Epidemiological Survey of Patients With Hemodialysis Complicated by Hepatitis C in Japan

Nowadays, interferon‐free direct‐acting antiviral (DAA) treatment is the standard of care for chronic hepatitis C patients. Some DAA regimens are highly effective and safe even for those with renal dysfunction/failure including those receiving HD. However, it remains unclear to what extent HD specialists gain knowledge about advances in anti‐hepatitis C virus (HCV) treatment. To clarify the current situation and identify problems in the treatment of HD patients with chronic hepatitis C, we performed a questionnaire survey at 36 HD facilities between June 2016 and September 2017. In a total of 3418 HD patients, 179 (5.2%) were positive for anti‐HCV antibody, and among these patients, 110/125 (88.0%) were positive for serum HCV RNA. Of the latter, only 42/110 (38.2%) patients received antiviral therapy. Moreover, HCV serotyping or genotyping was performed in 23/110 (20.9%) patients. In 26/49 (53.1%) of the remaining 68 untreated patients, “HD specialists do not know any HCV‐specific treatments” and “HD specialists have no opportunity to consult with a hepatologist” were the reasons cited for the lack of anti‐HCV treatment. This epidemiological study found that some HD patients with chronic hepatitis C had not yet received antiviral treatment despite the emergence of DAAs. To overcome such undesirable circumstances, medical cooperation between HD specialists and hepatologists should be required.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients: A Concept for Consideration

Hemodialysis patients potentially have an increased risk of infection with parenterally transmitted viral agents due to an impaired host immune response and multiple transfusion requirements. Viral hepatitis is considered as a problem for hemodialysis patients because 1.9% of all deaths among this population are related to the consequence of viral hepatitis. Hepatitis B virus (HBV) is one of the most important causes of transmitted infections by the parenteral route in hemodialysis patients. Occult HBV infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg), which harbors potential risk of HBV transmission through hemodialysis. There are conflicting reports on the prevalence of occult HBV infection (OBI) in hemodialysis patients. Considering the importance of occult HBV infection in hemodialysis patients and the growing evidence on this subject, the purpose of this review is to provide comprehensive information on OBI prevalence in hemodialysis patients and highlight the most important points in this issue.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients in Japan

Hepatitis B surface antigen is widely used in hepatitis B virus surveillance; patients who test negative for the antigen are judged to be uninfected. However, occult hepatitis B virus infection has been confirmed with hepatitis B virus DNA at low levels in the liver and peripheral blood in patients positive for hepatitis B core antibody or hepatitis B surface antibody, even if they test negative for hepatitis B surface antigen. To investigate the prevalence of occult hepatitis B virus in hemodialysis patients, we performed cross‐sectional analysis of 161 hemodialysis patients in two related institutions for hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody. Hepatitis B surface antigen, hepatitis B core antibody, or hepatitis B surface antibody was present in 45 patients (28.0%). Hepatitis B virus DNA was present in six patients (3.7%), all of whom also tested positive for hepatitis B core antibody. Hepatitis B surface antibody positivity was unrelated in only one of the six patients. Four of the six patients were positive for hepatitis B surface antigen; however, two (1.3%) of these with occult hepatitis B virus infection were found to be hepatitis B surface antigen negative. Occult hepatitis B virus infection may be missed in hepatitis B virus surveillance using hepatitis B surface antigen alone; therefore, routine hepatitis B core antibody screening is necessary. Patients who test positive for hepatitis B core antibody should undergo further hepatitis B virus DNA testing to enable accurate hepatitis B virus screening.     

Occult Hepatitis B Virus Infection in Japanese Chronic Hemodialysis Patients

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti‐HBc) was determined by various chemiluminescent immunoassays. HBV‐DNA was quantified in patients positive for anti‐HBc using quantitative real‐time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg‐positive and 218 (20.9%) were anti‐HBc‐positive. All HBsAg‐positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg‐negative and anti‐HBc‐positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.     

Seroprevalence of Hepatitis Viruses B, C, D and HIV Infection Among Hemodialysis Patients in Kerman Province, South-East Iran

Background

The prevalence of hepatitis viruses in hemodialysis patients has been reported to be much greater than in the general population. Attention to local data, effectively guides health planners so that they can control infections and prevent nosocomial transmissions.

Objectives

This cross sectional study was carried out to determine the prevalence of hepatitis B (HBV), hepatitis C (HCV), and hepatitis D (HDV) viruses, as well as the human immunodeficiency virus (HIV) in dialysis centers in the Kerman Province, in the southeast of Iran.

Patients and Methods

All hemodialysis patients (n = 228) in 7 centers were enrolled in the study. Hepatitis B surface antigens (HBsAg), HCV antibodies (Ab), HDV Ab and HIV Ab were measured using specific enzyme linked immunoassay kits (ULTRA kit, bioMérieux, France) and confirmed by a qualitative PCR assay.

Results

The studied group was comprised of 92 (40.4%) females and 136 (59.6%) males. The mean age of the patients was 51 ± 9.5 years and the duration of hemodialysis was 39.7 ± 7.9 months. Positive HBsAg was found in 7% of cases, HCV Ab in 7%, and patients with both viruses were detected in 1.7% cases. HIV Ab and HDV Ab were negative in all cases. Out of the other risk factors, frequency of blood transfusions was significantly correlated with positive HCV Ab (P < 0.008).

Conclusions

Prevalence of HBV and HCV in hemodialysis patients was moderate to low in the Kerman Province, as in other parts of the country. Strict adherence to protective measures could lead to even lower rates.     

Current Status of Hepatitis C Virus‐Infected Maintenance Hemodialysis Patients in Japan

Complete recovery using interferon therapy in Japanese hepatitis C virus (HCV)‐infected dialysis patients is difficult to achieve because >70 % of the HCV genotypes observed in Japan are type 1. In 2016, new direct‐acting antiviral drugs against HCV genotype 1 were reported to be effective and safe for HCV‐infected hemodialysis patients. Although new direct antiviral therapy has become available, no large‐scale studies evaluating the status of HCV infection in Japanese hemodialysis patients have been conducted since 2007. Therefore, we conducted a questionnaire survey to determine the current status of HCV infection in patients. Our results indicated that the HCV antibody prevalence was 5.02 %, and HCV RNA prevalence was 72.3 %. Genotype testing revealed that 62.1 % of patients had HCV genotype 1. New direct antiviral therapy may improve the survival of Japanese HCV‐infected dialysis patients.     

Occult Hepatitis B Virus Infection in Patients With Chronic Hepatitis C Treated With Antiviral Therapy

Background

Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver and/or in the serum of patients with negative results of hepatitis B s antigen (HBsAg) test with or without serological markers of previous viral exposure. The impact of OBI in patients with chronic hepatitis C (CHC) is still unclear.

Objectives

The Aim of this study was to assess OBI prevalence and its potential implications on treatment outcome in a cohort of patients with CHC underwent standard antiviral therapy.

Patients and Methods

Baseline serum samples from 137 HBsAg-negative CHC patients treated with pegylated-interferon and ribavirin (73 Responders/74 Non Responders),were retrospectively analyzed for HBV status.

Results

Seventy-three patients (53.3%) showed markers of previous exposure to HBV. HBV DNA was detected in 2 of 137 serum samples (1.5%), both carrying HBV antibodies. Liver biopsies and post-therapy sera were available for 35 patients (12 Responders/23 Non Responders). HBV DNA sequences were found in 13 of 35 specimens (37.1%), all of patients with HBV DNA negativity in basal and post-therapy serum samples. Among OBI-positive patients, 5 (38.5%) carried serological markers of HBV infection. Regarding therapy outcome, in the OBI-positive group there were 5 of 13 (38.5%) sustained virological responders (SVR) compared to 7 of 22 (31.8%) in the OBI-negative one.

Conclusions

Despite the high prevalence rate of liver HBV DNA in patients with CHC, SVR was not affected by occult HBV infection.     

慢性乙型肝炎肝组织ICAM-1 mRNA和ICAM-1表达及意义

目的探讨肝组织间粘附分子-1(ICAM-1)表达在慢性乙型肝炎(CHB)发病机理中的作用。方法用原位杂交和免疫组织化学技术检测11例正常人和50例慢性HBV感染者肝内ICAM-1 mRNA和ICAM-1表达情况。结果正常人和慢性无症状HBsAg携带者肝细胞无ICAM-1mRNA和ICAM-1表达,CHB患者肝细胞ICAM-1 mRNA和ICAM-1表达增强,阳性肝细胞多分布在汇管区周围和腺泡内炎症坏死区域;重度CHB患者肝细胞ICAM-1 mRNA和ICAM-1表达显著强于中、轻度CHB患者(P<0.05);肝细胞ICAM-1表达强度与肝组织炎症活动度呈显著正相关,p<0.01;肝细胞ICAM-1表达强的患者肝功能显著差于ICAM-1表达弱者,P<0.05。结论肝细胞ICAM-1表达在慢性乙型肝炎肝细胞坏死中起重要作用,肝细胞ICAM-1表达水平能较好反映其肝损害程度和肝功能状况。     

Evaluation of Zinc Plasma Level in Iranian Cirrhotic Patients due to Hepatitis B and Hepatitis C

Background and Aims

Zinc (Zn) has various significant roles in physiological functions of the liver. Furthermore, it has been reported that the administration of zinc has an important role in pharmacotherapy of viral hepatitis. Cirrhotic patients with decrease in plasma zinc level have been covered in previous studies. It is seemingly necessary to assess the zinc level, in Iranian cirrhotic patients, as a distinct population, Because of the large phytate amounts in Iranians diet. Regarding to etiology, disease progress, and treatment, there are some differences in the 2 most common causes of cirrhosis in the Iranian population (hepatitis B and hepatitis C) and it is possible that the zinc level may be different between the two. This study was done to shadow some lights on the subject.

Methods

Between April 2008 and November 2008, plasma zinc level was determined, by atomic absorption method, in 60 cirrhotic inpatients treated due to hepatitis B or hepatitis C in Talighani hospital (a referral center for gastrontestinal and liver diseases in Tehran, Iran).

Results

Mean ± standard deviation (SD) plasma zinc levels determined 0.34±0.22 mg/L and 0.37±0.22 mg/L in hepatitis B and hepatitis C patients respectively. Analysis of t-test showed there is no significant difference between 2 groups regarding to plasma zinc level (P = 0.745).

Conclusions

It is concluded that zinc level of studied cirrhotic patients is less than half of the normal range. Moreover, there is no difference in plasma zinc level between cirrhotic patients due to hepatitis B or hepatitis C. Regarding to this result, supplementation with complementary zinc, may be recommended in both groups in order to optimize the nutritional support and probably better the treatment response.     

维持血液透析的尿毒症病人乙型丙型肝炎病毒感染情况研究

目的　了解北京地区 (东城、宣武、朝阳区 )接受规律性血液透析患者 ,乙型肝炎病毒 (HBV)和丙型肝炎病毒 (HCV)的感染情况及其相关因素。方法　 1998年 3～ 12月在北京协和医院、朝阳医院等 4家医院血液净化中心 ,长期维持血液透析的尿毒症患者 2 2 5例 ,血透中心工作人员及健康献血者 5 0例为对照组。分别用PCR法和高敏PCR法检测HBVDNA、HCVRNA ,ELISA法检测乙肝两对半及丙肝抗体 ,并分析其与透析时间、输血、肝功能损害的关系。结果　 2 2 5例血液透析病人中 ,HCVRNA阳性 37例 (16 4 %) ;HBVDNA阳性 3例(1 33%)。多元回归分析表明 :输血和透析时间是丙型肝炎感染的危险因素。共有 3 0 %(3/ 99)的病人同时感染乙肝和丙肝 ,均有肝功能的损害和临床症状 ,8 1%(8/ 99)HBcAb阳性患者同时合并HCV感染。结论　血液透析病人乙肝和丙肝感染远高于对照组 ,透析时间和输血次数是丙肝感染的危险因素 ,HBV和HCV同时感染问题值得重视。     

湖北省维持性血液透析患者丙型肝炎病毒感染调查

目的：调查维持性血液透析患者丙型肝炎病毒（HCV）感染情况,并探讨其相关危险因素。方法;对湖北省84所医院3608例维持性血液透析（MHD）患者,采用ELISA法检测血清标志物HCV抗体。同时调查其输血史和透析史,进行相关性分析。结果：3608例MHD患者中,HCV感染率5．88％。有输血史HCV感染率（7．12％）显著高于无输血史者（2．13％,P〈0．01）。HCV阳转率透析时间小于1年为0．98％,透析1～2年为4．19％,透析2～3年为4．59％,透析3年以上为13．06％（P〈0．01）。且随着每周透析次数的增加,HCV的阳转率也明显上升（P〈0．05）。接受过1所医院透析的患者,HCV阳转率为3．09％,接受过2所为5．84％,接受过3所为7．44％,接受4所及以上为11．29％（P〈0．01）。结论：反复输血、透析时间长、透析次数多、接受多家医院透析是MHD患者感染HCV高的重要因素。减少输血、加强透析治疗环节院内感染的质量控制对预防HCV感染有重要意义。     

散发性戊型病毒性肝炎394例临床分析

目的:探讨武汉地区散发性戊型病毒性肝炎(HE)的临床特点及其预后。方法:对经血清学检测证实的394例HE患者进行分析。结果:临床上HE以散发形式发病为主,各种慢性肝病患者重叠感染HEV168例,相当常见(42.64%),其病死率(16.07%)明显高于单纯HE组(6.10%)(P<0.01)。老年(≥60岁)患者98例(24.87%),老年组HE患者黄疸高,持续时间长,平均病程为(36.3±4.0)d,较非老年组(24.4±2.3)d,明显延长(P<0.01);老年组并发症发生率(47.95%)明显高于非老年组(28.57%)(P<0.01);老年组重型肝炎发生率(22.45%)及病死率(13.33%)明显高于非老年组(9.18%)(P<0.05)及(5.33%)(P<0.01)。结论:HE发病率呈逐年增高趋势,慢性肝病重叠感染HEV及老年HE患者的病死率高,应引起重视。     

Occult Hepatitis B Virus Infection in Hemodialysis Patients With Isolated Hepatitis B Core Antibody: A Multicenter Study

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Occult HBV infection harbors potential risk of HBV transmission through hemodialysis (HD). The aim of this study was to assess the occult HBV infection in hemodialysis patients with isolated hepatitis B core antibody (anti-HBc). A total of 289 HD patients from five dialysis units in Tehran, Iran, were included in this study. Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (anti-HBs), anti-HBc, Hepatitis C antibody (anti-HCV), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of HD patients with isolated anti-HBc (HBsAg negative, anti-HBs negative and anti-HBc positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler. Of 289 patients enrolled in this study, 18 subjects (6.2%, 95% confidence interval (CI), 3.5%–8.9%) had isolated anti-HBc. HBV-DNA was detectable in 9 of 18 patients (50%, 95% CI, 27%–73%) who had isolated anti-HBc. Plasma HBV-DNA load was less than 50 IU/ml in all of these patients. Our study showed that detection of isolated anti-HBc could reflect unrecognized occult HBV infection in HD patients. The majority of these infections are associated with low viral loads.     

血清一氧化氮在病毒性肝炎中的临床意义

目的:探讨NO在病毒性肝炎中的作用及机制。方法:用分光光度比色分析法检测83例病毒性肝炎患者血清NO和内毒素水平。结果:各病毒性肝炎组NO和内毒素水平均高于正常对照组(P<0.01),重型肝炎组NO水平低于急性和慢性组(P<0.01),而内毒素水平高于急性和慢性组(P<0.01)。结论:病毒性肝炎患者NO水平明显升高,且可能对肝脏有保护作用,