Mechanism of intrauterine infection of hepatitis B virus

AIM:To explore the possible mechanism of intrauterineinfection of hepatitis B virus (HBV).METHODS:HBV DNA was detected in vaginal secretionand amniotic fluid from 59 HBsAg-positive mothers and invenous blood of their newborns by PCR.HBsAg and HBcAgin placenta were determined by ABC immunohistochemistry.RESULTS:The rate of HBV intrauterine infection was 40.1%(24/59).HBV DNA was detected in 47.5% of amniotic fluidsamples and 52.5% of vaginal secretion samples respectively.HBsAg and HBcAg were detected in placentas from HBsAg-positive mothers.The concentration of the two antigensdecreased from the mother's side to the fetus's side,in thefollowing order:maternal decidual cells > trophoblastic cells>villous mesenchymal cells > villous capillary endothelialcells.However,in 4 placentas the distribution was in thereverse order.HBsAg and HBcAg were detected in amnioticepithelial cells from 32 mothers.CONCLUSION:The main route of HBV transmission frommother to fetus is transplacental,from the mother side ofplacenta to the fetus side.However,HBV intrauterineinfection may take place through other routes.     

Occult hepatitis C virus infection: what does it mean?

Occult hepatitis C virus infection (OCI) is a recently identified entity of which the existence became evident when nucleic acid amplification assays of enhanced sensitivity were introduced for the detection of hepatitis C virus (HCV) genome and its replication. This form of HCV infection has been found to persist in the presence of antibodies against HCV and normal levels of liver enzymes for years after spontaneous or antiviral therapy‐induced resolution of hepatitis C and, therefore, can be termed as secondary OCI. HCV RNA in OCI circulate at fluctuating levels normally not exceeding 200 genome copies per millilitre of serum or plasma, while low levels of virus genome and its replicative intermediate RNA‐negative strand are detectable in the liver and, importantly, immune cells, which provide an opportunity to detect active virus replication without the need for acquiring a liver biopsy. In addition to secondary OCI, a form of OCI accompanied by persistently moderately elevated serum liver enzymes in the absence of antibodies to HCV, which can be termed as cryptogenic OCI, has also been described. The current understanding of the nature and characteristics of OCI, methods and pitfalls of its detection, as well as the documented and expected pathological consequences of OCI will be summarized in this review.     

Late reactivation of resolved hepatitis B virus infection: An increasing complication post rituximab‐based regimens treatment?

Reactivation of hepatitis B infection is an increasing problem for patients with lymphoma, even in resolved infections, who were treated with rituximab-based regimens. Our cases point out the need of prolonged prophylaxis in HBsAg-negative patients due to the high risk of developing fatal reactivation.     

Presence of hepatitis B virus markers in umbilical cord blood: Exposure to or infection with the virus?

BackgroundWe aimed to clarify whether presence of hepatitis B virus (HBV) markers in cord blood indicates exposure to or infection with HBV.MethodsWe prospectively recruited HBsAg-positive pregnant women and their neonates 2012 through 2015. All neonates received postnatal immunoprophylaxis. The infants were followed up at 7–14 months of age.ResultsTotally 329 HBsAg-positive pregnant women and 333 neonates were enrolled. No cord blood was anti-HBc IgM positive. A total of 290 (87.1%) neonates were followed up at 7–14 months of age and 6 (2.1%) of them were infected with HBV. Of 146 neonates born to HBeAg-negative mothers, 38 (26.0%) and 30 (20.5%) had detectable HBsAg and HBV DNA in cord blood respectively, but none of 126 infants followed up was infected. Of 187 neonates born to HBeAg-positive mothers, 92 (49.2%) and 79 (42.2%) had detectable HBsAg and HBV DNA in cord blood respectively; 6 (3.7%) of 164 infants followed up were infected. Of seven neonates with HBV DNA > 10⁵ IU/ml in cord blood, four had no infection and three others were infected.ConclusionPresence of HBsAg and/or HBV DNA, even at high levels, in cord blood just indicates exposure to, but not infection with HBV. Presence of HBV markers in cord blood cannot define intrauterine infection.     

Is hemodialysis a reason for unresponsiveness to hepatitis B vaccine? Hepatitis B virus and dialysis therapy

Impaired renal function is associated with a high risk of chronicity of hepatitis B virus (HBV) infection. Patients on hemodialysis (HD) or peritoneal dialysis are at an increased risk of viral transmission due to frequent necessity of blood product transfer as well as use of contaminated dialysate or dialysis materials. Additionally, health professionals may cause viral spread via contaminated hands and carelessness against hygiene rules. The frequency of chronic HBV infection may be as high as 80% in patients on renal replacement therapies. This is because HBV vaccination is essential to eliminate chronic HBV infection. However, response rates of HD patients to HBV vaccination vary between 10%-50%. Dialysis adequacy and early vaccination before the onset of dialysis therapy seem to be major determinants of high seroconversion rates. Older age, male gender, duration of dialysis therapy and nutritional status are other well-known factors associated with seroconversion rate. There are controversial reports regarding the role of the presence of diabetes mellitus, HCV positivity, erythropoietin resistance, hyperparathyroidism, and vitamin D inadequacy. The role of genetic alteration in the functions or production of cytokines still needs to be elucidated.     

Does antiviral therapy improve the clinical course of cirrhosis due to hepatitis C virus infection?

Treatment of hepatitis C with pegylated interferon plus ribavirin achieves viral eradication rates of between 50 and 80%. A large number of patients with sustained viral response show fibrosis regression. However, patients without viral response also show improvement. Patients with compensated cirrhosis due to hepatitis C virus can also be successfully treated. In these patients, viral eradication is usually followed by fibrosis non-progression and a reduction of portal hypertension, which undoubtedly modifies the clinical course of the process. In patients without virological response, the ability of antiviral maintenance therapy to alter the natural history of the disease is not clear and three large multicenter studies are currently underway. Preliminary data indicate that patients with cirrhosis treated with interferon as maintenance therapy show less progression than those treated with colchicine.     

Follow-up after curative resection for gastric cancer: Is it time to tailor it?

There is still no consensus on the follow-up frequency and regimen after curative resection for gastric cancer.Moreover,controversy exists regarding the utility of follow-up in improving survival,and the recommendations of experts and societies vary considerably.The main reason to establish surveillance programs is to diagnose tumor recurrence or metachronous cancers early and to thereby provide prompt treatment and prolong survival.In the setting of gastric malignancies,other reasons have been put forth:(1)the detection of adverse effects of a previous surgery,such as malnutrition or digestive sequelae;(2)the collection of data;and(3)the identification of psychological and/or social problems and provision of appropriate support to the patients.No randomized controlled trials on the role of follow-up after curative resection of gastric carcinoma have been published.Herein,the primary retrospective series and systematic reviews on this subject are analyzed and discussed.Furthermore,the guidelines from international and national scientific societies are discussed.Followup is recommended by the majority of institutions;however,there is no real evidence that follow-up can improve long-term survival rates.Several studies have demonstrated that it is possible to stratify patients submitted to curative gastrectomy into different classes according to the risk of recurrence.Furthermore,promising studies have identified several molecular markers that are related to the risk of relapse and to prognosis.Based on these premises,a promising strategy will be to tailor follow-up in relation to the patient and tumor characteristics,molecular marker status,and individual risk of recurrence.     

Surveillance for hepatocellular carcinoma in chronic viral hepatitis: Is it time to personalize it?

Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma (HCC), including those with cirrhosis, advanced fibrosis and special subgroups of chronic hepatitis B (CHB). Application of the standard surveillance strategy to all patients with chronic liver disease (CLD) with or without cirrhosis imposes major sustainability and economic burdens on healthcare systems. Thus, a number of HCC risk scores were constructed, mainly from Asian cohorts, to stratify the HCC prediction in patients with CHB. Similarly, even if less than for CHB, a few scoring systems were developed for chronic hepatitis C patients or cirrhotic patients with CLD of different etiologies. Recently, a few newsworthy HCC-risk algorithms were developed for patients with cirrhosis using the combination of serologic HCC markers and clinical parameters. Overall, the HCC risk stratification appears at hand by several validated multiple score systems, but their optimal performance is obtained only in populations who show highly homogenous clinic-pathologic, epidemiologic, etiologic and therapeutic characteristics and this limitation poses a major drawback to their sustainable use in clinical practice. A better understanding of the dynamic process driving the progression from CLD to HCC derived from studies based on molecular approaches and genetics, epigenetics and liquid biopsy will enable the identification of new biomarkers to define the individual risk of HCC in the near future, with the possibility to achieve a real and cost/effective personalization of surveillance.     

Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B virus infection?

The diagnosis of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA >or=2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg-negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA >2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading score >or=7 and/or stage >or=2 in Ishak's classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNA >or=200,000, 20,000-199,999, 2,000-19,999, and <2,000 IU/mL, respectively (P < 0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P = 0.025). All inactive carriers had HBV DNA <20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation. CONCLUSION: HBeAg-negative chronic HBV patients with persistently or transiently increased ALT and HBV DNA >or=20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA <20,000 and even <2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg-negative patients with persistently normal ALT and HBV DNA >2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow-up.