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Background and Aim Non‐alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are prevalent conditions sharing common pathogenic factors. We performed a systematic literature review and meta‐analysis aiming to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. Methods Relevant studies were systematically identified from scientific databases until 2019. We calculated pooled odds ratio (OR) using a random‐effect model, and heterogeneity was addressed through I 2. Subgroup analyses and meta‐regression for various covariates were performed. Results Of the 1833 studies retrieved, 23 studies with 7148 participants qualified for quantitative synthesis. The pooled result showed that women with PCOS had a 2.5‐fold increase in the risk of NAFLD compared to controls (pooled OR 2.49, 95% confidence interval [CI] 2.20–2.82). In subgroup analyses comparing PCOS to controls, South American/Middle East PCOS patients had a greater risk of NAFLD (OR 3.55, 95% CI 2.27–5.55) compared to their counterpart from Europe (OR 2.22, 95% CI 1.85–2.67) and Asia (OR 2.63, 95% CI 2.20–3.15). Insulin resistance and metabolic syndrome were more frequent in the PCOS group (OR 1.97, 95% CI 1.44–2.71 and OR 3.39, 95% CI 2.42–4.76, respectively). Study quality and body mass index (BMI) were the only covariates that showed a relationship with the outcome in the meta‐regression, with a regression coefficient of −2.219 (95% CI −3.927 to −0.511) and −1.929 (95% CI −3.776 to −0.0826), respectively. Conclusions This meta‐analysis indicates that premenopausal PCOS patients are associated with 2.5‐fold increase in the risk of NAFLD, and BMI seems to be the main cofactor., We performed a systematic literature review and meta‐analysis to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. Of 1833 studies, 23 studies with 7148 participants were included. Women with PCOS had a 2.5‐fold increase in the risk of NAFLD compared to controls (Pooled OR 2.49, 95% CI 2.20‐2.82; I2=55.2%, p=0.001). South American/Middle East populations had a greater risk of NAFLD (OR 3.55, 95% CI 2.27‐5.55).

To develop the evidence-based guidelines for managing mother-to-child transmission of hepatitis B virus in China, a multidisciplinary guideline development group was established. Clinical questions were identified from two rounds of surveys on the concerns of first-line clinicians. We conducted a comprehensive search and review of the literature. A grading of recommendations’ assessment, development, and evaluation system was adopted to rate the quality of evidence and the strength of recommendations. Recommendations were formulated based on the evidence, overall balance of benefits and harms (at individual and population levels), patient/health worker values and preferences, resources available, cost-effectiveness, and feasibility. Eventually, recommendations related to 13 main clinical concerns were developed, covering diagnostic criteria, treatment indications, antiviral therapy choice, timing to initiate and discontinue treatment, immunoprophylaxis strategy at birth, and how to deal with special situations, such as unintended pregnancy, assisted reproduction, and breastfeeding. The guidelines are intended to serve as guidance for clinicians and patients, to optimize the management of majority of pregnant women who are positive for hepatitis B surface antigen. Guideline registration: International Practice Guide Registration Platform (IPGRP-2018CN040).

Background The current outbreak of COVID‐19 has spread rapidly all over the world. Respiratory droplets and contaction with infected patients are the two major transmission routes. However, the value of tear virus nucleic acid is still not clear. We dynamic detected the SARS‐CoV‐2 in eye sample of one COVID‐19 patient with obstruction of common lacrimal ducts. Methods Besides the routine examination, nasopharyngeal and eye swab were continuously measured by polymerase chain reaction assay and next‐generation sequencing (NGS). Gene detection was performed for drug use guidance, and flow cytometry was performed to analyse the lymphocyte subsets. Results Nasopharyngeal swabs were positive for 22 days, but eye swabs were still continuously positive for 2 weeks after nasopharyngeal swabs turned negative. The low level of lymphocyte and the high level IL‐6 lasted for almost 4 weeks, then became near normal. Next‐generation sequencing (NGS) confirmed the existing of SARS‐CoV‐2, HSV1 and HHV6B virus nucleic acid. The gene detection for drug use guidance showed the genetic locus ABCB1 (3435T>C) rs1045642 belonged to type CC and it mean the efficiency of lopinavir–ritonavir would be significantly decreased. The flow cytometry of lymphocyte subsets showed PD‐1+ CD95+ cells was accounting for 94.8% in CD3+ CD8+ T subset and for 94.8% in CD3+ TCRγδ+ T subset. Conclusions As obstruction of common lacrimal duct, positively detection in one eye for 2 weeks more after nasopharyngeal swab became negative. More eye swabs should be collected from COVID‐19 patients, especially from those immunocompromised, those with eye symptoms and those had a history of ocular diseases.

Background Several antiviral agents licenced for blocking mother-to-child transmission (MTCT) of HBV, but their relative efficacy beginning from different trimesters has scarce been evaluated. We aimed to conduct a network meta-analysis to statistically differ the efficacy and safety of each antiviral agents initiating on different timings in preventing mother-to-infant transmission of HBV. Methods Studies were included from PubMed, EMBASE, Web of Science, and Cochrane databases through July 1, 2019. Eligible studies recruited randomized controlled trials and nonrandomized studies reporting about infant or/and maternal efficacy and safety outcomes and were screened by two investigators independently. Extracted data were analyzed by pair-wised and network meta-analysis, respectively. Results 3 Randomized and 32 nonrandomized studies enrolling 6738 pregnant female were included. Using network analysis, any antiviral agent interrupted HBV vertical transmission much more effectively than placebo. No agent showed significant efficacy different from others, but a strong trend toward significance was found in telbivudine and tenofovir, of which had the highest probability of being ranked the first- or second-best treatment for reducing MTCT of HBV. The treatment applied in the first and second trimester had a similar efficacy in preventing MTCT. Compared with the initiation during the third trimester, lower rate of MTCT was revealed when antiviral therapy was administrated before third trimester, (RR = 0.045, 95% CI 0.0053 to 0.20); a similar effect at delivery on suppressing maternal HBV DNA level and converting serum HBeAg were achieved if the timing of antiviral treatment started prior, but an obvious improvement of normalizing ALT flare was calculated out; no statistically differences among maternal and fetal safety outcomes were found if mothers received antiviral agents before pregnant 28 weeks. Conclusion This network meta-analysis recommended the earlier use of telbivudine or tenofovir, tends to be better to prevent MTCT of HBV in pregnancy with no increased adverse maternal or fetal outcomes.

Cardiovascular events are among the leading cause of mortality in kidney and liver transplant recipients. Thus, screening for cardiovascular disease and risk stratification for cardiovascular events constitute an important part of the pretransplant evaluation. In this review, we first summarize current guidelines in the cardiac risk assessment of kidney and liver transplant candidates. We then elaborate on the limitations of these guidelines, summarize the current knowledge gaps, and narrow down a spectrum of 6 themes that serve as challenges to research and practice development. This spectrum pertains to understanding the disease itself, which is challenging due to the altered cardiac physiology in these patients and current guidelines that do not adequately account for nonischemic diseases and events. We then describe the challenges in assessing these patients, their symptoms, and individualizing their risk of cardiovascular events with a special consideration for nontraditional risk factors. We also explore the limitations of the current and novel diagnostic tests and the lack of evidence of therapeutic efficacy in intervening in patients with asymptomatic disease. The transplant procedure itself can be a potential modifiable risk factor for cardiovascular events, that is, surgical technique, type of donor, and induction immunosuppression. Lastly, we describe the potential issues with the current literature when defining cardiac diseases and events across different studies and shortcomings of extrapolating data from the nontransplant literature. We conclude by proposing research and practice implications of our discussion and that there is a need for evidence to guide the revision of current guidelines.

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests.Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient's clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged.Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients.

Interferon (IFN) treatment is widely applied in viral hepatitis and multiple myeloproliferative diseases. However, there is considerable controversy on how to deal with unintended pregnancy during IFN treatment, even selective termination is suggested by hepatologists. To settle this clinical dilemma, we conducted a systematic review to retrieve all published articles involving IFN exposure during pregnancy up until March 31, 2021. Only 8 case reports that were relevant with outcomes of pregnant women with viral hepatitis exposed to IFN-α were retrieved, and 17 studies reporting pregnancy outcomes after exposure to type I IFNs involving 3,543 pregnancies were eligible for meta-analysis. No birth defect was reported in the case reports of pregnant women with viral hepatitis. The meta-analysis showed that risks of pregnancy outcomes and birth defects were not increased after exposure to IFN-α. Further comprehensive meta-analysis concerning the IFN-α and IFN-β exposure demonstrated that the risks of live birth (OR 0.89, 95% CI: 0.62–1.27), spontaneous abortion (OR 1.09, 95% CI: 0.73–1.63), stillbirth (OR 1.38, 95% CI: 0.51–3.72), preterm delivery (OR 1.24, 95% CI: 0.85–1.81), and maternal complications (OR 0.72, 95% CI: 0.38–1.38) were not increased in patients exposed to IFNs. The pooled estimates of live birth, spontaneous abortion, stillbirth, preterm delivery, and maternal complications were 85.2, 9.4, 0, 7.5, and 6.5%, respectively. Importantly, the risk of birth defects was not increased (OR 0.68, 95% CI: 0.39–1.20) after IFN exposure, with a pooled rate of 0.51%. Therefore, IFN exposure does not increase the prevalence of spontaneous abortion, stillbirth, preterm delivery, and birth defects. Clinical decision should be made after weighing up all the evidence.

Background & Aims There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. Methods Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. Results Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. Conclusions TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. Trial registration This study is ongoing and is registered with ClinicalTrials.gov, NCT03640728 (05/02/2019).

Background. HBV-resistant mutants in treatment-naïve patients may lead to antiviral treatment failure. It is not clear if HBV mutants are present in pregnant women and about the influence of the preexisting mutants on the short-term antiviral therapy during pregnancy. Method. We enrolled 73 pregnant women with high HBV DNA load and telbivudine (TBV) treatment during pregnancy in this retrospective study. The UDPS was used to detect the HBV mutations before and after the TBV treatment. Results. Before TBV treatment, the complexity of HBV quasispecies of all subjects was 0.40 ± 0.09; 41.1% (30/73) and 53.4% (39/73) subjects had rtM204I/V and rtN236 T/A detected, respectively; and 9.6% (7/73) patients had more than 20% frequency mutation of rtM204I/V, which was also similar with high frequency of rtN236 T/A mutation (41.1% vs. 53.4%,P=0.136; frequencies >20%: 9.6% vs. 5.5%,P=0.347). After TBV treatment, 71.2% (52/73) subjects had HBV DNA load ≥ 103 IU/mL at delivery. Among them, 75.0% of patients with rtM204I positive had HBV DNA load ≥103 IU/mL at delivery, which was comparable with the subjects without rtM204I (75.0% vs. 70.8%,P=0.710). No changes were found in the frequencies and the complexity of HBV quasispecies of rtM204I mutation after the TVB treatment. Conclusion. The prevalence of preexisting drug-resistant mutations among pregnant women was high using UPDS. However, the preexisting HBV mutation had limited influence on the efficacy of short-term TBV treatment, and TBV treatment during late pregnancy seemed not to increase the risk of emerging HBV-resistant mutants.

Background: Interferon (IFN) is widely applied in viral hepatitis and multiple oncologic diseases. Whereas, there is considerable controversy on how to deal with unintended pregnancy during IFN treatment. Methods: Following the guidelines of PRISMA, a systematic review was performed to retrieve all published articles involving IFN exposure during pregnancy. Electronic databases including PubMed, EMBASE, Cochrane Library, Web of Science, and major Chinese database were searched for possibly relevant articles published up to March 2020. Findings: From 9819 original references, 17 studies involving 3543 pregnancies were eligible for meta-analysis. Only 8 cases report were retrieved relevant with IFN-α exposure in pregnant women with viral hepatitis, and none presented birth defects. The meta-analysis evaluating safety of IFN-α showed risks of pregnancy outcomes, including birth defects were not higher than the control population. Further comprehensive meta-analysis concerning with IFN-α and IFN-β demonstrate the risks of live birth (OR 0.89, 95% CI: 0.62-1.27), spontaneous abortion (OR 1.09, 95% CI: 0.73-1.63), stillbirth (OR 1.38, 95% CI: 0.51-3.72), preterm delivery (OR 1.24, 95% CI: 0.85-1.81), and maternal complications (OR 0.72, 95% CI: 0.38-1.38) were comparable with the unexposed group. Additionally, the pooled estimates of live birth, spontaneous abortion, still birth, preterm deliveries, and maternal complications were 85.2%, 9.4%, 0%, 7.5%, and 6.5%, respectively. Importantly, the risk of birth defects was not increased (OR 0.68, 95% CI: 0.39-1.20) with pooled rate of 0.51 %. Interpretation: IFN exposure during pregnancy does not increase the risk of adverse outcomes. The rates of major pregnancy outcomes are comparable with general population and un-exposed population, which provides important information to both hepatologists and obstetricians regarding the risks of IFN exposure against potential risks of induced abortion. Funding: National Natural Science Foundation of China and Key R&D Program of Shaanxi. Declaration of Interests: All authors declare no competing interests.

The transparency and validity of assessing the candidacy of a patient for a solid organ transplant have recently been called into question by the media.1 Transplant centers perform a lengthy medical, surgical, and psychosocial evaluation on candidates with organ failure. This process ensures that there are no contraindications to surgery and to the use of long-term immunosuppressive medications. In addition, it helps ascertain if transplant candidates are likely to benefit from the transplant surgery over long term. Pretransplant nonadherence to prescribed therapy, medications, investigations, and clinical visits, is recognized as a relative or an absolute contraindication by transplant programs. For example, the Canadian Society of Transplantation states, given the use of immunosuppressive agents with a narrow therapeutic window, the impact of nonadherence to therapy on the risk of acute rejection and premature graft loss, and the scarcity of donor organs, nonadherence is a contraindication to kidney transplantation.2 This echoes the recommendations of some of the other major transplantation societies as summarized in Table 1.2-8 Most recommend delaying transplant surgery until patients have demonstrated adherence to therapy for 6 months. Table 1. Current Guidelines in the Assessment of Transplant Candidates With a History of Nonadherence.

Objectives A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. Results 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Non-alcoholic steatohepatitis (NASH), which is the progressive counterpart of the disease, is becoming the leading indication for liver transplantation in North America. Owing to the lack of symptoms, NASH is often an incidental diagnosis, resulting in a significant proportion of patients being diagnosed when advanced liver disease has already developed. NAFLD has recently been characterized as the hepatic manifestation of metabolic syndrome. Consequently, it is a multisystem disease that often co-exists with several other conditions, such as obesity, diabetes, cardiovascular diseases, and extra-hepatic malignancy, which have an impact on selection of transplant recipients. The complexity of diagnostic approach, need for multidisciplinary clinical management, and lack of a specific treatment further complicate the picture of this extremely prevalent liver condition. NAFLD patients with advanced liver disease should be considered for early referral to liver transplant clinics for careful metabolic and cardiovascular risk stratification because they have worse survival rates after liver transplantation than other patients with chronic liver disease. Early referral will also facilitate optimization of metabolic comorbidities before proceeding with transplantation. This review provides an overview of strategies to identify patients with advanced NAFLD, with an emphasis on the management of associated comorbidities and optimal timing of pre-transplant evaluation. Other topics that have been shown to affect recipient optimization, such as the role of lifestyle changes and bariatric surgery in the management of obesity, as well as sarcopenia in decompensated NASH-related cirrhosis, are addressed.

Background: HBV resistant mutants in treatment-naïve patients may lead to antiviral treatment failure. It’s not clear if HBV resistant mutants present in the pregnant women before the antiviral treatment and the influence of the pre-existing resistant mutants on the short-term Telbivudine (TBV) therapy during the late pregnancy.Method: We enrolled 73 pregnant women with high HBV DNA load and TBV treatment during the pregnancy from 2012 to 2015 in this retrospective study. All subjects were followed at least 52 weeks postpartum. The UDPS was used to detect the HBV mutations before and after the TBV treatment.Results: Before TBV treatment, the complexity of HBV quasispecies of all subjects was 0.40± 0.09. At primary drug resistance mutation sites, 41.1% (30/73) and 53.4% (39/73) subjects had rtM204I/V and rtN236T/A detected, respectively; 9.6% (7/73) patients had more than 20% frequency mutation of rtM204I/V, which was also similar with high frequency of rtN236T/A mutation (41.1% vs. 53.4%, P = 0.136; frequencies > 20%: 9.6% vs. 5.5%, P = 0.347). After TBV treatment, 71.2% (52/73) subjects still had HBV DNA load ≥ 103IU/mL at delivery. Among them, 75.0% patietns with rtM204I positive had HBV DNA load ≥ 103IU/mL at delivery, which was comparable with the subjects without rtM204I (75.0% vs. 70.8%, P = 0.710). No changes were found in the frequencies and the complexity of HBV quasispecies of rtM204I mutation after the TVB treatment.Conclusion: The prevalence of pre-existing drug resistant mutations among the pregnant women was high using UPDS. However, the pre-existing HBV mutation had limited influence on the efficacy of short-term TBV treatment, and TBV treatment during late pregnancy seemed not to increase the risk of emerging HBV resistant mutants.

Background & Aims: Polycystic ovary disease (PCOS) may be a risk factor for nonalcoholic fatty liver disease (NAFLD) due to common pathogenetic pathways, including insulin resistance and obesity. Both PCOS and NAFLD are more severe in South Asian women. Data on NAFLD in South Asian women with PCOS are lacking.Methods: We investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in PCOS patients from South Asia, through a routine screening program. NAFLD was defined as CAP >288 dB/m. Significant liver fibrosis (stage 2 and higher out of 4) was defined as TE measurement >8.0 kPa. Elevated ALT was defined as ALT >24 IU/L, as per upper limit of normal reported in South Asian women. Hyperandrogenism was defined as free androgen index >5. Predictors of NAFLD were determined by logistic regression analysis.Results: 101 PCOS patients (mean age 36.3 years) with no significant alcohol intake or viral hepatitis were included. Prevalence of NAFLD and significant liver fibrosis was 39.6% and 6.9%, respectively. Elevated ALT was observed in 40.0% and 11.5% of patients with and without NAFLD, respectively. After adjusting for duration of PCOS and insulin resistance measured by HOMA-IR, independent predictors of NAFLD were higher BMI (adjusted odds ratio [aOR] 1.30, 95% CI 1.13-1.52), hyperandrogenism (aOR 5.32, 95% CI 1.56-18.17) and elevated ALT (aOR 3.54, 95% CI 1.10-11.47). Lifetime cardiovascular risk was higher in patients with NAFLD compared to those without NAFLD (0.31+0.11 vs. 0.26+0.13).Conclusions: Despite their young age, NAFLD diagnosed by TE with CAP is a frequent comorbidity in South Asian women with PCOS and is strongly associated with higher BMI and hyperandrogenism. Non-invasive screening strategies could help early diagnosis and initiation of interventions, including counselling on weight loss, cardiovascular risk stratification and linkage to hepatology care where appropriate.

Background Tenofovir disoproxil fumarate (TDF) administration in the third trimester for pregnant women with high HBV DNA load has been accepted as a wise practice to prevent mother-to-infant transmission (MTIT). However, for those women who missed the optimal time window of antiviral prophylaxis, this treatment is lacking in the current clinical guidelines. Methods Forty-eight pregnant women who did not receive antiviral prophylaxis before 28 weeks of gestation were screened and were administrated with TDF plus hepatitis B immunoglobulin (HBIG; TDF+HBIG group) or TDF alone (TDF group). HBV DNA inhibition and the safety profile were compared between two groups. Results A decline of HBV DNA load was observed in both groups after a short period of treatment, and no infant had MTIT. However, compared with the TDF group, the speed of HBV DNA load decline was more rapid ( P=0.002) and a much more striking HBV DNA load decline in the first 4 weeks of treatment was exhibited in the TDF+HBIG group ( P=0.001). The percentages of mothers with HBV DNA 10 IU/ml and 3 log10 IU/ml at delivery were both much higher in the TDF+HBIG group than the TDF group ( P=0.034 and 0.024, respectively). TDF and HBIG were found to be well-tolerated with no safety concerns in the mothers and their infants. Conclusions TDF plus HBIG treatment resulted in a rapid HBV DNA load decline in high-risk women who missed the optimal time window of antiviral prophylaxis in pregnancy, which potentially protected infants from HBV infection.

SummaryBackground Hepatitis C virus (HCV) infection in patients undergoing haemodialysis is prevalent and aggressive. The treatment of chronic hepatitis C has been revolutionised by the advent of direct-acting antivirals (DAAs). However, the safety, efficacy, and tolerance of DAAs in the treatment of acute HCV infection in patients with end-stage renal disease who are on haemodialysis are unknown. Aim To evaluate the safety and efficacy of sofosbuvir plus daclatasvir in this specific, difficult-to-treat population. Methods We conducted a prospective and observational study of end-stage renal disease patients who were undergoing haemodialysis and were acutely infected with HCV. Patients received a half dose of sofosbuvir (200 mg) and a full dose of daclatasvir (60 mg) daily. The primary endpoint was the proportion of patients with sustained virological responses (SVRs); the other primary outcomes were safety and tolerability. Results Thirty-three patients were enrolled in the study. The median HCV RNA viral load at baseline was 6.8 log10IU/mL. Twenty-four patients were infected with HCV genotype 2a, seven patients with 1b, and two patients with 2a+1b. All patients achieved a SVR at 12 weeks after the end of treatment. The treatment was well tolerated, and there were no drug-related serious adverse events. Conclusion A half dose of sofosbuvir (200 mg once daily) plus a full dose of daclatasvir (60 mg once daily) were suitable for the treatment of acute HCV-infected patients who were undergoing end-stage renal disease and were on haemodialysis.

Hepatitis B virus (HBV) infections and adverse outcome have been demonstrated to show characteristics of familial clustering. The aim of this study was to investigate the prevalence of different HBV genotypes, HBV sub-genotypes, and Pre-S mutations associated with familial HBV infection clusters with unfavorable prognoses. Families presenting with clustered HBV infections and unfavorable prognoses were enrolled in this study. Non-clustered HBV-infected individuals were used as the control group. DNA extracted from patient serum samples was used to facilitate characterization of the HBV genotypes, HBV sub-genotypes, and Pre-S mutations by phylogenetic analysis. The Pre-S/S gene was successfully amplified in 83 patients from the clustering group and 105 patients from the sporadic group. The prevalence of genotype C in the clustering group (71/83, 85.54%) was significantly higher than in the sporadic group (77/105, 73.33%) (P = 0.042). The prevalence of sub-genotype C2 in the clustering group (33/83, 39.76%) was also higher than in the sporadic group (21/105, 20%) (P = 0.003). Analyses of functional mapping of pre-S sequences showed that the prevalence of the mutation in the S promoter site (nt 3045-3189 of pre-S1 domain) was significantly increased in the clustering group compared with the sporadic group (15.7% vs. 3.8%) (P = 0.009). This study suggests that genotype C, especially sub-genotype C2, may be associated with the progression of HBV infection in familial clustering infection cohorts with unfavorable prognoses. We also observed that the natural occurrence of S promoter mutations in the clustering group was significantly prevalent.

No or low hepatitis B (HB) vaccine response is more frequent in infants from HBsAg(+) mothers than those from HBsAg(-). Our previous study found temporary positivity of HBsAg in infants from HBsAg(+) mothers. In this study, we hypothesized that HBsAg in infant blunt immune response to standard hepatitis B vaccination.A total of 328 consecutive HBsAg(+) mothers and their offspring were enrolled. Blood samples were taken from mothers and their infants and quantified for HBsAg, anti-HBs titer and HBV DNA load concentration; Placenta samples were collected to stain for HBsAg.First, 6.7% infants (22/328) showed anti-HBs titer lower than 10 mIU/mL after HB vaccination (non-response to HB vaccine). HBsAg(+) newborns showed higher risk of non-response than HBsAg(-) infants (13.0% versus 5.0%, p = 0.016). Infants from high HBsAg titer mothers displayed higher risk of HBsAg positivity at birth than those from low titer mothers (45.3% versus 2.8%, p 0.001). HBsAg titer in mothers of HBsAg(+) newborns was much higher than mothers of HBsAg(-) newborns (p 0.001). All those data supported HBsAg can be transferred through placenta. Our hypothesis was further reinforced by immunostaining with specific antibody against HBsAg, a substantial higher prevalence (87.5% versus 30.8%, p = 0.024) and stronger immunostaining (p = 0.008) was demonstrated in HBsAg(+) group comparing with placenta of the HBsAg(-) group.No response to HB vaccine in infants of HBsAg(+) mothers was associated to the transplacental transfer of HBsAg.

Background & Aims Some patients with compensated advanced chronic liver disease (cACLD) require use of an extralarge probe for liver stiffness measurement (LSM), owing to overweight or obesity. However, the ability of noninvasive markers of portal hypertension and the controlled attenuation parameter (CAP) to determine which of these patients are at risk for decompensation has not been fully assessed. Methods We collected data from 272 patients with cACLD (LSM ≥10 kPa by XL probe; 57% with nonalcoholic steatohepatitis; mean body mass index, 33.8 ± 6.5 kg/m2; median Child-Pugh score, 5; median LSM, 16.8 kPa; mean CAP, 318 ± 66 dB/m) evaluated at 2 academic centers from 2015 through 2018. We collected clinical data on decompensation (ascites, portal hypertension bleeding, jaundice, hepatic encephalopathy) and severe bacterial infections; patients were followed up for a median of 17 months (interquartile range, 11–24 mo). We evaluated associations between these events and LSM, CAP, LSM∗spleen size/platelet count (LSPS), and portal hypertension risk scores. Results Decompensation occurred in 12 patients and severe bacterial infections developed in 5 patients. LSM, LSPS, and the portal hypertension risk score identified patients with decompensation with area under the receiver operating characteristic curve values of 0.848 (95% CI, 0.720–0.976; P Conclusions LSM, LSPS, and the portal hypertension risk score identify obese or overweight patients with cACLD who are at increased risk of decompensation and severe bacterial infection.

Background: A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged in Wuhan, China from December, 2019 Wuhan has

Background Sofosbuvir is the keystone of direct antiviral agents for the chronic hepatitis C (CHC). The safety of sofosbuvir in patients with stage 4–5 chronic kidney disease (CKD) needs further observation in real world. Case presentation Thirty-three patients with stage 5 CKD and hepatitis C virus (HCV) infection from 2 hemodialysis centers accepted sofosbuvir based treatment as we reported previously. Serum potassium concentrations were tested every 4 weeks or on demand. Ten of 33 patients showed recurrence of hyperkalemia. We summarized the characteristics of hyperkalemia occurrence in these 10 patients. Overall, 24 episodes of hyperkalemia were observed in these 10 patients, 21 were under treatment and 3 were after treatment. Patients with or without hyperkalemia before sofosbuvir treatment didn’t show significantly differences in the median frequencies of hyperkalemia episodes during the observation period (3.5 vs. 2, p = 0.264). Conclusions Patients with stage 5 CKD and HCV infection treated with sofosbuvir based regimens, even halved sofosbuvir, should be taken caution and closely monitoring serum potassium and renal function is necessary.

Mother-to-child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA > 106 IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow-up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P = 0.015). With intention-to-treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre, 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg > 4 and >5 log10 IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg > 4 log10 IU/mL.

Background and Aim The efficacy of telbivudine for breaking vertical transmission of hepatitis B virus has been well established. Data on the risk of postpartum flare after telbivudine withdrawal and efficacy of extended antiviral therapy after delivery are limited. Methods Chronic hepatitis B virus-infected women who received telbivudine beginning at week 24 or 28 of gestation were enrolled and then followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed. Results Of the 241 women who finished 52 weeks of follow-up, 33.6% had elevated serum alanine aminotransferase (ALT) during pregnancy. Telbivudine administration resulted in ALT normalization in 85.2% before delivery. Compared with women having a normal ALT level throughout pregnancy, those with elevated ALT had a significantly higher rate of ALT flare after telbivudine withdrawal (25.0% vs 11.9%; χ2 = 4.273, P = 0.039). Multivariate analysis indicated that only ALT elevation during pregnancy correlated with postpartum flare after telbivudine withdrawal. Those women with elevated ALT during pregnancy continued antiviral treatment to 52 weeks postpartum and had a significantly higher HBeAg seroconversion rate (P = 0.001) and a notable decrease in HBsAg titers (P = 0.001). Conclusion It is safe for the majority of women to withdraw telbivudine after delivery, whereas exciting serological response encourages extended antiviral therapy for mother with ALT elevation during pregnancy.

Background Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver disease in Western countries and is a frequently reported comorbidity in inflammatory bowel disease (IBD). A complex interaction among polygenic predisposition, IBD-specific risk factors, microbiome, multiple environmental and patients’ factors could explain the development of NAFLD in IBD. Gut dysbiosis is increasingly recognised as an important player in NAFLD, as well as in IBD pathogenesis. So far, no study has examined the gut microbiota composition in IBD patients with NAFLD. We aimed to characterise faecal microbiota according to NAFLD status in a pilot cohort of ulcerative colitis (UC) pancolitis in clinical remission. Methods This was a cross-sectional pilot study using transient elastography (TE) with controlled attenuation parameter (CAP) to diagnose NAFLD in UC pancolitis patients in clinical remission, defined as partial Mayo score ≤1. NAFLD was diagnosed non-invasively as CAP ≥248 dB/m. Exclusion criteria included: use of corticosteroids in the last year and antibiotics or probiotics/prebiotics in the last 2 months prior to inclusion; significant alcohol intake (AUDIT-C Results A total of 11 UC pancolitis patients in clinical remission were included (mean age 53 years, 36.4% male, time since IBD diagnosis 16 years). NAFLD was diagnosed in 7 cases (63.6%, mean CAP 291 dB/m). Patients with pancolitis and NAFLD had higher BMI (mean 31 vs. 22 kg/m2, p = 0.006) as well as waist circumference (mean 100 vs. 81 cm, p = 0.006) compared with those without NAFLD, but no other differences in demographic, clinical or pharmacological parameters were found between pancolitis with or without NAFLD. Patients with pancolitis and NAFLD clustered separately from those without NAFLD, when computing Bray Curtis dissimilarities (tested with Adonis, p = 0.006). In addition, patients with pancolitis and NAFLD presented with decreased bacterial richness (p = 0.017) but not diversity. This was accompanied by a significant increase of Bacteroides spp. relative abundance in faecal samples of patients with pancolitis and NAFLD (q = 0.017). Conclusion This pilot study demonstrates, for the first time, that, in UC pancolitis patients, NAFLD associates with altered gut microbiota composition. Further studies are needed to understand the exact role of gut microbiota in UC pancolitis with NAFLD and to evaluate the use of microbiota-directed approaches for the treatment of NAFLD in these patients.

To investigate the transmission routes of hepatitis B virus (HBV) in families with clusters of infection and unfavorable prognoses and to analyze the prevalence of liver cirrhosis (LC) or hepatocellular carcinoma (HCC) in the offspring of these families. Families with clusters of HBV infection and unfavorable prognoses were enrolled in the study, and general information and serum samples were collected. The prevalence of LC or HCC was compared in offspring of different genders whose parents were diagnosed with LC or HCC. This analysis comprised 102 probands with 51 siblings, 15 parents, 284 children, and 74 spouses. Interestingly, 88.2% of the siblings and 76.8% of the children of these probands were positive for hepatitis B surface antigen (HBsAg), compared with only 9.5% of the spouses (P

Liver sinusoids serve as the first line of defense against extrahepatic stimuli from the intestinal tract. Hepatic stellate cells (HSCs) are pericytes residing in the perisinusoidal space that integrate cytokine-mediated inflammatory responses in the sinusoids and relay these signals to the liver parenchyma. Oxidative stress has been shown to promote inflammation during acute liver failure (ALF). Whether and how oxidative stress is involved in HSC inflammation during ALF remains unclear. Level of systemic oxidative stress is reflected by superoxide dismutase (SOD). Thus, ALF patients were recruited to investigate the correlation between plasma SOD levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from ALF patients who had undergone liver transplantation. SOD2 expression and HSCs activation were investigated by immunohistochemistry. Inflammation, mitophagy, and apoptosis were investigated by immunoblot analysis and flow cytometry in HSCs treated with lipopolysaccharide (LPS) and reactive oxygen species (ROS) donors. The plasma SOD level was significantly increased in patients with ALF compared with those with cirrhosis (444.4 ± 23.58 vs. 170.07 ± 3.52 U/ml, P < 0.01) and was positively correlated with the Model for End-Stage Liver Disease-Na score ( R2 = 0.4720, P < 0.01). In vivo observations revealed that SOD2 immunostaining was increased in ALF patients and mice models, and in vitro experiments demonstrated that LPS/ROS promoted inflammation via inhibiting mitophagy. Moreover, the regulation of inflammation was apoptosis independent in HSCs. LPS-induced increases in oxidative stress promote inflammation through inhibiting mitophagy in HSCs during the process of ALF, providing a novel strategy for the treatment of patients with ALF. NEW & NOTEWORTHY Here we demonstrate that the serum superoxide dismutase (SOD) level is significantly increased in patients with acute liver failure (ALF), and, correlated with the Model for End-Stage Liver Disease-Na score, SOD level dropped in the remission stage of ALF. We identify that, in liver tissue from ALF patients and mice models, manganese-dependent SOD was overexpressed, and show lipopolysaccharide/H2O2 inhibits mitophagy via reactive oxygen species in hepatic stellate cells (HSCs). We show that inhibited mitophagy promotes inflammation in HSCs, whereas mitophagy inducer rescues HSCs from lipopolysaccharide-induced inflammation.

Background & Aims Diagnosis of preclinical compensated cirrhosis (occult cirrhosis, OC) is challenging due to lack of clinical findings. We evaluated prevalence and outcomes of OC by transient elastography (TE, Fibroscan®). Methods Eight hundred and seventy-one patients with compensated chronic liver disease (CLD) and TE examination were divided into: (i) OC (TE ≥ 13 kPa and no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (ii) clinically evident cirrhosis (TE ≥ 13 kPa with signs of cirrhosis); (iii) non-cirrhotic CLD (TE

BACKGROUND AND GOALS A series of changes in the immune system occur during pregnancy and puerperium. Currently, we aim to characterize both the natural changes in liver inflammation and its association with hepatitis B viremia during this special period. PATIENTS AND METHODS Chronic hepatitis B (CHB) gravidas were recruited and followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed throughout the period. RESULTS A total of 1097 CHB mothers had finished the entire follow-up including 451 accepting telbivudine, 178 accepting tenofovir, and 468 without antiviral therapy. Among the mothers, 11.94% went through hepatic flare in the first trimester and the rate decreased to 2.1% at the time of delivery. Nevertheless, a much higher frequency (19.78%) was observed in the early postpartum. Interestingly, alanine aminotransferase level decreased along with the development of pregnancy and then suddenly increased in the first month of puerperium. In addition, a downward trend was observed on the titer of HBsAg and HBeAg after delivery. Of note, an obvious higher frequency of alanine aminotransferase flare was revealed in mothers with high viremia (>6 log10 IU/mL). With multivariate analysis, only hepatitis B virus titer at baseline was strongly associated with hepatic flare during early postpartum (95% confidence interval, 1.012-3.049, P=0.045). The predictive rates of hepatic flare at baseline viral load of 6, 7, and 8 log10 IU/mL were 16.67%, 28.30%, and 30.60%, respectively. CONCLUSIONS CHB gravidas with high viremia should be monitored closely during entire pregnancy, and extended antiviral therapy is recommend to those mothers with baseline viremia >7 log10 IU/mL.

We previously found that hepatic stellate cell activation induced by autophagy maintains the liver architecture to prevent collapse during acute liver failure. Nitric oxide has shown to induce hepatic stellate cell apoptosis. Whether and how nitric oxide is involved in acute liver failure and autophagy remains unclear.Acute liver failure patients were recruited to investigate the correlation between plasma nitric oxide levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from acute liver failure patients who had undergone liver transplantation. The expression of nitric oxide synthases and hepatic stellate cell activation (alpha-SMA), and autophagic activity (LC3) were investigated by immunohistochemistry. Autophagy and apoptosis were investigated by immunoblot analysis, confocal microscopy, and flow cytometry in hepatic stellate cells treated with nitric oxide donors.Plasma nitric oxide level was significantly increased in patients with acute liver failure compared to those with cirrhosis (53.60±19.74 μM vs 19.40±9.03 μM, Z=-7.384, P.001) and positively correlated with MELD-Na score (r=.539, P.001), implicating nitric oxide in acute liver failure. At least some Nitric oxide was produced by overexpression of inducible nitric oxide synthases and endothelial nitric oxide synthases, but not neuronal nitric oxide synthases in the liver tissue. In vivo observation revealed that autophagy was inhibited in hepatic stellate cells based on decreased LC3 immunostaining, and in vitro experiments demonstrated that Nitric oxide can inhibit autophagy. Moreover, nitric oxide promoted hepatic stellate cell apoptosis, which was rescued by an autophagy inducer.Increased nitric oxide synthases/ nitric oxide promotes apoptosis through autophagy inhibition in hepatic stellate cells during acute liver failure, providing a novel strategy for the treatment of patients with acute liver failure.

Purpose of review This article reviews treatment options of the approved and soon-to-be approved direct-acting antivirals (DAA)-based therapies in individuals with hepatitis C virus (HCV) cirrhosis. Recent findings DAA-based therapies have been shown to be well tolerated and effective in achieving viral cure in individuals with compensated and decompensated cirrhosis. Preliminary studies suggest that viral eradication arrests fibrosis progression and could lead to fibrosis regression. Long-term benefits of successful HCV treatment in this population translate into less frequent hepatic decompensation and hepatocellular carcinoma development, improvements in liver disease severity, reduction of liver-related mortality, and potential obviation of the need for transplantation. The optimization of viral eradication rates requires longer duration therapy and/or more complex combinations of drugs, including ribavirin. Treatment decisions are guided by HCV genotype, renal function, drug-drug interactions, and the severity of cirrhosis. Safety concerns are paramount in individuals with advanced liver disease and continued vigilance for hepatotoxicity and other complications is warranted, especially in those with decompensated cirrhosis. Summary The availability of high potency DAA-based therapies with excellent safety profiles has transformed the HCV-infected cirrhotic population into a group that is no longer 'difficult-to-treat'. Understanding the pretreatment factors that predict clinical benefits vs. harm remains key in treating this population.

Background: Accumulating evidence has suggested that cell-free DNA (cf-DNA) enters the circulation following cell apoptosis or necrosis. An increased level of cf-DNA fragments has been found in the blood of mice with drug-induced liver damage. We sought to determine the role of cf-DNA in hepatocellular damage. Methods: Plasma samples were collected from 204 patients with hepatitis. The patients were divided into three groups according to liver pathologic characteristics: with chronic hepatitis (CH) and compensated liver cirrhosis (LC) (the group 1); with decompensated liver cirrhosis (DLC) (the group 2); with liver failure (LF), acute hepatitis (AH) and hepatocellular carcinoma (HCC) (the group 3). The cf-DNA was extracted with the phenol/chloroform/isoamyl alcohol (PCI) method and the plasma cf-DNA was quantified using real-time polymerase chain reaction (rt-PCR) for β-globin. The cf-DNA copies were converted to log2 values for comparison. Results: Cf-DNA was detected in all the 3 groups. The group 3 had a significantly higher cf-DNA level than the other two groups (17.70 ± 1.79, P = 0.002). The level of plasma cf-DNA was correlated with the baseline aniline transaminase (ALT) and aspertate transaminase (AST) activities (P 19.5), or with severe hepatocellular damage (ALT > 500 U/L). Conclusion: Plasma cell-free DNA may be a new promising, independent, non-invasive biomarker for hepatocellular damage.

The seroprevalence of hepatitis B virus (HBV) and its impact on pregnancy outcomes of women from Shaanxi Province (China) was assessed. Risk factors for mother-to-child transmission (MTCT) were evaluated based on HBV-related seroprevalence data. Viral markers and biochemical parameters were assessed in HBsAg-positive mothers and their infants out of 13,451 cases recruited. A pretested and structured questionnaire was used to test the general HBV knowledge. Descriptive statistics and logistic regression analysis were done to reveal possible risk factors for MTCT. The overall prevalence of HBsAg in pregnant women was 7.07% (951/13,451), and a rate as high as 9.40% was observed. Among the HBsAg-positive pregnant women, 30.49% (290/951) were HBeAg-positive, 22.08% (210/951) had HBV DNA levels >106 IU/mL and only 16.19% with a high risk of MTCT (34/210) had received antiviral treatment. The overall MTCT rate was 5.21%. Noteworthy, the risk ratio and 95% confidence interval (95% CI) of MTCT in HBeAg-negative mothers with HBV DNA levels >2 × 103 IU/mL and HBsAg >104 IU/mL was 26.062 (2.633–258.024), which was significantly higher than that of HBeAg-positive mothers with HBV DNA level >106 IU/mL. Moreover, the awareness and knowledge about HBV transmission, risk factors, and intervention for MTCT were generally lacking among HBsAg-positive mothers. As a higher HBsAg seroprevalence and a higher MTCT rate among HBeAg-negative mothers with lower HBV DNA level was observed, our study emphasizes different interventional criteria for HBeAg-positive and HBeAg-negative mothers. Extensive health education, routine screening, and immunization against HBV during pregnancy are highly warranted to minimize the possibility of perinatal transmission.

Background Neither HBV DNA nor HBsAg positivity at birth is an accurate marker for HBV infection of infants. No data is available for continuous changes of HBV markers in newborns to HBsAg(+) mothers. This prospective, multi-centers study aims at observing the dynamic changes of HBV markers and exploring an early diagnostic marker for mother-infant infection. Methods One hundred forty-eight HBsAg(+) mothers and their newborns were enrolled after mothers signed the informed consent forms. Those infants were received combination immunoprophylaxis (hepatitis B immunoglobulin [HBIG] and hepatitis B vaccine) at birth, and then followed up to 12 months. Venous blood of the infants (0, 1, 7, and 12 months of age) was collected to test for HBV DNA and HBV markers. Results Of the 148 infants enrolled in our study, 41 and 24 infants were detected as HBsAg(+) and HBV DNA(+) at birth, respectively. Nine were diagnosed with HBV infection after 7 mo follow-up. Dynamic observation of the HBV markers showed that HBV DNA and HBsAg decreased gradually and eventually sero-converted to negativity in the non-infected infants, whereas in the infected infants, HBV DNA and HBsAg were persistently positive, or higher at the end of follow-up. At 1 mo, the infants with anti-HBs(+), despite positivity for HBsAg or HBV DNA at birth, were resolved after 12 mo follow-up, whereas all the nine infants with anti-HBs(−) were diagnosed with HBV infection. Anti-HBs(−) at 1 mo showed a higher positive likelihood ratio for HBV mother-infant infection than HBV DNA and/or HBsAg at birth. Conclusions Negativity for anti-HBs at 1 mo can be considered as a sensitive and early diagnostic indictor for HBV infection in the infants with positive HBV DNA and HBsAg at birth, especially for those infants with low levels of HBV DNA load and HBsAg titer.

Hepatitis B virus (HBV) infection is a major public health problem, and HBV-related acute-on-chronic liver failure (ACLF) has an extremely poor prognosis. There is no standard approach for managing ACLF. Nucleos(t)ide analogue has been proven effective in suppressing viral replication, improving histology and biochemical, and decreasing the inflammatory response in patients with chronic hepatitis B. This study was designed to evaluate the short-term and long-term efficacy of nucleoside analogue treatment of patients with HBV-related ACLF. One hundred and six consecutive subjects were recruited from 2,308 patients with elevated alanine aminotransferase activity. Forty-two patients were treated with 0.5 mg entecavir (ETV) daily (ETV group); 30 patients received 100 mg lamivudine (LAM) daily (LAM group); 34 patients did not take any nucleos(t)ide analogues (non-NAs group). All eligible patients were given standard medical treatment. All the patients were followed up until death or until October 2010. The HBV DNA levels and the short-term and long-term efficacy of the drugs were evaluated. After 3 weeks of nucleoside analogue treatment and/or supportive therapy, HBV DNA levels were decreased when compared with the baseline level in the ETV group (7.04 ± 1.58 log(10) IU/mL vs. 4.03 ± 2.04 log(10) IU/mL, P = 0.001), the LAM group (7.25 ± 0.89 log(10) IU/mL vs. 4.33 ± 2.48 log(10) IU/mL, P = 0.01), and the non-NAs group (5.73 ± 0.96 log(10) IU/mL vs. 4.21 ± 1.47 log(10) IU/mL, P = 0.01). The ETV and LAM groups showed a similar accumulative mortality in the first 3 months of treatment (33.3% vs. 40%, χ(2) = 0.568, P = 0.374). The non-NAs group had a significantly high mortality, compared with the ETV group (64.7% vs. 33.3%, χ(2) = 7.163, P = 0.007), the LAM group (64.7% vs. 40%, χ(2) = 3.906, P = 0.042), and the nucleoside analogue group (ETV group + LAM group) (64.7% vs. 36.2%, χ(2) = 7.443, P = 0.006). All the 56 patients survived were followed up to October 2010. The median follow-up period was 7.3 months. Recurrence was observed in a total of 6 patients (10.72%), of whom 4 patients (33.33%) were from the non-NAs group, 2 (11.11%) from the LAM group after cessation LAM therapy by patients himself, and 0 from the ETV group (P = 0.003). Nucleoside analogue may improve the short-term and long-term prognosis of patients with HBV-related ACLF.

Using a nested-PCR genotyping system, we analyzed the viral genotypes in HBV-infected patients from HBV clustering infection families (CIFs), as compared with HBV infected patients without familial infection history. The patients in the CIF group showed significantly increased prevalence of genotype C infection, while genotype B was absent. Additionally, in the genotype C carriers younger than 50 years old, the prevalence of HCC and LC were significantly increased in CIF compared to the control. We found that HBeAg-positive HBV genotype C carriers are prone to develop end-stage liver diseases earlier than those infected by genotype B.

AIM: To investigate the expression and distribution of HBV in the ovaries and ova. METHODS: The immunohistochemistry method was used to detect the HBsAg and HBcAg in the ovaries of patients with chronic hepatitis B. RESULTS: Expression of HBsAg in the ova, granular and interstitial cells of the ovaries was located in the cytomembrane and cytoplasm. Expression of HBcAg in the ova, granular, interstitial and endothelial cells of interstitial blood vessels of the ovaries was found in the cytomembrane, cytoplasm, and nuclei. CONCLUSION: HBV can infect the ova at different stages of development and replicate in it.