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1.
Aliment Pharmacol Ther ; 51(4): 469-478, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31943297

RESUMO

BACKGROUND: To date, 14 single-nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB). AIM: To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)-positive CHB patients. METHODS: We performed a retrospective analysis of 1623 Han Chinese HBeAg-positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow-up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase-IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed. RESULTS: We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα-treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one-third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P-trend = 4.000 × 10-4 ) and HBsAg loss (P-trend = 0.010) in PegIFNα-treated patients. However, none of the SNPs were associated with treatment response in NUCs-treated patients. CONCLUSIONS: CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg-positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.

2.
Hepatol Int ; 14(1): 105-114, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31898210

RESUMO

BACKGROUND: Controversy exists on whether tenofovir disoproxil fumarate (TDF) is superior to entecavir (ETV) in lowering the risk of hepatocellular carcinoma (HCC) development. This meta-analysis was performed to clarify this issue with critical clinical and methodological considerations. METHODS: PubMed, EMBASE, and Cochrane Library were searched from inception to Oct 28, 2019. Randomized control trials and observational studies reporting the impact of TDF and ETV on the risk of HCC in patients with chronic hepatitis B (CHB) were eligible. Risk ratios (RRs) calculated with cumulative incidence rate and/or annual incidence rate, or hazard ratio (HR) were pooled using random-effect models. Subgroup analyses were performed to assess the potential impact of between-study level and within-study level factors. RESULTS: A total of 32 studies with 78,136 CHB patients were included. Overall cumulative incidence rate of HCC was lower in TDF group than ETV group (3.07% vs. 5.25%; RR 0.55; 95% CI 0.42-0.72). However, this difference was not statistically significant in pooled results of hazard ratio (HR 0.87; 95% CI 0.73-1.04) and RR calculated with annual incidence rate (RR 0.88; 95% CI 0.67-1.16). Potential confounding factors at between-study level included prior nucleos(t)ide usage, disease stage at baseline and region of study. More importantly, at within-study level, disparity in follow-up duration between TDF and ETV groups may impact the result, usually favoring a treatment with shorter follow-up duration. CONCLUSIONS: Compared with ETV, TDF treatment tended to have a lower overall cumulative incidence rate of HCC. However, disparity in follow-up duration may be a key factor to influence the result.

3.
J Viral Hepat ; 27(1): 45-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31520460

RESUMO

A simple, pangenotypic and effective treatment regimen for patients with a broad range of chronic hepatitis C virus (HCV) infections remains an unmet medical need. We conducted a phase 2, randomized, open study involving untreated patients with chronic HCV genotypes 1, 2, 3, or 6 infections. Patients without cirrhosis were randomly assigned in a 1:2 ratio to receive capsules of the NS5A inhibitor coblopasvir at a dose of 30 or 60 mg plus tablets of the nucleotide polymerase inhibitor sofosbuvir (400 mg) once daily for 12 weeks. Patients with cirrhosis received 60 mg coblopasvir plus sofosbuvir for 12 weeks. The primary endpoint was the sustained virologic response at 12 weeks after the end of therapy (SVR12). Of the 110 patients who were enrolled in the study, 59 were male, 62.7% had HCV genotype 1, 24.5% had genotype 2, 6.4% had genotype 3, and 6.4% had genotype 6. The average age was 45.5 years. A total of 10.9% of patients had compensated cirrhosis. The rate of SVR12 was 98.2% in the intention-to-treat (ITT). One genotype 6 patient with cirrhosis experienced virologic relapse. One genotype 2 patient without cirrhosis failed to complete the follow-up and quit the study. Serious adverse events (SAEs) were reported in 2 patients and were not related to coblopasvir and sofosbuvir. Most adverse events (AEs) did not require treatment. Coblopasvir plus sofosbuvir taken once daily for 12 weeks provided high rates of sustained virologic response (SVR) and had a good safety profile among patients with HCV genotypes 1, 2, 3, or 6 infections, including those with compensated cirrhosis.

4.
Clin Gastroenterol Hepatol ; 18(1): 196-204.e8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31042581

RESUMO

BACKGROUND & AIMS: Variants in STAT4 (rs7574865) have been associated with seroconversion to hepatitis B e antigen (HBeAg) and reduction in levels of hepatitis B virus (HBV) DNA in patients with chronic infection treated with interferon alpha (IFNA). We evaluated the associations among rs7574865, loss of HB surface antigen (HBsAg, a marker of functional cure of HBV infection), and response to treatment with pegylated IFNA (PegIFN) or nucleos(t)ide analogues (NUCs) in HBeAg-positive patients with chronic HBV infection. METHODS: We performed a retrospective analysis of 1823 HBeAg-positive patients with chronic HBV infection (954 patients treated with PegIFN and 869 patients treated with NUCs) included in 4 phase-4 multicenter randomized controlled trials. The Cochran-Armitage trend test was used to evaluate the association of rs7574865 genotype with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <2000 IU/mL) and loss of HBsAg at week 72, for patients given PegIFN, or week 104, for patients given NUCs. RESULTS: We found a significant association between rs7574865 genotype and CR (P = .004) and loss of HBsAg (P = .037) in patients treated with PegIFN. In patients with HBV genotype B infection, 43.6% of those with rs7574865 TT achieved a CR, compared to patients with rs7574865 GG (20.5%), and 7.7% had loss of HBsAg, compared to 1.9% of patients with rs7574865 GG. However, in patients treated with NUCs, we found no association of rs7574865 genotype with CR (P = .811) or loss of HBsAg (P=.439). CONCLUSIONS: In a retrospective analysis of data from 4 clinical trials, we found rs7574865 in STAT4 to be associated with functional cure of chronic HBV infection by PegIFN treatment, but not NUCs treatment, in HBeAg-positive patients with HBV genotype B infection.

5.
Clin Gastroenterol Hepatol ; 18(2): 457-467.e21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31306800

RESUMO

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

6.
Lancet Gastroenterol Hepatol ; 5(2): 167-228, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31852635

RESUMO

The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.

7.
Hepatol Int ; 13(6): 695-705, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31650510

RESUMO

BACKGROUND AND AIM: Cirrhosis is a controversial determinant of mortality in HBV-related acute-on-chronic liver failure (HBV-ACLF). The present study aimed to explore the effects of cirrhosis and the associated risk factors, especially its complications, on the outcome of HBV-ACLF. METHODS: A prospective-retrospective cohort of 985 patients was identified from the APASL-ACLF Research Consortium (AARC) database and the Chinese Study Group. Complications of ACLF (ascites, infection, hepatorenal syndrome, hepatic encephalopathy, upper gastrointestinal bleeding) as well as cirrhosis and the current main prognostic models were measured for their predictive ability for 28- or 90-day mortality. RESULTS: A total of 709 patients with HBV-ACLF as defined by the AARC criteria were enrolled. Among these HBV-ACLF patients, the cirrhotic group showed significantly higher mortality and complications than the non-cirrhotic group. A total of 36.1% and 40.1% of patients met the European Association for the Study of Liver (EASL)-Chronic Liver Failure consortium (CLIF-C) criteria in the non-cirrhotic and cirrhotic groups, respectively; these patients had significantly higher rates of mortality and complications than those who did not satisfy the CLIF-C criteria. Furthermore, among patients who did not meet the CLIF-C criteria, the cirrhotic group exhibited higher mortality and complication rates than the non-cirrhotic group, without significant differences in organ failure. The Tongji prognostic predictor model score (TPPMs), which set the number of complications as one of the determinants, showed comparable or superior ability to the Chinese Group on the Study of Severe Hepatitis B-ACLF score (COSSH-ACLFs), APASL-ACLF Research Consortium score (AARC-ACLFs), CLIF-C organ failure score (CLIF-C OFs), CLIF-C-ACLF score (CLIF-C-ACLFs), Model for End-Stage Liver Disease score (MELDs) and MELD-sodium score (MELD-Nas) in HBV-ACLF patients, especially in cirrhotic HBV--ACLF patients. Patients with two (OR 4.70, 1.88) or three (OR 8.27, 2.65) complications had a significantly higher risk of 28- or 90-day mortality, respectively. CONCLUSION: The presence of complications is a major risk factor for mortality in HBV-ACLF patients. TPPM possesses high predictive ability in HBV-ACLF patients, especially in cirrhotic HBV-ACLF patients.

8.
J Clin Gastroenterol ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31651571

RESUMO

BACKGROUND AND AIM: The prevalence of lean/nonobese nonalcoholic fatty liver disease (NAFLD) ranges widely in studies. Thus, here, we aimed to perform a meta-analysis on NAFLD prevalence in the lean or nonobese population to give clarity. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched to identify studies reporting NAFLD prevalence in the lean/nonobese population. Lean or nonobese was defined by body mass index cutoffs reported by authors in original studies. NAFLD prevalence based on community, population, or health checkups was combined with random-effect model after logit transformation. Subgroup analysis and meta-regression were further performed to investigate the heterogenicity. RESULTS: A total of 45 studies were enrolled in the final analysis, with 55,936 lean/nonobese subjects included, among whom 7351 NAFLD patients were diagnosed. Overall, the pooled NAFLD prevalence of the lean or nonobese population was 10.2% (95% confidence interval: 7.6%-13.6%) and 15.7% (95% confidence interval: 12.5%-19.6%), respectively. Compared with western studies, the NAFLD prevalence in the lean or nonobese population was lower in eastern studies. In addition, the NAFLD prevalence in both the lean and nonobese population showed a general upward trend during recent years. The prevalence was similar in community-based and health checkup-based studies. Lean/nonobese NAFLD patients had significantly lower rates of hypertension, lower uric acid and fasting plasma glucose, and a higher level of high-density lipoprotein than nonlean/obese patients. CONCLUSIONS: The prevalence of NAFLD in the lean/nonobese population is not rare in either the western or eastern regions of the world. This meta-analysis of prevalence assessment and clinical characteristics should enable higher confidence in more specific interventions and health care standards for these patients.

9.
Hepatol Res ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31652370

RESUMO

AIM: Chronic drug-induced liver injury (DILI) with persistent abnormal liver function tests (LFTs) >6 months after cessation of the insulting drugs could progress to cirrhosis. The aim of the present study was to identify the risk factors of chronic DILI for early recognition and better management. METHODS: History of drug intake and results of LFTs were retrospectively retrieved for patients with a discharge diagnosis of DILI for at least 1-year follow up. The risk factors independently associated with chronic DILI were analyzed by multiple logistic regression analyses. RESULTS: A total of 33 of the 140 DILI patients had persistent abnormal LFTs >6 months, which were considered as chronic DILI. It was found that the time intervals of alanine aminotransferase and total bilirubin decline from the peak to their half peak (T0.5ALT , T0.5TBIL ) were significantly longer in the chronic DILI group than that in the recovered group (P = 0.001 and P < 0.001). The risk factors associated with chronic DILI independently were T0.5TBIL (OR 1.315, 95% CI 1.038-1.668), longer period of insulting drug(s) intake (OR 1.018, 95% CI 1.003-1.033), mixed/cholestatic pattern (OR 97.159, 95% CI 1.866-5005.994). More importantly, receiver operating characteristic curve analysis showed that the prognostic value of T0.5TBIL for chronic DILI had a sensitivity of 60.0% at a specificity of 90.7% with the threshold of 16 days. CONCLUSIONS: The time intervals of total bilirubin decline from its peak to half of its peak (T0.5TBIL ) was an early independent predictive factor of chronic DILI, suggesting that T0.5TBIL might serve as an indicator for chronicity.

10.
Med Educ Online ; 24(1): 1679944, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31630670

RESUMO

Background: There is a strong need to include training of research methods in training programs for physicians. International clinical research training programs (CRTP) that comprehensively introduce the methodology of clinical research and combined with practice should be a priority. However, few studies have reported a multimodal international CRTP that provides clinicians with an introduction to the quantitative and methodological principles of clinical research. Objective: This manuscript is intended to comprehensively describe the development process and the structure of this multimodal training program. Methods: The CRTP was comprised of three distinct, sequential learning components: part 1 - a six-week online eLearning self-study; part 2 - a series of three weekly interactive synchronous webinars conducted between Durham, North Carolina, USA and Beijing, China; and part 3 - a five-day in-person workshop held at Beijing Friendship Hospital, Capital Medical University (BFH-CMU). Self-assessment quiz scores and participation rates were used to evaluate effectiveness of the training program. Participants' demographic characteristics, research experience, satisfaction and feedback on the program were collected using questionnaires. Results: A total of 50 participants joined the CRTP. Forty-four participants (88%) completed the program satisfaction questionnaires. The average quiz score of the six eLearning units varied from 31% to 73%. Among the three components of the program, the online eLearning self-study was felt to be the most challenging. Thirty-nine (89%) of the surveyed respondents were satisfied with all components of the training program. Among the respondents, 43 (98%) felt the training was helpful in preparing them for future clinical research projects and expressed willingness to recommend the program to other colleagues. Conclusions: We established a multimodal international collaborative training program. The program demonstrated acceptable participation rates and high satisfaction among Chinese clinicians. It provides a model that may be used by others developing similar international clinical research training programs for physicians.

11.
Cell Mol Immunol ; 16(12): 932-934, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31664221
12.
J Clin Transl Hepatol ; 7(3): 213-220, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608212

RESUMO

Background and Aims: Ravidasvir (RDV) is a new generation pangenotypic hepatitis C virus (HCV) NS5A inhibitor, with high barrier to baseline resistance-associated species. This is the first phase 2/3 study conducted in Mainland China confirming the efficacy and safety of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks in treatment-naïve noncirrhotic patients with genotype 1 infection in a large population. Methods: In this multicenter, randomized, double-blinded, placebo-controlled phase 2/3 trial (NCT03362814), we enrolled 424 treatment-naïve, noncirrhotic adult HCV genotype 1 patients. All patients were randomized at 3:1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day (body weight <75/≥75 kg) (n = 318) or placebo (n = 106) for 12 weeks. The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment, and the safety was evaluated and compared between treatment and placebo groups. Results: The overall rate of sustained virological response at 12 weeks after treatment is 99% (306/309, 95%, CI: 97%-100%) under per protocol set analysis. All patients harboring baseline NS5A resistance-associated species in the treatment group (76/76, per protocol set) achieved sustained virological response at 12 weeks after treatment. No treatment-related serious adverse events were reported. Laboratory abnormalities showed mild or moderate severity (grade 1 and grade 2) in liver function tests. Conclusions: In treatment-naïve, noncirrhotic HCV Chinese patients infected with HCV genotype 1, all-oral regimen of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks was highly efficacious, safe, and well tolerated.

13.
J Clin Transl Hepatol ; 7(3): 221-225, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608213

RESUMO

Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 µg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9-99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082.

14.
J Clin Transl Hepatol ; 7(3): 249-257, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608217

RESUMO

Background and Aims: Data are limited on the use of pegylated-interferon alpha-2a (peg-IFNα) in Chinese patients with chronic hepatitis B virus (HBV) infection (CHB). We evaluated the effectiveness and safety of peg-IFNα in Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice. Methods: In this prospective, multicenter, observational, non-interventional cohort study, patients were assessed for up to 1 year after peg-IFNα treatment cessation. Treating physicians established the dosing and treatment duration according to Chinese clinical practice. Effectiveness of peg-IFNα treatment was measured by the percentage of: patients with HBV DNA <2000 IU/mL and loss of hepatitis B surface antigen (commonly known as HBsAg); HBV DNA level at end of treatment (EOT), and 6 months and 1 year posttreatment; and time course change in quantitative HBV DNA and HBsAg. Results: At EOT, 6 months posttreatment, and 1 year posttreatment, the percentage of patients with HBV DNA <2000 IU/mL was 90.0%, 81.8%, and 82.2%, and that of patients with HBsAg loss was 6.5%, 9.4%, and 9.5%, respectively. The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment. The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment. The incidence of adverse events was 52.0%. Conclusions: Peg-IFNα has the potential to provide functional cure (HBsAg loss) for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China. Clinical Trial Registration: ClinicalTrials.gov (NCT01730508).

15.
World J Gastroenterol ; 25(36): 5403-5422, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576089

RESUMO

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists' consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.

16.
Chin Med J (Engl) ; 132(19): 2315-2324, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567376

RESUMO

BACKGROUND: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. METHODS: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. RESULTS: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. CONCLUSION: Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

17.
Hepatol Int ; 13(6): 766-776, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31559605

RESUMO

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) commonly affects subjects with obesity, yet non-obese NAFLD is increasingly being recognized. We aimed to investigate the clinicopathological and genetic characteristics of non-obese NAFLD patients. METHODS: The clinical, histological and genetic data of 84 NAFLD patients with biopsy for abnormal liver function test were reviewed. Both NAS-CRN and SAF scoring systems were applied for histopathological evaluation. PNPLA3 and TMS6F2 genotyping were also performed. RESULTS: All of the 84 patients were histologically diagnosed with non-alcoholic steatohepatitis (NASH), with 36 of them (42.9%) being non-obese (BMI < 25 kg/m2). Compared with the obese group, non-obese group were predominantly females (88.9% vs 52.1%, p < 0.001), tended to have higher prevalence of diabetes (p = 0.068). More importantly non-obese patients had a significant higher prevalence of advanced fibrosis (F ≥ 3) (58.3% vs 29.2%, p = 0.013), and a trend of higher degree of ballooning (p = 0.061). In addition, values of liver stiffness measurement were also significantly higher in non-obese group (12.1 kPa vs 8.1 kPa, p = 0.032). There was also a trend of higher prevalence of TM6SF2 T allele in non-obese group (p = 0.085), while the prevalence of PNPLA3 risk allele did not differ between two groups. Multivariate analysis showed that higher fasting glucose (p = 0.038) and lower serum platelets (p = 0.040) were two independent predictors for advanced fibrosis in non-obese patients. CONCLUSIONS: Non-obese NASH patients have a female predominance and more advanced fibrosis. Liver biopsy is crucial to evaluate the severity of disease in non-obese patients especially those with abnormal liver biochemistry. CLINICAL TRIAL NUMBER: NCT03386890.

18.
Hepatol Int ; 13(6): 788-799, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31552558

RESUMO

AIMS: Epidemiological studies on primary biliary cholangitis (PBC) show heterogeneity. The aim of the present study was to synthesize the prevalence, incidence and clinical course of PBC in the Asia-Pacific region. METHODS: PubMed, Medline, Cochrane library and EMBASE were searched for epidemiology and clinical course of PBC published up to July, 2019. Meta-analysis was conducted on the epidemiology and clinical course (decompensation, hepatocellular carcinoma and death/liver transplantation) of PBC patients. Random-effect model and fixed-effect model were used to evaluate the pooled prevalence, incidence, mortality/liver transplantation and their 95% confidence intervals as appropriate. Subgroup analysis was performed by stratification with gender, pre- and post-UDCA era, sub-region and publication year. Meta-regression was used to examine the heterogeneity. RESULTS: Out of 3460 studies, 18 studies from 7 countries/regions were finally included. The overall prevalence of PBC was 118.75 cases per million (95% CI 49.96-187.55) in the Asia-Pacific region, with the high, medium and low prevalence being in Japan and China (191.18 cases per million), New Zealand (99.16 cases per million) and South Korea and Australia (39.09 cases per million), respectively. The incidence of PBC was 8.55 cases per million per year (95% CI 8.05-9.06). The 5-year accumulative incidence of decompensation, HCC and death/liver transplantation in PBC patients was 6.95% (95% CI 2.07-11.83%), 1.54% (95% CI 0.9-2.19%) and 4.02% (95% CI 2.49-5.54%), respectively. CONCLUSION: In the Asia-Pacific region, the prevalence and incidence of PBC are higher than once expected. PBC tends to be diagnosed at older age and has a relatively low incidence of HCC in this region.

19.
Mod Pathol ; 32(12): 1795-1805, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31300804

RESUMO

Histologically, drug-induced liver injury could be classified into acute hepatitis, chronic hepatitis, acute cholestasis, chronic cholestasis, and cholestatic hepatitis. The correlation between these histologic patterns and long-term clinical outcomes has not been well established. Therefore, we conducted a retrospective cohort study to investigate the association of histologic patterns and long-term clinical outcomes defined as biochemical normalization, persistent abnormal liver biochemistry or death at designated time points. In this study, biochemical classification was determined by R-values; histologic injury pattern was determined by morphological features. Predictive ability of clinical outcomes by these two classifications was assessed using Receiver Operating Characteristic Curves. Logistic regression was performed to identify histologic factors associated with outcomes. Totally, 88 patients with drug-induced liver injury were included for final analysis. Biochemical and histologic classification were consistent in 50 (57%) cases. 53 (60%) cases showed biochemical normalization within 6 months, and a further 11 (13%), 16 (18%), and 6 (7%) cases within 1, 2, and 3 years, respectively. Compared with biochemical classification, histologic injury pattern had better predictive ability for abnormal biochemistry at 6 months (Areas under Receiver Operating Characteristic Curves 0.92 versus 0.60, P < 0.001) and 1 year (Areas under Receiver Operating Characteristic Curves 0.94 versus 0.69, P < 0.001). Interlobular bile duct loss in >25% portal areas was independently associated with abnormal biochemistry at 6 months, 1 year, and 2 years. In conclusion, histologic injury pattern is better correlated with clinical outcome at 6 months and 1 year than biochemical classification. Moderate bile duct loss is an important histologic feature associated with persistent biochemical abnormality at 6 months, 1 year, and 2 years.

20.
Hepatology ; 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31278760

RESUMO

Nucleos(t)ide analogues (NAs) have been widely used for the treatment of chronic hepatitis B (CHB). Because viral DNA polymerase lacks proofreading function (3' exonuclease activity), theoretically, the incorporated NAs would irreversibly terminate viral DNA synthesis. This study explored the natures of nascent hepatitis B virus (HBV) DNA and infectivity of progeny virions produced under NA treatment. HBV infectivity was determined by infection of HepG2-NTCP cells and primary human hepatocytes (PHHs). Biochemical properties of HBV DNA in the progeny virions were investigated by qPCR, northern blotting, or Southern blotting hybridization, sucrose gradient centrifugation, and in vitro endogenous DNA polymerase assay. Progeny HBV virions produced under NA treatment were mainly not infectious to HepG2-NTCP cells or PHHs. Biochemical analysis revealed that under NA treatment, HBV DNA in nucleaocapsids or virions were predominantly short minus-strand DNA with irreversible termination. This finding was supported by the observation of first disappearance of relaxed circular DNA and then the proportional decline of HBV-DNA levels corresponding to the regions of PreC/C, S, and X genes in serial sera of patients receiving NA treatment. Conclusion: HBV virions produced under NA treatment are predominantly replication deficient because the viral genomes are truncated and elongation of DNA chains is irreversibly terminated. Clinically, our results suggest that the viral loads of CHB patients under NA therapy vary with the different regions of genome being detected by qPCR assays. Our findings also imply that NA prevention of perinatal and sexual HBV transmission as well as infection of transplanted livers works not only by reducing viral loads, but also by producing noninfectious virions.

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