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.     

Change of Esophageal Motility in Cirrhotic Patients with Hepatitis Virus

Our previous study showed that two MKN45 variants, namely MKN45Lm-and MKN 45Lm selected by laminin adhesion in vitro, had different abilities of invasion and metastasis in vivo (inoculated in nude mice) and in vitro (in Boyden chamber), also had different expression of cysteine proteinase. In the present study, we investigated the cell apoptosis of this MKN45 variants by TUNEL and FACS methods. The results were shown significant different of cell apoptosis in this cell sublines. The MKN45Lm- cells had a small subdiploidy peak (3.5%) in DNA content analyzed by flow cytometry,     

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.     

Hepatitis C Virus Infection—Pathobiology and Implications for New Therapeutic Options

Despite progress in therapeutic approaches for the elimination of hepatitis C, chronic hepatitis C virus infection remains an important cause of liver disease. Therapeutic intervention with the currently available interferon-based treatment regimens is quite successful, but treatment is difficult to tolerate and is contraindicated in many patients. A better understanding of the HCV biology, immunopathology, and liver disease will help to design better therapeutic strategies. The American Association for the Study of Liver Diseases sponsored a single-topic conference on hepatitis C virus infection on March 4 and 5, 2005, to enhance our current knowledge in the areas of basic and clinical research related to antiviral and immunomodulatory therapies in hepatitis C disease. The faculty consisted of 23 invited experts in the field of viral hepatitis. The program was divided into four sections including: (a) replicative mechanisms and models; (b) viral-host interactions; and (c) antiviral drug development and new strategies; and (d) back to the bedside—current issues. This report summarizes each of the presentations sections. This report is from the 2005 Single Topic Conference on Hepatitis C. The conference was sponsored by the American Association for the Study of Liver Diseases with the support of the AASLD/Roche Pharmaceuticals Hepatitis Single Topic Conference Endowment.     

Association of Interleukin-18 Gene Polymorphisms with Hepatitis B Virus Clearance

The outcome of hepatitis B virus (HBV) infection can be affected by host immune factors. Interleukin-18 (IL-18) was originally discovered as an interferon-γ-inducing factor and plays a critical role in immune response. We assessed the association between the clearance of HBV infection and single-nucleotide polymorphisms (SNPs) in the IL-18 gene. Between March 2002 and December 2004, a total of 1,050 Korean subjects were enrolled in the study and divided into two groups: (1) the HBV spontaneous recovery group (n = 320) and (2) the chronic HBV carrier group (n = 730). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions ?667G>T, ?148G>C, +8925C>G, and +13925A>C. We observed that the subjects bearing the IL-18 ?148C allele [odds ratio (OR), 0.25; confidence interval (CI), 0.09–0.68; P = 0.01], the +8925G allele (OR, 0.36; CI, 0.15–0.88; P = 0.02), and the +13925C allele (OR, 0.25; CI, 0.13–0.82; P = 0.01) were significantly associated with HBV clearance in a recessive model. This study indicates that the ?148C, +8925G, and +13925C alleles of the IL-18 gene are likely associated with HBV clearance in a Korean population.     

Chronic Hepatitis C Virus and Celiac Disease,is there an Association?

Celiac disease (CD) has been epidemiologically associated with chronic hepatitis C (HCV), and CD activation after the initiation of interferon (IFN-α) in patients with HCV is documented. However, clear association of CD and HCV is lacking. A prospectively maintained database of 878 CD patients showed a prevalence of 0.68% (six patients). Symptoms of diarrhea, weight loss, and depression prompted the diagnosis of CD during or after IFN-α therapy in four cases. Also, 294 subjects with liver disease (195 with HCV, 80 normal controls and 19 disease controls) were prospectively screened for CD. The mean age of the subjects was 50.1 years (SD 12.3), 58% males:42% females. A total of 30% received IFN-α therapy (16% at the time of testing for CD). Two HCV patients (1%) had positive tTG-IgA but these had negative endomysial antibody (EMA) and normal duodenal biopsies. CD prevalence is not increased in patients with HCV. Routine screening of CD in HCV patients is not warranted, however, the presence of CD should be considered in the setting of clinical deterioration during or after IFN-α therapy.     

Activation of Tumor Necrosis Factor-α System in Chronic Hepatitis C Virus Infection

Tumor necrosis factor- (TNF-)plays a central role in the host's immunomodulatoryresponse to infective agents. To evaluate theTNF- system in patients with chronic hepatitis Cvirus (HCV) infection, plasma, serum, and peripheral bloodmononuclear cells (PBMC) were prospectively collectedfrom 53 patients and 33 healthy control subjects.Circulating TNF- and TNF receptors were assayed by their respective enzyme immunoassays. Inaddition, TNF- mRNA was quantitated in PBMC usinga branched DNA assay, and production of TNF- byPBMC with and without lipopolysaccharide was also assessed. Patients with chronic HCV infectionhad a higher level of circulating TNF- comparedto healthy control subjects (9.62 ± 6.01 vs 3.66± 1.23 pg/ml, P < 0.001). They also had highercirculating levels of TNF receptors compared to control(CD120a: 3323 ± 1267, pg/ml, N = 49 vs 1855± 422 pg/ml, N = 33, P < 0.001; CD120b: 1290± 650 pg/ml, N = 51, vs 863 ± 207 pg/ml,N = 33, P < 0.001). Plasma TNF- level correlated with circulatingCD120a (r = 0.52, N = 49, P < 0.001) and weakly withCD120b (r = 0.32, N = 51, P = 0.02). Plasma TNF-also correlated with markers of hepatocellular injury, including ALT (r = 0.34, N = 53, P = 0.01) and-GST (r = 0.31, N = 43, P = 0.042), but not withserum HCV RNA levels. There was no difference in theTNF- mRNA levels in PBMC between patients with chronic HCV infection (1.4 ± 1.9units/106 cells, N = 8) and healthy control subjects(2.1 ± 1.4 units/106 cells, N = 8, P = NS). Therewas also no difference in the spontaneous production ofTNF- by PBMC (1 × 10⁶ cells/ml)between patients with chronic HCV infection (14.2± 36.5 pg/ml, N = 11) and healthy subjects (11.9± 14.0 pg/ml, N = 14, P = NS). However, patientswith chronic HCV infection produced more TNF- upon stimulation withlipopolysaccharide compared to healthy control subjects(1278 ± 693 pg/ml, N = 11, vs 629 ± 689pg/ml, N = 14, P < 0.05). These data indicate thatthe TNF- system is activated in patients with chronicHCV infection.     

Effect of Acute Self-Limited Hepatitis C Virus (HCV) Superinfection on Hepatitis B Virus (HBV)-Related Cirrhosis. Virological Features of HBV–HCV Dual Infection

We investigated the virological impact of acute hepatitis C virus (HCV) superinfection on two patients with hepatitis B virus (HBV)-related cirrhosis. In both patients, chronic HBV-infection persisted while acute HCV infection resolved spontaneously. HBV DNA was transiently suppressed in both patients but increased with HCV resolution. In Case 1 (HBeAg-positive; wild type of basic core promoter [BCP] and precore [PreC]), fluctuations of HBV DNA and HBeAg state were accompanied by mutations of the BCP and PreC. In Case 2 (HBeAg-negative; mutant type of the BCP and PreC), changes in HBV DNA levels were associated with mutations of PreC. In both cases, mutant PreC changed to the wild type upon HCV resolution, and no nucleotide A insertion at position 193 of the HCV 5'-untranslated region, which influences HCV spontaneous clearance, was detected. The putative DNA-binding motif in the HCV core was SPRG (amino acids 99-102). HCV infection was associated with changes in the nucleotide sequences of the binding site for the nuclear receptor family in HBV enhancer 2 (Enh2) including the BCP rather than Enh1. Our results suggest that the impact of acute HCV infection on chronic HBV infection varies according to HBV virological state.