Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted ...Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.展开更多
Context: The appointment of the M6 is crucial because it is an indicator of the prognosis of the evolution of the care and the decision-making on the continuation of the AntiRetroViral Treatment. Objective: The object...Context: The appointment of the M6 is crucial because it is an indicator of the prognosis of the evolution of the care and the decision-making on the continuation of the AntiRetroViral Treatment. Objective: The objective of this study is therefore to present the virological and molecular profile of People Living with HIV under treatment with Dolutegravir 6 months after being put on ART in Kinshasa. Methods: The present study is a cross-sectional view at the sixth month of a prospective cohort to determine the virological and molecular profile of People Living with HIV (PLHIV) after 6 months of ART based on Dolutegravir (DTG) in Kinshasa. A sample of 5 mL of blood was taken from all HIV patients included. The collection of biological data was carried out under the same conditions as at inclusion. After extraction, Quantitative Real-Time PCR was carried out to determine the quantity of HIV RNA in the samples according to the protocols previously described. Reverse Transcription PCR (RT-PCR) and Nested PCR were carried out to amplify the regions of interest for Protease and Reverse Transcriptase for sequencing. Results: The median VL value was 2.92 log<sub>10</sub> RNA copies/mL. With 17.75% of patients experiencing major failure of first-line treatment. Subtype A is dominant with 13 cases (20.98%);followed by CRF_02AG (16.13%), subtypes C (14.52%), D (9.68%) and K (6.45%). The K65R (3 cases), T69P/N (6 cases), K70R (9 cases) and M184V (8 cases) mutations were listed as existing mutations for Nucleotide Reverse Transcriptase Inhibitors. Conclusion: After 6 months of ART, 59.67% of People Living with HIV on Tenofovir-Lamivudine-Dolutegravir is in therapeutic success while 40.33% are in a state of treatment failure. Subtype A remains dominant in the population of PLHIV. Resistance mutations were detected for Lamivudine and Tenofovir, but none for Dolutegravir.展开更多
Context: Despite the new recommendations “Test and Treat”, the virological and molecular parameters remain important information for Antiretroviral Treatment and adequate for monitoring of patients infected with HIV...Context: Despite the new recommendations “Test and Treat”, the virological and molecular parameters remain important information for Antiretroviral Treatment and adequate for monitoring of patients infected with HIV/AIDS. Objective: the Objective of this study is to present the virological and molecular profile of People Living with HIV starting Antiretroviral Therapy in Kinshasa in the era of the Dolutegravir. Methods: This was a transversal study to determine virological and molecular profile of People Living with HIV (PLHIV) starting an ARV Treatment. The patient’s inclusion period was from October 04, 2021 to February 15, 2022. A sample of 5 ml of blood was taken in a tube with EDTA anticoagulant for Molecular Biology analyzes (Viral Load and Sequencing) in all HIV patients, after reading and signing informed consent. The population was made up of adult patients over the age of 18, infected with HIV and starting ART. Results: 119 patients (56.3% of women) were included in this study, thus a sex-ratio of 1.29. The average age of patients included was 39.87 ± 12.36 years. The most represented age group is that of 36 to 45 with 37 patients (31.9%) followed by that from 26 to 35 years with 24 patients (20.7%). Out of 119 patients, 21 patients had an undetectable Viral Load (VL). The median value of VL was 4.16 log10 RNA copies/ml. 114 samples were successfully amplified. Subtype A was dominant with 23 cases (20.2%);followed by the subtype C and CRF02_AG each with 14.0%, and D (10.5 %). K65R (1.8%), T69P/N (4.4%), K70R (7.9%) and M184V (7.0%) mutations were listed as existing mutations for Nucleotide Transcriptase Inhibitors. Conclusion: 38 patients (31.93%) started the TARV with a positive virological prognosis. The subtype A remains dominant in Kinshasa with 23 cases (20.2%);followed by the subtype C and CRF02_AG each with 14.0%. For Inhibitors of Transcriptase Reverse Nucleotide;K65R, T69P/N, K70E/R and M184V mutations were found in patients’ naive of ARV Treatment.展开更多
AIM:To document the sustained virological response (SVR) in rapid virological responders (RVR) of genotype-3 chronic hepatitis C with standard interferon (SdIF). METHODS:Hepatitis C genotype-3 patients during the peri...AIM:To document the sustained virological response (SVR) in rapid virological responders (RVR) of genotype-3 chronic hepatitis C with standard interferon (SdIF). METHODS:Hepatitis C genotype-3 patients during the period July 2006 and June 2007 were included. Complete blood counts, prothrombin time, ALT, albumin, qualitative HCV RNA were done. SdIF and ribavirin were given for 4 wk and qualitative HCV RNA was repeated. Those testing negative were allocated to group-A while the rest were allocated to group-B. Treatment was continued a total of 16 and 24 wk for group A and B respectively. HCV RNA was repeated after 24 wk of treatment. End virological and sustained virological responses were compared by χ2 test. ROC of pretreatment age, ALT and albumin were plotted for failure to achieve SVR. RESULTS:Of 74 patients treated, RCV RNA after 16 wk of therapy became undetectable in 34 (45.9%) and was detectable in 40 (54.1%) and were allocated to groups A and B respectively. SVR was achieved in 58.8% and 27.8% in groups A and B respectively. SVR rates were significantly higher in patients who had RVR as compared to those who did not (P = 0.0;γ = 2). Both groups combined ETR and SVR were 70% and 33% respectively. ROC plots of pretreatment age, ALT and albumin for SVR showed only ALT to have a significantly large area under the curve.CONCLUSION:SVR rates were higher in patients who had RVR with SdIF and high pre treatment ALT values correlated to probability of having RVR.展开更多
AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had ...AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION: Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.展开更多
BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved...BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure.展开更多
BACKGROUND Characteristics of alterations of serum hepatitis B virus(HBV) RNA in different chronic hepatitis B(CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still c...BACKGROUND Characteristics of alterations of serum hepatitis B virus(HBV) RNA in different chronic hepatitis B(CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.AIM To investigate whether HBV RNA can predict virological response or HBeAg seroconversion during entecavir(ETV) treatment when HBV DNA is undetectable.METHODS The present study evaluated 61 individuals who were diagnosed and treated with long-term ETV monotherapy at the Department of Infectious Diseases of Peking University First Hospital(China) from September 2006 to December 2007.Finally, 30 treatment-naive individuals were included. Serum HBV RNA were extracted from 140 μL serum samples at two time points. Then they were reverse transcribed to cDNA with the HBV-specific primer. The product was quantified by real-time quantitative PCR(RT-PCR) using TAMARA probes. Statistical analyses were performed with IBM SPSS 20.0.RESULTS Level of serum HBV RNA at baseline was 4.15 ± 0.90 log10 copies/mL. HBV RNA levels showed no significant difference between the virological response(VR)and partial VR(PVR) groups at baseline(P = 0.940). Serum HBV RNA significantly decreased among patients who achieved a VR during ETV therapy(P < 0.001). The levels of HBV RNA in both HBeAg-positive patients with seroconversion group and those with no seroconversion increased after 24 wk of treatment. Overall, HBV RNA significantly but mildly correlated to HBsAg(r =0.265, P = 0.041), and HBV RNA was not correlated to HBV DNA(r = 0.242, P =0.062). Furthermore, serum HBV RNA was an independent indicator for predicting HBeAg seroconversion and virological response. HBeAg seroconversion was more likely in CHB patients with HBV RNA levels below4.12 log10 copies/mL before treatment.CONLUSION The level of serum HBV RNA could predict HBeAg seroconversion and PVR during treatment. In the PVR group, the level of serum HBV RNA tends to be increasing.展开更多
AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation param...AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.展开更多
AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divid...AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls(HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral Ld T daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array(CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97(123.26-492.79) pg/m L vs 184.50(135.56-292.16) pg/m L, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with Ld T [175.51(103.90-331.91) pg/m L vs 184.50(135.56-292.16) pg/m L, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB(r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to Ld T treatment at 24 wk(48.15% vs 15.79%, P = 0.023) and 52 wk(66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary nonresponse at week 12 after treatment initiation were lower than those in patients with primary response [64.44(49.85-172.08) pg/m L vs 190.54(121.35-355.28) pg/m L, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with Ld T. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to Ld T treatment.展开更多
AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred ...AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico Ⅱ". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that viruseradication following interferon treatment can last up to 20 years.展开更多
AIM: To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm 3 and without antiretroviral therapy; to describe different HBV-...AIM: To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm 3 and without antiretroviral therapy; to describe different HBV-HIV coinfection virological profiles; and to search for factors associated with HBs antigen (HBsAg) presence in these HIV positive patients.METHODS: During four months (June through September 2006), 491 patients were received in four HIV positive monitoring clinical centers in Abidjan. Inclusion criteria: HIV-1 or HIV-1 and 2 positive patients, age ≥ 18 years, CD4+ T-cell count < 500/mL and formal and signed consent of the patient. Realized blood tests included HIV serology, CD4+ T-cell count, quantitative HIV RNA load and HBV serological markers, such as HBsAg and HBc antibody (anti-HBcAb). We performed HBeAg, anti-HBe antibody (anti-HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients. Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb-positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg negative status and without anti-HBsAb. Univariate analysis (Pearsonχ 2 test or Fischer exact test) and multivariate analysis (backward step-wise selection logistic regression) were performed as statistical analysis. RESULTS: Mean age of 491 patients was 36 ± 8.68 years and 73.3% were female. Type-1 HIV was found in 97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO) clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172 (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm 3 (interquartile range: 221-470). One hundred and twelve patients had less than 200 CD4+ T-cell/mm 3 . Plasma HIV-1 RNA load was elevated (≥ 5 log 10 copies/mL) in 221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and 72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%), 21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and detectable HBV DNA) was 21.3%. Three parameters were significantly associated with the presence of HBsAg: male [odds ratio (OR): 2.2;P = 0.005; 95% confidence interval (CI): 1.3-3.8]; WHO stage 4 (OR: 3.2;P = 0.01;95% CI: 1.3-7.9); and aspartate aminotransferase (AST) level higher than the standard (OR: 1.9;P = 0.04; 95% CI: 1.02-3.8). CONCLUSION: HBV infection prevalence is high in HIV-positive patients. HBeAg positive chronic hepatitis and occult HBV infection are more frequent in HIVpositive patients than in HIV negative ones. Parameters associated with HBsAg positivity were male gender, AIDS status and increased AST level.展开更多
BACKGROUND： The definition of partial virological response （PVR） was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Wheth...BACKGROUND： The definition of partial virological response （PVR） was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Whether this rationale can be applied to all nucleotide analogues （NA） is not clear. This study was undertaken to analyze PVR influence on therapeutic outcomes during lamivudine, entecavir or tenofovir mono- therapy in NA-naive patients with chronic hepatitis B in routine clinical practice. METHODS： We retrospectively analyzed 150 NA-naive patients with chronic hepatitis B. These subjects received lamivudine, entecavir or tenofovir monotherapy between February 2001 and July2013. RESULTS： Sixty-nine patients were treated with lamivudine, 35 with entecavir, and 46 with tenofovir. The median therapeutic duration was 19.5 （6-147） months. PVR rates at 24 weeks were similar among three NAs （lamivudine 33.3%, entecavir 35.0%, tenofovir 32.4%, P--0.981）. For all three NAs, patients with a higher baseline viral load or HBeAg-positive status had a higher serum viral positive rate tested by polymerase chain reaction at week 24 and 48. Cumulative probability of virological breakthrough （VBR） for patients treated with lamivudine was 67% at 5 years, and PVR at 24 weeks was the independent risk factor for VBR （HR： 3.09; 95% CI： 1.09-8.74; P=0.034）; also lamivudine treated patients older than 50 years seemed to have a tendency for VBR （HR： 2.80; 95% CI： 0.99-8.18; P=0.052）. A majority of entecavir and tenofovir partial responders achieved and maintained virological response with prolonged monotherapy, except one entecavir treated patient who experienced VBR due to resistance mutations.CONCLUSIONS： Management strategy for lamivudine treatment should include adaptation of regimen according to PVR as an on-treatment response parameter due to its relation with unacceptably high VBR probability. Similar conclusion should not be directly related to entecavir or tenofovir treatment.展开更多
AIM： To determine which baseline factors of chronic hepatitis B patients are predictive of virological response to Peginterferon α-2b therapy. METHODS： A total of 21 HBeAg-positive chronic hepatitis B （CriB） pati...AIM： To determine which baseline factors of chronic hepatitis B patients are predictive of virological response to Peginterferon α-2b therapy. METHODS： A total of 21 HBeAg-positive chronic hepatitis B （CriB） patients treated with Peginterferon α-2b were recruited. They were treated with Peginterferon α-2b （0.5-1.0 μg/kg per week） for 24 wk and followed up for 24 wk. Clinical and laboratory data of the patients were determined at pretreatment and at week 12, at 24 during treatment, and at week 48 during follow up. RESULTS： Ten patients achieved a virological response at the end of treatment. Their baseline serum alanine aminotransferase （ALT）, thyroid-stimulating hormone （TSH）, and total thyroxin （TT4） levels were significantly different from those who failed treatment. The positive predictive values （PPV） and negative predictive values （NPV） of ALT, TSH, and TT4 were 75% and 89 %, 75% and 89 %, and 75% and 75%, respectively. Moreover, combinations of the baseline ALT and TT4, ALT and TSH, TT4 and TSH levels had much higher PPV and NPV （86% and 88%, 89% and 100%, 83% and 100%, respectively）.CONCLUSION： Baseline serum ALT, TSH, and TT4 levels, especially in combination, have high predictive values of virological response to Peginterferon α-2b in HBeAg-positive CriB patients.展开更多
AIM: Predictive value of serum b2-microglobulin (b2m)levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM).METHODS...AIM: Predictive value of serum b2-microglobulin (b2m)levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM).METHODS: Serum b2m levels were calculated during treatment in 25 CHB patients under long-term LAM monotherapy (group A) and 12 patients under initial interferon plus LAM treatment followed by LAM monotherapy (group B), using the MEIA technology. We used Cox proportional hazard models in order to investigate the association between serum b2m levels and VB.RESULTS: Seven of 25 patients (28%), 9/25 (36%) and 14/25 (56%) from group A and 0/12, 2/12 (16.6%) and 3/12 (25%) from group B exhibited VB at months 12, 24 and 36 of treatment, respectively. All patients, from both groups, who did not show VB exhibited b2m elevation in mo 3. The duration of b2m elevation was significantly longer in the virological responder's subgroup from group A than the non-responder's one (7.3±2.6 vs 3.8±3.4 mo,P = 0.02). In comparison to group A patients whose b2m levels were increased at 3 mo, patients whose b2m levels were decreased had 4.6 times higher risk of experiencing VB (RR = 4.6, P = 0.024). When baseline variables were simultaneously included in the same Cox model, decreased b2m status was still associated with increased risk of VB (RR = 12.2, P = 0.03).CONCLUSION: In HBeAg-negative CHB patients under either long-term LAM monotherapy or initial combination treatment, serum b2m levels at 3 mo of treatment,compared to baseline ones, might be a predictor of risk for VB.展开更多
AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination the...AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.展开更多
AIM:To investigate the virological relapse rate in hepatitis B e antigen(HBeAg)-negative patients after antiviral therapy discontinuation and analyze the factors associated with virological relapse.METHODS:Among patie...AIM:To investigate the virological relapse rate in hepatitis B e antigen(HBeAg)-negative patients after antiviral therapy discontinuation and analyze the factors associated with virological relapse.METHODS:Among patients diagnosed with chronic hepatitis B infection between May 2005 and July2010,204 were eligible for analysis.The Kaplan-Meier method and log-rank test were used to calculate the cumulative rate of relapse and compare cumulative relapse rates between groups.The Cox proportional hazards regression model was used to evaluate the predictive factor of virological relapse.RESULTS:The 2 and 1 year cumulative risks of virological relapse after antiviral therapy discontinuation were 79.41%(162/204) and 43.82%(71/162),respectively.Multivariate analysis revealed that only post treatment hepatitis B surface antigen(HBsAg)level was associated with virological relapse {P= 0.011).The cumulative risk of virological relapse was higher in the patients with HBsAg levels ≥1500 IU/L than in those with HBsAg levels < 1500 IU/L(P= 0.0013).The area under the curve was 0.603(P= 0.033).The cutoff HBsAg value for predicting virological relapse was 1443IU/L CONCLUSION:We found that the virological relapse rate remained high after antiviral therapy discontinuation in the HBeAg-negative patients and that the post treatment HBsAg levels predicted virological relapse.展开更多
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,...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.展开更多
Background:The progress of liver diseases may not stop after viral eradication.This study aimed to provide data on long-term prognosis of patients with hepatitis C virus(HCV)infection who underwent pegylated interfero...Background:The progress of liver diseases may not stop after viral eradication.This study aimed to provide data on long-term prognosis of patients with hepatitis C virus(HCV)infection who underwent pegylated interferon plus ribavirin(PR)regimen and achieved a sustained virological response 24 weeks post-treatment(SVR24).Methods:Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up.Baseline characteristics were profiled.The incidence of hepatocellular carcinoma(HCC),progression of liver disease(increase in liver stiffness or occurrence of decompensated complication),and HCV recurrence was all monitored.The accumulative and annualized incidence rates(AIRs)of these adverse events were analyzed,and the risk factors were also examined.Results:In total,151 patients reached a median follow-up time of 103 weeks.Among them,two had an incidence of HCC during the surveillance with AIR of 0.68%(95%CI:0.00-1.63%).Six patients showed progression of liver disease with AIR of 2.05%(95%CI:0.42%-3.68%).Three patients who had risky behaviors encountered HCV reinfection.The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients,including HCC and progression of liver disease(AIR:6.17%vs.1.42%,P=0.039).Conclusions:The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period,but the risk level was low.Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones.HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.展开更多
Previous studies have suggested that host genetic polymorphisms may affect virological response to pegylatedinterferon and ribavirin（PEG-IFN/ ribavirin） therapy in chronic HCV infection.IL28 B and MxA are the most i...Previous studies have suggested that host genetic polymorphisms may affect virological response to pegylatedinterferon and ribavirin（PEG-IFN/ ribavirin） therapy in chronic HCV infection.IL28 B and MxA are the most intensively studied genes in Chinese Han population.The current research is to summarize published data and evaluate the overall association of meaningful SNPs in these two genes with virological response to interferon-based therapy.Literature search was performed in online database and a systematic review was conducted based on the search results.Meaningful single nucleotide polymorphisms（SNPs） were summarized and analyzed for odds ratio（OR） and 95%confidence intervals（95%CI）.Data manipulation and statistical analyses were performed by using STATA 12.0and Review Manager version 5.1.Eighteen papers were included for final data analysis.Three SNPs of IL28 B and two SNPs of MxA were found to be associated with higher sustained virological response（SVR） to interferon therapy.The ORs and 95%CIs of each variant were：IL28B rs8099917 TT（OR：4.35,95%CI：3.10-6.12）,IL28 B rs12979860CC（OR：5.37,95%CI：3.95-7.31）,IL28 B rs7248668 CC（OR：3.50,95%CI：2.30-5.35）,MxA rs2071430 GT（OR：2.03,95%CI：1.31-3.13）,and MxA rsl7000900 AC/AA（OR：1.82,95%CI：1.17-2.83）.The genotypes of IL28 B rs8099917,rsl2979860,rs7248668,MxA rs2071430,and MxA rs17000900 were strong SVR predictors for PEG-IFN/ribavirin-treated HCV patients in Han Chinese population.Our findings suggest that host genetic variations are associated with virological response to interferon therapy of chronic HCV in Han Chinese patients.展开更多
AIM: To assess the clinical, biochemical, and virological outcome during long-term follow-up of chronic hepatitis C patients with sustained virological response following effective antiviral therapy.METHODS: This stud...AIM: To assess the clinical, biochemical, and virological outcome during long-term follow-up of chronic hepatitis C patients with sustained virological response following effective antiviral therapy.METHODS: This study was a retrospective cohort study including 171 sustained responders defi ned as HCV RNA PCR negative at 6 mo after the end of effective antiviral treatment (SVR-6). Clinical signs and symptoms, bio- chemical hepatic parameters, ultrasonography and HCV RNA PCR were followed.RESULTS: Mean follow-up period was 35.38 ± 22.2 mo after the end of treatment. Twenty-seven (15.8%) responders had evidence of cirrhosis before treatment. Forty-eight (28.1%), 107 (62.6%) and 6 (3.5%) patients were genotype 1, 3, and 6 respectively, while 10 patients (5.8%) were unclassifi ed. There were no virological and biochemical relapses during the period of follow-up. None of the patients showed evidence of hepatic decom- pensation. However, there were 3 patients (1.8%) de- veloping hepatocellular carcinoma at 14, 18, 29 mo after treatment discontinuation, two of whom had evidence of cirrhosis prior to therapy.CONCLUSION: The study shows that during a follow- up interval for about 3 years in 171 chronic hepatitis C patients with sustained viral response after effective antiviral treatment there were no evident signs of either biochemical or clinical relapse of liver disease in all but three patients who developed hepatocellular carcinoma.展开更多
基金supported by grants from the 2021 Graduate Education Innovation Program Project of Guangxi Zhuang Autonomous Region [YCBZ2021041]the National innovative training program for college students [202100001580]grants from the National Natural Science Foundation of China [NSFC,31860040]。
文摘Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
文摘Context: The appointment of the M6 is crucial because it is an indicator of the prognosis of the evolution of the care and the decision-making on the continuation of the AntiRetroViral Treatment. Objective: The objective of this study is therefore to present the virological and molecular profile of People Living with HIV under treatment with Dolutegravir 6 months after being put on ART in Kinshasa. Methods: The present study is a cross-sectional view at the sixth month of a prospective cohort to determine the virological and molecular profile of People Living with HIV (PLHIV) after 6 months of ART based on Dolutegravir (DTG) in Kinshasa. A sample of 5 mL of blood was taken from all HIV patients included. The collection of biological data was carried out under the same conditions as at inclusion. After extraction, Quantitative Real-Time PCR was carried out to determine the quantity of HIV RNA in the samples according to the protocols previously described. Reverse Transcription PCR (RT-PCR) and Nested PCR were carried out to amplify the regions of interest for Protease and Reverse Transcriptase for sequencing. Results: The median VL value was 2.92 log<sub>10</sub> RNA copies/mL. With 17.75% of patients experiencing major failure of first-line treatment. Subtype A is dominant with 13 cases (20.98%);followed by CRF_02AG (16.13%), subtypes C (14.52%), D (9.68%) and K (6.45%). The K65R (3 cases), T69P/N (6 cases), K70R (9 cases) and M184V (8 cases) mutations were listed as existing mutations for Nucleotide Reverse Transcriptase Inhibitors. Conclusion: After 6 months of ART, 59.67% of People Living with HIV on Tenofovir-Lamivudine-Dolutegravir is in therapeutic success while 40.33% are in a state of treatment failure. Subtype A remains dominant in the population of PLHIV. Resistance mutations were detected for Lamivudine and Tenofovir, but none for Dolutegravir.
文摘Context: Despite the new recommendations “Test and Treat”, the virological and molecular parameters remain important information for Antiretroviral Treatment and adequate for monitoring of patients infected with HIV/AIDS. Objective: the Objective of this study is to present the virological and molecular profile of People Living with HIV starting Antiretroviral Therapy in Kinshasa in the era of the Dolutegravir. Methods: This was a transversal study to determine virological and molecular profile of People Living with HIV (PLHIV) starting an ARV Treatment. The patient’s inclusion period was from October 04, 2021 to February 15, 2022. A sample of 5 ml of blood was taken in a tube with EDTA anticoagulant for Molecular Biology analyzes (Viral Load and Sequencing) in all HIV patients, after reading and signing informed consent. The population was made up of adult patients over the age of 18, infected with HIV and starting ART. Results: 119 patients (56.3% of women) were included in this study, thus a sex-ratio of 1.29. The average age of patients included was 39.87 ± 12.36 years. The most represented age group is that of 36 to 45 with 37 patients (31.9%) followed by that from 26 to 35 years with 24 patients (20.7%). Out of 119 patients, 21 patients had an undetectable Viral Load (VL). The median value of VL was 4.16 log10 RNA copies/ml. 114 samples were successfully amplified. Subtype A was dominant with 23 cases (20.2%);followed by the subtype C and CRF02_AG each with 14.0%, and D (10.5 %). K65R (1.8%), T69P/N (4.4%), K70R (7.9%) and M184V (7.0%) mutations were listed as existing mutations for Nucleotide Transcriptase Inhibitors. Conclusion: 38 patients (31.93%) started the TARV with a positive virological prognosis. The subtype A remains dominant in Kinshasa with 23 cases (20.2%);followed by the subtype C and CRF02_AG each with 14.0%. For Inhibitors of Transcriptase Reverse Nucleotide;K65R, T69P/N, K70E/R and M184V mutations were found in patients’ naive of ARV Treatment.
文摘AIM:To document the sustained virological response (SVR) in rapid virological responders (RVR) of genotype-3 chronic hepatitis C with standard interferon (SdIF). METHODS:Hepatitis C genotype-3 patients during the period July 2006 and June 2007 were included. Complete blood counts, prothrombin time, ALT, albumin, qualitative HCV RNA were done. SdIF and ribavirin were given for 4 wk and qualitative HCV RNA was repeated. Those testing negative were allocated to group-A while the rest were allocated to group-B. Treatment was continued a total of 16 and 24 wk for group A and B respectively. HCV RNA was repeated after 24 wk of treatment. End virological and sustained virological responses were compared by χ2 test. ROC of pretreatment age, ALT and albumin were plotted for failure to achieve SVR. RESULTS:Of 74 patients treated, RCV RNA after 16 wk of therapy became undetectable in 34 (45.9%) and was detectable in 40 (54.1%) and were allocated to groups A and B respectively. SVR was achieved in 58.8% and 27.8% in groups A and B respectively. SVR rates were significantly higher in patients who had RVR as compared to those who did not (P = 0.0;γ = 2). Both groups combined ETR and SVR were 70% and 33% respectively. ROC plots of pretreatment age, ALT and albumin for SVR showed only ALT to have a significantly large area under the curve.CONCLUSION:SVR rates were higher in patients who had RVR with SdIF and high pre treatment ALT values correlated to probability of having RVR.
基金Supported by the research grant of the Chungbuk National University in 2004
文摘AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION: Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.
文摘BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure.
文摘BACKGROUND Characteristics of alterations of serum hepatitis B virus(HBV) RNA in different chronic hepatitis B(CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.AIM To investigate whether HBV RNA can predict virological response or HBeAg seroconversion during entecavir(ETV) treatment when HBV DNA is undetectable.METHODS The present study evaluated 61 individuals who were diagnosed and treated with long-term ETV monotherapy at the Department of Infectious Diseases of Peking University First Hospital(China) from September 2006 to December 2007.Finally, 30 treatment-naive individuals were included. Serum HBV RNA were extracted from 140 μL serum samples at two time points. Then they were reverse transcribed to cDNA with the HBV-specific primer. The product was quantified by real-time quantitative PCR(RT-PCR) using TAMARA probes. Statistical analyses were performed with IBM SPSS 20.0.RESULTS Level of serum HBV RNA at baseline was 4.15 ± 0.90 log10 copies/mL. HBV RNA levels showed no significant difference between the virological response(VR)and partial VR(PVR) groups at baseline(P = 0.940). Serum HBV RNA significantly decreased among patients who achieved a VR during ETV therapy(P < 0.001). The levels of HBV RNA in both HBeAg-positive patients with seroconversion group and those with no seroconversion increased after 24 wk of treatment. Overall, HBV RNA significantly but mildly correlated to HBsAg(r =0.265, P = 0.041), and HBV RNA was not correlated to HBV DNA(r = 0.242, P =0.062). Furthermore, serum HBV RNA was an independent indicator for predicting HBeAg seroconversion and virological response. HBeAg seroconversion was more likely in CHB patients with HBV RNA levels below4.12 log10 copies/mL before treatment.CONLUSION The level of serum HBV RNA could predict HBeAg seroconversion and PVR during treatment. In the PVR group, the level of serum HBV RNA tends to be increasing.
文摘AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.
文摘AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls(HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral Ld T daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array(CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97(123.26-492.79) pg/m L vs 184.50(135.56-292.16) pg/m L, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with Ld T [175.51(103.90-331.91) pg/m L vs 184.50(135.56-292.16) pg/m L, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB(r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to Ld T treatment at 24 wk(48.15% vs 15.79%, P = 0.023) and 52 wk(66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary nonresponse at week 12 after treatment initiation were lower than those in patients with primary response [64.44(49.85-172.08) pg/m L vs 190.54(121.35-355.28) pg/m L, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with Ld T. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to Ld T treatment.
文摘AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico Ⅱ". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that viruseradication following interferon treatment can last up to 20 years.
文摘AIM: To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm 3 and without antiretroviral therapy; to describe different HBV-HIV coinfection virological profiles; and to search for factors associated with HBs antigen (HBsAg) presence in these HIV positive patients.METHODS: During four months (June through September 2006), 491 patients were received in four HIV positive monitoring clinical centers in Abidjan. Inclusion criteria: HIV-1 or HIV-1 and 2 positive patients, age ≥ 18 years, CD4+ T-cell count < 500/mL and formal and signed consent of the patient. Realized blood tests included HIV serology, CD4+ T-cell count, quantitative HIV RNA load and HBV serological markers, such as HBsAg and HBc antibody (anti-HBcAb). We performed HBeAg, anti-HBe antibody (anti-HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients. Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb-positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg negative status and without anti-HBsAb. Univariate analysis (Pearsonχ 2 test or Fischer exact test) and multivariate analysis (backward step-wise selection logistic regression) were performed as statistical analysis. RESULTS: Mean age of 491 patients was 36 ± 8.68 years and 73.3% were female. Type-1 HIV was found in 97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO) clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172 (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm 3 (interquartile range: 221-470). One hundred and twelve patients had less than 200 CD4+ T-cell/mm 3 . Plasma HIV-1 RNA load was elevated (≥ 5 log 10 copies/mL) in 221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and 72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%), 21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and detectable HBV DNA) was 21.3%. Three parameters were significantly associated with the presence of HBsAg: male [odds ratio (OR): 2.2;P = 0.005; 95% confidence interval (CI): 1.3-3.8]; WHO stage 4 (OR: 3.2;P = 0.01;95% CI: 1.3-7.9); and aspartate aminotransferase (AST) level higher than the standard (OR: 1.9;P = 0.04; 95% CI: 1.02-3.8). CONCLUSION: HBV infection prevalence is high in HIV-positive patients. HBeAg positive chronic hepatitis and occult HBV infection are more frequent in HIVpositive patients than in HIV negative ones. Parameters associated with HBsAg positivity were male gender, AIDS status and increased AST level.
文摘BACKGROUND： The definition of partial virological response （PVR） was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Whether this rationale can be applied to all nucleotide analogues （NA） is not clear. This study was undertaken to analyze PVR influence on therapeutic outcomes during lamivudine, entecavir or tenofovir mono- therapy in NA-naive patients with chronic hepatitis B in routine clinical practice. METHODS： We retrospectively analyzed 150 NA-naive patients with chronic hepatitis B. These subjects received lamivudine, entecavir or tenofovir monotherapy between February 2001 and July2013. RESULTS： Sixty-nine patients were treated with lamivudine, 35 with entecavir, and 46 with tenofovir. The median therapeutic duration was 19.5 （6-147） months. PVR rates at 24 weeks were similar among three NAs （lamivudine 33.3%, entecavir 35.0%, tenofovir 32.4%, P--0.981）. For all three NAs, patients with a higher baseline viral load or HBeAg-positive status had a higher serum viral positive rate tested by polymerase chain reaction at week 24 and 48. Cumulative probability of virological breakthrough （VBR） for patients treated with lamivudine was 67% at 5 years, and PVR at 24 weeks was the independent risk factor for VBR （HR： 3.09; 95% CI： 1.09-8.74; P=0.034）; also lamivudine treated patients older than 50 years seemed to have a tendency for VBR （HR： 2.80; 95% CI： 0.99-8.18; P=0.052）. A majority of entecavir and tenofovir partial responders achieved and maintained virological response with prolonged monotherapy, except one entecavir treated patient who experienced VBR due to resistance mutations.CONCLUSIONS： Management strategy for lamivudine treatment should include adaptation of regimen according to PVR as an on-treatment response parameter due to its relation with unacceptably high VBR probability. Similar conclusion should not be directly related to entecavir or tenofovir treatment.
基金Supported by"973"Program No.2007CB512800National Natural Science Foundation of China,No.30771905+1 种基金Mega-projects of Science Research,No.008ZX10002-008Beijing Municipal Science&Technology Commission,No. D08050700650803
文摘AIM： To determine which baseline factors of chronic hepatitis B patients are predictive of virological response to Peginterferon α-2b therapy. METHODS： A total of 21 HBeAg-positive chronic hepatitis B （CriB） patients treated with Peginterferon α-2b were recruited. They were treated with Peginterferon α-2b （0.5-1.0 μg/kg per week） for 24 wk and followed up for 24 wk. Clinical and laboratory data of the patients were determined at pretreatment and at week 12, at 24 during treatment, and at week 48 during follow up. RESULTS： Ten patients achieved a virological response at the end of treatment. Their baseline serum alanine aminotransferase （ALT）, thyroid-stimulating hormone （TSH）, and total thyroxin （TT4） levels were significantly different from those who failed treatment. The positive predictive values （PPV） and negative predictive values （NPV） of ALT, TSH, and TT4 were 75% and 89 %, 75% and 89 %, and 75% and 75%, respectively. Moreover, combinations of the baseline ALT and TT4, ALT and TSH, TT4 and TSH levels had much higher PPV and NPV （86% and 88%, 89% and 100%, 83% and 100%, respectively）.CONCLUSION： Baseline serum ALT, TSH, and TT4 levels, especially in combination, have high predictive values of virological response to Peginterferon α-2b in HBeAg-positive CriB patients.
文摘AIM: Predictive value of serum b2-microglobulin (b2m)levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM).METHODS: Serum b2m levels were calculated during treatment in 25 CHB patients under long-term LAM monotherapy (group A) and 12 patients under initial interferon plus LAM treatment followed by LAM monotherapy (group B), using the MEIA technology. We used Cox proportional hazard models in order to investigate the association between serum b2m levels and VB.RESULTS: Seven of 25 patients (28%), 9/25 (36%) and 14/25 (56%) from group A and 0/12, 2/12 (16.6%) and 3/12 (25%) from group B exhibited VB at months 12, 24 and 36 of treatment, respectively. All patients, from both groups, who did not show VB exhibited b2m elevation in mo 3. The duration of b2m elevation was significantly longer in the virological responder's subgroup from group A than the non-responder's one (7.3±2.6 vs 3.8±3.4 mo,P = 0.02). In comparison to group A patients whose b2m levels were increased at 3 mo, patients whose b2m levels were decreased had 4.6 times higher risk of experiencing VB (RR = 4.6, P = 0.024). When baseline variables were simultaneously included in the same Cox model, decreased b2m status was still associated with increased risk of VB (RR = 12.2, P = 0.03).CONCLUSION: In HBeAg-negative CHB patients under either long-term LAM monotherapy or initial combination treatment, serum b2m levels at 3 mo of treatment,compared to baseline ones, might be a predictor of risk for VB.
基金Supported by Instituto de Investigacion La Princesa and CI-BERehd from Instituto de Salud Carlos Ⅲ, Madrid, Spain
文摘AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.
基金Supported by Natural Science Foundation of Jiangsu Province,China,No.BK2011515Medical Project of Health Department Jiangsu Province,No.H201248+1 种基金Preventive Medicine research projects of Jiangsu Province,No.Y2012016the Social Development Project of Zhenjiang City,No.SH2013056
文摘AIM:To investigate the virological relapse rate in hepatitis B e antigen(HBeAg)-negative patients after antiviral therapy discontinuation and analyze the factors associated with virological relapse.METHODS:Among patients diagnosed with chronic hepatitis B infection between May 2005 and July2010,204 were eligible for analysis.The Kaplan-Meier method and log-rank test were used to calculate the cumulative rate of relapse and compare cumulative relapse rates between groups.The Cox proportional hazards regression model was used to evaluate the predictive factor of virological relapse.RESULTS:The 2 and 1 year cumulative risks of virological relapse after antiviral therapy discontinuation were 79.41%(162/204) and 43.82%(71/162),respectively.Multivariate analysis revealed that only post treatment hepatitis B surface antigen(HBsAg)level was associated with virological relapse {P= 0.011).The cumulative risk of virological relapse was higher in the patients with HBsAg levels ≥1500 IU/L than in those with HBsAg levels < 1500 IU/L(P= 0.0013).The area under the curve was 0.603(P= 0.033).The cutoff HBsAg value for predicting virological relapse was 1443IU/L CONCLUSION:We found that the virological relapse rate remained high after antiviral therapy discontinuation in the HBeAg-negative patients and that the post treatment HBsAg levels predicted virological relapse.
文摘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.
基金supported by the Research Project of Health Commission of Sichuan Province(No.17PJ006)。
文摘Background:The progress of liver diseases may not stop after viral eradication.This study aimed to provide data on long-term prognosis of patients with hepatitis C virus(HCV)infection who underwent pegylated interferon plus ribavirin(PR)regimen and achieved a sustained virological response 24 weeks post-treatment(SVR24).Methods:Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up.Baseline characteristics were profiled.The incidence of hepatocellular carcinoma(HCC),progression of liver disease(increase in liver stiffness or occurrence of decompensated complication),and HCV recurrence was all monitored.The accumulative and annualized incidence rates(AIRs)of these adverse events were analyzed,and the risk factors were also examined.Results:In total,151 patients reached a median follow-up time of 103 weeks.Among them,two had an incidence of HCC during the surveillance with AIR of 0.68%(95%CI:0.00-1.63%).Six patients showed progression of liver disease with AIR of 2.05%(95%CI:0.42%-3.68%).Three patients who had risky behaviors encountered HCV reinfection.The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients,including HCC and progression of liver disease(AIR:6.17%vs.1.42%,P=0.039).Conclusions:The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period,but the risk level was low.Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones.HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.
基金was supported by the National Natural Science Foundation of China(Grant No.81102164 and No.81102165)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Previous studies have suggested that host genetic polymorphisms may affect virological response to pegylatedinterferon and ribavirin（PEG-IFN/ ribavirin） therapy in chronic HCV infection.IL28 B and MxA are the most intensively studied genes in Chinese Han population.The current research is to summarize published data and evaluate the overall association of meaningful SNPs in these two genes with virological response to interferon-based therapy.Literature search was performed in online database and a systematic review was conducted based on the search results.Meaningful single nucleotide polymorphisms（SNPs） were summarized and analyzed for odds ratio（OR） and 95%confidence intervals（95%CI）.Data manipulation and statistical analyses were performed by using STATA 12.0and Review Manager version 5.1.Eighteen papers were included for final data analysis.Three SNPs of IL28 B and two SNPs of MxA were found to be associated with higher sustained virological response（SVR） to interferon therapy.The ORs and 95%CIs of each variant were：IL28B rs8099917 TT（OR：4.35,95%CI：3.10-6.12）,IL28 B rs12979860CC（OR：5.37,95%CI：3.95-7.31）,IL28 B rs7248668 CC（OR：3.50,95%CI：2.30-5.35）,MxA rs2071430 GT（OR：2.03,95%CI：1.31-3.13）,and MxA rsl7000900 AC/AA（OR：1.82,95%CI：1.17-2.83）.The genotypes of IL28 B rs8099917,rsl2979860,rs7248668,MxA rs2071430,and MxA rs17000900 were strong SVR predictors for PEG-IFN/ribavirin-treated HCV patients in Han Chinese population.Our findings suggest that host genetic variations are associated with virological response to interferon therapy of chronic HCV in Han Chinese patients.
基金Supported by The Gastroenterological Association of Thailand
文摘AIM: To assess the clinical, biochemical, and virological outcome during long-term follow-up of chronic hepatitis C patients with sustained virological response following effective antiviral therapy.METHODS: This study was a retrospective cohort study including 171 sustained responders defi ned as HCV RNA PCR negative at 6 mo after the end of effective antiviral treatment (SVR-6). Clinical signs and symptoms, bio- chemical hepatic parameters, ultrasonography and HCV RNA PCR were followed.RESULTS: Mean follow-up period was 35.38 ± 22.2 mo after the end of treatment. Twenty-seven (15.8%) responders had evidence of cirrhosis before treatment. Forty-eight (28.1%), 107 (62.6%) and 6 (3.5%) patients were genotype 1, 3, and 6 respectively, while 10 patients (5.8%) were unclassifi ed. There were no virological and biochemical relapses during the period of follow-up. None of the patients showed evidence of hepatic decom- pensation. However, there were 3 patients (1.8%) de- veloping hepatocellular carcinoma at 14, 18, 29 mo after treatment discontinuation, two of whom had evidence of cirrhosis prior to therapy.CONCLUSION: The study shows that during a follow- up interval for about 3 years in 171 chronic hepatitis C patients with sustained viral response after effective antiviral treatment there were no evident signs of either biochemical or clinical relapse of liver disease in all but three patients who developed hepatocellular carcinoma.
