New perspective on the natural course of chronic HBV infection

Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.

Molecular therapy and prevention of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxins (alcohol, aflatoxin BI) and various inherited metabolic liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency. Central to the molecular pathogenesis of HCC are mutations of various genes and genetic/chromosomal instability that result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. Alterations in the structure or expression of several tumor suppressor genes and oncogenes have been described. In addition, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation appear to be involved. The prognosis of HCC patients is generally very poor. Most studies have shown a five-year survival rate of less than 5% in symptomatic patients. HCC has been found to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCC revealed a long-term survival of patients only with small asymptomatic HCC that could be treated surgically or nonsurgically. For patients with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy are urgently needed. Apart from exploring and refining new HCC treatment strategies, the implementation of the existing measures or the development of novel measures to prevent HCC is most important. Primary HCC prevention could have a major impact on the incidence of HCC. Further, secondary prevention of a local recurrence or of new HCC lesions in patients after successful surgical or nonsurgical HCC treatment is of paramount importance and is expected to significantly improve disease-free and overall survival rates of patients. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement or in part replace the existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduced HCC incidence and an improved clinical outcome for patients with HCC, one of the most devastating malignancies worldwide.

Predictors of unfavorable outcome at 90 days in basilar artery occlusion patients

BACKGROUND In a previous study,basilar artery occlusion(BAO)was shown to lead to death or disability in 80%of the patients.The treatment for BAO patients in the acute stage includes thrombolysis and intra-arterial thrombectomy,but not all patients benefit from these treatments.Thus,understanding the predictors of outcome before initiating these treatments is of special interest.AIM To determine the predictors related to the 90-d clinical outcome in patients with BAO in an Asian population.METHODS We performed a retrospective case review of patients admitted to a tertiary stroke center between 2015 and 2019.We used the international classification of diseases-10 criteria to identify cases of posterior circulation stroke.A neurologist reviewed every case,and patients fulfilling the criteria defined in the Basilar Artery International Cooperation Study were included.We then analyzed the patients’characteristics and factors related to the 90-d outcome.RESULTS We identified a total of 99 patients as real BAO cases.Of these patients,33(33.3%)had a favorable outcome at 90 d(modified Rankin Scale:0–3).Moreover,72 patients received intra-arterial thrombectomy,while 13 patients received intravenous tissue-type plasminogen activator treatment.We observed a favorable outcome in 33.3%of the cases and an unfavorable outcome in 66.7%of the cases.We found that the initial National Institutes of Health Stroke Scale(NIHSS)score and several BAO symptoms,including impaired consciousness,tetraparesis,and pupillary abnormalities,were significantly associated with an unfavorable outcome(P<0.05),while cerebellar symptoms were associated with a favorable outcome(P<0.05).In the receiver operating characteristic(ROC)analysis,the areas under the ROC curve of initial NIHSS score,impaired consciousness,tetraparesis,cerebellar symptoms,and pupillary abnormalities were 0.836,0.644,0.727,0.614,and 0.614,respectively.Initial NIHSS score showed a higher AUROC(0.836)compared to BAO symptoms.CONCLUSION The most important predictor of an unfavorable outcome was the initial NIHSS score.BAO symptoms,including tetraparesis,impaired consciousness,and pupillary abnormality were also related to an unfavorable outcome.

Uterine cervical carcinoma treated with chemoradiotherapy: impact of three-month MRI follow-up on clinical management and outcome

Aim:The aim of this study was to evaluate the impact of MRI performed three months after treatment on further follow-up interventions and outcome in patients with uterine cervical carcinoma treated with definitive chemoradiotherapy.Methods:Sixty consecutive women diagnosed with uterine cervical cancer FIGO 2009 stage IB1-IVA during 2011-2012 treated with definitive chemoradiotherapy/radiotherapy with curative intent at the Department of Gynaecological Oncology at Karolinska University Hospital were retrospectively included.A review of MRI reports and medical records with focus on follow-up interventions associated to imaging was performed.Results:On follow-up MRI three months post treatment,29/60 women had complete remission(mrCR),24/60 women had partial remission(mrPR)and 7/60 had progressive disease(mrPD).In patients with mrCR,no additional procedures were performed.The group with mrPR had 27 additional MRIs,3 PET/CT examinations and 9 biopsy procedures,none leading to diagnosis of residual tumour.Locoregional control rate was 96%after 6.5 months(median).No patient had cervical relapse only;2/53 had cervical relapse in combination with non-regional lymph nodes and distant relapse.There was no statistically significant difference in overall survival between patients with mrCR and mrPR(HR=2.2,P=0.21).Conclusion:Patients with residual changes on MRI at three months post treatment have a low risk for locoregional recurrence.If this is not recognised,follow-up MRI results in unnecessary additional procedures with low impact on treatment outcome.Further studies are needed regarding the most appropriate imaging modality and timing of post-treatment evaluation.