Hepatitis delta virus propagation enabled by hepatitis C virus—Scientifically intriguing,but is it relevant to clinical practice?

In vitro cell culture experiments and animal models have demonstrated that hepatitis delta virus (HDV) can theoretically propagate being enveloped by human pathogenic viruses other than hepatitis B virus (HBV), namely hepatitis C virus (HCV) and dengue virus. However, the clinical relevance of these findings and whether HDV replication occurs in real‐world hepatitis B surface antigen (HBsAg)–negative HCV patient cohorts remain unknown. To this aim, we analysed 323 HCV‐RNA–positive and HBsAg‐negative sera for the presence of HDV‐RNA and anti‐HDV antibodies (anti‐HDV). All 323 (100%) samples were negative for HDV‐RNA. Interestingly, 8/316 samples tested positive for anti‐HDV. The HBV serology of these eight patients showed a positive result for HBV core antibodies (anti‐HBc) indicating a seroconversion of an acute HBV infection in the past. None of the anti‐HBc–negative patients were positive for anti‐HDV. Our results indicate a distinctly low probability of replicative HDV infection in HCV mono‐infected patients in Germany. Current German clinical guidelines rightly recommend performing HDV screening only in HBsAg‐positive patients. However, larger studies on this subject should be performed in regions that are endemic for chronic HBV/HDV as well as HCV infections.     

Role of hepatitis B, C, and D viruses in dual and triple infection: influence of viral genotypes and hepatitis B precore and basal core promoter mutations on viral replicative interference

The interactions among hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) were studied by measuring HBV-DNA and HCV-RNA levels and by determining the influence of viral genotypes and mutations in HBV basal core promoter (BCP) and precore regions. We included 65 consecutive patients, 25 HBV/HCV, 18 HBV/HDV, and 22 HBV/HCV/HDV. Controls consisted of 55 patients with chronic HBV and 55 with chronic HCV infection. HBV-DNA and HCV-RNA levels were lower in coinfections than in single infections (P <.05). HBV/HCV coinfection was associated with lower HBV viremia (8.2 x 10(4) copies/mL) and lower HCV-RNA levels (7 x 10(5) IU/mL), than the corresponding control group (P <.05), with more marked decrease in HBV replication (P <.05). Moreover, in HBV/HCV coinfection and in triple coinfection we observed an inverse relationship between HBV-DNA and HCV-RNA levels (P <.05). HBV/HDV coinfection was associated with lower HBV viremia (2.5 x 10(4) copies/mL) than that found in HBV infection (P <.05). Patients with triple coinfection showed lower HBV-DNA and HCV-RNA levels than control groups (P <.05). Prevalence of precore mutations was lower in HCV coinfections (P <.05). No significant association was observed between HCV-RNA levels and HBV precore mutations, BCP mutations or HBV genotypes, or between HBV-DNA levels and HCV genotypes (P <.05). In conclusion, HCV exhibited stronger inhibitory action in the reciprocal inhibition seen in HBV/HCV coinfection. HDV was the dominant virus in HBV/HDV coinfection and in triple coinfection, and had a greater unfavorable influence on HCV than on HBV replication. The reciprocal inhibition of viral replication seemed to be little influenced by the inherent genomic factors studied.     

Orthotopic liver transplantation in hepatic cirrhosis: on the problem of infection of the transplant with persistent hepatitis viruses]

269 orthotopic liver transplantations (OLT) were performed in 253 patients at our institution from September 1988 to May 1992. 121 patients had end-stage cirrhosis secondary to viral hepatitis type B, delta, or type non-A non-B and C respectively. Reinfection of the graft by persistent viruses is a potential complication in these cases. Passive immunization with anti-HBs hyperimmunoglobulin (HIg) can prevent clinically relevant reinfection of the graft in patients with hepatitis B virus (HBV) infection and low replication rates. Patients with high replication rates will rarely benefit from OLT. Patients with hepatitis delta virus (HDV) infection usually experience HDV reinfection of the graft with subsequent chronic hepatitis although prophylaxis with anti-HBs-HIg was performed. Treatment with interferon alpha had no apparent effect on the incidence of graft reinfection with HBV in this series, but the replication rate of HDV was reduced. Persistent hepatitis C viruses (HCV) usually infect the graft; this was demonstrated in 17 patients by means of the polymerase chain reaction. HCV infection usually causes a mild form of acute hepatitis with transition to a chronic course. Therefore the significance of persistent viral infection lies in the potential for chronic hepatitis in the transplanted organ rather than in the danger of acute injury of the allograft.     

Management of HBV, HCV, and HDV coinfection

Worldwide, chronic hepatitis B virus (HBV) infection is the most common cause of chronic liver disease. Concurrent hepatitis C (HCV) or hepatitis D (HDV) infection is common because of their shared routes of transmission. Studies show that concurrent HBV/HCV or HBV/HDV infections may be associated with a fulminant course of acute hepatitis, more severe forms of chronic liver disease, and higher risk for development of hepatocellular carcinoma. Virologic markers in HBV patients coinfected with HCV or HDV are dynamic and have different patterns. The replication of one virus may dominate the other and antiviral therapeutic strategies should target the dominant virus. Standard interferon-α or pegylated interferon is usually the treatment of choice for HBV/HCV and HBV/HDV coinfection. Adding ribavirin or lamivudine may benefit HBV patients coinfected with HCV but is ineffective against HDV. Treatment guidelines have not been established for chronic HBV coinfection with either HCV or HDV; therefore, management decisions usually depend on the clinical experience of the treating physician and the sparse data available regarding treatment options.     

Longitudinal evaluation of viral interactions in treated HIV-hepatitis B co-infected patients with additional hepatitis C and D virus

Summary  Virological interactions of hepatitis B (HBV), hepatitis C (HCV) and hepatitis D (HDV) viruses in HIV-infected patients have been poorly characterized especially under treatment influences. Undetection rates of hepatitis viruses were longitudinally analyzed in a 3-year cohort of 308 HIV–HBV co-infected patients and compared using Generalized Estimating Equation models adjusted for age, HIV-RNA, CD4 cell-count and antiviral treatment. Chronic hepatitis co-infection in HIV-infected patients (age years, SD) was: 265 HBV (40.7, 8.2); 19 HBV–HCV (39.7, 4.1); 12 HBV–HDV (35.2, 9.9); 12 HBV–HCV–HDV (39.2, 5.2). At inclusion, treatment with lamivudine/tenofovir was not significantly different between co-infection groups. HBV suppression was significantly associated with HDV (aOR = 3.85, 95%CI 1.13–13.10, P  =   0.03) and HCV tri-infection (aOR = 2.65, 95%CI 1.03–6.81, P  =   0.04), but marginally associated with HIV–HBV–HCV–HDV (aOR = 2.32, 95%CI 0.94–5.74, P  =   0.07). In quad-infection, lower HDV-undetectability ( vs HIV–HBV–HDV, P  =   0.2) and higher HCV-undetectability ( vs HIV–HBV–HCV, P  =   0.1) were demonstrated. The degree of HBV suppression varied between visits and co-infection groups [range of aOR during follow-up ( vs HIV–HBV co-infection): HIV–HBV–HCV = 2.23–5.67, HIV–HBV–HDV = 1.53–15.17]. In treated co-infected patients, HDV expressed continuous suppression over HCV- and HBV-replications. Peaks and rebounds from undetectable hepatitis B, C and/or D viremia warrant closer follow-up in this patient population. HDV-replication was uncontrolled even with antiviral treatment.     

Tracing hepatitis C and Delta viruses to estimate their contribution in HCC rates in Mongolia

An estimated incidence of hepatocellular carcinoma (HCC) in Mongolia is currently one of the highest in the world. According to previous reports, the sero-prevalence of hepatitis B (HBV) and hepatitis C (HCV) viruses in general population of the country is very high (HBV, 10% and HCV, 15%, respectively). Moreover, the majority (75-100%) of the HBV-infected individuals have co-infection with hepatitis Delta virus (HDV). Despite reported observations that HBV + HDV/HCV co-infection have significantly stronger association with HCC when compared with HCV-monoinfection, the later is still frequently observed among Mongolian HCC patients (39%). In this study, an approach based on principles of population genetics and mathematical epidemiology was used to trace an epidemic history of HCV and HDV. In agreement with the sero-epidemiological and social-historical background of the country, the results have demonstrated that the viruses had different epidemic dynamics in Mongolia; HCV was characterized by earlier epidemic expansion, whereas HDV spread with approximately 50 years lag. This may explain the comparable contribution of the HCV-monoinfection and HBV + HDV co-infection in current HCC rate despite different levels of risk of carcinogenesis. Used approach is useful in evaluation of current and prospective disease burden.     

Replication status and histological features of patients with triple (B, C, D) and dual (B, C) hepatic infections

In patients with multiple hepatotropic viral infections (B and C, or B, C and D), the reciprocal influence of each virus remains controversial. The aims of this study were twofold: first, to determine the impact of multiple infection on the replication status of B, C and D viruses and on histological features; and second, to compare patients with multiple infection to patients infected only with the hepatitis C virus (HCV). We retrospectively included 50 patients with multiple infection and 50 control HCV patients, who were matched on independent factors associated with fibrosis, such as age, gender, alcohol consumption and duration of infection. The replication status of hepatitis B virus (HBV), HCV and hepatitis D virus (HDV), and histological lesions, were determined. In patients with multiple infection, HCV RNA was present less frequently (44% vs 98%, P  < 0.001) and the prevalence of cirrhosis was higher (35% vs 8%, P  < 0.001). Among patients with triple infection ( n  = 16), HBV replication was observed in 25%, HCV RNA was detectable in only two ( P  < 0.0001) and HCV viremia was significantly lower than in the matched HCV patients (0 vs 54.7, P  < 0.0001). Among patients with dual infection ( n  = 34), HCV RNA was present less frequently in those with serological markers of active HBV infection than in those without (30% vs 79%, P  = 0.01). Hence, multiple infection is associated with a decrease of HCV replication. Cirrhosis seems to be more frequently observed in patients with multiple infection. In patients with triple infection, serum HCV RNA and markers of HBV replication were absent in 80%, suggesting that HDV acts as a dominant virus. In patients with dual infection, HBV and HCV exert an alternative, dominant replication.     

Coinfection with hepatitis B and C or B, C and δ viruses results in severe chronic liver disease and responds poorly to terferon-a treatment

SUMMARY. Chronic coinfection with the hepatitis B (HBV) and hepatitis δ (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-α2b (IFN-α) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied: 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-α2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and δ coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone. Short-and long-term responses to doses of IFN-α that are used to treat HCV are infrequent, but further studies are required to determine whether higher-dose IFN-α may benefit patients with combined hepatitis virus infections.     

The significance of infections with two types of viral hepatitis demonstrated by histologic features in chimpanzees

In view of the recognized importance of necroinflammatory episodes in chronic hepatitis B virus (HBV) infection, chimpanzees, either HBV surface antigen (HBsAg) carriers or noninfected (naive), were infected with other primary hepatotropic viruses to evaluate histologic alterations and changes in virologic and biochemical markers of infection. The advantages of studies on chimpanzees are the availability of serial biopsy specimens and the viral type-specific histologic lesions, not as well recognized in humans. Infection with hepatitis A and non-A, non-B (NANB) agents produced more severe lesions in chronic HBsAg carrier chimpanzees than in naive animals. During this superinfection, the specific expression of the second agent was predominant, indicating that the exacerbation is caused by the second agent, but that carriers are prone to more severe disease than the naive chimpanzees. Hepatitis delta virus (HDV) infections were always coexistant with HBV and superinfection of carriers produced histologic changes more severe than those seen in any other type of viral hepatitis. Such HDV infections revealed less evidence of lymphocytotoxicity but rather of cytotoxicity, and sometimes resembled in appearance the histopathology of NANB. Coinfection of HDV and HBV and superinfection of HBV-carriers with NANB resulted in hepatitis that was far less severe than superinfection of HDV in HBV carriers, greatly in keeping with human experiences. HBV replication was suppressed transiently in both NANB and HDV superinfection. This implies that in exacerbations during chronic HBV infections of humans, suppression of HBV replication markers indicates superinfection, for instance, by NANB for which markers are so far not widely available; by contrast, elevated markers of HBV replication suggest reactivation of the original HBV infection.     

Genotypic variability of hepatitis viruses associated with chronic infection and the development of hepatocellular carcinoma

At least five hepatitis viruses are known to date. Infection by enterically transmitted viruses (HAV and HEV) is generally benign compared with the disease caused by parenterally transmitted viruses (HBV, HCV, and HDV). Chronic infection by HBV is common and may evolve to cirrhosis and hepatocellular carcinoma (HCC). Eight HBV genotypes (A-H) have been described, with the South American genotype F being the most divergent. Seven clades of HDV have been described; among them, the South American genotype III is associated to a high frequency of fulminant hepatitis. HCV infection leads to a high rate of chronicity and HCC. From the six HCV genotypes, infection with genotype 1 might have the worst prognostic. Chronic infection by HCV and HBV is the major risk factor for HCC, which occurs, in the majority of the cases, as a consequence of cirrhosis. However, there is growing evidence that some HBV and HCV proteins might contribute to the generation of HCC. Some HBV and HCV variants and specific mutations within the viral genomes might be more frequently associated with the evolution to HCC. Although more studies are needed, emerging evidence indicates that it might be important to address the genetic variability of these viruses and their contribution to the development of HCC.     

乙型肝炎患者重叠感染HCV及HDV临床意义探讨

本文对305例乙型肝炎患者的血清标本回顾性地检测了HCV及HDV感染标志,结果有48.2％的乙肝患者重叠感染了HCV和/或HDV,其中双重感染率:HBV/HCV 15.4％,HBV/HDV 21.0％;三重感染率:HBV/HCV/HDV同时感染占11.8％,急性盱炎(AH)、厄症状表面抗原携带者(ASC),慢迁肝(CPH).慢活肝(CAH)、肝硬化(CIR)、重型肝炎(SH)及原发性肝癌(PHC)患者的抗-HCV检出率分别为:6.7％、6.7％、22.5％.29.7％、36.4％、38.5％、33.3％:其DHV的检出率分别为:10.0％、13.3％、25.0％、35.9％、41.1％、53.8％、42.9％。肝病越严重,其HCV及HDV的感染率就越高,提示HBV重叠感染HCV及HDV时可以促使肝脏病变加重。合并HCV及HDV感染者的HBV复制率较低。     

Suppression of hepatitis C virus (HCV) replication by hepatitis D virus (HDV) in HIV-infected hemophiliacs with chronic hepatitis B and C

Most hemophiliacs who are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have high serum levels of HCV RNA. To study the impact of multiple hepatitis virus infections, we evalated all eight chronic carriers of hepatitis B surface antigen (HBsAg) from a previously studied cohort of 99 hemophiliacs with chronic HIV and HCV infections. Stored serum or plasma samples were tested for antibody to hepatitis D virus (anti-HDV) by ELISA; qualitatively for HCV RNA, HBV DNA, and HDV RNA by the polymerase chain reaction (PCR); and quantitively for HIV RNA, HCV RNA, and hepatitis B virus (HBV) DNA by a quantitative branched DNA signal amplification assay. HCV RNA was detected in only one of five patients with HDV infections on a cross-sectional study, and this individual had low levels (<3.5×10⁵ genome eq/ml) of HCV RNA. In contrast, all three without HDV infections had high levels (>1.5×10⁷ genome eq/ml) of HCV RNA. HIV RNA was present in all eight patients. There was no correlation between the level of HIV RNA and the presence of hepatitis viruses. Three of the eight patients (38%) died of liver failure and another has hypersplenism with hypoprothrombinemia. We conclude that HDV infection appears to suppress HCV replication and that liver failure is common in adult HIV-infected hemophiliacs with chronic HCV and HBV infections. These findings have implications for the therapy of HCV-infected hemophiliacs who are HBsAg positive.This study was supported by the Brandywine Valley Hemophilia Foundation, and the Alice Livingston Trout Family Fund.Dr. Battegay was supported by the Swiss National Science Foundation, the Conrad Gessner Stipendium, and the Schweizerische Stiftung fur medizinisch biologische stipendien.     

Hepatitis delta virus RNA in serum of patients with chronic delta hepatitis

We studied 28 patients with chronic delta hepatitis for the presence of hepatitis delta virus (HDV) RNA in serum. The hot start polymerase chain reaction (PCR) method, in which the reaction begins at 60–80° C, showed a higher sensitivity than conventional PCR reaction. Additionally, the presence of hepatitis B (HBV) and C virus (HCV) infections were determined by PCR. HDV RNA was detected in 26 patients (93%), HBV DNA in 22 (79%), and HCV RNA in only one. Detection of HDV RNA correlated very well with detection of hepatitis delta antigen by immunostaining in the liver. In six patients HDV RNA was detectable despite the absence of HBV DNA in serum, suggesting that high levels of HBV are not required for HDV replication. Of 29 control patients with chronic hepatitis B without antibody to HDV, none had detectable HDV RNA, while all had HBV DNA in serum. Detection of HDV RNA with PCR proved highly sensitive and specific, demonstrating that virtually all patients with chronic HDV infection had ongoing viral replication.     

Profile of patients triply infected with HIV and the hepatitis B and C viruses in the HAART era

HIV-HCV-HBV-coinfected patients were assessed to characterize the viral interactions in the setting of HIV coinfection and in the HAART era. All positive anti-HCV antibody and HBs antigen-positive HIV-infected patients were identified at five HIV clinics. Antihepatitis delta (HDV) antibody, serum HIV RNA, HCV RNA, and HBV DNA quantification and genotype determinations were performed. Out of 67 patients identified 47 (70%) were receiving anti-HBV therapy. HCV RNA and HBV DNA were detectable in 52.5% and 37% of patients, respectively. All possible patterns were found, regardless of anti-HBV therapy. HDV coinfection was associated with undetectable HCV RNA [RR 9.52 (95% CI 1.85-49.01); p = 0.007]. Independent factors predicting undetectable HBV DNA lacked HBeAg [RR 13.94 (95% CI 3.05-63.72); p = 0.001] and use of anti-HBV therapy [RR 11.42 (95% CI 2.43-53.54); p = 0.002]. Replication and genotypes of HCV or HBV had no impact on the replication of the other virus. In conclusion, in this cohort of triple infection (HBV/HCV/HIV) various viral patterns were identified. Spontaneous HCV clearance was frequent, and it was independently associated with HDV coinfection. In the absence of HBV therapy, HBV most often actively replicates. HBV/HCV replication or genotypes were not related to the replication of the other virus.     

Virushepatitis A–E

Five hepatotropic hepatitis viruses have been identified: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV). HAV and HEV are transmitted orally, HBV, HCV and HDV via blood and other body fluids. This review summarizes the biological characteristics of the different viruses and the established means of preventing infection.     

HDV Seroprevalence in HBsAg-Positive Patients in China Occurs in Hotspots and Is Not Associated with HCV Mono-Infection

HDV infection causes severe liver disease, the global health burden of which may be underestimated due to limited epidemiological data. HDV depends on HBV for infection, but recent studies indicated that dissemination can also be supported by other helper viruses such as HCV. We used a rapid point-of-care test and an ELISA to retrospectively test for antibodies against the Hepatitis Delta antigen (anti-HDV-Ab) in 4103 HBsAg-positive and 1661 HBsAg-negative, anti-HCV-positive sera from China and Germany. We found that the HDV seroprevalence in HBsAg-positive patients in China is limited to geographic hotspots (Inner Mongolia: 35/251, 13.9%; Xinjiang: 7/180, 3.9%) and high-risk intravenous drug users (HBV mono-infected: 23/247, 9.3%; HBV-HCV co-infected: 34/107, 31.8%), while none of the 2634 HBsAg carriers from other metropolitan regions were anti-HDV-Ab-positive. In Germany, we recorded an HDV seroprevalence of 5.3% in a university hospital environment. In a cohort of HBsAg-negative, anti-HCV-positive patients that were not exposed to HBV before (anti-HBc-negative), HDV was not associated with HCV mono-infection (Chinese high-risk cohort: 0/365, 0.0%; German mixed cohort: 0/263, 0.0%). However, 21/1033 (2.0%) high-risk HCV patients in China with markers of a previously cleared HBV infection (anti-HBc-positive) were positive for anti-HDV-Ab, with two of them being positive for both HDV and HCV RNA but negative for HBV DNA. The absence of anti-HDV-Ab in HCV mono-infected patients shows that HCV cannot promote HDV transmission in humans.     

Chronic evolution of acute hepatitis B: the significance of simultaneous infections with hepatitis C and D. Copenhagen Hepatitis Acuta Programme

Seventy-six of 77 consecutive patients with hepatitis B surface antigen (HBsAg)-positive acute hepatitis were reevaluated using anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), and IgM anti-hepatitis B core (HBc) testing. Anti-HCV and/or anti-HDV was found in 32 patients (42%). The presence of these markers was significantly associated with intravenous drug abuse (p less than 10(-6). Sixty-nine patients were IgM anti-HBc-positive, of whom two (3%) (95% confidence limits, 1-12%) became chronic HBsAg carriers with histologically verified chronic liver disease; both were anti-HCV and anti-HDV-negative. Among the remaining 67 IgM anti-HBc-positive patients 8 had HBV and HDV co-infection, 3 had HBV and HCV co-infection, and 1 had HBV, HCV, and HDV co-infection. Twenty-two had evidence of preceding or past HCV infection; two developed chronic active hepatitis in spite of HBsAg clearance. Seven patients with IgM anti-HBc negative. One was a chronic HBsAg carrier with HDV superinfection. One had subclinical acute HBV infection and became a chronic HBsAg carrier. In a further two patients reactivation of replication in a chronic HBV infection could not be disregarded. Three patients could not be classified; all had acute recent onset of symptoms, cleared HBsAg within 6 months, but lacked IgM anti-HBc. It is concluded that HCV and HDV superinfections in HBV carriers mimicking acute HBV infection with chronic evolution are rarely encountered in the present population in spite of high frequency of both HCV and HDV markers.     

Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain

INTRODUCTION: There are very limited data about the prevalence of multiple hepatitis virus infections in HIV infected individuals. In HIV uninfected individuals with triple BCD hepatitis, hepatitis D virus (HDV) appears to be the dominant virus. However, in HIV infected patients with triple hepatitis it is not known if HDV replication inhibits hepatitis B virus (HBV) and/or hepatitis C virus (HCV) replication. METHODS: We calculated the prevalence of single (B or C), dual (BC) and triple (BCD) hepatitis in 423 HIV-infected patients with positive HCV serum antibodies and/or positive serum HBsAg. In patients with multiple infections we performed an evaluation of serum markers of HBV, HCV and HDV replication. RESULTS: The prevalence of multiple hepatitis was 4.7% (95% confidence interval, 2.7-6.7%). Multiple hepatitis occurred only among patients who acquired HIV through injection drug use. The most common multiple hepatitis was triple BCD. Patients with hepatitis BC and past or chronic hepatitis D were significantly more likely to have cirrhosis and a negative serum HBeAg and HCV PCR than patients with single hepatitis B or hepatitis C. Patients with chronic hepatitis D showed uniform suppression of HBV and HCV replication markers. CONCLUSIONS: In our geographic area approximately 5% of HIV infected patients with hepatitis suffer multiple hepatitis virus infection. In patients with triple hepatitis BCD virus infection, HDV appears to be the dominant virus causing inhibition of both HBV and HCV replication.     

Autoimmune hepatitis in patients with chronic HBV and HCV infections: patterns of clinical characteristics,disease progression and outcome

We retrospectively investigated the characteristics, patterns of disease progression, outcome and difficulties in the management in 11 patients with concurrent autoimmune hepatitis (AIH) and HBV or HCV infections (5 HCV and 6 HBV including 2 with HDV co-infection) since there are scarce data on this issue. HCV or HBV diagnosis preceded that of AIH in all patients by many years. At initial clinical and histological assessment almost half of patients had cirrhosis (45.5%) with the group of AIH and HCV carrying the highest frequency (4/5; 80%). In two thirds of patients, mostly with HCV and HBV/HDV, AIH was assumed to be IFNalpha-induced and experienced difficulties in achieving sustained virological response. On the contrary, the outcome of patients with HBV and AIH was better compared to those with AIH and HCV or HDV. In conclusion, chronic viral hepatitis infections concomitant with AIH are often very difficult to recognize and therefore, a significant delay in AIH diagnosis in this specific group of patients is usual. HBV patients with concomitant AIH seem to carry the most favorable outcome compared to those with HCV probably because of the use of nucleos(t)ide analogues which contrary to IFN-alpha can control HBV replication with no adjacent effect, related to exacerbation of autoimmune phenomena.     

Role of hepatitis B virus, hepatitis D virus and other determinants on suppression of hepatitis C viraemia in HIV infected patients with chronic HCV infection: a longitudinal evaluation

The role of hepatitis B virus (HBV) or hepatitis D virus (HDV) coinfections as determinants of hepatitis C virus (HCV) suppression in the setting of HIV-HCV coinfection are poorly understood. Our aim was to assess whether HCV viral replication may be affected by HBV or HDV coinfection in the setting of immunodeficiency driven by HIV.Among the 138 enrolled patients 28(20.3%) tested HCV RNA negative and 110 (79.7%) tested HCV RNA negative. The HCV RNA negative patients showed an higher rate of HBsAg positivity compared with those tested HCVRNA positive [12/28 (42.9%) and 5/110 (4.6%), respectively]. Patients with HCV-HBV-HDV coinfection had the highest chance of having an undetectable HCV RNA (adjusted odds ratio (AOR): 92.0, 95% confidence interval (CI) 5.7-1483.5, p<0.0001). Furthermore, HBV coinfection per se was also found to be independently associated with negative HCV viraemia (AOR: 18.5, 95% CI 2.4-143.5, p<0.0001). HBsAg-positive patients with negative HCV viraemia maintained undetectable levels over time. Our results support a direct role of HBV and HDV coinfections in suppressing HCV viraemia in HIV infected patients. This effect is durable over time, and is not influenced by HAART including anti-HBV drugs.