在男同志中性傳播C肝的流行現正同時涉及愛滋病毒感染者和非感染者

資料來源：Michael Carter, aidsmap news，發佈時間：2019年3月29日，財團法人台灣紅絲帶基金會編譯

根據臨床傳染病期刊發表的研究報告，於2016年至2017年間，在法國里昂使用暴露前預防投藥（PrEP）的男男間性行為者（MSM）急性C肝（HCV）的發生率增加了10倍。而愛滋病毒陽性之MSM當中其C肝之發生率也增加了一倍，主要是由於再次感染。有明顯的群聚感染現象，超過一半的感染者涉及愛滋病毒陽性和愛滋病毒陰性的男性。

「我們的世代研究清楚地表明，HCV之流行已經在HIV陰性的MSM族群中傳播」，作者評論道。 「在使用PrEP的MSM當中，AHI ［急性C型肝炎的發生率］特別高」。作者認為，在MSM族群中控制HCV流行的措施，應包括對所有高風險行為的人進行常規和頻繁的檢測。對於那些被診斷患有急性感染的患者，採用直接作用的抗病毒藥物（DAA）並快速的啟動HCV之治療和採取減害措施是需要的。

現在已有相當多的證據顯示在愛滋病毒陽性MSM者當中HCV的性傳播，而在愛滋病毒陰性MSM當中C肝之爆發流行目前已被報告。里昂的研究人員希望進一步了解HIV陽性和HIV陰性MSM中HCV傳播的動態，包括發生率、群聚情形和相關風險因素。因此，他們設計了一項包括2014年至2017年間，在該市被記錄的MSM中所有急性HCV病例的研究。對HCV樣本進行了遺傳分析，以確定感染是否聚集以及是否存在明顯的傳播網絡。

在研究期間，共有108例急性HCV感染，涉及96例MSM（80例首次感染和28例再感染）。 HCV的危險因素包括靜脈注射藥物（33％）、鼻吸吸食藥物（34％）、集體性行為（69％）和拳交（24％）。

在79％的愛滋病毒陽性和96％的愛滋病毒陰性男性當中至少有一項危險因素被報告。

HIV陰性患者明顯比HIV陽性患者年齡小（中位年齡37歲對應 47歲，p = 0.02），更有可能報告曾使用藥物（96％對應 40％，p <0.001）和拳交（50％對應 15％，p = 0.02）。當HCV被診斷時，有三分之二的HIV陰性之男性正在接受PrEP。此外在愛滋病毒陰性MSM當中另有12％的HCV感染於PrEP篩查過程中被採集到。

每年診斷的急性HCV病例數量從2014年的20例倍增加到2017年的40例。在2017年，HIV陰性的男性佔急性C肝診斷的45％。

愛滋病毒陽性MSM之C肝的發生率更增加了一倍以上，從2014年的每100人年1.1例增加到2017年的每100人年2.4例。然而，這種增加僅在再感染上有顯著意義，從2014年的每100人年的4.8例增加到 2017年每100人年的11.8例；而首次感染之比率則保持相對穩定，同期每100人年增加1.1至1.5例。相較之下， PrEP使用者中首次感染的發生率，則在2016年至2017年間增加了10倍，從每100人年的0.3例增加到2017年每100人年的3.0例。

有8％的病例中觀察到C肝自發性治癒。有94人其HCV採用治療直接作用的抗病毒藥物（DAA）治療，平均在估計感染日期後5個月進行。整體的持續病毒學抑制反應（SVR, Sustained Virologic Response，指治療結束後追蹤六個月以上的期間，不但 ALT/GPT值維持正常，Ｃ型肝炎病毒核糖核酸也測不到，即可以說是治療成功）比率為96％。

最常見的HCV基因型別是1a（55％），4d（31％）和3a（7％）。系統發生上的分析顯示，有96％的急性感染屬於一個群聚。有八個不同的集簇 – 包含3到27個序列被確認。所有的集簇都涉及到愛滋病毒感染者，而其中5個集簇還涉及愛滋病毒陰性者。儘管目前正推動此一波流行的是急性感染，仍有六個集簇感染涉及2014年之前感染HCV的個體，

對五個最大集簇感染的分析顯示，有四個與藥物使用有密切相關（作45％至85％的男性），拳交（50％）是其中另一個的額外風險因素。 2016年1月至2017年7月期間的17起感染涉及密切​​相關的病毒，這些感染發生在共享多種風險因素的個體中。 2017年6月至8月期間診斷出涉及6名患者的一組病患，均報告了鼻吸吸食藥物和近期細菌性的性病感染，可能顯示這些患者係在單一事件中的HCV傳播。

「這項研究揭示了近年來法國里昂MSM族群中急性C肝感染流行病學上的變化，透過分享高風險活動，如藥愛(chemsex) 和創傷性的性行為，從HIV感染者傳播到HIV陰性者」，作者寫道。 「所有集簇感染都是從感染愛滋病毒的MSM開始的，這表明該流行病始於這一人群，隨後蔓延到HIV陰性的MSM族群當中」。

作者認為他們的研究結果對於控制MSM族群中性傳播的HCV具有重要意義。 他們敦促所有具有高風險行為的MSM應定期和規律的篩查HCV。且應在急性HCV診斷後儘早提供直接作用的抗病毒藥物（DAA）治療和減害措施，從而限制向外壙大傳播的風險。

針對同一組患者的進一步分析在2019年的反轉錄病毒和伺機會性感染會議（CROI 2019）上發表。 這表明了對C肝之快速診斷、治療和滅害措施的重要性。 估計每個罹患急性HCV感染的MSM，在未來5個月內將會把感染傳播給其他2.35個 MSM。

Epidemic of sexually transmitted hepatitis C in gay men now involves both HIV-positive and HIV-negative men

Michael Carter , Published: 29 March 2019

Incidence of acute hepatitis C virus (HCV) among men who have sex with men (MSM) who use pre-exposure prophylaxis (PrEP) in Lyon increased tenfold between 2016 and 2017, according to research published in Clinical Infectious Diseases. There was also a doubling of incidence among HIV-positive MSM, mainly as a result of reinfection. There were distinct clusters of infections, over half involving both HIV-positive and HIV-negative men. 

“Our cohort study clearly demonstrates that the HCV epidemic has now spread in HIV-negative MSM,” comment the authors. “The incidence of AHI [acute hepatitis C incidence] was particularly high in PrEP-using MSM.” The authors believe that measures to control the HCV epidemic among MSM should include routine and frequent testing for all high-risk individuals. For those diagnosed with acute infection, rapid initiation of HCV therapy with direct-acting antivirals (DAAs) and harm reduction is needed.

There’s now considerable evidence of sexual transmission of HCV among HIV-positive MSM. Outbreaks are now being reported among HIV-negative MSM. Investigators in Lyon wanted to further understand the dynamics of HCV transmission among both HIV-positive and HIV-negative MSM, including incidence, clustering and risk factors. They therefore designed a study involving all cases of acute HCV among MSM documented in the city between 2014 and 2017. HCV samples were genetically analysed to see if infections were clustered and whether there were distinct transmission networks.

During the study period, there were a total of 108 acute HCV infections involving 96 MSM (80 first infections and 28 reinfections). Risk factors for HCV included injecting drug use (33%), snorting drugs (34%), group sex (69%) and fisting (24%).

At least one risk factor was reported by 79% of HIV-positive and 96% of HIV-negative men.

HIV-negative patients were significantly younger than HIV-positive individuals (median age, 37 vs 47 years, p = 0.02) and were more likely to report drug use (96% vs 40%, p < 0.001) and fisting (50% vs 15%, p = 0.02). Two-thirds of HIV-negative men were receiving PrEP at the time of HCV diagnosis. An additional 12% of HCV infections among HIV-negative MSM were picked up at PrEP screening.

The number of acute HCV cases diagnosed per year doubled from 20 cases in 2014 to 40 cases in 2017. By 2017, HIV-negative men represented 45% of acute diagnoses.

Incidence in HIV-positive MSM more than doubled, from 1.1 cases per 100 person-years in 2014 to 2.4 cases per 100 person years in 2017. However, this increase was only significant for reinfections, increasing from 4.8 per 100 person-years in 2014 to 11.8 cases per 100 person-years in 2017. The rate of first infections remained relatively stable, increasing from 1.1 to 1.5 cases per 100 person-years over the same period. In contrast, incidence of first infections among PrEP users increased tenfold between 2016 and 2017, from 0.3 cases per 100 person-years to 3.0 cases per 100 person-years in 2017.

Spontaneous cure was observed in 8% of cases. HCV therapy using DAAs was initiated by 94 people, an average of five months after the estimated date of infection. The overall sustained virological response rate was 96%.

The most frequent HCV genotypes were 1a (55%), 4d (31%) and 3a (7%). Phylogenetic analysis showed that 96% of acute infections belonged to a cluster. Eight distinct clusters – involving between three and 27 sequences – were identified. All the clusters involved an individual with HIV, with five also involving an HIV-negative man. Six clusters involved an individual who was infected with HCV before 2014, though acute infections were now driving the epidemic.

Analysis of the five largest clusters showed that four were strongly associated with drug use (45 to 85% of men), with fisting (50%) an additional risk factor in one of them. Seventeen infections between January 2016 and July 2017 involved closely related virus. These infections were in individuals sharing multiple risk factors. One cluster of patients diagnosed between June and August 2017 involved six patients, all reporting nasal drug use and with a recent bacterial STI, possibly suggesting HCV transmission between these individuals at a single event.

“This study reveals the changing epidemiology of AHI in MSM in Lyon, France, in recent years, spreading from HIV-infected patients to HIV-negative patients through sharing of high risk activities such as chemsex and traumatic sexual practices,” write the authors. “All clusters started with an HIV-infected MSM, suggesting that the epidemic started in this population and later spread to HIV-negative MSM.”

The authors believe their findings have important implications for the control of sexually transmitted HCV in MSM. They urge that all MSM with high-risk behaviour should be routinely and regularly screened for HCV. DAA therapy and harm reduction should be provided early following diagnosis of acute HCV, thus limiting the risk of onward transmission.

A further analysis of the same group of patients was presented to the Conference on Retroviruses and Opportunistic Infections (CROI 2019). This showed the importance of rapid diagnosis, treatment and harm reduction. Each MSM with acute HCV infection was estimated to pass on the infection to 2.35 other MSM within five months.

Ramière C et al. Patterns of HCV transmission in HIV-infected and HIV-negative men having sex with men. Clin Infect Dis, online edition, 2019.

Danesh G et al. Phylodynamics of HCV acute infection in men having sex with men. Conference on Retroviruses and Opportunistic Infections (CROI 2019), Seattle, poster 594, 2019.