Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Occupational therapy's role in promoting the“Learn the Signs.Act Early.”developmental monitoring program to public health employees

Background:Occupational therapists can play a key role in early identifica-tion of delay at the population health level by providing education to public health employees on how to implement developmental monitoring with caregivers of children birth to age 5.Methods:A pretest posttest design was utilized to assess the online education and training that was provided to Department of Public Health employees(N=339),including Head Start,Special Supplemental Nutrition Program for Women,Infants and Children,Home Visiting,and Early Intervention.Results:Analysis of pretest‐posttest survey data showed significant results for all 12 key learning outcomes.Six out of 12 outcomes were found to have a large effect size(d>0.8),4 outcomes indicated a medium effect size(d>0.5),and 2 outcomes had a small effect size(d>0.2).Participants gained knowledge of the“Learn the Signs.Act Early.”(LTSAE)developmental monitoring program,the difference between developmental monitoring and screening,the state's referral system and age‐appropriate parental engagement activities through knowledge of child development.Conclusions:Occupational therapists are child development specialists who can provide education on developmental monitoring and activities for parental engagement.The online course proved to be an effective platform to promote LTSAE within state agencies.

Advances in early diagnosis and therapy of pancreatic cancer

BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis. DATA SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articles were from CHKD (China Hospital Knowledge Database) RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy. CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

Effects of early rehabilitation therapy on patients with mechanical ventilation

BACKGROUND: For patients in intensive care unit(ICU), mechanical ventilation is an effective treatment to survive from acute illness and improve survival rates. However, long periods of bed rest and restricted physical activity can result in side effects. This study aimed to investigate the feasibility of early rehabilitation therapy in patients with mechanical ventilation.METHODS: A randomized controlled trial was carried out. Sixty patients, with tracheal intubation or tracheostomy more than 48 hours and less than 72 hours, were admitted to the ICU of the Affiliated Hospital of Medical College, Qingdao University, from May 2010 to May 2012. These patients were randomly divided into a rehabilitation group and a control group. In the rehabilitation group, rehabilitation therapy was performed twice daily, and the training time and intensity were adjusted according to the condition of the patients. Early rehabilitation therapy included heading up actively, transferring from the supine position to sitting position, sitting at the edge of the bed, sitting in chair, transferring from sitting to standing, and ambulating bedside. The patient's body mass index, days to first out of bed, duration of mechanical ventilation, length of ICU stay, APACHE II score, highest FiO2, lowest PaO2/FiO2 and hospital mortality of patients were all compared between the rehabilitation group and the control group. The differences between the two groups were compared using Student's t test.RESULTS: There was no significant difference in body mass index, APACHE II score, highest FiO2, lowest PaO2/FiO2 and hospital mortality between the rehabilitation group and the control group(P>0.05). Patients in the rehabilitation group had shorter days to first out of bed(3.8±1.2 d vs. 7.3±2.8 d; P=0.00), duration of mechanical ventilation(5.6±2.1 d vs. 12.7±4.1 d; P=0.005) and length of ICU stay(12.7±4.1 d vs. 15.2±4.5 d; P=0.01) compared with the control group.CONCLUSION: Early rehabilitation therapy was feasible and effective in improving the outcomes of patients with mechanical ventilation.

Feasible endoscopic therapy for early gastric cancer

AIM: To analyze the relationship between lymph node metastasis and clinical pathology of early gastric cancer(EGC) in order to provide criteria for a feasible endoscopic therapy.METHODS: Clinical data of the 525 EGC patients who underwent surgical operations between January 2009 and March 2014 in the West China Hospital of Sichuan University were analyzed retrospectively. Clinical pathological features were compared between different EGC patients with or without lymph node metastasis, and investigated by univariate and multivariate analyses for possible relationships with lymph node metastasis.RESULTS: Of the 2913 patients who underwent gastrectomy with lymph node dissection, 529 cases were pathologically proven to be EGC and 525 cases were enrolled in this study, excluding 4 cases of gastric stump carcinoma. Among 233 patients with mucosal carcinoma, 43(18.5%) had lymph node metastasis. Among 292 patients with submucosal carcinoma, 118(40.4%) had lymph nodemetastasis. Univariate analysis showed that gender, tumor size, invasion depth, differentiation type and lymphatic involvement correlated with a high risk of lymph node metastasis. Multivariate analysis revealed that gender(OR = 1.649, 95%CI: 1.091-2.492, P = 0.018), tumor size(OR = 1.803, 95%CI: 1.201-2.706, P = 0.004), invasion depth(OR = 2.566, 95%CI: 1.671-3.941, P = 0.000), histological differentiation(OR = 2.621, 95%CI: 1.624-4.230, P = 0.000) and lymphatic involvement(OR = 3.505, 95%CI: 1.590-7.725, P = 0.002) wereindependent risk factors for lymph node metastasis. Comprehensive analysis showed that lymph node metastasis was absent in patients with tumor that was limited to the mucosa, size ≤ 2 cm, differentiated and without lymphatic involvement.CONCLUSION: We propose an endoscopic therapy for EGC that is limited to the mucosa, size ≤ 2 cm, differentiated and without lymphatic involvement.

Endoscopic Mucosal Resection: Therapy for Early Colorectal Cancer

We review the use of Endoscopic Mucosal Resection in the treatment of early colorectal cancer. Newer endoscopic imaging modalities have lead to earlier detection of advanced lesions thus enabling endoscopic curative therapy of lesions that would otherwise need surgery. Early outcomes data suggest promising results. But further long term prospective studies are needed.

Aluminum phosphate gel reduces early rebleeding in cirrhotic patients with gastric variceal bleeding treated with histoacryl injection therapy

BACKGROUND Esophageal-gastro varices bleeding(EGVB)is the most widely known cause of mortality in individuals with cirrhosis,with an occurrence rate of 5%to 15%.Among them,gastric varices bleeding(GVB)is less frequent than esophageal varices bleeding(EVB),but the former is a more critical illness and has a higher mortality rate.At present,endoscopic variceal histoacryl injection therapy(EVHT)is safe and effective,and it has been recommended by relevant guidelines as the primary method for the treatment of GVB.However,gastric varices after endoscopic treatment still have a high rate of early rebleeding,which is mainly related to complications of its treatment,such as bleeding from drained ulcers,rebleeding of varices etc.Therefore,preventing early postoperative rebleeding is very important to improve the quality of patient survival and outcomes.AIM To assess the efficacy of aluminium phosphate gel(APG)combined with proton pump inhibitor(PPI)in preventing early rebleeding after EVHT in individuals with GVB.METHODS Medical history of 196 individuals with GVB was obtained who were diagnosed using endoscopy and treated with EVHT in Shenzhen People's Hospital from January 2016 to December 2021.Based on the selection criteria,101 patients were sorted into the PPI alone treatment group,and 95 patients were sorted into the PPI combined with the APG treatment group.The incidences of early rebleeding and corresponding complications within 6 wk after treatment were compared between both groups.Statistical methods were performed by two-sample t-test,Wilcoxon rank sum test andχ2 test.RESULTS No major variations were noted between the individuals of the two groups in terms of age,gender,Model for End-Stage Liver Disease score,coagulation function,serum albumin,hemoglobin,type of gastric varices,the dose of tissue glue injection and EV that needed to be treated simultaneously.The early rebleeding rate in PPI+APG group was 3.16%(3/95),which was much lower than that in the PPI group(12.87%,13/101)(P=0.013).Causes of early rebleeding:the incidence of gastric ulcer bleeding in the PPI+APG group was 2.11%(2/95),which was reduced in comparison to that in the PPI group(11.88%,12/101)(P=0.008);the incidence of venous bleeding in PPI+APG group and PPI group was 1.05%(1/95)and 0.99%(1/101),respectively,and there was no significant difference between them(0.999).The early mortality rate was 0 in both groups within 6 wk after the operation,and the low mortality rate was related to the timely hospitalization and active treatment of all patients with rebleeding.The overall incidence of complications in the PPI+APG group was 12.63%(12/95),which was not significantly different from 13.86%(14/101)in the PPI group(P=0.800).of abdominal pain in the PPI+APG group was 3.16%(3/95),which was lower than that in the PPI group(11.88%,12/101)(P=0.022).However,due to aluminum phosphate gel usage,the incidence of constipation in the PPI+APG group was 9.47%(9/95),which was higher than that in the PPI group(1.98%,2/101)(P=0.023),but the health of the patients could be improved by increasing drinking water or oral lactulose.No patients in either group developed spontaneous peritonitis after taking PPI,and none developed hepatic encephalopathy and ectopic embolism within 6 wk of EVHT treatment.CONCLUSION PPI combined with APG can significantly reduce the incidence of early rebleeding and postoperative abdominal pain in cirrhotic patients with GVB after taking EVHT.

Early rehabilitation and neuroprotective drug therapy outcomes in elderly patients with acute stroke

Sixty elderly patients, viro cluffered from acute stroke and were admitted within a 1-year period to the Department of Geriatrics in the First Affiliated Hospital of School of Medicine, Zhejiang University, China, underwent early rehabilitation in combination with neuroprotective drug therapy. Limb movement, cognitive functions and daily life self-care ability in elderly patients upon admission and discharge were assessed using the Hunt-Hess scale, functional independence measures and mini-mental state examination. The mean duration of hospital stay among the 60 patients was 35 days. Upon discharge, 42 （75%） of the patients exhibited cognitive impairment to varying degrees, and 25 （45%） of the 56 stroke patients who underwent rehabilitation evaluation attained independence in daily living activities, 11 （20%） required intermittent supervision, and 20 （36%） required 24-hour constant supervision during performance of these activities. Results demonstrated that early rehabilitation treatment in combination with neuroprotective therapy for acute stroke was effective.

Youngest case of an early gastric cancer after successful eradication therapy

A 28-year-old woman visited our clinic with a chief complaint of epigastralgia. She had received successful Helicobacter pylori (H. pylori ) eradication therapy 5 years before. We repeated esophagogastroduodenoscopy, and a discolored depressed area with reddish spots and converging folds, 20 mm in size, was detected. No atrophic change including intestinal metaplasia or nodular gastritis was seen endoscopically. Two endoscopic biopsies revealed undifferentiated adenocarcinoma. No H. pylori was found, and the 13 C-urea breath test was also negative. Abdominal computed tomography demonstrated no nodal involvement, distant metastasis or fluid collection. She underwent a laparoscopyassisted distal gastrectomy. Histologically, the resected specimen revealed an early undifferentiated gastric cancer that had invaded deeply into the submucosal layer. Nodal involvement was histologically confirmed.No atrophic change or H. pylori infection was evident histologically. This is the youngest patient ever reported to have developed a node-positive early gastric cancer after eradication of H. pylori .

Use of Early Goal-Directed Therapy in the Emergency Department before and after the Sepsis Trilogy

The management of sepsis evolved recently with the publication of three large trials (referred to as the sepsis trilogy) investigating the efficacy of early goal-directed therapy (EGDT). Our goal was to determine if the publication of these trials has influenced the use of EGDT when caring for patients with severe sepsis and septic shock in the emergency department (ED). In February 2014, we surveyed a sample of board-certified emergency medicine physicians regarding their use of EGDT in the ED. A follow-up survey was sent after the publication of the sepsis trilogy. Data was analyzed using 95% confidence intervals to determine if there was a change in the use of EGDT following the publication of the above trials. Subgroup analyses were also performed with regard to academic affiliation and emergency department volume. Surveys were sent to 308 and 350 physicians in the pre-and post-publication periods, respectively. Overall, ED use of EGDT did not change with publication of the sepsis trilogy, 48.7% (CI 39.3% - 58.2%) before and 50.5% (CI 40.6% - 60.3%) after. Subgroup analysis revealed that academic-affiliated EDs significantly decreased EGDT use following the sepsis trilogy while nonacademic departments significantly increased EGDT use. Use of EGDT was significantly greater in community departments versus academic departments following the publication of the sepsis trilogy. There was no change overall in the use of EGDT protocols when caring for patients with severe sepsis and septic shock, but subgroup analyses revealed that academic departments decreased their use of EGDT while community departments increased use of EGDT. This may be due to varying rates of uptake of the medical literature between academic and community healthcare systems.

Effect of tea polyphenols combined with photodynamic therapy on the efficacy and RANKL and Shh levels in patients with early peri-implantitis

Objective: To analyze the effect of tea polyphenols combined with photodynamic therapy on the efficacy and RANKL and Shh levels in patients with early peri-implantitis. Methods:Eighty patients with early peri-implantitis admitted to our hospital from January 2017 to December 2018 were randomly divided into the observation group and the control group;the control group was treated with photodynamic therapy, and the observation group was treated with tea polyphenols combined with photodynamic therapy. The levels of mPLI, PPD, mSBI and BOP were measured before treatment and 3 months after the treatment, and the levels of CRP, TNF-α, IL-6, RANKL and Shh in the gingival crevicular fluid were measured. Results:The levels of mPLI, PPD, mSBI and BOP in the observation group were significantly lower than those in the control group, and the difference was statistically significant (P<0.05). The levels of CRP, TNF-α, IL-6, RANKL and Shh in the gingival crevicular fluid were observed in the observation group. The differences were significantly lower than the control group, and the difference was statistically significant (P<0.05). Conclusions: The combination of tea polyphenols and photodynamic therapy for patients with early peri-implantitis can significantly improve clinical efficacy and reduce the inflammatory response, and can effectively improve the levels of RANKL and Shh in gingival crevicular fluid.

Progress in the Early Mobilization of Patients after Cardiac Intervention

Early activity has a positive effect on the rehabilitation process of patients after cardiac intervention. This paper summarizes the concept and significance of early activity after cardiac intervention, the best time and mode of different types of early activity after cardiac intervention, and the factors affecting early activity, aiming to provide a basis for clinical medical staff to provide safe and effective guidance of early activity after cardiac intervention.

Postoperative serum tumor markers-based nomogram predicting early recurrence for patients undergoing radical resections of pancreatic ductal adenocarcinoma

BACKGROUND Early recurrence(ER)is associated with dismal outcomes in patients undergoing radical resection for pancreatic ductal adenocarcinoma(PDAC).Approaches for predicting ER will help clinicians in implementing individualized adjuvant therapies.Postoperative serum tumor markers(STMs)are indicators of tumor progression and may improve current systems for predicting ER.AIM To establish an improved nomogram based on postoperative STMs to predict ER in PDAC.METHODS We retrospectively enrolled 282 patients who underwent radical resection for PDAC at our institute between 2019 and 2021.Univariate and multivariate Cox regression analyses of variables with or without postoperative STMs,were performed to identify independent risk factors for ER.A nomogram was constructed based on the independent postoperative STMs.Receiver operating characteristic curve analysis was used to evaluate the area under the curve(AUC)of the nomogram.Survival analysis was performed using Kaplan-Meier survival plot and log-rank test.RESULTS Postoperative carbohydrate antigen 19-9 and carcinoembryonic antigen levels,preoperative carbohydrate antigen 125 levels,perineural invasion,and pTNM stage III were independent risk factors for ER in PDAC.The postoperative STMs-based nomogram(AUC:0.774,95%CI:0.713-0.835)had superior accuracy in predicting ER compared with the nomogram without postoperative STMs(AUC:0.688,95%CI:0.625-0.750)(P=0.016).Patients with a recurrence nomogram score(RNS)>1.56 were at high risk for ER,and had significantly poorer recurrence-free survival[median:3.08 months,interquartile range(IQR):1.80-8.15]than those with RNS≤1.56(14.00 months,IQR:6.67-24.80),P<0.001).CONCLUSION The postoperative STMs-based nomogram improves the predictive accuracy of ER in PDAC,stratifies the risk of ER,and identifies patients at high risk of ER for tailored adjuvant therapies.

CBASP Adapted to Child Play Therapy Structure to Prevent Early-Onset Persistent Depressive Disorder

The current paper is a theoretical proposal that interfaces the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and its emphasis on interpersonal consequences with the structured order of a Play Therapy Model for troubled 3 - 8-year-old children. This proposal is not a research paper or a review of literature;instead, it is a treatment proposal that is novel and untested. CBASP psychotherapy, an empirically validated treatment, was developed originally to treat the persistently depressed adult. CBASP’s major focus of interpersonal consequation will be interfaced with a Play Therapy structured model to rectify the maladaptive preoperational functioning of five interpersonal types of problem-children. The types are classified interpersonally using D.J. Kiesler’s Interpersonal Message Inventory (IMI). Kiesler’s IMI is employed in this proposal as an ongoing assessment modality, a source of information to make treatment strategy consequation decisions, and thirdly as an evaluative outcome variable. The troubled child types described herein frequently become candidates for early-onset Persistent Depressive Disorder (PDD) unless rescued by successful treatment. The origins of early-onset PDD arise in dysfunctional households where toxic interpersonal relationships predominate: where “survival from abuse,” not growth, describes the child’s modal developmental experiences. These children are often exposed to either serious traumas (e.g., sexual abuse, loss of a parent, physical abuse, physical or emotional neglect) or psychological insults (e.g., continuous, and chronic verbal and nonverbal abuse). The result, in the most serious cases, is a maturational stunting at the preoperational stage of development which, as noted above, if not successfully resolved, thrusts the child into early-onset PDD.

Therapeutic potential of stem cells in subarachnoid hemorrhage

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

游泳联合早期抚触在新生儿神经系统发育迟缓护理中的应用

目的探讨游泳联合早期抚触在新生儿神经系统发育迟缓护理中的应用效果。方法选取2020年3月至2022年6月郑州市妇幼保健院秦岭院区收治的108例神经系统发育迟缓新生儿,以随机数字表法分成干预组(n=54)与对照组(n=54),干预组采用游泳联合早期抚触护理,对照组采用常规新生儿护理,两组均干预3个月,比较两组干预前、干预后神经行为情况、生长发育情况、智力发育情况。结果两组干预后新生儿神经行为测定(NBNA)评分均提高,且干预组评分高于对照组,差异有统计学意义(P<0.05);两组干预后头围、身长、体重均升高,且干预组高于对照组,差异有统计学意义(P<0.05);干预后两组智力发展指数(MDI)评分均提高,且干预组高于对照组,差异有统计学意义(P<0.05)。结论游泳联合早期抚触干预应用于神经系统发育迟缓新生儿中能够改善新生儿神经行为,促进其生长发育和智能发育。

A new breakthrough:ESD using a newly developed grasping type scissor forceps for early gastrointestinal tract neoplasms

Endoscopic submucosal dissection(ESD) has allowed the achievement of histologically curative en bloc resection of gastrointestinal neoplasms regardless of size,permitting the resection of previously non-resectable tumors.The ESD technique for treatment of early gastric cancer has spread rapidly in Japan and a few other Asian countries due to its excellent eradication rate compared to endoscopic mucosal resection.Although numerous electrosurgical knives have been developed for ESD,technical difficulties and high complication rates(bleeding and perforation) have limited their use worldwide.We developed the grasping type scissor forceps(GSF) to resolve such ESD-related problems.Our animal and preliminary clinical studies showed that ESD using GSF is a safe(no intraoperative complication) and technically efficient(curative en bloc resection rate 92%) method for dissection of early gastrointestinal tumors.The use of GSF is a promising option for performing ESD on early stage GI tract tumors both safely and effectively.

Expanded endoscopic therapy criteria should be cautiously used in intramucosal gastric cancer

Objective： Accurate estimation of lymph node metastasis （LNM） in intramucosal gastric cancer is essential to select less invasive treatment options and even avoid surgery. The aim of this study was to evaluate combined clinicopathological features to predict the presence of LNM. Methods： A retrospective review of data from 386 intramucosaL gastric cancer patients who underwent gastrectomy with extended lymphadenectomy from 2003 to 2010 was conducted. The mutual relation between clinicopathological characteristics and LNM was analyzed. Results： LNM was detected in 40 （10.4%） of the 386 patients. Histological typeand vascular or lymphatic invasion presence showed a positive correlation with LNM occurrence by univariate analysis. Multivariate analysis revealed that histological type was the only factor associated with LNM. Combined clinicopathologic characteristics would be more predictable for LNM. We found no LNM when we used combined clinicopathological characteristics conforming to Japanese absolute indications for endoscopic therapy. The LNM rate was as high as 8.7% when Japanese expanded criteria were used. Univariate analysis in cancer conformity to expand endoscopic submucosal dissection （ESD） indication also revealed that the undifferential type was the only significant factor for LNM. Conclusions： It was possible to predict intramucosal gastric cancer cases without LNM using combined clinicopathological characteristic analysis. Extended indication for ESD should be cautiously used for intramucosal gastric cancer patients.

Treatment of early gastric cancer in the Western World

The incidence rate of gastric cancer is much higher in Asia than in the Western industrial nations.According to the different screening programs in Japan and Korea about fifty percent of treated patients had an early tumor stage.In contrast,European and American patients with gastric cancer had an advanced tumor stage.Therefore,the experience for the various therapeutic options for gastric cancer may be different between these regions.In this review we tried to point out the treatment modalities in Western industrial countries for early gastric cancer.

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.