ABSTRACT
BACKGROUND & AIMS: The incidence of chronic hepatitis B (CHB) is declining due to successful implementation of vaccination programs and widespread use of antiviral therapy. We aimed to study time-trends in disease characteristics and comorbidities in newly referred CHB patients. METHODS: We collected information on hepatitis B virus (HBV) related disease characteristics (including hepatitis B e-antigen (HBeAg) status, viremia, stage of liver fibrosis and indication for treatment and/or hepatocellular carcinoma (HCC) surveillance) and presence of comorbidities in all CHB patients referred to our center from 1980 through 2020. Patient characteristics were compared according to referral date (before 2000, between 2000 and 2010 and after 2010). RESULTS: We identified 1515 eligible patients. Patients referred after 2010 were older (36 versus 34 years, p < 0.001), more often non-Caucasian (82.3% versus 55.0%, p < 0.001) and more frequently HBeAg negative (81.5% versus 49.8%, p < 0.001) when compared to patients referred before 2000. Adjusted for ethnicity, sex and age, patients referred after 2010 were less likely to have significant fibrosis (adjusted odds ratio [aOR]:0.178, p < 0.001) or indication for antiviral therapy (aOR:0.342, p < 0.001) but were more likely to be affected by the metabolic syndrome (aOR:1.985, p = 0.013), hepatic steatosis (aOR:1.727, p < 0.001) and metabolic dysfunction associated fatty liver disease (MAFLD) (aOR:1.438, p = 0.013). CONCLUSIONS: The characteristics of the CHB populations are changing. Newly referred patients are older, have less active HBV related liver disease but are more likely to be co-affected by MAFLD. These findings provide guidance for adequate allocation of resources to cope with the changing characteristics of the CHB population. FUNDING: Foundation for Liver and Gastrointestinal Research Rotterdam, the Netherlands and Gilead Sciences.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/drug therapy , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/complications , Hepatitis B e Antigens , Liver Neoplasms/epidemiology , Liver Neoplasms/complications , Hepatitis B virus , Liver Cirrhosis/epidemiology , Liver Cirrhosis/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/drug therapy , Antiviral Agents/therapeutic use , DNA, ViralABSTRACT
Benign liver tumors form a heterogeneous group. The most frequent forms include simple cysts, hemangiomas, focal nodular hyperplasia and hepatocellular adenomas. They are often incidentally detected during routine sonography. The diagnosis of a liver tumor not uncommonly causes anxiety and insecurity in those affected, which is why a rapid and reliable diagnostic procedure should be carried out. Because some tumors, particularly hepatocellular adenomas, are of prognostic relevance due to the potential risk of malignant transformation, a correct classification should always be strived for. The type and extent of diagnostic clarification depend on the clinical and patient-related risk factors. This article describes the most important benign space-occupying lesions. The etiology, clinical manifestations and diagnostics as well as possible necessary treatment measures are presented.
Subject(s)
Cysts , Focal Nodular Hyperplasia , Hemangioma , Liver Diseases , Liver Neoplasms , Cysts/diagnosis , Cysts/therapy , Diagnosis, Differential , Focal Nodular Hyperplasia/diagnosis , Focal Nodular Hyperplasia/therapy , Hemangioma/diagnosis , Hemangioma/therapy , Humans , Liver Diseases/diagnosis , Liver Diseases/therapy , Liver Neoplasms/diagnosis , Liver Neoplasms/therapyABSTRACT
Chronic hepatitis C virus (HCV) infection is a global public health issue, which is associated with high rates of morbidity and mortality. The development of direct acting antivirals (DAAs) has transformed treatment: they offer us highly-effective therapy with superior tolerability compared to interferon-containing regimens. In 2016, the World Health Organization (WHO) therefore adopted several ambitious viral hepatitis elimination targets, aiming for a 90% reduction in new infections and a 65% reduction in mortality by 2030. The ultimate goal is to eliminate HCV completely. It is reasonable that these goals may be achieved in the Netherlands due to the low prevalence of chronic HCV, the availability of DAAs, and excellent healthcare infrastructure. This paper describes a national effort to curtail the HCV epidemic in the Netherlands through an HCV retrieval and linkage to care project (CELINE: Hepatitis C Elimination in the Netherlands).
Subject(s)
Disease Eradication/methods , Epidemics , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/prevention & control , Mass Screening/methods , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Humans , Netherlands/epidemiology , PrevalenceSubject(s)
Antiviral Agents/therapeutic use , Communication Barriers , Hepatitis B, Chronic/drug therapy , Patient Compliance/statistics & numerical data , Adult , Age Factors , Female , Follow-Up Studies , Hepatitis B, Chronic/epidemiology , Humans , Lost to Follow-Up , Male , Netherlands/epidemiology , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. AIM: To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). METHODS: Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses. RESULTS: A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin < 10 g/dL). CONCLUSION: In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR.
Subject(s)
Antiviral Agents/blood , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/drug therapy , Ribavirin/blood , Ribavirin/therapeutic use , Adult , Antiviral Agents/pharmacokinetics , Drug Therapy, Combination , Female , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/drug therapy , Liver Cirrhosis/virology , Male , Middle Aged , Prospective Studies , Ribavirin/pharmacokinetics , Sofosbuvir/therapeutic use , Sustained Virologic ResponseABSTRACT
An abundance of noninvasive scores have been associated with fibrosis and hepatocellular carcinoma (HCC) development. We aimed to compare the prognostic ability of these scores in relation to liver histology in chronic hepatitis B (CHB) patients. Liver biopsies from treatment-naïve CHB patients at one tertiary care centre were scored by a single hepato-pathologist. Laboratory values at liver biopsy were used to calculate the PAGE-B, REACH-B, GAG-HCC, CU-HCC and FIB-4 scores. Any clinical event was defined as HCC development, liver failure, transplantation and mortality. HCC and mortality data were obtained from national database registries. Of 557 patients, 40 developed a clinical event within a median follow-up of 10.1 (IQR 5.7-15.9) years. The PAGE-B score predicted any clinical event (C-statistic.86, 95% CI: 0.80-0.92), HCC development (C-statistic .91) and reduced transplant-free survival (C-statistic .83) with good accuracy, also when stratified by ethnicity, antiviral therapy after biopsy or advanced fibrosis. The C-statistics (95% CI) of the REACH-B, GAG-HCC, CU-HCC and FIB-4 scores for any event were .70 (0.59-0.81), .82 (0.75-0.89), .73 (0.63-0.84) and.79 (0.69-0.89), respectively. The PAGE-B event risk assessment improved modestly when combined with the Ishak fibrosis stage (C-statistic .87, 95% CI: 0.82-0.93). The PAGE-B score showed the best performance in assessing the likelihood of developing a clinical event among a diverse CHB population over 15 years of follow-up. Additional liver histological characteristics did not appear to provide a clinically significant improvement.
Subject(s)
Hepatitis B, Chronic/epidemiology , Adult , Biomarkers , Biopsy , Cause of Death , Female , Hepatitis B, Chronic/mortality , Hepatitis B, Chronic/pathology , Humans , Kaplan-Meier Estimate , Liver/pathology , Male , Middle Aged , Netherlands/epidemiology , Outcome Assessment, Health Care , Population Surveillance , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Young AdultABSTRACT
Treatment options for chronic hepatitis C virus (HCV) infection have drastically changed since the development and licensing of new potent direct-acting antivirals (DAAs). The majority of DAAs are extensively metabolized by liver enzymes and have the ability to influence cytochrome P450 (CYP) enzymes. Additionally, these DAAs are both substrates and inhibitors of drug transporters, which makes the DAAs both possible victims or perpetrators of drug-drug interactions (DDIs). There is a high prevalence of mental illnesses such as depression or psychosis in HCV-infected patients; therefore, psychoactive medications are frequently co-administered with DAAs. The majority of these psychoactive medications are also metabolized by CYP enzymes but remarkably little information is available on DDIs between psychoactive medications and DAAs. Hence, the aim of this review is to provide an overview of the interaction mechanisms between DAAs and psychoactive agents. In addition, we describe evidenced-based interactions between DAAs and psychoactive drugs and identify safe options for the simultaneous treatment of mental illnesses and chronic HCV infection.
Subject(s)
Antiviral Agents/pharmacology , Cytochrome P-450 Enzyme System/drug effects , Hepatitis C, Chronic/drug therapy , Mental Disorders/drug therapy , Psychotropic Drugs/pharmacology , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , Drug Interactions , Humans , Psychotropic Drugs/pharmacokinetics , Psychotropic Drugs/therapeutic useABSTRACT
Hepatitis B core-related antigen (HBcrAg), a new serum marker, may be useful in monitoring chronic hepatitis B infection. HBcrAg was measured in 175 hepatitis B e antigen-positive patients treated with entecavir (ETV) with or without peginterferon (PEG-IFN) add-on therapy. Decline in HBcrAg was stronger in patients with vs. without combined response (ETV: -3.22 vs. -1.71 log U/mL, p <0.001; PEG-IFN add-on: -3.16 vs. -1.83 IU/mL, p <0.001) and in patients with vs. without hepatitis B surface antigen (HBsAg) response (ETV: -2.60 vs. -1.74 log U/mL, p <0.001; PEG-IFN add-on: -2.38 vs. -2.15 log U/mL, p = 0.31). HBcrAg was associated with combined response (adjusted odds ratio 0.3, 95% confidence interval 0.2-0.5, p <0.001), but was not superior to quantitative HBsAg (qHBsAg).
Subject(s)
Antiviral Agents/therapeutic use , Drug Monitoring/methods , Guanine/analogs & derivatives , Hepatitis B Core Antigens/blood , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/drug therapy , Adult , Female , Guanine/therapeutic use , Humans , Interferon-alpha/therapeutic use , Male , Randomized Controlled Trials as Topic , Young AdultABSTRACT
BACKGROUND & AIMS: Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios. METHODS: Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario. RESULTS: The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 4 5% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2. CONCLUSIONS: A substantial reduction in HCV-related disease burden is possible with increases in treatment uptake as the efficacy of current therapies is high. Further reduction of HCV-related disease burden may be achieved through increases in diagnosis and preventative measures. These results might inform the further development of effective disease management strategies in the Netherlands.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C/epidemiology , Adolescent , Adult , Aged , Cost of Illness , Disease Progression , Female , Hepatitis C/drug therapy , Hepatitis C/prevention & control , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/prevention & control , Humans , Male , Middle Aged , Models, Statistical , Monte Carlo Method , Netherlands , Prevalence , Treatment Outcome , Young AdultABSTRACT
PURPOSE: The aim of the present prospective European multicenter study was to demonstrate the non-inferiority of point shear wave elastography (pSWE) compared to transient elastography (TE) for the assessment of liver fibrosis in patients with chronic hepatitis C. MATERIALS AND METHODS: 241 patients with chronic hepatitis C were prospectively enrolled at 7 European study sites and received pSWE, TE and blood tests. Liver biopsy was performed with histological staging by a central pathologist. In addition, for inclusion of cirrhotic patients, a maximum of 10â% of patients with overt liver cirrhosis confirmed by imaging methods were allowed by protocol (nâ=â24). RESULTS: Owing to slower than expected recruitment due to a reduction of liver biopsies, the study was closed after 4 years before the target enrollment of 433 patients with 235 patients in the 'intention to diagnose' analysis and 182 patients in the 'per protocol' analysis. Therefore, the non-inferiority margin was enhanced to 0.075 but non-inferiority of pSWE could not be proven. However, Paired comparison of the diagnostic accuracy of pSWE and TE revealed no significant difference between the two methods in the 'intention to diagnose' and 'per protocol' analysis (0.81 vs. 0.85 for Fâ≥â2, pâ=â0.15; 0.88 vs. 0.92 for Fâ≥â3, pâ=â0.11; 0.89 vs. 0.94 for Fâ=â4, pâ=â0.19). Measurement failure was significantly higher for TE than for pSWE (pâ=â0.030). CONCLUSION: Non-inferiority of pSWE compared to TE could not be shown. However, the diagnostic accuracy of pSWE and TE was comparable for the noninvasive staging of liver fibrosis in patients with chronic hepatitis C.
Subject(s)
Elasticity Imaging Techniques/methods , Hepatitis C, Chronic/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Adult , Aged , Biopsy , Female , Hepatitis C, Chronic/pathology , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/pathology , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Young AdultABSTRACT
BACKGROUND: Before stopping nucleos(t)ide analogue (NA) treatment in chronic hepatitis B (CHB), 6-12 months of consolidation therapy is recommended. AIM: To investigate the effect of consolidation therapy on off-treatment outcomes in CHB patients. METHODS: We included 94 patients who stopped NA after at least 1 year of therapy. Patients could be HBeAg-positive or HBeAg-negative at start-of-treatment, but were HBeAg-negative and had undetectable HBV DNA at time of discontinuation. Consolidation therapy was defined as treatment after the first undetectable HBV DNA (and HBeAg loss for HBeAg-positive patients) until NA cessation. RESULTS: At 3 years, 74% of the start-of-treatment HBeAg-positive and 75% of the start-of-treatment HBeAg-negative patients developed HBV DNA >2000 IU/mL at a single time point, whereas a persistent virological relapse (≥2 tests of HBV DNA >2000 IU/mL 6 months apart within 1 year) developed in 49% of the start-of-treatment HBeAg-positive and 53% of the start-of-treatment HBeAg-negative patients. For both HBeAg-positive and HBeAg-negative patients, consolidation therapy of ≥3 years was associated with lower persistent virological relapse rates compared to <1 year (1-year relapse rate: 25% vs. 54%; P = 0.063 and 24% vs. 57%; P = 0.036, respectively). At 3 years, 9% of the HBeAg-positive and 14% of the HBeAg-negative patients became HBsAg-negative. Prolonged consolidation therapy increased the likelihood of HBsAg loss. Two cirrhotic patients developed hepatic decompensation but both recovered. CONCLUSIONS: After nucleos(t)ide analogue discontinuation, relapse was common in patients with chronic hepatitis B. Prolongation of consolidation therapy beyond 3 years decreased the risk of persistent virological relapse and increased the likelihood of HBsAg loss.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Surface Antigens/analysis , Hepatitis B e Antigens/analysis , Hepatitis B, Chronic/drug therapy , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Treatment OutcomeABSTRACT
Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.
Subject(s)
Hepatitis C, Chronic/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Child , Child, Preschool , Drug Utilization/statistics & numerical data , Female , Global Health , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/surgery , Humans , Infant , Infant, Newborn , Liver Transplantation/statistics & numerical data , Male , Middle Aged , Prevalence , Young AdultABSTRACT
The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.
Subject(s)
Antiviral Agents/therapeutic use , Cost of Illness , Hepatitis C, Chronic/drug therapy , Mass Screening , Models, Biological , Disease Progression , Global Health , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/epidemiology , Humans , Prevalence , Treatment OutcomeABSTRACT
Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.
Subject(s)
Antiviral Agents/therapeutic use , Cost of Illness , Hepatitis C, Chronic/epidemiology , Models, Biological , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Disease Progression , Female , Global Health , Hepatitis C, Chronic/drug therapy , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prevalence , Young AdultABSTRACT
BACKGROUND: A new era for the treatment of chronic hepatitis C is about to transpire. With the introduction of the first-generation protease inhibitors the efficacy of hepatitis C treatment improved significantly. Since then, the therapeutic agenda has moved further forward with the recent approval of sofosbuvir and the expected approval of agents such as simeprevir and daclatasvir. This paper, developed parallel to the approval of sofosbuvir, is to serve as a guidance for the therapeutic management of chronic hepatitis C. METHODS: We performed a formal search through PubMed, Web of Science and ClinicalTrials.gov to identify all clinical trials that have been conducted with EMA-approved new agents in hepatitis C; for this version (April 2014) we focused on sofosbuvir. For each disease category, the evidence was reviewed and recommendations are based on GRADE. RESULTS: We identified 11 clinical trials with sofosbuvir and for each disease category recommendations for treatment are made. Not all disease categories were studied extensively and therefore in some cases we were unable to provide recommendations. CONCLUSION: The recent approval of sofosbuvir will most likely change the therapeutic landscape of chronic hepatitis C. The use of sofosbuvir-containing regimens can shorten the duration of therapy, increase efficacy and result in less side effects, compared with standard of care. The efficacy relative to standard of care needs to be weighed against the increased costs of sofosbuvir. With future approval of the other direct-acting antivirals, the outcome of hepatitis C treatment will likely improve further and this guidance will be updated.
Subject(s)
Antiviral Agents/pharmacology , Hepatitis C, Chronic/drug therapy , Protease Inhibitors/pharmacology , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Genotype , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/genetics , Heterocyclic Compounds, 3-Ring/pharmacology , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Practice Guidelines as Topic , Protease Inhibitors/therapeutic use , Simeprevir , Sofosbuvir , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Uridine Monophosphate/analogs & derivatives , Uridine Monophosphate/pharmacology , Uridine Monophosphate/therapeutic useABSTRACT
BACKGROUND: Polymorphisms of the HLA-DP gene are associated with the natural clearance of the hepatitis B virus in Asian patients. AIM: To investigate the association of HLA-DP polymorphisms with response to peginterferon (PEG-IFN) in Caucasian chronic hepatitis B (CHB) patients. METHODS: We studied 262 Caucasian chronic hepatitis B patients infected with HBV genotype A or D, treated with PEG-IFN for 1 year in two randomised controlled trials (HBV 99-01 and PARC study). Response was defined as an HBV DNA <2000 IU/mL at 6 months post-treatment. Variations at HLA-DPA1 and HLA-DPB1 were genotyped. RESULTS: Of the 262 patients, 58% was HBeAg-positive and HBV genotype A and D was observed in 32% and 68%, respectively. At 6 months post-treatment, 57 (22%) patients had achieved an HBV DNA <2000 IU/mL. HLA-DPB1 was independently associated with virological response [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI):1.1-3.0, P = 0.025], and with an undetectable HBV DNA (adjusted OR 2.4 95% CI: 1.2-4.7, P = 0.015) when adjusted for HBeAg status and other known response modifiers. In HBeAg-positive patients, combined HBeAg seroconversion with HBV DNA <2000 IU/mL was increasingly observed with each addition of an HLA-DPB1 G-allele (adjusted OR 2.7, 95% CI: 1.2-5.9, P = 0.012). Furthermore, HLA-DPA1 and HLA-DPB1 haplotype block GG showed comparable results for virological and combined response. CONCLUSION: In this large cohort of Caucasian chronic hepatitis B patients infected with HBV genotypes A or D, polymorphisms of HLA-DP are independently associated with both virological and serological response to PEG-IFN therapy at 6 months post-treatment.
Subject(s)
HLA-DP alpha-Chains/genetics , HLA-DP beta-Chains/genetics , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/genetics , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , DNA, Viral/analysis , Female , Genotype , Haplotypes , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/immunology , Humans , Male , Middle Aged , Polymorphism, Genetic , White People/genetics , Young AdultABSTRACT
Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk for complications following sustained virological response (SVR). Therefore, we aimed to evaluate treatment efficacy with the number needed to treat (NNT) to prevent clinical endpoints. Mortality and cirrhosis-related morbidity were assessed in an international multicentre cohort of consecutively treated patients with HCV genotype 1 infection and cirrhosis. The NNT to prevent death or clinical disease progression (any cirrhosis-related event or death) in one patient was determined with the adjusted (event-free) survival among patients without SVR and adjusted hazard ratio of SVR. Overall, 248 patients were followed for a median of 8.3 (IQR 6.2-11.1) years. Fifty-nine (24%) patients attained SVR. Among patients without SVR, the adjusted 5-year survival and event-free survival were 94.4% and 80.0%, respectively. SVR was associated with reduced all-cause mortality (HR 0.15, 95% CI 0.05-0.48, P = 0.002) and clinical disease progression (HR 0.16, 95% CI 0.07-0.36, P < 0.001). The NNT to prevent one death in 5 years declined from 1052 (95% CI 937-1755) at 2% SVR (interferon monotherapy) to 61 (95% CI 54-101) at 35% SVR (peginterferon and ribavirin). At 50% SVR, which might be expected with triple therapy, the estimated NNT was 43 (95% CI 38-71). The NNT to prevent clinical disease progression in one patient in 5 years was 302 (95% CI 271-407), 18 (95% CI 16-24) and 13 (95% CI 11-17) at 2%, 35% and 50% SVR, respectively. In conclusion, the NNT to prevent clinical endpoints among cirrhotic patients with HCV genotype 1 has declined enormously with the improvement of antiviral therapy.