Profound suppression of chronic hepatitis C following superinfection with hepatitis B virus.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar transmission routes; thus, coinfection is frequent. The consequences of acute HBV infection in patients with chronic hepatitis C are unknown. METHODS: We describe a 47-year-old male with chronic hepatitis C who acquired HBV and then spontaneously and apparently completely cleared HCV but developed chronic hepatitis B. Five serum samples collected over 14 months and lymphoid cells obtained after acquiring HBV were tested for HCV and HBV by both standard assays and ultra-sensitive polymerase chain reaction/nucleic acid hybridization (PCR/NAH) (sensitivity approximately 2 IU/ml). RESULTS: After superinfection with HBV, HBV surface antigen-positive chronic hepatitis developed with readily detectable HBV DNA. All sera collected after acquisition of HBV, which tested negative for HCV RNA by standard laboratory assay, were positive for HCV genomes when analysed by PCR/NAH. Peripheral lymphoid cells carried HBV DNA and covalently closed circular DNA, but were negative for HCV. CONCLUSIONS: This is the first reported case of profound suppression of chronic hepatitis C after superinfection with HBV and establishment of chronic hepatitis B. It is hypothesized that HBV infection precipitated generalized and/or virus-specific cellular immune responses that profoundly suppressed HCV replication and yet failed to inhibit progression to chronic hepatitis B.     

Occult hepatitis B virus infection in Greek patients with chronic hepatitis C and in patients with diverse nonviral hepatic diseases

Occult hepatitis B virus (HBV) infection has been reported in patients with chronic hepatitis C who are negative for HBV surface antigen (HBsAg). However, the significance of 'silent' HBV in hepatitis C virus (HCV) infection is unknown. We investigated 540 subjects for the presence of occult HBV in Greek HCV patients, patients with nonviral liver diseases and healthy donors in an attempt to determine the frequency and importance of this phenomenon. One hundred and eighty-seven anti-HCV(+)/HBsAg(-) patients' sera were investigated for the presence of HBV-DNA by polymerase chain reaction. Two hundred and eighty-two selected blood donors (positive for antibodies to HBV core antigen) and 71 patients with various nonviral hepatic diseases consisted the control groups [both controls were anti-HCV(-)/HBsAg(-)]. HBV-DNA was detected in 26.2% of HCV-infected patients vs 8.5% of patients with nonviral diseases (P = 0.003) and 0/282 of donors (P = 0.0000). HBV-DNA was neither associated with HBV markers, nor with the clinical status of HCV and nonHCV patients. Neither epidemiological, histologic and virologic data nor the response to therapy were associated with the HBV-DNA detection. Hence one quarter of HCV-infected patients had occult HBV infection. Similar findings were not found in both control groups. Occult HBV infection in Greek patients with chronic hepatitis C does not seem to modify the progression of chronic liver disease. Further studies of longer duration are needed in order to clarify the role of 'silent' HBV infection in HCV-infected patients.     

Incidence of extrahepatic cancers among individuals with chronic hepatitis B or C virus infection: A nationwide cohort study

This study examined the association between chronic HBV or HCV infection and the risk of extrahepatic cancers. A total of 537 103 adults aged ≥20 years without history of cancer were identified from the Korean National Health Insurance Service‐National Sample Cohort between 2003 and 2013. The difference in cancer incidence was compared between those with and without chronic HBV or HCV infection. During 3 854 130 person‐years of follow‐up (median follow‐up: 8.0 years), 19 089 participants developed cancer. After adjusting for sex, body mass index, smoking, drinking, income percentile, residential area and comorbidities, hazard ratios (HRs) for incident extrahepatic cancer were significantly higher in participants with chronic HBV infection (HR: 1.27, 95% confidence interval [CI]: 1.20‐1.35), HCV infection (HR: 1.31, 95% CI: 1.16‐1.48) or HBV/HCV dual infection (HR: 1.41, 95% CI: 1.31‐1.72) compared to participants without HBV or HCV infection. In chronic HBV infection, the cancer risk was higher for haematologic malignancy [HR (95% CI) = 2.46 (1.92‐3.15)], gallbladder [1.55 (1.05‐2.29)], pancreas [1.52 (1.07‐2.15)], stomach [1.39 (1.22‐1.58)], lung [1.27 (1.04‐1.55)], colorectum [1.21 (1.03‐1.42)] and thyroid cancer [1.20 (1.05‐1.36)]. In chronic HCV infection, the cancer risk was higher for testis [10.34 (1.35‐79.78)], gallbladder [2.90 (1.62‐5.18)], prostate [2.51 (1.65‐3.82)] and thyroid cancer [1.46 (1.10‐1.93)]. In conclusion, chronic HBV or HCV infection was not only associated with an increased risk of liver cancer, but also associated with an increased risk of multiple extrahepatic cancers.     

Challenge of managing hepatitis B virus and hepatitis C virus infections in resource-limited settings

The global burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and coinfection represents a major public health concern, particularly in resource-limited settings. Elimination of HCV by 2030 has become foreseeable, with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries (LMICs). However, access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices. Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal. Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection, and with improved access to medications, the most significant barrier remains access to affordable diagnostics and preventive strategies. The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs, albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage. This review underpins the HBV and HCV management challenges in resource-limited settings, highlighting the current status and suggested future elimination strategies in some of these countries. Global efforts should continue to improve awareness and political commitment. Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.     

慢性丙型肝炎患者HCV基因型分析

目的研究慢性丙型肝炎患者HCV基因型概况。方法采用基因芯片法检测HCV基因分型;采用PCR法测定HCV RNA定量。结果在570例患者中,HCV RNA阳性552例（95%）,其中1b型400例（72.4%）,2a型63例（11.4%）,3a型20例（3.6%）,3b型20例（3.6%）,1b＋2a型12例（2.1%）,1a型2例（0.4%）,6型7例（1.26%）,1b＋3a型1例（0.18%）,2a＋1b型3例（0.5%）,未定型24例（4.3%）;不同HCV基因型感染者血清HCVRNA水平无统计学差异（P〉0.05）。结论本组患者HCV基因型以1b型为主,2a型次之,多种混合型的出现提示HCV基因型呈现多样化趋势。     

HDV重叠感染可增加慢性乙型肝炎患者的肝细胞癌风险

HDV的重叠感染可加速慢性乙型肝炎患者的肝病进程,尤其肝细胞癌(HCC)的发生风险明显增高。但HDV的致癌机制有待进一步探索,治疗方式及效果也亟待突破。综述了HDV相关HCC流行病学新特点、致病机制的新认识和诊疗进展等,对推进研发更精准的HDV检测手段、更有效的治疗药物及减少HDV相关HCC具有重要意义。     

Hepatitis B and C virus infection and risk of haematological malignancies

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are classified as oncogenic human viruses. Chronic HBV and HCV infections are associated with higher risk of haematological malignancy development. Direct and indirect oncogenic mechanisms have been demonstrated for both HBV and HCV in several studies. HCV and overt/occult HBV infections in patients with oncohaematological disease constitute an impediment and a threat during immunosuppressive chemotherapy treatment. We review the HBV and HCV oncogenic mechanisms and the impact and the safety of antiviral treatment in patients with haematological malignancies.     

慢性HBV/HCV感染人群伴随的免疫相关表现

慢性HBV/HCV感染者常常伴有自身免疫系统紊乱,在丙型肝炎中尤为常见。介绍了慢性丙型肝炎患者免疫状态紊乱的机制,出现非器官特异性自身抗体的比例,以及伴随的免疫相关疾病,如混合型冷球蛋白血症、肾小球肾炎、干燥综合征、甲状腺疾病、2型糖尿病的临床表现、诊断和治疗等。简述了慢性乙型肝炎患者免疫状态紊乱的机制、相关的免疫表现以及抗病毒治疗对其的影响。慢性乙型或丙型肝炎的抗病毒治疗可以减轻伴随的免疫系统疾病,但是不宜采用干扰素治疗,因此,乙型肝炎患者应采用核苷和核苷酸类药物治疗,丙型肝炎患者应采用直接抗病毒药物治疗。     

Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States

Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%–5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%–2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09–5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU.     

Therapeutic effects of pegylated interferon plus ribavirin in chronic hepatitis C patients with occult hepatitis B virus dual infection

Background and Aim: Occult hepatitis B virus (HBV) infection is defined by the detectable serum HBV–DNA in HBV surface antigen‐negative patients. This retrospective study aims to evaluate the therapeutic effects of combined pegylated interferon (PEG–IFN) plus ribavirin (RBV) in patients with concurrent occult HBV/hepatitis C virus (HCV) dual infection. Methods: In total, 126 consecutive chronic hepatitis C (CHC) patients who received combined PEG–IFN and RBV therapy were included. Patients were divided into the occult HBV/HCV dual infection group or the HCV‐monoinfected group according to whether or not they had the detectable serum HBV–DNA. The biochemical and virological responses to combined therapy were compared between these two groups. Serum HCV‐RNA and HBV–DNA were checked before treatment, at the end of treatment as well as at 6‐ and 12‐months' follow up in the occult HBV/HCV group. Result: Six patients were seropositive for HBV–DNA and were included in the occult HBV/HCV dual infection group. There were no statistical differences in the biochemical and virological responses to combined therapy between these two groups. Undetectable serum HBV–DNA was noted at the end of the treatment and the 6‐ and 12‐months' follow up in patients with occult HBV/HCV dual infection. Conclusion: Occult HBV infection in CHC patients is rare. The biochemical and virological responses to combined PEG–IFN and RBV therapy might be similar in CHC patients with or without occult HBV infection. The serum HBV–DNA level was low in patients with occult HBV/HCV dual infection who responded to combined therapy.     

HLA typing in chronic type B, D and C hepatitis

Aims: We aimed to test the hypothesis that susceptibility to chronic HBV, HDV or HCV infections or their pathology is influenced by host genetic factors.Methods: The Human Leukocyte Antigens (HLA) (A, B, DR and DQ) were determined by microlym- phocytotoxicity assay in patients with chronic C (n=117), B (n=97) or D (n=27) hepatitis and their frequencies were compared with those of 489 healthy controls.Results: No statistically significant association was found between any HLA antigen and chronic B or D hepatitis. A significantly higher frequency of HLA-B14 was observed in patients with chronic persistent or active C hepatitis (16.7% of 90 versus 5.9% of 489, χ²=10.9, pc<0.05, Relative Risk=3.17, Etiological Fraction=0.11). The frequency of HLA-DR5 was lower in HCV positive patients (24.8%) than in controls (45%, χ²=15.1, pc<0.005, RR=0.4, EF=−0.37).Conclusions: No correlation could be observed between clearance of HBV or HDV and HLA phenotype. Immunogenetic factors may have a role in determining susceptibility to chronic HCV hepatitis, and in Italian patients HLA-DR5 is a protective factor.     

Distribution of hepatitis B virus genotypes among patients with chronic infection.

Hepatitis B virus (HBV) can be classified into at least eight genotypes, A-H. We evaluated the distribution HBV genotypes among patients with chronic infection. METHODS: We consecutively evaluated adult patients with chronic HBV infection from Salvador, Brazil. Patients were classified according to HBV infection chronic phases based on HBV-DNA levels and presence of serum HBV markers. HBV-DNA was qualitatively and quantitatively detected in serum by polymerised chain reaction (PCR). Isolates were genotyped by comparison of amino acid mutations and phylogenetic analysis. RESULTS: One-hundred and fourteen patients were evaluated. HBV-DNA was positive in 96 samples. HBV genotype was done in 76. Mean age was 36 +/- 11.3. In 61 of 76 cases subjects were classified as inactive HBsAg carriers. Their mean HBV serum level was 1760 copies/ml and 53 of 61 were infected with HBV genotype A, seven with HBV genotype F and one with genotype B. Twelve of the 76 patients had detectable hepatitis B e-antigen (HBeAg) in serum. Ten were infected with HBV genotype A and two with genotype F; most had increased alanine aminotransferase and high HBV-DNA levels. Three patients were in the immunotolerant phase, two were infected with HBV genotype A and one with genotype F. HBV subtyping showed subtypes adw2 and adw4. CONCLUSIONS: HBV genotype A adw2 and genotype F adw4 were the most prevalent isolates found. We could not find differences in genotype distribution according to HBV clinical phases and DNA levels. We did not detect HBV genotype D in contrast to a previous study in our center with acute hepatitis B. All inactive HBsAg carriers had low HBV-DNA levels.     

Impact of occult hepatitis B virus infection and prior hepatitis B virus infection on development of hepatocellular carcinoma in patients with liver cirrhosis due to hepatitis C virus

Objective. Although hepatitis B virus (HBV) DNA can be detected in liver or sera of patients without serum hepatitis B surface antigen (HBsAg), its clinical relevance in hepatocarcinogenesis remains controversial. This observational cohort study was conducted to clarify the risk factors, including the presence of serum HBV DNA and hepatitis B core antibody (anti-HBc), for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). Material and methods. The study comprised 123 patients with LC due to HCV, and negative for HBsAg. The risk factors for HCC development were analyzed by univariate and multivariate analysis. Serum samples were assayed for HBV DNA using real-time polymerase chain reaction. Results. Serum HBV DNA was detectable in 14 patients (11.4%) and serum anti-HBc in 96 (78.0%). During the follow-up period (mean 53.3 months), 80 patients (65.0%) developed HCC. The cumulative HCC development rate was significantly higher in the anti-HBc-positive group than in the anti-HBc-negative group (p=0.0039), but did not differ between the serum HBV DNA-positive and -negative groups (p=0.8570). The multivariate analysis indicated that male gender, alpha-fetoprotein (AFP) 20 ng/ml or greater, average serum alanine aminotransferase (ALAT) 80 IU/l or greater and the presence of anti-HBc were independent risk factors for development of HCC (p=0.038, p=0.013, p=0.020 and p=0.001, respectively). Conclusions. Serum anti-HBc, which indicates a previous HBV infection, has clinical significance in hepatocarcinogenesis in patients with HCV-related LC, but serum HBV DNA does not. Therefore, anti-HBc in serum is a significant predictor for HCC.     

Influence of human immunodeficiency virus infection on hepatitis δ virus superinfection in chronic HBsAg carriers

SUMMARY. It is generally agreed that hepatitis B virus (HBV) replication is reduced by hepatitis δ virus infection (HDV) and augmented by human immunodeficiency virus (HIV) infection. However, the precise nature of the interactions between HBV. HDV and HIV is controversial. The aim of this study was to evaluate the impact of HIV infection on HBV and HDV replication, and on histological scores during δ virus super-infection in HDV-positive. chronic carriers of hepatitis B surface antigen (HBsAg). We studied 38 men and six women, 15 of whom were HIV-positive and all of whom had at least one marker of HDV infection. Serum hepatitis B e antigen (HBeAg), HBV DNA, HDV RNA, anti-δ antigen antibodies (anti-HD) IgM, anti-HD IgG and hepatitis δ antigen (HDAg) were tested for in the serum and liver, respectively; anti-hepatitis C virus (HCV) antibodies were detected using a second-generation recombinant immunoblot assay. Histological specimens were scored blindly according to Knodell's classification for periportal and intralobular necrosis, portal inflammation and fibrosis. HBV DNA was detected more frequently in the HIV-positive patients than in those who were HIV-negative (25 vs 0% P = 0.01), while markers of HDV replication (serum anti-HD IgM. serum HDV RNA and liver HDAg) were as frequent in the HIV-positive patients (69%, 40% and 50% respectively) as in those who were HIV-negative (75%, 52% and 30%. respectively; P>0.05). By contrast, 31% of the HIV-positive patients were serum HDAg-positive compared to only 6% of the HIV-negative patients (P = 0.001). HDV antigenaemia and anti-HD antibodies usually fluctuated in the HIV-positive patients during follow-up. The mean Knodell score was similar in the HIV-positive (11.5 ± 3.2) and HIV-negative (10.7 ± 2) subgroups, as was the mean semi-quantitative index of hepatic necrosis, inflammation and fibrosis. Our results provide evidence that in HDV-positive patients: (1) HIV infection counters the inhibitory effect of HDV superinfection on HBV replication; (2) serum anti-HD IgM, HDV RNA and liver HDAg are not more frequent in HIV-positive than in HIV-negative patients, suggesting that HIV infection has no effect on HDV replication (although the significance of the increased frequency of HD antigenaemia remains unclear): (3) the histological severity of liver disease is not influenced by HIV status.