Hepatocellular Carcinoma in Hepatitis D: Does it Differ from Hepatitis B Monoinfection?

Background/Aim:

Hepatitis D virus (HDV) superinfection in patients with chronic hepatitis B leads to accelerated liver injury, early cirrhosis, and decompensation. It may be speculated that hepatocellular carcinoma (HCC) may differ in these patients from hepatitis B virus (HBV) monoinfection. The aim of this study was to compare clinical aspects of hepatocellular carcinoma in patients of hepatitis D with HBV monoinfection.

Patients and Methods:

A total of 92 consecutive HCC cases seropositive for antibody against HDV antigen (HDV group) were compared with 92 HBsAg-positive and anti-HDV-negative cases (HBV group).

Results:

The features including sex, body mass index, presence of ascites, serum biochemistry, gross tumor appearance, child class, barcelona cancer liver clinic and okuda stages were not significantly different between the 2 groups. Decreased liver size was noticed more in cases of HDV compared with HBV group where the liver size was normal or increased (P=0.000). HDV patients had lower platelets (P=0.053) and larger varices on endoscopy (P=0.004). Multifocal tumors and elevated alpha-fetoprotein level >1000 IU/mL were more common in HBV group (P=0.040 and P= 0.061). TNM classification showed more stage III-IV disease in HBV group (P=0.000).

Conclusion:

Decreased liver size and indirect evidence of more severe portal hypertension and earlier TNM stage compared with HBV monoinfection indicate that HDV infection causes HCC in a different way, possibly indirectly by inducing inflammation and cirrhosis.     

Hepatitis

2005226 Characteristics of peripheral blood T lymphocyte subsets in hepatitis B patients. FAN Zhen-ping(范振平),et al. Center Bio Ther, Instit Infect Dis, 302 Hosp Chin PLA, Beijing 100039. World Chin J Digestol, 2005;13(2): 194-197. Objective: To characterize the T-lymphocyte subsets in peripheral blood of patients with acute and chronic hepatitis B, and to explore their relations with the disease state. Methods: Peripheral blood     

Are Hepatitis B Virus and Celiac Disease Linked?

Background and Aims

It has been hypothesized that nonintestinal inflammatory diseases such as hepatitis B virus (HBV) and hepatitis C virus (HCV) may trigger immunologic gluten intolerance in susceptible people. This hypothesis suggests a possible epidemiological link between these two diseases, although this assumption is still a matter of debate.

Methods

We conducted a retrospective study to assess the prevalence of celiac disease in HBV carrier patients who had been infected in childhood.

Results

None of the HBV carrier patients had immunoglobulin A antiendomysium and immunoglobulin A anti-tissue transglutaminase, but 6 patients and 1 recovered subject had immunoglobulin A antigliadin and/or immunoglobulin G antigliadin. Moreover, no patient treated with interferon therapy showed any serological marker of celiac disease.

Conclusions

Due to the small sample size, we cannot claim that there is no association between celiac disease (CD) and HBV, although in our study we did not find any CD patients. A sample size that is more representative of the prevalence of CD in Italy would better support the establishment of any possible connection between CD and HBV.     

How Can We Make Decision for Patients With Chronic Hepatitis B According to Hepatitis B Virus (HBV) DNA Level?

Background:

HBeAg negative hepatitis B infection exerts both inactive carrier state and chronic active hepatitis, which are sometimes difficult to differentiate. Serial hepatitis B virus (HBV) DNA quantification, alanine transaminase (ALT) measurement, and liver histology assessment can help to differentiate these forms of hepatitis B infection.

Objectives:

We aimed to clarify the clinical and laboratory characteristics of HBeAg negative hepatitis B patients.

Patients and Methods:

Patients with hepatitis B, referred to Tehran Blood Transfusion Hepatitis Clinic from 2011 to 2013, were included and followed for one year. Laboratory assessments including liver function tests, HBV DNA quantification, and liver biopsy (for some cases) were performed.

Results:

Two hundred forty-three HBeAg negative hepatitis B patients were stratified into three groups based on to their HBV DNA level including group 1 (G1) with HBV DNA level < 2000 IU/mL, group 2 (G2) with HBV DNA level 2000-20000 IU/mL, and group 3 (G3) with HBV DNA level > 20000 IU/mL. The G2 had more similarity to G1 than G3 regarding their clinical characteristics.

Conclusions:

It is concluded that most HBeAg negative hepatitis B patients with serum HBV DNA level of 2000-20000 IU/mL, persistent normal ALT concentration, and no or mild liver damage on biopsy can be clinically managed as HBV inactive carriers.     

Hepatitis B virus reactivation in a patient undergoing steroid-free chemotherapy

A 62-year-old Japanese man who was positive for hepatitisB surface antigen(HBsAg)and anti-HBe antibody,underwentchemotherapy for non-Hodgkin's lymphoma(NHL).Mutationswere detected in the precore region(nt1896)of HBV.Because steroid-containing regimen may cause reactivationof hepatitis B virus(HBV)and hepatitis may progress to befulminant after its withdrawal,we administered CHO(CPA,DOX and VCR)therapy and the patient obtained completeresponse.However,he developed acute exacerbation ofhepatitis due to HBV reactivation.Recovery was achievedwith lamivudine(100 mg/d)and plasma exchange.Thepresent case suggests that acute exacerbation of hepatitiscan occur with steroid-free regimen.Because the efficacyof the prophylactic use of lamivudine has been reportedand the steroid enhances curability of malignant lymphoma,the steroid containing regimen with prophylaxis oflamivudine should be evaluated further.     

Hepatitis B virus cccDNA clearance: killing for curing?

Chronic hepadnavirus infections cause liver damage with ongoing death and regeneration of hepatocytes. In the present study, we set out to quantify the extent of liver turnover by measuring the clonal proliferation of hepatocytes by using integrated viral DNA as a genetic marker for individual hepatocyte lineages. Liver tissue from woodchucks with chronic woodchuck hepatitis virus (WHV) infection was assayed for randomly integrated viral DNA by using inverse PCR. Serial endpoint dilution of viral-cell junction fragments into 96-well plates, followed by nested PCR and DNA sequencing, was used to determine the copy number of specific viral cell junctions as a measure of the clonal distribution of infected cell subpopulations. The results indicated that the livers contained a minimum of 100,000 clones of >1,000 cells containing integrated DNA, representing at least 0.2% of the hepatocyte population of the liver. Because cells with integrated WHV DNA comprised only 1-2% of total liver cells, it is likely that the total number of clones far exceeds this estimate, with as much as one half of the liver derived from high copy clones of >1,000 cells. It may be inferred that these clones have a strong selective growth or survival advantage. The results provide evidence for a large amount of hepatocyte proliferation and selection having occurred during the period of chronic WHV infection (approximately 1.5 years) in these animals.     

Is Hepatitis C Virus Positivity a Contributing Factor to Occult Hepatitis B Virus Infection in Hemodialysis Patients?

Hepatitis B (HBV) infections continue to occur in adult hemodialysis units. Occult HBV infection (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive) may be a contributing factor in these patients. This study was designed to (1) investigate the prevalence of occult HBV infection in hemodialysis patients and (2) compare the prevalence of occult HBV infection among hepatitis C (HCV)-positive and HCV-negative hemodialysis patients. The study included 138 patients on chronic hemodialysis. Eighty-four patients were HCV positive and 54 were HCV negative. HBV DNA testing was performed by polymerase chain reaction. We also recorded general characteristics of the patients, duration of hemodialysis, and serum alanine aminotransferase and aspartate aminotransferase levels. Twenty-one (15.2%) of the 138 hemodialysis patients were HBV DNA positive. Nine (16.6%) of the 54 anti-HCV antibody negative hemodialysis patients were HBV DNA positive. Twelve (14.2%) of the 84 anti-HCV antibody positive patients were HBV DNA positive. The prevalence in anti-HCV Ab positive and negative hemodialysis patients were same (P > .05). Hemodialysis duration, demographic features, and biochemical parameters were not significantly different in patients with and without occult HBV infection in both HCV-positive and -negative hemodialysis patients (P > .05). HCV positivity is not a contributing factor to occult HBV infection in hemodialysis patients. None of the parameters tested help to distinguish patients with occult HBV infection from those who are HBV DNA negative.     

Clinical Analysis of Polyethylene Glycol Interferon-α Treatment in 155 Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) Patients

PurposeThis study aims to investigate the antiviral effect of polyethylene glycol (PEG)-interferon α-2a and PEG-interferon α-2b treatment on hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) at the 48th week of treatment and the 24th and 48th week after withdrawal, in order to provide guidance on the antiviral treatment of HBeAg-positive CHB patients.Material and methodsAntiviral treatment was performed on 155 HBeAg-positive CHB patients. Among these patients, 66 patients received PEG-interferon α-2a treatment and 89 patients received PEG-interferon α-2b treatment; and these treatments were administered by subcutaneous injection, once per week, which lasted for 48 weeks. Other antiviral and hepatoprotective drugs were not used during the treatment.ResultsAt the 48th week of treatment, ALT recovery rate, HBsAg seroconversion rate, HBeAg seroconversion rate and HBV DNA titers dropped below 200 IU/mL rate were 69.7%, 6.1%, 27.3% and 50.0%, respectively, in the PEG-interferon α-2a group; and were 70.8%, 6.7%, 33.7% and 62.9%, respectively, in the PEG-interferon α-2b group. At the 24th and 48th week of follow-up after withdrawal, HBsAg seroconversion rate in these two groups did not change; and HBeAg seroconversion rate further increased. Furthermore, HBV DNA revealed a low recurrence rate. The difference between these two groups was not significantly significant.ConclusionsPEG-interferon α-2a and PEG-interferon α-2b are effective antiviral drugs for the treatment of HBeAg-positive CHB, which has a HBsAg seroconversion rate of more than 5%. Furthermore, this sustained response effect was maintained at the 24th and 48th week of follow-up after withdrawal.     

Acute Hepatitis B in Western Sweden – Genotypes and Transmission Routes

A retrospective study of acute hepatitis B (AHB) during 1995-1996 in G?teborg, Sweden, was carried out to investigate whether the increasing number of hepatitis B virus (HBV) carriers due to immigration in northwestern Europe has influenced the incidence or genotype heterogenicity. 24 cases of AHB were identified, the probable transmission route of which was intravenous drug use (IVDU) in 11 (46%), heterosexual in six (25%), homosexual in one, hemodialysis in two and unknown in four cases. In no case was the source an immigrant with chronic HBV infection. Genotype D was seen in 12 patients, seven being anti-HCV-positive IVD users, two probably infected heterosexually and three with an unknown source. Genotype A was found in six patients: three IVD users, a sexual partner of an IVD user and two dialysis patients. Genotype B was found in one patient infected during travel to Vietnam, and genotype C in one patient, probably infected sexually from a previously identified chronic carrier. In conclusion, genotype D is the main genotype and IVDU still the major risk factor for AHB in Goteborg, while transmission from immigrants appears to be of minor importance despite the fact that this group comprises over 90% of the young, highly infectious carriers.     

The Expression of Hypoxia-Inducible Factor-1α in Hepatitis B Virus-Related Hepatocellular Carcinoma: Correlation with Patients’ Prognosis and Hepatitis B Virus X Protein

Hypoxia inducible factor-1α (HIF-1α) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1α was found in 37 of the 72 (51.39%) tumor specimens, and significantly correlated with venous invasion and lymphonode invasion. Patients with high expression of HIF-1α had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1α expression was a borderline independent factor of overall survival. HIF-1α expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1α protein expression in vitro. These results suggested that HIF-1α, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients. Dr. Huahong Xie, Dr. Jiugang Song, and Dr. Kaige Liu contributed equally to this study.     

Is There Any Value to Hepatitis B Virus Genotype Analysis?

Hepatitis B may cause a varying spectrum of diseases ranging from an asymptomatic or mild anicteric acute illness, to severe or fulminant hepatitis. Similarly, the outcome of chronic hepatitis B is variable. Viral factors associated with outcome of chronic hepatitis B virus (HBV) infection include hepatitis B e antigen status, HBV DNA, genotype, and HBV variants. HBV genotypes and subgenotypes have been associated with differences in clinical and virological characteristics, indicating that they may play a role in the virus-host relationship. A total of ten hepatitis B virus genotypes have been defined with a distinct geographical distribution. Hitherto, genotypes A, B, C and D have been studied most extensively. The HBV genotype appears to influence not only the natural history of HBV related liver disease but also the response to HBV treatment. HBV genotypes are also linked with both core promoter and BCP mutations. Progression to chronic infection appears to occur more frequently following acute infection with genotypes A and D than with the other studied genotypes. Genotypes A and B appear to have higher rates of spontaneous HBeAg seroconversion. More advanced liver disease and progression to HCC is more often seen in chronic infection with genotypes C and D in contrast to genotypes A and B. More specifically, genotypes A1, C, B2–B5 and H appear to be associated with more serious complications than genotypes A2, B1 and B6. These observations suggest important pathogenic differences between HBV genotypes. Genotypes A and B have higher response rates to interferon based therapy than genotypes C and D. Knowledge of HBV genotype enables clinicians to identify those patients at increased risk of disease progression whilst aiding the selection of appropriate antiviral therapy. Genotyping and monoclonal subtyping can provide useful information for epidemiological studies. In conclusion, genotyping of chronic HBV infections can help practicing physicians identify those at risk of disease progression and determine optimal anti-viral therapy.