Hepatitis C Virus Ribonucleic Acid Research Articles

CDC's New Hepatitis C Virus Testing Recommendations for Perinatally Exposed Infants and Children: A Step Towards Hepatitis C Elimination.

New U.S. Centers for Disease Control and Prevention (CDC) guidelines for hepatitis C virus (HCV) testing of perinatally exposed infants and children released in 2023 recommend a nucleic acid test (NAT) for detection of HCV ribonucleic acid (i.e., NAT for HCV RNA) at 2-6 months of age to facilitate early identification and linkage to care for children with perinatally acquired HCV infection. Untreated hepatitis C can lead to cirrhosis, liver cancer, and premature death and is caused by HCV, a blood-borne virus transmitted most often among adults through injection drug use in the United States. Perinatal exposure from a birth parent with HCV infection is the most frequent mode of HCV transmission among infants and children. New HCV infections have been increasing since 2010, with the highest rates of infection among people aged 20-39 years, leading to an increasing prevalence of HCV infection during pregnancy. In 2020, the CDC recommended one-time HCV screening for all adults aged 18 years and older and for all pregnant persons during each pregnancy. Detecting HCV infection during pregnancy is key for the identification of pregnant persons, linkage to care for postpartum treatment, and identification of infants with perinatal exposure for HCV testing. It was previously recommended that children who were exposed to HCV during pregnancy receive an antibody to HCV (anti-HCV) test at 18 months of age; however, most children were lost to follow-up before testing occurred, leaving children with perinatal infection undiagnosed. The new strategy of testing perinatally exposed children at age 2-6 months was found to be cost-effective in increasing the identification of infants who might develop chronic hepatitis C. This report describes the current perinatal HCV testing recommendations and how they advance national hepatitis C elimination efforts by improving the health of pregnant and postpartum people and their children.

Prevalence and associated risk factors of hepatitis C antibody and RNA among people who inject drugs in Puerto Rico

IntroductionAs a public health crisis, hepatitis C viral infection (HCV) is highly prevalent among people who inject drugs (PWID). We aimed to assess factors associated with HCV antibody (Ab) and HCV ribonucleic acid (RNA) positivity among PWID in Puerto Rico. MethodsThe study recruited a total of 150 persons in rural and peri-urban community settings through the respondent-driven sampling method and administered a structured questionnaire. We conducted HIV and HCV testing using dried blood spots (DBS). We examined correlates of HCV infection with sociodemographics, drug use patterns, and injection practices using regression in bivariate and multivariable analysis. ResultsOf the 150 participants, 89 % were male; 11 % were female; 72 % identified as mixed race; and the median duration of drug injection was 17.8 years. The mean age was 43.1 years, with 64 % of the population being from 23 to 45 years old. Among study participants (n = 150), the prevalence of HCV Ab was 73 %, and HCV RNA was 53 %. Factors significantly associated with HCV Ab and RNA included older age, increasing years of injection, incarceration, injecting other people, and identifying as Black. The belief that syringe air blowing reduces HCV transmission was also independently associated with HCV Ab positivity. ConclusionsOur findings regarding risk factors associated with HCV infection show the need to enhance prevention and control strategies for reducing transmission among PWID. Direct-acting antiviral treatment, sustained access to harm reduction, and culturally tailored services will be required to substantially reduce rates of HCV. Community-based treatment models and treatment in correctional settings are needed.

The Efficacy and Safety of Sofosbuvir and Daclatasvir Treatment in Children and Adolescents With Thalassemia and Hepatitis C Virus Infection

Thalassemia patients are susceptible to hepatitis C virus (HCV) infection due to blood transfusions. Currently, data on treating HCV in thalassemic children with direct-acting antivirals is lacking. This study was performed to determine the efficacy and safety of sofosbuvir-daclatasvir combination therapy in thalassemic children and adolescents. A nonrandomized, open-label, interventional study was carried out in a tertiary care hospital. Consecutive noncirrhotic treatment-naïve thalassemic patients with HCV infection with viremia, within the age group of 6-18 years, were treated with the combination of sofosbuvir-daclatasvir: 200mg+30mg for age 6-11 years (Group A) and 400mg+60mg for age 12-18 years (Group B). The primary endpoint was sustained virological response at 12 weeks (SVR12). A total of 70 patients (Group A 45, 64% male; Group B 25, 40% male) were recruited. The mean age was 8.5 years and 13.9 years in the two groups. Mean HCV Ribonucleic acid (RNA) levels in Groups A and B were 446906.1 IU/ml and 256187.8 IU/ml, respectively. SVR12 was achieved in 43 of 45 (95.5%) patients on an intention-to-treat basis and 43 of 44 (97.7%) patients on a perprotocol basis in Group A, and all patients in Group B (100%). In both groups, there was a significant improvement in biochemical parameters. Among the two patientswho did not achieve SVR12 in Group A, one required termination of therapy due to urticaria. Sofosbuvir-daclatasvir based treatment in noncirrhotic, treatment-naive thalassemic children and adolescents infected with HCV is effective and safe.

Does a detectable HCV RNA at the end of DAA therapy herald treatment failure?

Background & aimsThe study aimed to assess the phenomenon of achieving sustained virologic response (SVR) in patients with detectable ribonucleic acid (RNA) of hepatitis C virus (HCV) at the end of treatment (ET) with direct-acting antivirals (DAA), find how this is affected by the type of regimen, and how patients experiencing this differed from non-responders with detectable HCV RNA at the ET. MethodsThe study included all consecutive patients with detectable HCV RNA at the ET selected from the EpiTer-2 database, a retrospective national multicentre project evaluating antiviral treatment in HCV-infected patients in 2015–2023. ResultsOf the 16106 patients treated with IFN-free regimens with available HCV RNA assessment at the ET and at follow-up 12 weeks after treatment completion (FU), 1253 (7.8%) had detectable HCV RNA at the ET, and 1120 of them (89%) finally achieved SVR. This phenomenon was significantly more frequent in pangenotypic regimens, 10.3% vs. 4.7% in genotype-specific options (p < 0.001), and the highest proportion was documented for glecaprevir/pibrentasvir (13.7%), and velpatasvir/sofosbuvir ± ribavirin (6.9%). Patients ET + FU- treated with these two pangenotypic regimens (n = 668) had less advanced liver disease, were less frequently infected with genotype (GT) 3, and were significantly more likely to be treatment-naïve than 61 non-responders. ConclusionsWe documented 7.8% rate of patients with detectable HCV RNA at the ET, of whom 89% subsequently achieved SVR, significantly more frequently in the population treated with pangenotypic regimens. Less severe liver disease, more often GT3 infection, and a higher percentage of treatment-naive patients distinguished this group from non-responders.

Molecular Epidemiology of HCV RNA Genotype-3 in Dhaka City, Bangladesh.

Hepatitis C virus (HCV) is a causative agent that causes chronic liver diseases worldwide. It is a little, enclosed, single-stranded ribonucleic acid (RNA) virus. The recognition of the pathogenic HCV genotype is critical for the remedy of its sufferers. The aim of this study was to identify the HCV RNA genotype to decide the correct treatment of hepatitis C positive sufferers in Bangladesh. Blood samples were collected from 390 individuals and isolated RNA (60 µg) from blood plasma. Extracted RNA was used for quantitative HCV RNA, and complementary DNA (cDNA) was prepared by polymerase chain reaction (PCR) conducted by reverse transcriptase enzyme. This cDNA amplified in multiplex by RT-PCR, which was performed with specific set of primers. The HCV RNA genotype was detected 297 of 390 patients. Of the 390 test samples, 200 (51.28%) samples were from males and 190 (48.71%) were from females, with age ranging from 5 to 78 years. In all, 166 of 200 male samples and 131/190 female samples were found positive for HCV. Of these 390 participants included in the study, 213 (54.61%) were identified as genotype 3 positive, 78 (20%) as genotype 1 positive, 6 (1.53%) as genotype 6 positive, and the remaining 93 (23.85%) samples were unclassified due to low/undetected viral load. In this study, we detected the highest percentage (30.89%) of genotype 3 HCV in patients aged 51 to 60 years. The results suggested that genotype 3 HCV is frequently present in Bangladesh and it is usually responses better to interferon therapy. However, genotype 1 and 6 HCV have also been found circulating in this country, which demands longer treatments and effective control measures.

Predictors for Liver Cirrhosis in Patients with Hepatitis C Virus: A Cross-Sectional Study

Background: Cirrhosis is one of the most critical health problems with a great economic burden on the health system. Objectives: This study evaluated cirrhosis predictors in patients with hepatitis C virus (HCV). Methods: A total of 608 patients with HCV were included in the present study within 2011 and 2017 and divided into two groups based on the presence and absence of cirrhosis. Demographic and laboratory data (e.g., blood group, aspartate transaminase (AST), alanine transaminase (ALT), prothrombin time (PT), platelet count, anti-HCV antibodies, and virus level count) were collected by referring to patients’ files and compared between the two groups. Predictive factors were determined using the regression model. Results: In this study, 85 patients (13.9%) had liver cirrhosis. Univariate analysis showed that hepatic enzymes AST, ALT, platelet count, PT, partial thromboplastin time, international normalized ratio, and HCV ribonucleic acid levels in cirrhosis patients were significantly higher than in non-cirrhosis patients (P &lt; 0.05). Adjusted logistic regression analysis showed age &lt; 45 years (adjusted odds ratio (ORAdj): 1.11, P = 0.028), male gender (ORAdj: 2.08, P = 0.023), co-infection with hepatitis B virus (HBV) infection (ORAdj: 2.58, P = 0.001), and alcohol consumption (ORAdj: 1.87, P = 0.001) were predictive factors for cirrhosis in patients with HCV Conclusions: This study showed that in patients with hepatitis C, age &gt; 45 years, male gender, alcohol consumption, and co-infection with HBV significantly increased the risk of liver cirrhosis.

Hepatitis C virus care cascade among people who inject drugs in Puerto Rico: Minimal HCV treatment and substantial barriers to HCV care

BackgroundPeople who inject drugs (PWID) in Puerto Rico are disproportionately affected by the hepatitis C virus (HCV) epidemic. However, there is a scarcity of data on the HCV care cascade among PWID in Puerto Rico. This study aims to describe the HCV cascade of care among PWID in Puerto Rico, identify gaps, and explore barriers to HCV care. MethodsParticipants were recruited using respondent-driven sampling and tested for both HCV antibodies (Ab) and RNA (ribonucleic acid) using rapid testing and dried blood spot samples (DBS). The cascade of care was estimated based on the DBS HCV Ab and RNA results, as well as self-reported data on HCV screening, linkage to care, treatment uptake and sustained virologic response collected through a questionnaire. The cascade was constructed sequentially, with each step using the number of people from the preceding step as the base denominator. The survey also assessed participants' perceived barriers to HCV care. ResultsOut of 150 participants, 126 (84%) had previously been HCV screened, 87% (109/126) were HCV Ab positive, 72% (79/109) were RNA positive,48% (38/79) were linked to care, 32% (12/38) initiated treatment, 58% (7/12) finished treatment, and 71% (5/7) achieved SVR. Barriers to HCV care included concerns about drug abstinence requirements, access to transportation, stigma in healthcare settings, and lack of knowledge about HCV treatment sites. ConclusionThis study provides insights into the HCV cascade of care among PWID in Puerto Rico for the first time and highlights limited diagnosis, treatment uptake, and barriers to care.

Real-World Effectiveness of 8-Week Glecaprevir/Pibrentasvir in Treatment-Naïve, Compensated Cirrhotic HCV Patients.

The EXPEDITION-8 clinical trial has demonstrated that treatment-naïve patients with compensated cirrhosis (TN/CC) of HCV genotypes 1-6 can achieve a 98% intent-to-treat sustained virologic response rate 12weeks post-treatment with an 8-week glecaprevir/pibrentasvir (G/P) regimen. Further real-world evidence is needed to support the effectiveness of 8-week G/P in a clinical practice setting and to consolidate these treatment recommendations. The aim of this study is to contribute real-world evidence for the effectiveness of an 8-week G/P treatment in TN/CC patients with HCV genotypes 1-6. Retrospective real-world data from 494 TN/CC patients with HCV genotypes 1-6 were collected between August 2017 to December 2020 from the Symphony Health Solutions administrative claims database. Demographic and clinical characteristics were collected at baseline. Patients were required to have a follow-up HCV ribonucleic acid level at least 8weeks or more after the end of treatment. The percentage of patients achieving a sustained virologic response (SVR) is reported. The majority of patients were male (58%) and Caucasian (40%), with a mean age of 58years; 74%, 12%, 12%, and 1% of patients were HCV genotype 1, 2, 3, and 4-6 infected, respectively. SVR was achieved in 95.5% of all patients. Across patient subgroups, SVR was achieved in 95.6% of patients with HCV genotype 3 and in 93% of HCV patients with a recent diagnosis of illicit drug use or abuse (within 6months prior to G/P initiation). Early real-world evidence indicates high effectiveness of the 8-week G/P regimen in TN/CC patients of HCV genotypes 1-6 from a large US claims database.

Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) As a Biomarker for Lymphoid Malignancy with HCV Infection.

The hepatitis C virus (HCV) is potentially associated with liver cancer, and advances in various drugs have led to progress in the treatment of hepatitis C and attempts to prevent its transition to liver cancer. Furthermore, reactivation of HCV has been observed in the treatment of lymphoma, during which the immortalization and proliferation of lymphocytes occur, which leads to the possibility of further stimulating cytokines and the like and possibly to the development of lymphoid malignancy. There are also cases in which the disappearance of lymphoid malignancy has been observed by treating HCV and suppressing HCV-Ribonucleic acid (RNA), as well as cases of recurrence with an increase in HCV-RNA. While HCV-associated lymphoma has a poor prognosis, improving the prognosis with Direct Acting Antivirals (DAA) has recently been reported. The reduction and eradication of HCV-RNA by means of DAA is thus important for the treatment of lymphoid malignancy associated with HCV infection, and HCV-RNA can presumably play a role as a biomarker. This review provides an overview of what is currently known about HCV-associated lymphoma, its epidemiology, the mechanisms underlying the progression to lymphoma, its treatment, the potential and limits of HCV-RNA as a therapeutic biomarker, and biomarkers that are expected now that DAA therapy has been developed.

Assessing feasibility of a modified same-day test-and-treat model for hepatitis C among rural people who inject drugs

BackgroundDespite advancements in hepatitis C virus (HCV) treatment, low uptake among hard-to-reach populations remains a global issue. The current study aimed to assess the feasibility of a modified same-day test-and-treat model in improving HCV care for people who inject drugs (PWID) living in resource-constrained rural areas.MethodsA pilot study was conducted in four primary healthcare (PHC) centers in Malaysia. The model's key features included on-site HCV ribonucleic acid (RNA) testing using a shared GeneXpert® system; noninvasive biomarkers for cirrhosis diagnosis; and extended care to PWID referred from nearby PHC centers and outreach programs. The feasibility assessment focused on three aspects of the model: demand (i.e., uptake of HCV RNA testing and treatment), implementation (i.e., achievement of each step in the HCV care cascade), and practicality (i.e., ability to identify PWID with HCV and expedite treatment initiation despite resource constraints).ResultsA total of 199 anti-HCV-positive PWID were recruited. They demonstrated high demand for HCV care, with a 100% uptake of HCV RNA testing and 97.4% uptake of direct-acting antiviral treatment. The rates of HCV RNA positivity (78.4%) and sustained virologic response (92.2%) were comparable to standard practice, indicating the successful implementation of the model. The model was also practical, as it covered non-opioid-substitution-therapy-receiving individuals and enabled same-day treatment in 71.1% of the participants.ConclusionsThe modified same-day test-and-treat model is feasible in improving HCV care for rural PWID. The study finding suggests its potential for wider adoption in HCV care for hard-to-reach populations.

レジオネラ肺炎を契機に発症したAcute–on–chronic liver failureの救命例(A case of acute–on–chronic liver failure caused by Legionella pneumonia)

レジオネラ肺炎は，多臓器不全を合併し致死的な経過をたどることがある。今回，ACLFに伴う肝性脳症を合併するも，人工肝補助療法を導入し，救命し得た症例を経験したので報告する。症例は50歳の男性で，高度意識障害と多臓器不全のため近隣病院から転院搬送された。搬入時より意識レベルはJCS III–300であり，血液検査でアンモニアが高値であった。肝性脳症と診断し，直ちにon–line HDFによる人工肝補助療法を開始した。第2病日に尿中レジオネラ抗原が陽性となったことから，レジオネラ肺炎と診断し，それに伴って多臓器不全を発症した状態であると判断した。抗生剤については，メロペネム，レボフロキサシン，アジスロマイシンを投与した。凝固障害に対しては，適宜輸血を実施した。合計3回のon–line HDFとCHDFを交互に実施し，緩徐に意識レベルの改善が得られ，第5病日には意識清明となった。第8病日にICUを退出し，第20病日に転院した。ACLFは，最近定義された新しい疾患概念であり，代償性あるいは非代償性肝硬変に増悪因子が加わって，高度の肝機能異常を呈する病態である。治療については症候に対する対症療法が中心であり，本症例では人工肝補助療法を導入したことで覚醒が得られ，救命に寄与したと考えられた。 Legionella pneumonia may be complicated by multiple organ failure and may result in death. We herein report a case of hepatic encephalopathy associated with acute–on–chronic liver failure, which was successfully rescued by artificial liver support therapy. A 50–year–old man was transferred from a nearby hospital due to severe disturbance of consciousness and multiple organ failure. His level of consciousness was Japan coma scale III–300, and a blood test revealed a high level of ammonia. Hepatic encephalopathy was diagnosed as the cause of consciousness disturbance, and artificial liver support therapy with on–line hemodiafiltration was started immediately. On Day 2, Legionella pneumonia was diagnosed because urinary Legionella antigen was positive. For antibiotics, meropenem, levofloxacin, and azithromycin were administered. Blood transfusion was performed as needed for coagulopathy. The patient’s level of consciousness gradually improved, and he became lucid on Day 5. He was discharged from the intensive care unit on Day 8 and transferred to another hospital on Day 20. We believe that the rapid introduction of artificial liver support therapy enabled the patient to regain consciousness. レジオネラ肺炎は，多臓器不全を合併することで，致死的な経過をたどることがある。アルコール多飲歴が感染のリスクであるため，大酒家であればその発症に注意を払う必要がある。一方，大酒家は肝硬変に罹患していることが多く，acute–on–chronic liver failure（ACLF）を発症することで，慢性肝不全が急激に進行する可能性がある。今回，レジオネラ肺炎の感染を契機にACLFを発症し肝性脳症に陥るも，on–line hemodiafiltration（HDF）による人工肝補助療法を導入することで，覚醒が得られた症例を経験したので報告する。 本論文に倫理委員会の承諾は必要がない。また本論文は個人情報保護法に基づいて匿名化がなされ，患者またはその家族より論文の出版に関する同意を得ている。 患 者：50歳の男性 主 訴：なし（高度意識障害） 既往歴：急性腹膜炎で手術歴あり，C型肝炎ウイルス（hepatitis C virus: HCV）感染後 sustained virological response，アルコール依存症（精神科病院に入院歴あるも通院は自己中断） 内服歴：常用薬なし。健康食品，サプリメントや漢方薬の使用なし 家族歴：肝疾患の家族歴なし 生活歴：温泉や循環式風呂の入浴なし。加湿器の使用なし。飲酒はアルコール度数9%の缶チューハイ2,500mL/day。喫煙は20本/dayを30年間。アレルギー歴なし。生肉の摂取なし。職業は土木建築業。両肩から両前腕にかけて刺青あり 現病歴：搬送数日前から車上生活を送っていた。搬送当日，河川敷に本人の車両が放置されており，警察官が周囲を捜索したところ，車両から約400m離れた土手で倒れている本人を発見し救急要請された。全身に明らかな外傷は認めず，車内には飲酒後と思われる空き缶が散在していた。過量服薬や違法薬物の使用の痕跡はなかった。直近二次病院に搬送されたが，Japan Coma Scale（JCS）III–300の高度意識障害と黄疸があり，採血では肝機能障害，腎機能障害，凝固障害，電解質異常を認めた。体幹部の単純computed tomography（CT）では両側スリガラス陰影と脂肪肝を疑わせる肝臓の斑状低吸収域を認めたが，明らかな胸腹水は認めなかった。前医では対応困難であり，多臓器不全に対する集中治療目的に当院の救命救急センターに緊急転院搬送となった。 入院時現症：身長168cm，体重70.7kg，body mass index 25.0kg/m2，意識レベル Glasgow Coma Scale（GCS）E1V1M1，体温36.9度，血圧135/81mmHg，脈拍110/min・整，呼吸数30/min，SpO2 98%（酸素マスク5L/min）であった。瞳孔は左右同大5mmで対光反射は両側迅速，眼球結膜に黄染を認めた。胸部聴診では，心音は整で雑音はなく，両側胸部でcoarse cracklesを聴取した。腹部は膨満，軟で腹部正中に手術痕あり，右季肋部に肝臓を三横指触知し，波動は認めず，クモ状血管腫や女性化乳房も認めなかった。両側下腿に軽度の圧痕性浮腫を認めた。 入院時検査所見：当院で再検した血液検査（Table 1）では，貧血，凝固障害，肝機能障害，腎機能障害，電解質異常と多臓器不全を呈していた。新型コロナウイルス感染症の迅速抗原検査およびpolymerase chain reaction（PCR）検査は陰性であった。HCV ribonucleic acid（RNA）は陰性であった。また，尿中薬物検査キットもすべて陰性であった。頭部CTでは意識障害を来しうる脳出血や腫瘤性病変は認めなかった。体幹部単純CT（Fig. 1）では，両側上葉優位に浸潤影や網状影を認め，下葉に淡い濃度上昇を伴う陰影を認めたが，明らかな胸水貯留は指摘できなかった。肝形態は保たれており，肝臓周囲には腹水は認めず，胆嚢の浮腫性変化も認めなかった。入院時の血液検査結果では，FIB–4スコアは20.9点で，C型肝硬変の判別式は20点であった。 CT scans of the patient. A: Day 1, B: Day 7, C: Day 15 The abnormal chest opacity gradually improved. B showed ascites accumulation (white arrow), but C showed improvement. 入院後経過（Fig. 2）：病歴や所見からは元々アルコール性慢性肝硬変が背景にあり，何らかの要因で急性増悪し，ACLFおよび肝性脳症を来したものと考えた。肝性脳症については，犬山分類 grade Vであり，右内頸静脈からバスキュラーアクセスを確保し，直ちにon–line HDF（透析膜：FIX250E；ニプロ，血流量200mL/min，透析液流量500mL/min，補充液流量5,000mL/hour）を開始した。On–line HDFに伴い，血清カリウムとリンの低下が懸念され，適宜補正を行った。貧血と凝固障害に対しては，輸血を行い，ビタミンK製剤の投与を行った。消化管出血の懸念があったため，経鼻胃管は挿入せずに，経肛門的にラクツロースの注腸を開始した。分岐鎖アミノ酸製剤の投与については，窒素負荷につながり，肝性脳症を助長する可能性があると判断したため実施しなかった。On–line HDF終了後は，continuous hemodiafiltration（透析膜：セプザイリス；バクスター，血流量100mL/min，補充液流量400mL/min，排液量800mL/min，透析液流量400mL/min，以下CHDF）での血液浄化を開始した。敗血症の可能性は否定できず，各種培養を採取した後に，メロペネム（meropenem: MEPM）の投与を開始した。呼吸不全については，マスクでの酸素投与のみで酸素化が維持可能であり，努力呼吸も認めなかったことから，気管挿管や人工呼吸器管理は見送った。肺炎像の鑑別目的に，第2病日に実施した尿中レジオネラ抗原（リボテスト；旭化成ファーマ）が陽性となったため，レジオネラ肺炎と確定診断し，病態としてレジオネラ肺炎が契機となりACLFを発症したものと考えた。また，レボフロキサシン（levofloxacin: LVFX）の静注を開始した。培養検査については，当院ではbuffered charcoal yeast extract（BCYE）培地を常備しておらず，ヒメネス染色も外部発注の検査となること，尿中抗原陽性であれば，感染症法の四類感染症の定義を満たすことから実施しなかった。喀痰loop–mediated isothermal amplification（LAMP）法については外注であったが提出し，結果，良好な喀痰が得られなかったことと，LVFXを投与後に検体を採取した影響のためか陰性であった。一方で，第2病日のアンモニアが280μg/dLと増悪していたため，分岐鎖アミノ酸製剤は引き続き投与せず，2回目のon–line HDFを導入した。On–line HDF後の採血では，アンモニアが130μg/dLと改善しており，意識レベルも改善を認めた。第3病日に，重症のレジオネラ肺炎と判断し，LVFXに加えて，アジスロマイシン（azithromycin: AZM）の静注を開始し，AZMについては合計5日間投与した。同日の採血では，アンモニアは改善傾向であったが，依然として意識障害が残存していたため，3回目のon–line HDFを実施した。その後は乏尿が続いていたため，腎代替療法としてCHDFによる除水を継続した。3回目のon–line HDF施行後より，徐々に意識レベルは改善し，第4病日には軽度の見当識障害を認めるのみとなった。黄疸については，皮膚掻痒感の訴えに対し軟膏塗布での対症療法，経過観察とした。第6病日より食事（蛋白20g制限食）とリファキシミンの内服を開始した。第7病日に体幹部CTを再検査したところ，肺炎像については改善傾向を認め，新たに腹水が貯留していた。同日，自尿が増加傾向であったため，CHDFから離脱した。全身状態として経過が順調であったことから，第8病日にICUを退室した。また，入院時に採取した培養検査がすべて陰性であったことを確認し，MEPMの投与は終了した。第12病日にLVFXは内服へ移行し，静注と内服で合計21日間の抗生剤治療を予定した。一般床に転棟後は，羽ばたき振戦や異常行動を認めることなく経過した。第15病日に体幹部CTを再検し，肺炎像と腹水が消退傾向であることを確認した。第20病日に肝不全や黄疸に対する治療継続目的，およびリハビリテーション継続目的に，独歩で近隣病院に転院した。 Clinical course of the patient. i.v: intravenous drip, p.o: per os 今回，ACLFを合併し，肝性脳症により昏睡状態に陥るも，on–line HDFを用いた人工肝補助療法を導入することで，覚醒が得られたレジオネラ肺炎の1例を経験した。我々が渉猟し得た限りでは，本邦で類似症例の報告はなく，本症例はレジオネラ肺炎が契機となってACLFを合併し，on–line HDFを用いることで救命し得た初の報告である。 レジオネラ菌（Legionella pneumophilla）は，1976年の米国在郷軍人会で発生した重症肺炎の原因菌として，1977年に初めて同定された好気性ブドウ糖非発酵グラム陰性桿菌である1。世界中の土壌中や環境水中に存在し，埃やエアロゾルとして吸入することで感染が成立する。市中肺炎のみならず，院内肺炎の起因菌としても重要である。細胞内寄生菌のため，細胞内へ移行し効果を発揮するβ–ラクタム系の抗菌薬は無効であり，早期の治療介入のためには鑑別すべき疾患として挙げることが必要である。ところが，確定診断のためにはヒメネス染色やBCYE培地での細菌培養，喀痰LAMP法といった，施設によっては外部発注での検査が必要となることが課題であった。近年ではその報告件数は増加傾向となっており2，要因として，1999年に感染症法の四類感染症に指定されたことや，2003年に尿中抗原検査が保険適応となったことが挙げられる。 重症度という点に着目すると，レジオネラ肺炎はしばしば多臓器不全を合併し，致死的な経過をたどることがある2。高柳らの報告によれば，死亡は65例中6例で，死因として敗血症性ショックや腎不全，播種性血管内凝固，多臓器不全の併発によるものであった2。とくに，多臓器不全を合併した3例中2例が死亡しており，レジオネラ肺炎に多臓器不全を合併した場合の致死率は極めて高いことが推察される。また，レジオネラ肺炎の発症リスクとして，高齢，男性，免疫抑制状態，慢性肺疾患，アルコール多飲歴，悪性腫瘍，鉄過剰症，tumor necrosis factor–α（TNF–α）治療歴，および喫煙が挙げられている3。本症例では，アルコール多飲歴やアルコール依存症の既往歴を認めていたことから，確定診断はされていないものの，基礎疾患としてアルコール性慢性肝硬変の存在が示唆され，発症リスクが高かったと推測された。また，肝硬変による免疫不全状態と考えれば，重症化しやすい素因も併せ持っていたと推測された。すなわち，アルコール多飲歴，肝硬変，レジオネラ肺炎の三者が，相互に悪影響を及ぼしたため，重症化に至ったと考えられた。 そのような背景のなかで，本症例ではレジオネラ肺炎が契機となってACLFを発症したと考えた。そもそも肝不全とは，肝細胞の減少ないし機能低下によって生体の恒常性が維持できなくなることであり，発症から肝不全に至るまでの期間で，急性，遅発性，慢性に分類されている4。急性肝不全とは「肝炎の発症から8週間以内に，高度の肝機能障害に基づいて昏睡II度以上の昏睡を来し，プロトロンビン時間が40%以下を示すもの」と定義される4。一方で，ACLFとは，「Child–Pughスコアが5～9点の代償性ないし非代償性肝硬変に，アルコール多飲，感染症，消化管出血，原疾患増悪などの増悪因子が加わって，28日以内に高度の肝機能異常に基づいて，プロトロンビン時間INRが1.5以上ないし同活性が40%以下で，血清総ビリルビン値が5.0mg/dL以上を示す症例」と厚生労働省の研究班により2018年に定義された5。急性肝不全とACLFは，正常肝あるいは肝予備能が正常の慢性肝疾患が背景にあるかどうか，という点で差別化された。診断に至るまでの因果関係として，急性肝不全が先行し，全身状態が悪化した後にレジオネラ肺炎を二次的に合併した，という可能性についても考慮されたが，レジオネラ肺炎が多臓器不全を発症しうる2という点を根拠に，本症例では，元々アルコール多飲に伴った肝硬変が存在し，レジオネラ肺炎を契機にACLFを発症したものと考えた。 ACLFの治療については，肝移植を除けば特異的かつ決定的なものはない6。原因に対する治療や，症候に対する対症療法が基本となる7。アルコール性慢性肝炎に準じたステロイドの投与については考慮したが，本症例では実施しなかった。肺野の異常陰影が，間質性肺炎の急性増悪であった場合，なおのことステロイドの投与が考慮されたが，レジオネラ肺炎の診断に至ったためにその必要性が低下し，人工肝補助療法での治療が奏功しない場合に，その実施を検討する方針としていたためである。血漿交換（plasma exchange: PE）についても，まずはon–line HDFで肝性脳症治療を進め，覚醒が得られない場合に実施を検討する方針としていた。幸い，on–line HDFとCHDFによる治療が奏功したため，血漿交換の導入は不要であった。肝移植については，現実的な問題として多臓器不全を呈しており，全身麻酔に耐えうるかが不明であったこと，背景にアルコール依存症があり，断酒もできていないことから，適応はないと判断した。 急性肝不全の内科的治療における両輪は，蛋白合成能（とくに血液凝固因子）の補助と解毒能の代替である8。前者については，新鮮凍結血漿（fresh frozen plasma: FFP）の輸血やアルブミン投与，ビタミンK製剤の補充を行うことが基本となる。本症例では，プロトロンビン時間40%を目標に適宜FFPを投与した。後者については，解毒すべき物質，すなわち肝性脳症の原因物質の排除が必要となる。本邦では，欧米と比較して肝移植のドナーが見つかりにくいという背景から人工肝補助療法が発展してきた9。肝性脳症の原因物質の代表の一つにアンモニアがあり10，アンモニアは肝性脳症患者の主たる死亡原因である脳浮腫および脳ヘルニアを惹起する可能性が示唆されている11。すなわち，人工肝補助療法の最大の目的は，肝性脳症から覚醒させ，意識障害を改善させることにある。アンモニアは分子量17g/moLと低分子であるため，小分子除去に効率の良い血液透析（hemodialysis: HD）が有効と考えられるが，実際にはHDでの肝性脳症の覚醒率は40%程度である12。これは，アンモニア以外に中分子の肝性脳症物質が関与しているためと考えられている（中分子仮説）が，具体的な物質の同定までは至っていない13。ほか，PE，血液濾過（hemofiltration: HF）での覚醒率は37.5%，78%程度である12。単独での実施は効果に乏しく，両者の利点を併せ持ったHDFが有効と考えられる。とくに，中央配管から供給される純水を透析液と置換液として使用し，前希釈法によるon–line HDFが効率的かつ経済的であるという報告が挙がっている14。本邦では，PEとHDFによるコンビネーション法が主流とされる15が，本症例では，まずon–line HDFを実施し，効果が得られない場合にPEを併用する方針としていた。結果，PEは回避することができ，on–line HDF単独でも良好な覚醒が得られ，脳ヘルニアに至ることなく経過した。覚醒率が高いということは，ICU入室期間の短縮にもつながる。合併症や続発症の低減などによる要素が，救命に寄与したと考えられた。本症例を通して，急性肝不全による肝性脳症のみならず，ACLFによる肝性脳症に対しても，on–line HDFによる人工肝補助療法が効果的であることが示唆された。 人工肝補助療法におけるon–line HDFの注意すべき点の一つとして，透析液が腎不全用であることが挙げられる16。すなわち，カリウム，リンが透析液中に不足しており，重炭酸が過剰に含まれている。アンモニアと同様に，カリウムとリンも小分子であるため，on–line HDFの開始に伴い急激に低下する可能性があり，注意が必要である。本症例では，HDF開始前と開始後約2時間が経過した時点，終了後の3ポイントで血液検査を実施し，カリウムとリンの値を逐一確認し，適宜補正を行った。また，薬剤や栄養についても影響を受けるため注意が必要と考えられる。本症例では，とくに抗生剤治療において，濃度依存性のLVFXと腎機能に応じて調整不要のAZMが治療の主軸であったため，on–line HDFの影響を考慮することなく治療を進めることが可能であった。 レジオネラ肺炎を契機としてアルコール性慢性肝硬変を背景にACLFを合併し，肝性脳症に陥った症例を経験した。肝性脳症に対して，on–line HDFによる人工肝補助療法を導入したことで覚醒が得られ，救命し得たと考えられた。 本論文における利益相反はない。

Hepatitis C care cascade in a large academic healthcare system, 2012 to 2018.

To determine the hepatitis C virus (HCV) care cascade among persons who were born during 1945 to 1965 and received outpatient care on or after January 2014 at a large academic healthcare system. Deidentified electronic health record data in an existing research database were analyzed for this study. Laboratory test results for HCV antibody and HCV ribonucleic acid (RNA) indicated seropositivity and confirmatory testing. HCV genotyping was used as a proxy for linkage to care. A direct-acting antiviral (DAA) prescription indicated treatment initiation, an undetectable HCV RNA at least 20 weeks after initiation of antiviral treatment indicated a sustained virologic response. Of the 121,807 patients in the 1945 to 1965 birth cohort who received outpatient care between January 1, 2014 and June 30, 2017, 3399 (3%) patients were screened for HCV; 540 (16%) were seropositive. Among the seropositive, 442 (82%) had detectable HCV RNA, 68 (13%) had undetectable HCV RNA, and 30 (6%) lacked HCV RNA testing. Of the 442 viremic patients, 237 (54%) were linked to care, 65 (15%) initiated DAA treatment, and 32 (7%) achieved sustained virologic response. While only 3% were screened for HCV, the seroprevalence was high in the screened sample. Despite the established safety and efficacy of DAAs, only 15% initiated treatment during the study period. To achieve HCV elimination, improved HCV screening and linkage to HCV care and DAA treatment are needed.

Acute hepatitis C virus infection: clinical update and remaining challenges.

Acute hepatitis C virus (HCV) infection is a global health concern with substantial geographical variation in the incidence rate. People who have received unsafe medical procedures, used injection drugs, and lived with human immunodeficiency virus are reported to be most susceptible to acute HCV infection. The diagnosis of acute HCV infection is particularly challenging in immunocompromised, reinfected, and superinfected patients due to difficulty in detecting anti-HCV antibody seroconversion and HCV ribonucleic acid from a previously negative antibody response. With an excellent treatment effect on chronic HCV infection, recently, clinical trials investigating the benefit of direct-acting antivirals (DAAs) treatment for acute HCV infection have been conducted. Based on the results of cost-effectiveness analysis, DAAs should be initiated early in acute HCV infection prior to spontaneous viral clearance. Compared to the standard 8-12 week-course of DAAs for chronic HCV infection, DAAs treatment duration may be shortened to 6-8 weeks in acute HCV infection without compromising the efficacy. Standard DAA regimens provide comparable efficacy in treating HCV-reinfected patients and DAA-naïve ones. For cases contracting acute HCV infection from HCV-viremic liver transplant, a 12-week course of pangenotypic DAAs is suggested. While for cases contracting acute HCV infection from HCV-viremic non-liver solid organ transplants, a short course of prophylactic or pre-emptive DAAs is suggested. Currently, prophylactic HCV vaccines are unavailable. In addition to treatment scale-up for acute HCV infection, practice of universal precaution, harm reduction, safe sex, and vigilant surveillance after viral clearance remain critical in reducing HCV transmission.

Comparative Study between ELISA and TrueNat for Hepatitis B Virus and Hepatitis C Virus among Antenatal Women Attending Tertiary Care Medical Institute in Manipur, India

Introduction: Viral hepatitis is one of the leading causes of death and disability. Nearly 1.5 million people die every year from Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) related liver diseases. Reported consequences of HBV and HCV infection in pregnancy include an increased likelihood of occurrence of preterm delivery and low birth weight and perinatal transmission. Aim: To compare Enzyme-Linked Immunosorbent Assay (ELISA) and closed system Polymerase Chain Reaction (PCR) TrueNat for the detection of HBV and HCV among antenatal women attending a tertiary care medical institute. Materials and Methods: This was a hospital-based crosssectional study conducted at the Department of Microbiology, JNIMS, Imphal, Manipur, India, during the period from December 2020 to January 2022. Serum samples were tested using ELISA as well as on the TrueNat PCR. Data was analysed using Statistical Package for the Social Sciences (SPSS) version 23.0. Results: Out of 60 samples, using ELISA (QUALISA), 24 were found to be positive for HBV surface antigen (HBsAg) and 14 were found to be positive for HCV antibodies (HCV Ab). On further testing using TrueNat chip-based closed system Real Time-PCR (RT-PCR) Test, 12 were found to be positive for HBV Deoxyribonucleic Acid (DNA) and five were found to be positive for HCV Ribonucleic Acid (RNA). Conclusion: TrueNat PCR could eliminate the problem of false positivity in the detection of HBV and HCV. It is useful to make clinical decisions on starting antiviral therapy and also in documenting the efficacy of the antiviral therapy.

The Screening of Hepatitis B and Hepatitis C Virus Infection among HIV-Infected Inpatients and Evaluation of Correlated Characteristics in a General Hospital in Shenyang, Liaoning, China.

Background: In this study, we surveyed the prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) and hepatitis C virus (HCV) antibody (anti-HCV) among inpatients with human immunodeficiency virus (HIV) infection and analyzed the correlated factors. Methods: We conducted a retrospective data collection of the HIV-infected inpatients in our hospital from January 2010 to December 2020. We utilized multivariate logistic regression to identify the correlated factors. Results: The proportion of patients screened for HBsAg was 81.8%, which increased from 66.7% in 2010 to 85.7% in 2020. The proportion of patients with anti-HCV screening was 73.9%, which increased from 58.3% in 2010 to 86.7% in 2020. The prevalence of HBsAg positivity was 10.9%, which decreased from 15.0% in the period of 2010-2015 to 9.0% during 2016-2020. Positive anti-HCV was identified in 4.1% of cases. Compared to 4.8% in the period of 2010-2015, there was a similar prevalence of anti-HCV at 3.1% during 2016-2020. Among the HBsAg-positive cases, HBV deoxyribonucleic acid was screened in 70.8% of cases. Among the anti-HCV positive cases, HCV ribonucleic acid (RNA) was screened in 90% of cases. Albumin &lt; 30 g/L, thrombocytopenia and aspartate aminotransferase (AST) &gt; 40 U/L were associated with HBsAg positivity. AST &gt; 40 U/L and higher CD4-positive T lymphocyte counts were associated with HIV/HCV coinfection. Conclusions: The routine screening for both HBV and HCV among HIV-positive inpatients has been greatly improved in the past decade. However, screening for the complete HBV serological markers in HIV-positive inpatients and HCV genotyping among HCV RNA-positive cases leaves much to be desired. A concerted effort should be made to improve HBV vaccine compliance in the HIV-positive population and provide direct-acting antiviral therapies to HCV RNA-positive patients.

Factors Associated with Sustained Virologic Response to Hepatitis C Treatment in a Homeless-Experienced Cohort in Boston, 2014-2020.

Engaging people experiencing homelessness or unstable housing in hepatitis C virus (HCV) treatment is critical to achieving HCV elimination. To describe HCV treatment outcomes, including factors associated with retention through the treatment cascade, for a cohort of individuals treated in a homeless health center in Boston. Retrospective cohort study. All individuals who initiated HCV treatment with Boston Health Care for the Homeless Program's HCV treatment program between January 2014 and March 2020 (N = 867). The primary outcome was sustained virologic response (SVR), defined as an HCV ribonucleic acid (RNA) level ≤ 15 IU/mL at least 12 weeks after treatment completion. We used multivariable logistic regression to examine the association between baseline variables and SVR. Process-oriented outcomes included treatment completion, assessment for SVR, and achievement of SVR. Of 867 individuals who started HCV treatment, 796 (91.8%) completed treatment, 678 (78.2%) were assessed for SVR, and 607 (70.0%) achieved SVR. In adjusted analysis, residing in stable housing (OR 3.83, 95% CI 1.85-7.90) and age > 45 years old (OR 1.53, 95% CI 1.04-2.26) were associated with a greater likelihood of achieving SVR. Recent drug use (OR 0.63, 95% CI 0.41-0.95) was associated with a lower likelihood of SVR. Age, housing status, and drug use status impacted retention at every step in the treatment cascade. A large proportion of homeless-experienced individuals engaging in HCV treatment in a homeless health center achieved SVR, but enhanced approaches are needed to engage and retain younger individuals, those with recent or ongoing substance use, or those experiencing homelessness or unstable housing. Efforts to achieve HCV elimination in this population should consider the complex and overlapping challenges experienced by this population and aim to address the fundamental harm of homelessness itself.

Non-targeted hepatitis C virus screening in acute care healthcare settings in the Southern Appalachian region.

ObjectivesThe objective of this study was to evaluate the performance of non‐targeted hepatitis C virus (HCV) screening in emergency departments (EDs) and other healthcare settings in terms of patients identified with HCV infection and linked to HCV care.MethodsIn the Southern Appalachian region of the United States, we developed non‐targeted HCV screening and linkage‐to‐care programs in 10 institutions at different healthcare settings, including EDs, outpatient clinics, and inpatient units. Serum samples were tested for HCV antibodies, and if positive, reflexed to HCV ribonucleic acid (RNA) testing as a confirmatory test for active infection. Patients with positive RNA tests were contacted to link them to HCV care.ResultsBetween 2017 and 2019, among 195,152 patients screened for HCV infection, 16,529 (8.5%) were positive by antibody testing, 10,139 (5.2% of screened patients and 61.3% of patients positive by antibody test) were positive by RNA testing, and 5778 (3.0% of screened patients and 57.0% of patients positive by RNA test) were successfully linked to HCV care. Among 83,645 patients screened in EDs, 9060 (10.8%) were positive by HCV antibody, and 5243 (6.3%) were positive by RNA test. Among patients positive by RNA testing, linkage to care was lower for patients screened in the ED (44.1%) compared with outpatient clinics (67.6%) (P < 0.01) and inpatient units (50.9%) (P < 0.01).ConclusionsNon‐targeted HCV screening in acute care settings can identify large numbers of people with HCV infection. To optimize the utility of these screening programs, future work is needed to develop best practices that consistently link these patients to HCV care.

Prevalence of syphilis coinfection in hepatitis C virus positive prenatal patients from Alberta during a pilot routine screening program.

BACKGROUND: Alberta routinely screens pregnant patients for select communicable diseases. Hepatitis C virus (HCV) was added to the prenatal screening panel as part of a provincial pilot program in February 2020. This retrospective cross-sectional study aimed to characterize the prevalence of syphilis coinfections in prenatal patients infected with HCV following implementation of the pilot program.METHODS: Routine prenatal HCV and syphilis testing data were extracted from the Public Health Laboratory Information System over a 21-month period. HCV positivity was defined as HCV enzyme immunoassay (EIA) reactive with detected HCV ribonucleic acid (RNA) following molecular confirmation, and positive results were examined for syphilis coinfections. All patients reactive on a syphilis EIA and confirmatory Treponema pallidum particle agglutination (TPPA) or follow-up rapid plasma reagin (RPR) test were considered positive for syphilis. Descriptive statistics for coinfected patients were analyzed. RESULTS: Eighty-seven prenatal patients were identified to be positive for HCV. Of those, 19 (21.8%) were reactive on the syphilis EIA and 17 (19.5%) had confirmed infections with the TPPA or RPR tests. For HCV/syphilis coinfected patients, the majority resided in metropolitan regions (64.6%), were from the lowest income quintile neighbourhoods (47.1%) and had previously tested positive for HCV (82.4%) and syphilis (64.6%) at the public health laboratory. CONCLUSIONS: The prevalence of syphilis coinfections in prenatal patients infected with HCV is high in Alberta. HCV/syphilis coinfection prevalence should be further investigated in other jurisdictions and prenatal cohorts to better understand testing and treatment options for prevention of congenital transmission.

Risk factors for hepatitis C virus infection at a large urban emergency department.

In 2020, Centers for Disease Control and Prevention (CDC) released guidelines recommending HCV screening in all adults 18 years and older. In the current study, we aimed to identify risk factors for HCV infection in an ED population. We performed a retrospective analysis of ED patients ≥ 18 years who were screened for HCV between 28 November 2018, and 27 November 2019, at a single urban, quaternary referral academic hospital. An HCV-antibody immunoassay (HCV-Ab) was used for screening; positive results were confirmed by measuring HCV ribonucleic acid (RNA). The outcome of interest was the number of new HCV diagnoses (presence of viremia by HCV RNA testing). Multiple logistic regression models were used to identify risk factors associated with a new HCV diagnosis. 16,722 adult patients were screened for HCV (mean age: 46 ± 15 years; 51% female). HCV seroprevalence was 5%. Independent risk factors for HCV included increasing age [10-year aOR 1.26 (95% CI 1.23, 1.30)], male sex [aOR 1.25 (95% CI 1.03, 1.51)], undomiciled housing status [aOR 2.8 (95% CI 2.3, 3.5)], history of tobacco use [aOR 3.0 (95% CI 2.3, 3.9)], history of illicit drug use [aOR 3.6 (95% CI 2.9, 4.5)], Medicaid insurance status [aOR 4.0 (95% CI 2.9, 5.5)] and Medicare insurance status [aOR 1.6 (95% CI 1.1, 2.2)].The ED services a high-risk population with regards to HCV infection. These data support universal screening of ED patients for HCV. Risk factor profiles could improve targeted screening at institutions without universal testing protocols.

Sofosbuvir-Velpatasvir Full Dose in Chronic Hepatitis C in End-Stage Renal Disease: An Observational Study from a Himalayan Region

Background Treatment of chronic hepatitis C (CHC) in the setting of chronic kidney disease and end-stage renal disease (ESRD) is challenging. Objectives We planned to evaluate the efficacy and safety of full dose of combination of sofosbuvir-velpatasvir in the treatment of CHC in patients with ESRD or those on maintenance hemodialysis. Methods The prospective observational study was conducted in a tertiary care center in North India where all patients with chronic kidney disease (CKD) were assessed. Those with hepatitis C virus (HCV) antibody positivity underwent testing for HCV ribonucleic acid and were treated if eligible. Full dose of sofosbuvir-velpatasvir was administered daily for 12 weeks (or 24 weeks for decompensated liver disease). Results Of the 162 patients (mean age: 43.08 ± 12.08 years, 114 males), 125 were on regular hemodialysis. Twenty-four (15%) had evidence of liver cirrhosis, out of which four patients had evidence of decompensation. One hundred forty-two patients (87.6%) had an early virological response. Most patients, 160 (98.7%), obtained end of therapy viral clearance and sustained virological response at 12 weeks after therapy. Two patients died, and rest of the patients completed therapy. The adverse effects noticed were nausea (20%), vomiting (18%), headache (10%), and weakness (7%). Conclusion A combination of sofosbuvir and velpatasvir is effective and safe in treating CHC in the setting of CKD.