攜帶 HIV 的男同性戀和雙性戀男性中很少有自發的C型肝炎清除

建議在近期診斷後立即治療，而不是等待自發清除

資料來源：基思·奧爾康 / 2022 年 10 月 5 日 /aidsmap / 財團法人台灣紅絲帶基金會編譯

圖片：弗拉德.奧爾洛夫/Shutterstock.com

一項大型歐洲研究發現，只有不到八分之一的攜帶 HIV 的男同性戀或雙性戀男性自發清除了最近感染的C型肝炎。研究人員表示，如果在診斷出患有持續危險行為的男同性戀或雙性戀男性的一個月內C型肝炎病毒水平沒有下降，則應提供直接作用的抗病毒治療——在某些情況下，醫生不應等待，而應確診後即給予治療。

該研究結果發表在《臨床傳染病》雜誌上，來自 PROBE-C 研究，這是一項對西歐 HIV 感染者近期肝炎感染的觀察性世代研究。該研究旨在評估 HIV 感染者C型肝炎的自發清除率以及對急性感染期間開始的C型肝炎治療的反應。

在 25% 至 50% 的未感染 HIV 的人中觀察到C型肝炎的自發清除，並且在女性中更為常見。在 HIV 感染者中，世代研究報告自發清除率在 5% 到 20% 之間。

確定自發清除的頻率以及何時不再可能發生，可以讓醫生決定何時向近期感染的人提供直接作用的抗病毒治療。治療急性感染可能會限制C型肝炎在男同性戀和雙性戀男性中的性傳播，而等待自發清除——這可能是一個低概率事件——可能會允許C型肝炎進一步的傳播。

該研究招募了在過去一年內C型肝炎 RNA 檢測呈陽性且C型肝炎 RNA 檢測呈陽性 12 個月前C型肝炎抗體或 RNA 檢測呈陰性的 HIV 感染者。

如果人們的C型肝炎抗體檢測呈陰性且肝酶正常，隨後 ALT 持續升高且C型肝炎病毒 (HCV) 抗體呈陽性，則他們也有資格參加這項研究。

該研究在 2007 年至 2017 年間招募了 464 名參與者；除了七個人之外，其他人都是男人。幾乎所有參與者都透過男性之間的性行為接觸過C型肝炎。在研究招募的參與者中，只有 0.7% 的人共用注射設備是C型肝炎傳播的危險因素。 51 名參與者再次感染C型肝炎。

91% 的人正在接受抗反轉錄病毒治療，90% 的人病毒載量受到抑制，參與者的中位 CD4 計數為 574。

55 名參與者 (12%) 發生自發清除，中位時間為首次 HCV-RNA 檢測陽性後 13 週，其中四分之三的所有清除發生在 18 週內。診斷後 4 週，HCV RNA 沒有下降至少兩個對數值，這與持續感染或慢性感染的可能性非常高有關。

該研究的調查人員表示，這一發現毫無疑問應該在何時開始對被診斷為近期感染的人進行治療：正如歐洲愛滋病臨床學會指南所反映的那樣，直接作用的抗病毒治療應該在診斷後四周開始如果 HCV 病毒載量沒有下降二個對數值（102即下降100倍）。

在 144 週的追蹤期內，79% 的參與者隨後開始了C型肝炎治療。參與者在診斷後的中位時間為 14 週開始聚乙二醇干擾素治療，相比之下，開始直接抗病毒治療的人在診斷後 44 週。延遲啟動直接作用抗病毒治療是由於在急性感染期間使用直接作用抗病毒藥物的核銷和許可上的限制。在 2017 年開始引入直接抗病毒藥物後，只有 14% 的確診患者能夠在 24 週內開始治療，而 2007 年這一比例為 75%。

接受直接抗病毒藥物治療的治癒率為 93%；在接受聚乙二醇干擾素的人群中，這一比例為 73%。

研究人員表示，他們的研究結果強化了建議，即在診斷出最近的C型肝炎感染後應立即開始直接抗病毒治療，以限制進一步的傳播。雖然早期C型肝炎治療的長期益處尚不清楚，但研究人員表示，與未感染 HIV 的人相比，不治療的後果對 HIV 感染者來說是顯而易見的：肝臟變化的進展更快，肝硬化和其他併發症的發展更早。

參考文獻：

Monin MB et al.  HIV 陽性 MSM 中最近獲得的C型肝炎病毒的低自發清除率（PROBE-C 研究）。 《臨床傳染病》，2022 年 8 月 25 日於線上發表。DOI：https://doi.org/10.1093/cid/ciac680

Spontaneous hepatitis C clearance rare in gay and bisexual men with HIV

Immediate treatment after recent diagnosis recommended in preference to waiting for spontaneous clearance

Keith Alcorn / 5 October 2022 / aidsmap

Vlad Orlov/Shutterstock.com

Fewer than one in eight gay or bisexual men with HIV spontaneously cleared a recent infection with hepatitis C, a large European study has found. The study investigators say that if hepatitis C virus levels don’t decline within a month of diagnosis in gay or bisexual men with ongoing risk behaviour, direct-acting antiviral treatment should be offered – and in some cases, doctors should not wait, but should offer treatment upon diagnosis.

The findings, published in the journal Clinical Infectious Diseases, come from the PROBE-C study, an observational cohort study of recent hepatitis infections in people with HIV in western Europe. The study was designed to evaluate the rate of spontaneous clearance of hepatitis C in people with HIV and responses to treatment for hepatitis C initiated during acute infection.

Spontaneous clearance of hepatitis C has been observed in between 25% and 50% of people without HIV and is more common in women. In people with HIV, cohort studies have reported spontaneous clearance rates between 5% and 20%.

Determining how often spontaneous clearance happens and when it is no longer likely to happen could enable doctors to decide when to offer direct-acting antiviral therapy to people with recent infection. Treating acute infection could limit the sexual transmission of hepatitis C among gay and bisexual men, whereas waiting for spontaneous clearance – which may be a low-probability event – could permit further hepatitis C transmission.

The study recruited people with HIV with a positive hepatitis C RNA test within the past year and a negative hepatitis C antibody or RNA test 12 months prior to the positive hepatitis C RNA test.

People were also eligible to join the study if they had a negative hepatitis C antibody test and a history of normal liver enzymes followed by a persistent increase in ALT and a positive hepatitis C virus (HCV) antibody result.

The study enrolled 464 participants between 2007 and 2017; all but seven were men. Almost all participants were exposed to hepatitis C through sex between men. Sharing of injecting equipment was a risk factor for hepatitis C transmission in only 0.7% of those recruited to the study. Fifty-one participants had been reinfected with hepatitis C.

Ninety-one percent were taking antiretroviral treatment, 90% had a suppressed viral load and the median CD4 count of participants was 574.

Spontaneous clearance occurred in 55 participants (12%), a median of 13 weeks after the first positive HCV-RNA test, with three-quarters of all clearances occurring by 18 weeks. The absence of an HCV RNA decline of at least two logs, four weeks after diagnosis, was associated with a very high probability of persistent, or chronic, infection.

The study investigators say that this finding leaves no doubt as to when treatment should start in people who have been diagnosed with recent infection: as reflected in European AIDS Clinical Society guidelines, direct-acting antiviral treatment should start four weeks after diagnosis if HCV viral load has not fallen by two logs.

Seventy-nine percent of participants subsequently initiated hepatitis C treatment in the 144-week follow-up period. Participants started pegylated interferon treatment a median of 14 weeks after diagnosis, compared to 44 weeks after diagnosis for people initiating direct-acting antiviral treatment. The delay in initiating direct-acting antiviral treatment was due to reimbursement and licensing restrictions on the use of direct-acting antivirals during acute infection. Only 14% of people diagnosed after the introduction of direct-acting antivirals in 2017 were able to initiate treatment within 24 weeks, compared to 75% in 2007.

The cure rate in people receiving direct-acting antivirals was 93%; in people receiving pegylated interferon, it was 73%.

The study investigators say that their findings reinforce recommendations that direct-acting antiviral treatment should start as soon as recent hepatitis C infection is diagnosed, to limit onward transmission. Although the long-term benefit of early hepatitis C treatment is unclear, the investigators say that the consequence of not treating is clear in people with HIV: faster progression of liver progression and earlier development of liver cirrhosis and other complications, compared to people without HIV.

References

Monin MB et al. Low spontaneous clearance rates of recently acquired hepatitis C virus in HIV-positive MSM (the PROBE-C study). Clinical Infectious Diseases, published online 25 August 2022.

DOI: https://doi.org/10.1093/cid/ciac680