Intrahepatic Infection Research Articles

Polycystic intrahepatic infection caused by Enterococcus casseliflavus: a case report and literature review

BackgroundEnterococcus casseliflavus is a rare pathogenic bacterium that is characterized by vancomycin resistance and can lead to multiple infections in the human body. This report describes a rare case of polycystic intrahepatic infection with E. casseliflavus which necessitated antibiotic treatment and surgical intervention involving cystic drainage.Case PresentationA 59-year-old woman, a long-term hemodialysis patient, was hospitalized due to a 5-day history of fever, abdominal pain, and diarrhea, which were possibly caused by the ingestion of contaminated food. Her blood culture yielded a positive result for E. casseliflavus, and she was initially treated with piperacillin/tazobactam and linezolid. Later, the antibiotic regimen was adjusted to include meropenem and linezolid. Despite treatment, her body temperature remained elevated. However, subsequent blood cultures were negative for E.casseliflavus.Conventional CT scans and ultrasound examinations did not identify the source of infection. However, a PET-CT examination indicated an intrahepatic cyst infection. Following MRI and ultrasound localization, percutaneous intrahepatic puncture and drainage were performed on the 20th day. Fluoroquinolones were administered for 48 days. On the 32nd day, MRI revealed a separation within the infected cyst, leading to a repeat percutaneous drainage at a different site. Subsequently, the patient’s temperature returned to normal. The infection was considered resolved, and she was discharged on the 62nd day. Follow-up results have been favorable thus far.ConclusionsBased on the findings from this case, it is recommended to promptly conduct PET-CT examination to exclude the possibility of intracystic infection in cases of polycystic liver infection that are challenging to control. Furthermore, timely consideration should be given to puncture drainage in difficult cases.

The hepatitis delta virus and chronic hepatitis D.

The hepatitis delta virus and chronic hepatitis D.

From the Editor’s Desk...

From the Editor’s Desk...

Comprehensive characterization of viral integrations and genomic aberrations in HBV-infected intrahepatic cholangiocarcinomas.

Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and HBV infection, little is known about the relevant oncogenic effects. We sought to identify the landscape and mechanism of HBV integration, along with the genomic architecture of HBV-infected iCCA (HBV-iCCA) tumors. We profiled a cohort of 108 HBV-iCCAs using whole-genome sequencing, deep sequencing, and RNA sequencing, together with preconstructed data sets of HBV-infected HCC (HBV-HCC; n=167) and combined hepatocellular cholangiocarcinoma (HBV-cHCC/CCA; n=59), and conventional (n=154) and fluke-related iCCAs (n=16). Platforms based on primary iCCA cell lines to evaluate the functional effects of chimeric transcripts were also used. We found that HBV had inserted at multiple sites in the iCCA genomes in 45 (41.7%) of the tumors. Recurrent viral integration breakpoints were found at nine different sites. The most common insertional hotspot (7 tumors) was in the TERT (telomerase reverse transcriptase) promoter, where insertions and mutations (11 tumors) were mutually exclusive, and were accompanied by promoter hyperactivity. Recurrent HBV integration events (5 tumors) were also detected in FAT2 (FAT atypical cadherin 2), and were associated with enrichment of epithelial-mesenchymal transition-related genes. A distinctive intergenic insertion (chr9p21.3), between DMRTA1 (DMRT like family A1) and LINC01239 (long intergenic non-protein coding RNA 1239), had oncogenic effects through activation of the mammalian target of rapamycin (mTOR)/4EBP/S6K pathway. Regarding the mutational profiles of primary liver cancers, the overall landscape of HBV-iCCA was closer to that of nonviral conventional iCCA, than to HBV-HCC and HBV-cHCC/CCA. Our findings provide insight into the behavior of iCCAs driven by various pathogenic mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.

Clinical application of laparoscopy combined with choledochoscopy in patients with bilioenteric anastomotic stricture with access via the jejunal loops.

ObjectiveBilioenteric anastomotic stricture is a serious complication following choledochojejunostomy. Some patients develop intrahepatic lithiasis and biliary tract infection without dilation of the intrahepatic bile duct. The present study was performed to investigate the safety and efficacy of laparoscopy combined with choledochoscopy in patients with bilioenteric anastomotic stricture with access via the jejunal loops.MethodsThe data of 10 patients (7 men and 3 women; mean age, 60.8 ± 9.7 years; age range, 51–76 years) with potential bilioenteric anastomotic stricture without dilation of the intrahepatic bile duct from January 2015 to December 2019 were retrospectively reviewed.ResultsAll 10 patients underwent surgery, and their clinical parameters were recorded. The mean surgery time was 181.5 ± 35.4 minutes, and the mean estimated blood loss was 32.0 ± 15.5 mL. No patients developed serious complications during the perioperative period. The short-term outcome analysis at 12 months indicated that the stenosis had been effectively dilated and that the liver function had improved.ConclusionsThe results of the present study demonstrated that laparoscopy combined with choledochoscopy with access via the jejunal loops is feasible in the treatment of bilioenteric anastomotic stricture and intrahepatic lithiasis.

Glucose Homeostasis Is Dysregulated in Ducks Infected with Duck Hepatitis B Virus

Introduction: The association between hepatitis B virus (HBV) infection and the development of diabetes remains controversial. This study examined the effect of HBV infection on glucose homeostasis using a duck HBV (DHBV) model. Methods: Plasma DHBV DNA was detected by quantitative polymerase chain reaction (PCR). Tissue infection of DHBV was determined by detecting DHBV covalently closed circular DNA (cccDNA) with a method of rolling circle amplification combined with cross-gap PCR, and verified by fluorescence in situ hybridization assay. An intravenous injection glucose tolerance test (GTT) was used to analyze the effect of DHBV infection on glucose tolerance. Results: Of the finally included 97 domestic ducks, 53 (54.6%) were congenitally infected by DHBV. The positive rate of DHBV cccDNA in the liver, kidney, pancreas, and skeletal muscle of the infected ducks was 100, 75.5, 67.9, and 47.2%, respectively. The DHBV-infected ducks had higher blood glucose levels at 15 and 30 min post-load glucose (p < 0.01 and p < 0.001, respectively) in the GTT, much more individuals with greater glucose area under curve (p < 0.01), and a 57% impaired glucose tolerance (IGT) rate, as compared with noninfected controls. In addition, the subgroups of the infected ducks with DHBV cccDNA positive in skeletal muscle maintained the higher blood glucose level up to 2 h post-load glucose during the GTT and had a 76% IGT rate. Conclusion: These results suggest that DHBV intrahepatic and extrahepatic infection impairs glucose tolerance, and thus evidence the association of DHBV infection with the dysregulation of glucose metabolism.

An adaptable soft-mold embossing process for fabricating optically-accessible, microfeature-based culture systems and application toward liver stage antimalarial compound testing.

Advanced cell culture methods for modeling organ-level structure have been demonstrated to replicate in vivo conditions more accurately than traditional in vitro cell culture. Given that the liver is particularly important to human health, several advanced culture methods have been developed to experiment with liver disease states, including infection with Plasmodium parasites, the causative agent of malaria. These models have demonstrated that intrahepatic parasites require functionally stable hepatocytes to thrive and robust characterization of the parasite populations' response to investigational therapies is dependent on high-content and high-resolution imaging (HC/RI). We previously reported abiotic confinement extends the functional longevity of primary hepatocytes in a microfluidic platform and set out to instill confinement in a microtiter plate platform while maintaining optical accessibility for HC/RI; with an end-goal of producing an improved P. vivax liver stage culture model. We developed a novel fabrication process in which a PDMS soft mold embosses hepatocyte-confining microfeatures into polystyrene, resulting in microfeature-based hepatocyte confinement (μHEP) slides and plates. Our process was optimized to form both microfeatures and culture wells in a single embossing step, resulting in a 100 μm-thick bottom ideal for HC/RI, and was found inexpensively amendable to microfeature design changes. Microfeatures improved intrahepatic parasite infection rates and μHEP systems were used to reconfirm the activity of reference antimalarials in phenotypic dose-response assays. RNAseq of hepatocytes in μHEP systems demonstrated microfeatures sustain hepatic differentiation and function, suggesting broader utility for preclinical hepatic assays; while our tailorable embossing process could be repurposed for developing additional organ models.

2511 Acute Cholestatic Hepatitis E Infection: Immune Dissociation With Intra-Hepatic Replication

INTRODUCTION: There is a lack of understanding of immune modulation during acute hepatitis E virus (HEV) infection. We evaluate the immune response during a case of autochthonous acute HEV genotype 3 infection in the Netherlands. CASE DESCRIPTION/METHODS: A 73 y/o patient initially presented with typical features of acute hepatitis. Extensive work up showed detectable HEV RNA in blood with positive IgM and genotype-3 molecular detection. The liver enzymes improved, there was viral clearance from blood and the patient was discharged home. However, on follow up appointment he was found to have severe cholestasis, was readmitted and passed away shortly. Real time PCR of liver biopsy revealed presence of HEV in liver tissue, suggestive of active intrahepatic infection despite clearance in blood. Peripheral immune evaluation performed via Pro-carta multiplex array showed that during the phase of detectable HEV RNA in serum, there was a surge of T-cell related immune mediators, as well as IFN-a and IP-10 characteristic of viral infections. After clearance of the virus in blood and development of cholestatic hepatitis, several inflammatory markers subsided, followed by an increase in immune factors related to anti-inflammatory activity as well as monocyte/macrophage related markers likely due to the intrahepatic presence of the virus. DISCUSSION: Our case describes a dissociation of intra- and extra-hepatic immune responses during acute HEV infection. As the shedding of the virus became solely intrahepatic, we observed an immune profile reflective of the activity of hepatic resident cells reflecting “competing immune interests' during HEV infection. Moreover, it exposes a less-known aspect of HEV: intra-hepatic morbidity despite lack of detection in blood.

Risk factors of intrahepatic biloma and secondary infection after thermal ablation for malignant hepatic tumors

Objective: This study aimed to evaluate the risk factors of biloma formation and secondary infection after thermal ablation for malignant hepatic tumors.Patients and methods: A total of 58 patients with 68 bilomas after thermal ablation were recruited as the complication group, and 61 patients with 72 lesions without major complications were selected randomly as the control group. The potential risk factors for biloma formation were analyzed with the chi-square test and multivariate logistic regression analysis. To determine the optimum management method for biloma, patients with secondary infection were included for the subgroup analysis of risk factors.Results: A history of transcatheter arterial chemoembolization (TACE) treatment (odds ratio [OR]: 3.606, 95% confidence interval [CI]: 1.165–11.156, p = .026) and tumor location (OR: 37.734, 95% CI: 13.058–109.034, p = .000) were independent predictors of biloma formation. Among the 58 patients with biloma, 49 (84.5%) showed no symptoms (i.e., the asymptomatic group), while the remaining 9 (15.5%) developed symptoms related to secondary infections (i.e., the symptomatic group). There were significant differences in the history of biliary manipulation (p = .031) between the symptomatic and asymptomatic groups.Conclusion: A history of TACE treatment and the distance from the biliary tract were independent predictors of biloma formation after thermal ablation. Therefore, protecting the bile duct (i.e., cooling of the bile duct and combing thermal ablation with chemical ablation) should be considered for high-risk patients. Moreover, active monitoring and management should be performed for patients with bilomas who underwent biliary surgery before.

Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice

Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species. Peg-IFNα and peg-IFNλ reduced HDV viremia (1.4 log and 1.2 log, respectively) and serum HBsAg levels (0.9-log and 0.4-log, respectively). Intrahepatic quantification of genomic and antigenomic HDV RNAs revealed a median ratio of 22:1 in untreated mice, resembling levels determined in HBV/HDV infected patients. Both IFNs greatly reduced intrahepatic levels of genomic and antigenomic HDV RNA, increasing the amounts of HDAg- and antigenomic RNA-negative hepatocytes. ETV-mediated suppression of HBV replication (2.1-log) did not significantly affect HBsAg levels, HDV productivity and/or release. In humanized mice lacking adaptive immunity, IFNs but not ETV suppressed HDV. Viremia decrease reflected the intrahepatic reduction of all HDV markers, including the antigenomic template, suggesting that intracellular HDV clearance is achievable.

Preventing intrahepatic infection after ablation of liver tumours in biliary-enteric anastomosis patients

Purpose: To assess the value of bowel preparation plus targeted antibiotics for preventing intrahepatic infections after MWA of liver tumours in BEA patients.Materials and methods: This retrospective study included 21 patients (divided into two groups) with a history of BEA undergoing ultrasound-guided MWA of liver tumours from November 2008 to June 2014. Group A (n = 10) received single-antibiotic therapy (cefazedone 2 g bid 4, amoxicillin and flucloxacillin sodium 2 g bid 3, levofloxacin 0.5 g qd 3) after ablation, and group B (n = 11) received bowel preparation before ablation plus combined antibiotic therapy (imipenem and cilastatin sodium 1 g 1/12 h, linezolid 0.6 g 1/12 h). Patients were followed for 3 months. Incidences of fever, bacteraemia, and intrahepatic infections were compared, including the duration of fever and length of hospital stay.Results: Following ablation, in group A, 90% of the patients (9/10) had fever, 60% (6/10) had bacteraemia, 60% (6/10) had liver abscess, and 10% (1/10) had biliary tract infection. In group B, no cases of bacteraemia or intrahepatic infection were reported, and the incidences of fever, bacteraemia, and liver abscess were substantially lower than group A (p = 0.002, 0.004, 0.004). Duration of fever and length of hospital stay were markedly shorter than group A (p = 0.002 0.003).Conclusions: Bowel preparation plus targeted antibiotic therapy can significantly reduce the incidences of fever, bacteraemia, and intrahepatic infections in BEA patients undergoing MWA of liver tumours. These preliminary results need to be further validated in randomised trials.

Review article: novel therapies for hepatitis B virus cure - advances and perspectives.

Current anti-viral therapies, interferon and nucleos(t)ide analogues, have been proven to reduce the progression of chronic hepatitis B (CHB). However, covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) persists, resulting in viral relapse after the discontinuation of treatment. To discuss and review novel therapies for chronic hepatitis B infection. Recent published studies which searched from PubMed were comprehensive reviewed. The key words include chronic hepatitis B, hepatitis B virus cure, covalently closed circular DNA, direct acting anti-virals and host targeting agents. Several novel agents through viral and host targets approaches are under investigations towards functional cure of HBV. On the one hand, direct acting anti-virals targeting virus itself, such as HBV new polymerase inhibitor, entry inhibitor, engineered site-specific nucleases and RNA interference, could inhibit amplification of cccDNA as well as intrahepatic HBV infection and eliminate or silence cccDNA transcription. Inhibitors of HBV nucleocapsid assembly suppress capsid formation and prevent synthesis of HBV DNA. On the other hand, host targeting agents (HTA) include lymphotoxin-β receptor agonist, toll-like receptor agonist, immune checkpoint inhibitors and adenovirus-based therapeutic vaccine. Through enhancing innate and adaptive immune responses, these agents could induce noncytolytic destruction of cccDNA or attack HBV-infected hepatocytes. With these promising approaches, we hope to reach global hepatitis B virus control in the middle of this century.

Hepatitis B virus: new therapeutic perspectives.

Current antiviral therapies have dramatically improved the long-term outcomes of patients with chronic hepatitis B virus (HBV) infection. Both interferon (IFN) and nucleos(t)ide analogue (NA) treatments have been shown to reduce the progression of liver disease in chronic hepatitis B (CHB) patients. However, persistent covalently closed circular DNA (cccDNA) can result in a viral relapse after discontinuation of antiviral treatment. On the basis of extensive research on the HBV lifecycle and virus-host interactions, several new agents focusing on viral and host targets are under development to cure HBV. New polymerase inhibitors, tenofovir alafenamide and besifovir provide effective and safer treatment for CHB patients. Agents targeting cccDNA, such as engineered site-specific nucleases and RNA interference therapeutics could eliminate cccDNA or silence cccDNA transcription. Inhibitors of HBV nucleocapsid assembly suppress capsid formation and prevent synthesis of HBV DNA. The HBV entry inhibitor, Myrcludex-B, has been shown to effectively inhibit amplification of cccDNA as well as the spread of intrahepatic infection. Agents targeting host factors that enhance innate and adaptive immune responses, including the lymphotoxin-β receptor agonist, toll-like receptor agonist, immune checkpoint inhibitors and adenovirus-based therapeutic vaccine, could play a critical role in the elimination of HBV-infected cells. With all of these promising approaches, we hope to reach the ultimate goal of a cure to HBV in the near future.

The effects of different preoperative biliary drainage methods on complications following pancreaticoduodenectomy.

The objective of this study was to investigate the effects of different preoperative biliary drainage (PBD) methods on complications in jaundiced patients following pancreaticoduodenectomy. We retrospectively analyzed 270 extrahepatic bile duct cancer patients who underwent pancreaticoduodenectomy. A total of 170 patients without PBD treatment were defined as the non-PBD group. According to different PBD methods, 45, 18, and 37 patients were classified into the percutaneous transhepatic biliary drainage (PTBD), endoscopic nasobiliary drainage (ENBD), and endoscopic retrograde biliary stent (ERBS) groups, respectively. Clinical characteristics and complications were compared among the 4 groups.Preoperative cholangitis occurred in 14 (8.2%) and 8 (21.6%) patients in the non-PBD and ERBS group, respectively (P = 0.04). Compared with the non-PBD group, delayed gastric emptying (DGE) and wound infection occurred significantly more often in the ERBS group. The incidence of severe complications was significantly lower in the PTBD group than the non-PBD group (P = 0.03). Postoperative hospital stay and complication rates were significantly higher in the ERBS group than the PTBD group. There were no significant differences in complications between ENBD and other groups.In conclusion, PTBD can improve surgical outcomes by reducing severe complication rate in jaundiced patients following pancreaticoduodenectomy. ERBS increased the rates of DGE and wound infection due to high incidence of cholangitis before operative intervention and should be avoided. ENBD carried no special effect on complications and needs further analysis.

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3+ and TUNEL+ hepatocytes, as well as total, CD4+, CD8+, Foxp3+ and CD20+ lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3+r = 0.74, p < 0.0001; TUNEL+r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3+ cell count was increased in severe hepatitis (p = 0.009). Total, CD4+, CD8+ and Foxp3+ lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8+ cells correlated with infected (r = 0.495, p 0.04) and TUNEL+ hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3+ hepatocytes (r = 0.387, p 0.04). In adults, CD8+ was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8+ r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

Inferring viral dynamics in chronically HCV infected patients from the spatial distribution of infected hepatocytes.

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, we are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.

IL-33 Induces Nuocytes and Modulates Liver Injury in Viral Hepatitis

Molecules containing damage-associated molecular patterns play an important role in many pathogenic processes. In this study, our aim was to investigate the role of IL-33, a damage-associated molecular pattern molecule, in adenovirus (Ad)-induced liver inflammation. Ad-infected mice exhibited a steadily increased IL-33 and its receptor IL-1R-like 1 expression in the liver during the first week of infection. Treatment of exogenous IL-33 resulted in a great decrease in the serum alanine aminotransferase levels and the number of Councilman bodies in the liver. Attenuated liver injury by IL-33 correlated with an increase in T regulatory cells but with a decrease in macrophages, dendritic cells, and NK cells in the liver. IL-33 enhanced both type 1 (IL-2 and IFN-γ) and type 2 (IL-5 and IL-13) immune responses in infected mice. However, IL-33 inhibited TNF-α expression in hepatic T cells and macrophages, and significantly reduced TNF-α levels in the liver. We found that in addition to its direct effects, IL-33 strongly induced novel nuocytes in the livers and spleens of infected mice. When cocultured with nuocytes, hepatic T cells and macrophages expressed lower levels of TNF-α. The IL-33-treated mice also demonstrated a slight delay, but no significant impairment, in eliminating an intrahepatic infection with Ad. In conclusion, this study reveals that IL-33 acts as a potent immune stimulator and a hepatoprotective cytokine in acute viral hepatitis. Its direct immunoregulatory functions and ability to induce novel nuocytes further suggest to us that it may be a potentially promising therapeutic candidate for the management of viral hepatitis.

Occult HBV infection among Egyptian hepatocellular carcinoma patients

BackgroundOccult HBV infection accelerates the progression of liver fibrosis, cirrhosis, and finally leading to hepatocellular carcinoma (HCC). This study analyzed the occult HBV-genotypes in HCC patients.MethodsTo achieve our objective, matched serum and tissue samples were collected from 40 HCC patients. Three sets of primers were used for the HBV-DNA detection by nested-PCR, which cover the HBV-genome; Core, Surface and X genes. Genotyping system based on PCR using type-specific primers was applied on HBV-DNA positive samples.ResultsIntrahepatic occult HBV-DNA was detected in 62.5%, whereas; Serum occult HBV-DNA were detected in only 22.5% of HCC patients. In patients' positive for both anti-HBs and anti-HBc, 10% had occult HBV in serum. In serologically negative HCV patients, 63% had intrahepatic HBV-DNA, and 21% had HBV-DNA in serum samples. HBV-genotype D (32%) and B (24%) attributed predominantly to intrahepatic HBV infections in HCC patients, whereas HBV-genotype A (4%) and C (8%) infections were the least observed.ConclusionThis is the first study to show the genotypes of occult HBV infection in HCC Patients. We suggest that B or D may influence the outcome of HBV infection which may lead to the development of HCC.

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)-positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV-positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti-hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti-hepatitis B core antigen (anti-HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti-HBc-positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV-positive individuals who are positive for anti-HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN-mediated eradication of HCV.

Hepatitis B reactivation in allogeneic hemopoietic stem cell transplantation setting: A pediatric experience

Reactivation of HBV is a well known complication in patients undergoing HSCT. Lamivudine treatment appears to prevent hepatitis B virus reactivation and to decrease the mortality in at risk HSCT patients. We describe HBV reactivation occurred in three allogeneic HSCT pediatric patients coming from Eastern Europe, one of whom was successfully treated with lamivudine. Our experience confirms that HBV-DNA may persist as intra-hepatic infection or in extra-hepatic sites and that HBV reactivation may appear during immunodepression. Careful and complete screening for HBV markers is mandatory before HSCT, especially in children coming from countries at risk for HBV. Furthermore, a treatment with lamivudine could also represent an efficacious prophylaxis in pediatric patients to avoid HBV reactivation and to decrease the development of severe hepatic disease.