series of CPS patients, tumours were all benign, multiple, and of hepatocellular origin, and different tumours were present simultaneously in two patients. Tumour enlargement or new nodules were common during follow-up.

Pregnancy in women with portal vein thrombosis: results of a multicentric European study on maternal and fetal management and outcome.

BACKGROUND & AIMS: Women of childbearing age account for approximately 25% of patients with non-cirrhotic portal vein thrombosis (PVT). We aimed at assessing maternal and fetal outcome in pregnant women with known PVT. METHODS: We performed a retrospective analysis of the files of women with chronic PVT in three European referral centers between 1986 and 2010. RESULTS: Forty-five pregnancies, 28 (62%) treated with low molecular weight heparin, occurred in 24 women. Nine (20%) were lost before gestation week 20. Preterm birth occurred in 38% of deliveries: there were 3 births at week 24-25, 7 at week 32-36, and 26 after week 37. A term birth with a healthy infant occurred in 58% of pregnancies. Cesarean section was used in 53% of deliveries. Two women developed HELLP syndrome. A favorable outcome happened in 64% of pregnancies. Pregnancies with an unfavorable outcome were associated with a higher platelet count at diagnosis. Bleeding from esophageal varices occurred in 3 patients during pregnancy, all without adequate primary prophylaxis. Genital or parietal bleeding occurred postpartum in 4 patients, only one being on anticoagulation therapy. Thrombotic events occurred in 2 patients, none related to lower limbs or mesenteric veins. There were no maternal deaths. CONCLUSIONS: In pregnant PVT patients treated with anticoagulation on an individual basis, the rate of miscarriage and preterm birth appears to be increased. However, fetal and maternal outcomes are favorable for most pregnancies reaching gestation week 20. High platelet counts appear to increase the risk for unfavorable outcome. Pregnancy should not be contraindicated in stable PVT patients.

The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference*.

Worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600,000 and 350,000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, which in turn ranks as the third cause of cancer death worldwide. Within the WHO European region, approximately 14 million people are chronically infected with HBV, and nine million people are chronically infected with HCV. Lack of reliable epidemiological data on HBV and HCV is one of the biggest hurdles to advancing policy. Risk groups such as migrants and injecting drug users (IDU) tend to be under-represented in existing prevalence studies; thus, targeted surveillance is urgently needed to correctly estimate the burden of HBV and HCV. The most effective means of prevention against HBV is vaccination, and most European Union (EU) countries have universal vaccination programmes. For both HBV and HCV, screening of individuals who present a high risk of contracting the virus is critical given the asymptomatic, and thereby silent, nature of disease. Screening of migrants and IDUs has been shown to be effective and potentially cost-effective. There have been significant advances in the treatment of HCV and HBV in recent years, but health care professionals remain poorly aware of treatment options. Greater professional training is needed on the management of hepatitis including the treatment of liver cancer to encourage adherence to guidelines and offer patients the best possible outcomes. Viral hepatitis knows no borders. EU Member States, guided by the EU, need to work in a concerted manner to implement lasting, effective policies and programmes and make tackling viral hepatitis a public health priority.

Hypercoagulability in cirrhosis: causes and consequences.

Decreased levels of most coagulation factors and thrombocytopenia are the main haemostatic abnormalities of cirrhosis. As a consequence, this condition was, until recently, considered as the prototype acquired coagulopathy responsible for bleeding. However, recent evidence suggests that it should, rather, be regarded as a condition associated with normal or even increased thrombin generation. The bleeding events that occur in these patients should, therefore, be explained by the superimposed conditions that frequently occur in this setting. Due to elevated levels of factor VIII (procoagulant driver) in combination with decreased protein C (anticoagulant driver), which are typically found in patients with cirrhosis, a procoagulant imbalance, defined as a partial resistance to the in vitro anticoagulant action of thrombomodulin, can be demonstrated. Whether this in vitro hypercoagulability is truly representative of what occurs in vivo remains to be established. However, the hypothesis that it may have clinical consequences is attractive and deserves attention. The possible consequences that we discuss herein include whether (i) cirrhosis is a condition associated with increased risk of venous thromboembolism or portal vein thrombosis; (ii) the hypercoagulability associated with cirrhosis has any other role outside coagulation (i.e. progression of liver fibrosis); and (iii) anticoagulation should be used in cirrhosis. Although apparently provocative, considering anticoagulation as a therapeutic option in patients with cirrhosis is now supported by a rationale of increasing strength. There may be subgroups of patients who benefit from anticoagulation to treat or prevent thrombosis and to slow hepatic fibrosis. Clinical studies are warranted to explore these therapeutic options.

Molecular epidemiology of Escherichia coli bacteremia in liver transplant recipients.

The characteristics of Escherichia coli strains causing bacteremia in profoundly immunosuppressed patients such as transplant recipients are undefined. The phylogenetic group and the virulence genotype of 57 distinct E. coli strains that caused bacteremia in 53 liver transplant recipients were investigated, and the association of these characteristics with host factors and in-hospital mortality was examined. Phylogenetic groups A, B1, B2, and D accounted for 39%, 10%, 25%, and 26% of the isolates, respectively. The most prevalent virulence genes were fyuA (yersiniabactin system: 70%) and iutA (aerobactin system: 63%), whereas hlyA (alpha-hemolysin) and cnf1 (cytotoxic necrotizing factor 1) occurred in only 14% and 12% of isolates, respectively. Most virulence genes were significantly more prevalent among group B2 and D isolates, vs. group A and B1 isolates. The overall rate of in-hospital mortality after E. coli bacteremia was 20%. Predictors of mortality included onset of bacteremia within 30 days of transplantation or during the intensive care unit stay, and non-urinary source and cutaneous source, but not E. coli phylogenetic group or virulence profile. Compared with historical E. coli bloodstream isolates from non-transplant patients, those from liver transplant recipients are characterized by a higher prevalence of groups A and B1 isolates and reduced virulence gene content. This finding can be explained by the severely immunocompromised status of the patients and the predominance of abdominal-source bacteremic episodes. Time of onset and source of bacteremia, not bacterial characteristics, predict mortality.

Sequential therapy with adefovir dipivoxil and pegylated interferon alfa-2a for HBeAg-negative patients.

To assess the impact of sequential therapy with adefovir dipivoxil (ADV) and pegylated interferon alfa-2a (PEG-IFN) on virological (serum HBV-DNA) and serological (serum HBsAg) response in 20 consecutive HBeAg-negative patients. Patients received ADV for 20 weeks, then ADV and PEG-IFN for 4 weeks and lastly PEG-IFN for 44 weeks. Serum HBV-DNA and HBsAg were assessed at baseline, during therapy (weeks 20, 44 and 68) and follow-up (weeks 92 and 116). Sustained virological response (SVR) was defined as serum HBV-DNA <10 000 copies/mL (partial) or <70 copies/mL (complete) 24 weeks after stopping treatment. A serological response was defined as a serum HBsAg decrease ≥1 log(10) IU/mL at the end of treatment. Baseline median serum HBV-DNA and HBsAg levels were 7.6 log(10) copies/mL and 3.8 log(10) IU/mL, respectively. Ten patients (50%) achieved SVR, six of them had partial response and four complete response. Four patients (20%) achieved serological response. Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5, 1.6 and 2.0 log(10) IU/mL at treatment week 20, 44 and 68, respectively. Partial SVRs showed a slight and slow decline in serum HBsAg level (0.1, 0.4, and 0.6 log IU/mL at weeks 20, 44 and 68, respectively). On-treatment serum HBsAg decrease had a high accuracy to predict SVR (AUROC = 0.88). Our results suggest that sequential therapy might be an interesting strategy for HBeAg-negative patients. Serum HBsAg kinetics seem to be an accurate tool to predict SVR. Large clinical trials are needed to explore this strategy with more potent analogues.

Insulin resistance and geographical origin: major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) genotype 4 (HCV-4) is increasing in prevalence in Western countries. However, little is known about the severity of the disease and response to treatment. The aim of this study was to assess the predictors (logistic regression) of severe fibrosis (METAVIR score F3-F4), and sustained virological response (SVR) to peginterferon and ribavirin in 226 consecutive HCV-4 patients (Egyptians 40%, Europeans 35% and Africans 24%). PATIENTS AND METHODS: Insulin resistance was assessed using the homeostasis model (HOMA-IR). Serum HCV-RNA level (bDNA) and subtypes of HCV (LiPA) were determined for all patients. RESULTS: Insulin resistance (HOMA-IR >3) was present in 105 patients (46%), and was associated with: age >45 years (OR, 2.614; 95% CI, 1.316 to 5.194), body mass index (BMI) >25 kg/m(2) (OR, 2.105; 95% CI, 1.048 to 4.229), serum HCV-RNA >800 000 IU/ml (OR, 3.143; 95% CI, 1.503 to 6.574), severe fibrosis (OR, 2.657; 95% CI, 1.214 to 5.818), and steatosis >30% (OR, 2.488; 95% CI, 1.105 to 5.602). Severe fibrosis was present in 67 patients (29%) and was associated with Egyptian origin (OR, 5.872; 95% CI, 2.747 to 12.553), excessive alcohol intake (OR, 5.311; 95% CI, 1.287 to 21.924), and HOMA-IR >3 (OR, 3.864; 95% CI, 1.859 to 8.034). 108 patients received a 48 week course of peginterferon plus ribavirin. SVR (undetectable serum HCV-RNA (TMA) 24 weeks after treatment stopping) was achieved in 59 patients (55%) and was associated with Egyptian origin (OR, 13.119; 95% CI, 3.089 to 55.706), HOMA-IR <2 (OR, 5.314; 95% CI, 1.953 to 14.459), and non-severe fibrosis (OR, 8.059; 95% CI, 2.512 to 25.855). CONCLUSION: Insulin resistance and geographical origin are major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4 patients. Insulin resistance is frequently encountered in these patients, and correlated independently with serum HCV-RNA.

Gene expression and hepatitis C virus infection.

Hepatitis C virus (HCV) is a major cause of chronic liver disease, with about 170 million people infected worldwide. Up to 70% of patients will have persistent infection after inoculation, making this disease a significant cause of morbidity and mortality. The severity of disease varies widely, from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Since the discovery of HCV, the treatment of hepatitis C has considerably improved. Recently, combination of pegylated interferons with ribavirin gives a response rate of about 55%. Treatment is indicated in patients with moderate or severe fibrosis. The tolerability of combination treatment is relatively poor, with a frequent flu-like syndrome and an impaired quality of life. In addition to viral and environmental behavioural factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes in HCV infection. The sequencing of the human genome, together with the development of high-throughput technologies that measure the function of the genome, have afforded unique opportunities to develop profiles that can distinguish, identify and classify discrete subsets of disease, predict the disease outcome or predict the response to treatment. This paper reviews the published literature on gene expression associated with HCV infection (HCV infection, fibrosis progression), and also according to response to treatment.