High hepatitis B virus load in a patient with severe polyarthritis nodosa

One of the extra-hepatic manifestations of hepatitis B virus is polyarteritis nodosa (PAN). It may involve medium- and small-sized arteries in any organ. Concurrency of these two diseases may be life threatening and both should be treated. Herein, we report on a patient with severe PAN and high hepatitis B virus load. The patient was an 18-year-old boy with multiple progressive wounds in the skin, referred to our center. The preliminary evaluation showed vasculitis in the skin biopsy compatible with PAN. He was treated with low dose prednisolone and lamivudine for three years. However, his condition got worse and ulcers on his leg became life threatening. The viral load was 17,000,000 copy/mL. The wound developed superimposed resistant bacterial infection. The patient was then treated with two antiviral drugs-lamivudin 100 mg/day plus adefovir 10 mg/day-and high dose cyclophosphamide (750 mg, once a month) and prednisolone (60 mg/day for one month). After six months of treatment, viral load decreased to 100,000 copy/mL and wounds healed. We concluded that high viral load of hepatitis B virus may play an important role in the severity of PAN. We recommend combination therapy with two antiviral agents with high dose of immunosuppressive drugs until both the diseases resolve significantly.     

慢性乙型肝炎抗病毒治疗的困境和进展

慢性乙型肝炎(CHB)由乙型肝炎病毒(HBV)感染引起,易反复发作引起肝脏损伤,严重威胁人类健康。CHB治疗最根本、最关键的是抗HBV治疗,抗HBV治疗在近年来取得了很大的进展,基因治疗、免疫治疗等新技术为抗HBV治疗提供了新的发展方向,但抗HBV治疗仍面临难以突破的困境。本文就抗HBV治疗的困境和进展进行综述。     

Overlap between systemic sclerosis and polyarteritis nodosa: A case report

BackgroundSystemic sclerosis (SSc) is a multiorgan connective tissue disease characterized by vasculopathy, inflammation, autoimmunity, and fibrosis in the skin, lungs and other organs. The occurrence of frank vasculitis is uncommon.Case presentationA 36-year old male patient with limited cutaneous SSc developed multiple necrotic ulcers on both legs and feet and gangrene of several toes, followed by an acute onset of axonal sensorimotor neuropathy affecting both radial and peroneal nerves, severe testicular pain with gangrenous patches over the scrotum. The hepatitis B virus (HBV) core antibody was positive while HB surface antigen and surface antibody, HAV and HCV antibodies were negative. The polymerase chain reaction for HBV and HCV showed no detectable viraemia. Antineutrophil cytoplasmic antibodies, cryoblobulins, anticardiolipin antibodies, lupus anticoagulant, antimitochondrial and anti- liver-kidney microsomal antibodies were negative. Pelvi-abdominal ultrasound and portal vein Doppler study showed a coarse and heterogeneous echo-texture of the liver, splenomegaly, moderate ascites and an enlarged, patent portal vein. Fibroscan revealed grade III liver fibrosis. He had an attack of haematemesis with elevation of the liver enzymes and low serum albumin and prothrombin concentrations. He was diagnosed as a case of polyarteritis nodosa. He was successfully treated by methylprednisolone intravenous pulses, followed by oral prednisone 40 mg/day. Plasmapheresis and six monthly doses of 1000 mg intravenous cyclophosphamide. Prednisone was gradually tapered to 5 mg/day with addition of azathioprine 100 mg/day.ConclusionThe association between systemic sclerosis and polyarteritis nodosa is very rare. The co-existence of SSc and vasculitis necessitates modification of the treatment plan.     

慢性乙丙型肝炎重叠感染后血清病毒标志物的变化

目的为了探讨病毒之间的干扰现象，作者对慢性乙丙型病毒性肝炎重叠感染患者的血清肝炎病毒标志物的变化进行研究。方法１９９２年１月＿１９９４年１０月连续在我院住院确诊的慢性乙丙型病毒性肝炎重叠感染患者６０例，同期连续收住院的单纯慢性乙型肝炎患者１１０例作为对照组，比较两组患者入院时的血清乙型肝炎病毒标志物，并对观察组中２０例患者进行了随访，随访期０．５＿３年。结果入院时观察组ＨＢｅＡｇ和抗＿ＨＢｃＩｇＭ阳性率较对照组显著减少（１９／６０对５２／１０６，８／６０对２９／１１０，Ｐ＜０．０５），ＨＢｓＡｇ阴性率和抗＿ＨＢｅ阳性率显著增高（１０／／６０对５／１１０，Ｐ＜０．０１；３８／６０对４８／１０６，Ｐ＜０．０５）。观察组２０例随访发现，ＨＢＶ＿ＤＮＡ阳性及ＨＢＶ＿ＤＮＡ，ＨＣＶ＿ＲＮＡ二项同时阳性例数都比入院时明显减少（４／２０对１０／２０，Ｐ＜０．０５；１／２０对７／２０，Ｐ＜０．０５）。结论慢性乙丙型病毒性肝炎重叠感染时存在病毒干扰现象     

Management of hepatitis B and C infections in rheumatologic disease

Hepatitis B and C viruses present dual considerations in rheumatic disease as both etiologic factors and important comorbidities that must be assessed and addressed. This review summarizes the link between hepatitis B and arthritis and polyarteritis nodosa as well as hepatitis C and arthritis, Sicca syndrome and cryoglobulinemic vasculitis. Recent data pertaining to the antiviral management in these conditions, especially regarding the use of the direct-acting antivirals in hepatitis C, are also presented. Additionally, guidance on testing and treatment of hepatitis B and C as comorbidities in the context of systemic inflammatory rheumatic conditions and the use of disease-modifying antirheumatic therapy are discussed.     

Replication of clinical hepatitis B virus isolate and its application for selecting antiviral agents for chronic hepatitis B patients

AIM： To establish a cell model harboring replicative clinical hepatitis B virus （HBV） isolates and evaluate its application in individualized selection of anti-HBV agents for chronic hepatitis B （CHB） patients.
METHODS： The full-length HBV genomic DNA from 8 CHB patients was amplified by polymerase chain reaction （PCR）. All the patients were treated with lamivudine for at least seven months and finally became resistant to lamivudine. The amplified HBV DNA fragments were inserted into pHY106 vectors by Sap Ⅰ digestion. The recombinant plasmids containing 1.1 copies of HBV genome were transiently transfected into Huh7 cell line, and the levels of HBsAg, HBeAg and intercellular HBV replicative intermediates were determined by ELISA and Southern blot analysis, respectively, with or without lamivudine and adefovir treatment. The antiviral treatment with adefovir was administered to the patients and analyzed in parallel.
RESULTS： A total of 25 independent HBV isolates were obtained from the sera of 8 patients, each patient had at least two isolates. One isolate from each individual was selected and subcloned into pHY106 vector, including 5 isolates with YVDD mutation and 3 isolates with YIDD mutation. All recombinant plasmids harboring HBV isolates were transfected into Huh7 cells. The results indicated that HBV genome carried in HBV replicons of clinical HBV isolates could effectively replicate and express in Huh7 cells. Adefovir, but not lamivudine, inhibited HBV replication both in vitro and in vivo, and in vitro inhibition was dose-dependent.
CONCLUSION： The novel method described herein enables individualized selection of anti-HBV agents in clinic and is useful in future studies of antiviral therapy for CHB.     

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified.     

Short‐term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus–related polyarteritis nodosa

Objective

To assess the efficacy and safety of lamivudine, an antiviral agent that strongly inhibits hepatitis B virus (HBV) DNA replication, combined with plasma exchanges after short‐term corticosteroids for HBV‐related polyartertitis nodosa (PAN).

Methods

Ten patients (8 men, 2 women, mean ± SD age 50.4 ± 14.4 years) with previously untreated HBV‐related PAN were included in a multicenter, prospective, observational trial. Oral prednisone (1 mg/kg/day) was given for 1 week, then tapered and withdrawn within 1 week. Then, lamivudine (100 mg/day or less in the case of renal insufficiency) was started for a maximum of 6 months. Plasma exchanges were performed simultaneously and scheduled as follows: 3/week for 3 weeks, 2/week for 2 weeks, then 1/week until hepatitis B e antigen (HBeAg) to anti‐HBe antibody (HBeAb) seroconversion was obtained or until 2–3 months of clinical recovery was sustained. The primary trial endpoint was clinical recovery from HBV‐PAN at 6 months. The secondary endpoint was loss of detectable serum HBeAg and HBV DNA, and HBeAg to HBeAb seroconversion at 9 months.

Results

One death, attributed to catheter‐related septicemia, was recorded. At 6 months, all 9 survivors had achieved clinical recovery and by 9 months, 6 of 9 (66%) had seroconverted.

Conclusion

The strategy of short‐term steroids followed by lamivudine and plasma exchanges effectively led to recovery from HBV‐PAN. Because of its oral administration and good safety profile, lamivudine should henceforth be considered the antiviral agent of choice to treat HBV‐related PAN.

     

Non-initiation of hepatitis C virus antiviral therapy in patients with human immunodeficiency virus/hepatitis C virus co-infection

AIM: To assess whether reasons for hepatitis C virus(HCV) therapy non-initiation differentially affect racial and ethnic minorities with human immunodeficiency virus(HIV)/HCV co-infection.METHODS: Analysis included co-infected HCV treatment-na?ve patients in the University of North Carolina CFAR HIV Clinical Cohort(January 1, 2004 and December31, 2011). Medical records were abstracted to document non-modifiable medical(e.g., hepatic decompensation, advanced immunosuppression), potentially modifiable medical(e.g., substance abuse, severe depression, psychiatric illness), and non-medical(e.g., personal,social, and economic factors) reasons for non-initiation. Statistical differences in the prevalence of reasons for non-treatment between racial/ethnic groups were assessed using the two-tailed Fisher's exact test. Three separate regression models were fit for each reason category. Odds ratios and their 95%CIs(Wald's) were computed.RESULTS: One hundred and seventy-one patients with HIV/HCV co-infection within the cohort met study inclusion. The study sample was racially and ethnically diverse; most patients were African-American(74%), followed by Caucasian(19%), and Hispanic/other(7%). The median age was 46 years(interquartile range = 39-50) and most patients were male(74%). Among the 171 patients, reasons for non-treatment were common among all patients, regardless of race/ethnicity(50% with ≥ 1 non-modifiable medical reason, 66% with ≥1 potentially modifiable medical reason, and 66% with ≥ 1 non-medical reason). There were no significant differences by race/ethnicity. Compared to Caucasians, African-Americans did not have increased odds of nonmodifiable [adjusted odds ratio(a OR) = 1.47, 95%CI: 0.57-3.80], potentially modifiable(a OR = 0.72, 95%CI: 0.25-2.09) or non-medical(a OR = 0.90, 95%CI: 0.32-2.52) reasons for non-initiation.CONCLUSION: Race/ethnicity alone is not predictive of reasons for HCV therapy non-initiation. Targeted interventions are needed to improve access to therapy for all co-infected patients, including minorities.     

HIV polyarteritis nodosa-like vasculitis presenting as chronic abdominal pain

Vasculitic syndromes are a rare entity in patients with human immunodeficiency virus (HIV), in the order of <1%. Though the underlying mechanism is thought to involve cell or immune-complex-mediated inflammation, the common finding within the wide spectrum of vasculitides is inflammation of the blood vessel wall. Furthermore, polyarteritis nodosa (PAN)-like vasculitis associated with HIV infection presents differently from classic or idiopathic PAN, thereby making diagnosis difficult for even the most astute clinician. We present the case of a young HIV-infected woman with chronic abdominal pain that went undiagnosed for over 1 year despite an extensive workup until rheumatologic disorders were considered in the differential. Mesenteric angiogram revealed extensive small vessel microaneurysms consistent with PAN-like vasculitis. The patient responded well to corticosteroid therapy and remained symptom-free upon discharge. Despite its relatively low prevalence, vasculitides such as PAN should be considered in patient with unexplained symptoms after thoroughly completing an evaluation for more common diseases, especially considering its good prognosis associated with corticosteroid therapy.     

Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded by rapid clearance of HCV-RNA from serum

Background/Aims: Prediction of response to interferon therapy is important in the management of chronic hepatitis C. Pre-therapy data are valuable but they may be inaccurate in some cases. Our aim was to investigate whether the biochemical and virological events that occur early during interferon therapy in chronic hepatitis C may predict the final result of the treatment.Methods: ALT and serum HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a standard 6-month course of interferon therapy. Eleven patients with a sustained response, 23 who responded but subsequently relapsed and 19 who did not respond were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV).Results: After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained responders, in 26% of transient responders (p=0.02) and in none of the non-responders. Corresponding figures after 8 weeks of therapy were 82% in sustained responders, 61% in transient responders and 9% in non-responders. The difference between sustained and transient responders at this times was not significant. After 4 weeks of therapy, 82% of sustained responders, 52% of transient responders and none of the non-responders presented normalization of alanine transferase. The difference between sustained and transient responders was not significant. Corresponding figures for normalization of alanine transferase at 8 weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained responders, 70% of transient responders and none of the non-responders had cleared HCV-RNA from serum.Conclusions: A rapid normalization of alanine transferase induced by interferon therapy is associated with response, but does not differentiate between transient and permanent response. In contrast, clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is significatively associated with sustained response. Testing for HCV-RNA early during interferon administration may be valuable for further decisions concerning therapy in patients with chronic hepatitis C.     

Human immunodeficiency virus and hepatitis C virus/hepatitis B virus co-infection in Southern Brazil: clinical and epidemiological evaluation

Hepatitis B virus, hepatitis C virus and human immunodeficiency virus share a similar transmission pathway and are often diagnosed in the same patient. These patients tend to have a faster progression of hepatic fibrosis. This cross-sectional study describes the demographic features and clinical profile of human immunodeficiency virus/hepatitis co-infected patients in Paraná, Southern Brazil. A total of 93 human immunodeficiency virus-infected patients attending a tertiary care academic hospital in Southern Brazil were included. Clinical, demographic and epidemiological data were evaluated. Hepatitis B virus and/or hepatitis C virus positive serology was found in 6.6% of patients. The anti-hepatitis C virus serum test was positive in 85% (79/93) of patients, and the infection was confirmed in 72% of the cases. Eighteen patients (19%) were human immunodeficiency virus/hepatitis B virus positive (detectable HBsAg). Among co-infected patients, there was a high frequency of drug use, and investigations for the detection of co-infection were conducted late. A low number of patients were eligible for treatment and, although the response to antiretroviral therapy was good, there was a very poor response to hepatitis therapy. Our preliminary findings indicate the need for protocols aimed at systematic investigation of hepatitis B virus and hepatitis C virus in human immunodeficiency virus-infected patients, thus allowing for early detection and treatment of co-infected patients.     

MiR-122 in hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched microRNA-122 (miR-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that the level of miR-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the well-documented phenomenon that miR-122 promotes HCV accumulation, inhibition of miR-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, miR-122 is also known to block HBV replication, and HBV has recently been shown to inhibit miR-122 expression; such a reciprocal inhibition between miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of miR-122.     

Hepatitis B-associated vasculitis in Alaska Natives: viral genotype, clinical and serologic outcome.

BACKGROUND: The highest incidence of hepatitis B virus (HBV)-associated vasculitis in the world has been reported in Alaska Natives. We examined the incidence of HBV-associated vasculitis before and after mass HBV vaccine immunization and the association between HBV genotype and vasculitis in a population-based cohort study in Alaska natives chronically infected with HBV. METHODS: Genotyping was performed in vasculitis cases and 644 hepatitis B-positive controls without vasculitis using polymerase chain reaction and sequencing of the S gene. Occurrence of HBV vasculitis from 1974 to 2004 was calculated. HBV vasculitis patients and controls were also tested for basal core promoter and precore mutations. RESULTS: Fifteen cases of HBV-associated vasculitis were identified: 13 (86%) had genotype D and one each genotype A and F. Genotype D was more commonly found in patients with vasculitis than controls [odd ratio (OR)=5.9, confidence interval (95% CI) 1.2, 21.8; P<0.015). CONCLUSIONS: HBV-associated vasculitis was associated with genotype D.     

An autopsy case of hepatitis B (HB) antigen-positive polyarteritis nodosa, with reference to immunopathological studies of vascular lesions

An autopsy case of an 11-year-old boy with polyarteritis nodosa is described in which the onset of the disease was associated with the presence of hepatitis B (HB) antigens (Ag) in the cytoplasm and nuclei of hepatocytes as detected by immunohistological methods. Deposits of HBsAg, HBeAg, IgG, IgM, C3, and C1q were demonstrated in systemic vascular lesions. It is considered that the arteritis was due to deposition in the arteries of immune complexes formed by HBAg and HB antibodies. Received: February 10, 2000 / Accepted: July 13, 2000     

HBV/HIV重叠感染的抗病毒治疗

随着人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染率快速增长,乙型肝炎病毒(hepatitis B virus,HBV)/HIV重叠感染成为一种临床易见疾病.HBV/HIV重叠感染使HBV和HIV的生物学行为发生改变,进而相互影响病情进展,使得HBV/HIV重叠感染患者的抗病毒...     

HBV相关性肾炎的抗病毒治疗

乙型肝炎病毒相关性肾炎(hepatitis B virus associated glomerulonephritis,HBV-GN)是HBV感染的表现之一.已有多种药物被用于治疗HBV-GN,但迄今为止尚无最佳的治疗方案.抗病毒(包括干扰素和核苷类似物)治疗HBV-GN能有效抑制HBV复制、缓解蛋白尿,且HBeAg的...     

Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma:A meta-analysis

AIM:To investigate the impact of postoperative antiviral treatment on tumor recurrence and survival of patients with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection-related primary hepatocellular carcinoma(HCC) after curative therapy.METHODS:We performed a meta-analysis of randomized and non-randomized control trials from electronic search and manual search.The fixed effect model of Mantel-Haenszel method and the random effect model of Der Simonian and Laird method were used for homogeneo...     

Treatment of hepatitis B virus-related polyarteritis nodosa: two case reports and a review of the literature

A substantial number of cases of polyarteritis nodosa (PAN) are related to hepatitis B virus (HBV) infection. Different treatment strategies are reported in the literature. The aim of this study was to review 15 years of literature (1988–2002) to determine the optimal treatment for HBV-related PAN at present, and to discuss the indications and mechanism of action of corticosteroids in HBV-related PAN, as many physicians are reluctant to use these in the presence of HBV infection. The first patient stopped his initial treatment, relapsed and died of cerebral infarction. The second case illustrates the favorable outcome with the standard treatment: corticosteroids, lamivudine and plasma exchanges. If adequate follow-up is possible, antiviral agents as well as corticosteroids are indicated in HBV-related PAN. Corticosteroids diminish inflammation and corticosteroid withdrawal induces an alanine aminotransferase (ALT) rebound in patients with a low baseline ALT level. Antiviral agents are essential, as they reduce the production of HBV antigens and help to achieve hepatitis B early antigen (HBeAg) seroconversion. Plasma exchanges reduce the level of circulating immune complexes and are included in the treatment protocol of all recent studies. However, their effect has not been evaluated in controlled trials. We concluded that if adequate follow-up is possible, antiviral agents as well as corticosteroids are indicated in HBV-related PAN.Abbreviations ALT Alanine aminotransferase - HBV Hepatitis B virus - PAN Polyarteritis nodosa