Introduction

The Baveno Consensus Workshops recommend gastroscopy for advanced chronic liver disease (CLD) patients to detect varices, with Grade 2 or 3 varices advised to receive prophylactic treatment using non-selective beta blockers (NSBB) or band ligation [1-2].
Western Health (WH) is a tertiary health service serving a population of 1.2 million, primarily in socioeconomically disadvantaged Melbourne suburbs with a high density of non-English speaking background (NESB) immigrants with low health literacy [3-4]. This demographic presents challenges such as poor health service engagement, impacting guideline adherence and patient management.

Aims & Methods

The objective of this study is to evaluate adherence to the Baveno criteria for variceal management among CLD patients at WH.
We retrospectively collected data from the electronic medical records of all CLD patients admitted to WH in 2021. We documented demographics, presenting complaints, underlying liver disease, adherence to varices screening and treatment. Univariate and multivariable logistic regression assessed predictors of liver-related mortality, which is defined as death resulting directly from a CLD complication at a 2-year follow-up.

Results

Our study included 275 CLD patients (mean age 60 years, SD 13; 64% male), 142 (52%) were born in Australia and 116 (42 %) were immigrants from NESB. The leading causes of CLD were alcohol-related (62%, n=169), metabolic liver disease (20 %, n=56), Hepatitis C (15 %, n=42) and B (4 %, n=10). Cirrhosis developed in 92 % (n=253) of patients, with 30 % (n=75) classified as Child-Pugh score A, 40 % (n=102) as B, and 30% (n=76) as C. Ascites (23.3%, n=64), hepatic encephalopathy (16%, n=44), and variceal bleeding (9.5%, n=27) were the common presenting complaints. 245 patients met BAVENO criteria for variceal screening, 77.6% (n=190) underwent gastroscopy, revealing Grade 1 varices in 33.6% (n=43) and Grade 2 or 3 varices in 36.7% (n=47). Follow-up gastroscopy was scheduled for 56.7% (n=21) without initial varices and 75.6% (n=31) with Grade 1 varices. Among those with Grade 2 or 3 varices, 80.9% (n=38) underwent variceal banding, with 94.7% (n=36) receiving follow-up gastroscopy. However, only 19.1% (n=9) were prescribed NSBB. Of the 27 variceal bleeding cases, 21 warranted varices screening, yet only 11 had prior gastroscopy. Within these, 6 patients had Grade 1 and 1 had Grade 2 varices. The Grade 2 varices were ligated but NSBB was not initiated.
Univariate regression showed correlation between reduced liver-related mortality and variceal screening (OR 0.42, 95% CI 0.22–0.81, p=0.01) as independent variable, confirmed by multivariate logistic regression, after adjusting for confounders like age and Child-Pugh scores. Intriguingly, among unscreened patients, the most common cause of death is infection (n=10, 16.1%), only 4 had variceal bleeding with no resulting deaths. This is possibly due to selection bias as high-risk patients with prior varices bleeding history were more likely to be connected to the service.

Conclusion

Our study shows that variceal screening reduces liver-related mortality, yet it also reveals deficiencies in the current clinical approach to screening and treating varices at WH. These deficiencies may arise from various challenges, including communication barriers such as language constraints or time limitations in outpatient clinics, as well as patient factors such as limited health literacy resulting in poor compliance. Efforts should be directed towards improving the uptake of varices surveillance and enhancing the utilization of NSBB among patients.

References

1. de Franchis R; Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015 Sep;63(3):743-52. doi: 10.1016/j.jhep.2015.05.022. Epub 2015 Jun 3.
2. de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974. doi: 10.1016/j.jhep.2021.12.022. Epub 2021 Dec 30. Erratum in: J Hepatol. 2022 Apr 14
3. Australian Bureau of Statistics. Regional Population Growth, Australia, 2019-20. [cited 2024 April 25]. Available from: https://dbr.abs.gov.au/region.html?lyr=sa4&rgn=213
4. Chiu HT, Tsai HW, Kuo KN, Leung AYM, Chang YM, Lee PH, Hou WH. Exploring the Influencing Factors of Health Literacy among Older Adults: A Cross-Sectional Survey. Medicina (Kaunas). 2020 Jul 2;56(7):330.

Introduction

Persistent High-Risk Human Papillomavirus (HR-HPV) infection can lead to an anal high-grade squamous intraepithelial lesion (HSIL), the precursor lesion to anal squamous cell carcinoma (SCC). Anal cytology and HR-HPV testing are strategies used for anal SCC screening. Anal HR-HPV prevalence in HIV-negative MSM and in MSM living with HIV (MSM-HIV) is 41% and 74%, respectively. The use of Pre-Exposure Prophylaxis (PrEP) in HIV-negative MSM to prevent HIV contraction created a new Sexual Minority Group among MSM, i.e. MSM using PrEP (MSM-PrEP). The aim of this study was to determine the prevalence of anal HR-HPV infection and abnormal anal cytology in MSM-PrEP and MSM-HIV.

Aims & Methods

MSM-PrEP and MSM-HIV were enrolled in this mono-centric study during consultations at the S-clinic and the HIV-reference centre respectively. Patient characteristics, sexual behavior and demographics were collected using a questionnaire, completed on the day of the anal swab testing.

Results

We enrolled 150 MSM-PrEP and 152 MSM-HIV. Quality of anal swabs was sufficient in respectively 96.7% (n=145) and 96.1% (n=146). HR-HPV prevalence in MSM-PrEP was comparable with HR-HPV prevalence in MSM-HIV; respectively 74.5% (n=108) and 76.6% (n=111) tested positive for at least one HR-HPV (p=0.78). No significant difference in abnormal cytology was seen; 53.1% (n=77) of the MSM-PrEP and 57.2%(n=83) of MSM-HIV had either ASCUS, ASC-H, LSIL or HSIL (p=0.56).

Conclusion

The risk of HR-HPV infection and abnormal anal cytology in MSM-PrEP is comparable to that in MSM-HIV, both of which are higher than observed in HIV-negative MSM not using PrEP. This heightened prevalence of HPV in MSM-PrEP poses an increased risk for HSIL. Recent guidelines on anal screening from International Anal Neoplasia Society recommend screening for anal cancer in both MSM-HIV and HIV-negative MSM, reflecting respective anal cancer incidence rates of 70-100 per 100,000 person-years and 18-34 per 100,000 person-years. Our findings suggest that MSM-PrEP constitutes a distinct risk group for anal SCC positioned between MSM-HIV and HIV-negative MSM not using PrEP.

References

Gaisa M, Gypsyamber D et al. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021;8(9):531-43.
Machalek D, Poynten M, Jin F et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13(5):487-500.
Stier E, Clarke M, Deshmukh A et al. International Anal Neoplasia Society's consensus guidelines for anal cancer screening.Int.J.Cancer.2024;154:1694-1702.

Clinical Case Summary

A 76yo woman with a 5-year history of non-secreting adrenal adenoma underwent a MRI for follow-up. The MRI showed multiple liver nodules in the left lobe of the liver, the larger 52 mm in size. She reported neither hepatic nor other systemic diseases, and she denied alcohol consumption. An abdominal ultrasound performed 3 months before presentation was negative for liver lesions.
HBV, HCV and HIV infections and immune-mediated liver diseases were excluded. GGT was 3 times over the upper limit and C-reactive protein was slightly increased. AST, ALT, ALP and tumor markers were within normal ranges.
A CT scan confirmed the presence of multiple liver lesions in the left lobe, raising suspicion of metastasis.
A biopsy of the largest nodule was performed, but it was inconclusive. In suspicion of sampling error, the patient underwent a second biopsy of the major nodule, and the slides were reviewed by another expert pathologist. PCR for M. tuberculosis complex DNA tested negative on biopsied liver tissue, and both QuantiFERON test and mycobacterial culture on stools returned negative results.
Our initial hypothesis was a malignant lesion, either primary or secondary. Moreover, both biopsies failed to detect any malignant cells. In contrast, the pathologist’s review described areas of reparative connective tissue and the presence of necrosis associated with granulomatous inflammation. Small epithelioid, non-necrotizing sarcoid granulomas were also detected.
Considering the results of the blood tests, the histological findings, and the (rare) possibility of sarcoidosis with both necrotizing and non-necrotizing granulomas, the patient was finally diagnosed with hepatic sarcoidosis. This diagnosis is additionally supported by the slight alterations in the liver profile, which include GGT and/or ALP elevation in cases of hepatic involvement. After 9 months a new CT scan was performed. Liver lesions were no longer evident, even though she had not undergone any type of therapy.

References

1. Iannuzzi MC, Rybicki BA. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153–65.
2. Rosen Y. Four decades of necrotizing sarcoid granulomatosis: what do we know now? Arch Pathol Lab Med. 2015 Feb;139(2):252–62.
3. Graf C, Arncken J, Lange CM, Willuweit K, Schattenberg JM, Seessle J, et al. Hepatic sarcoidosis: Clinical characteristics and outcome. JHEP Reports. 2021 Dec;3(6):100360.
4. Bennett D et al. Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis. Respir Res. 2020 Dec;21(1):6.
5. Ricker W et al. Sarcoidosis: A Clinicopathologic Review of Three Hundred Cases, Including Twenty- Two Autopsies. Am J Clin Pathol. 1949 Aug 1;19(8):725–49.
6. Mitchell DN et al. Sarcoidosis: histopathological definition and clinical diagnosis. Journal of Clinical Pathology. 1977 May 1;30(5):395–408.
7. Rosen Y. Pathology of Sarcoidosis. Semin Respir Crit Care Med. 2007 Feb;28(1):036–52.
8. Mukhopadhyay S et al. Pulmonary Necrotizing Granulomas of Unknown Cause. Chest. 2013 Sep;144(3):813–24.
9. Kennedy PTF et al. Natural history of hepatic sarcoidosis and its response to treatment: European Journal of Gastroenterology & Hepatology. 2006 Jul;18(7):721–6.
10. Nguyen V et al. Spontaneous Resolution of Symptomatic Hepatic Sarcoidosis. Case Reports in Gastrointestinal Medicine. 2018 Aug 1;2018:1–4.

Introduction

Persistent high-risk Human Papillomavirus (HR-HPV) infection can lead to an anal high-grade squamous intraepithelial lesion (HSIL), the precursor lesion to anal squamous cell carcinoma (SCC).
HR-HPV prevalence is higher in men who have sex with men living with HIV (MSMLWH) than in HIV-negative MSM, respectively 74% and 37-41% (1,2). The use of Pre-Exposure Prophylaxis (PrEP) in HIV-negative MSM to prevent HIV contraction created a new Sexual Minority Group among MSM, i.e. MSM using PrEP. The aim of this study was to determine the prevalence of anal HR-HPV infection and abnormal anal cytohistology in MSM using PrEP and MSMLWH. Preliminary data are reported here and final results are expected in coming months.

Aims & Methods

MSM using PrEP and MSMLWH were enrolled in this mono-centric study during consultations at the S-clinic and the HIV-reference centre respectively. Patient characteristics, sexual behavior and demographics were collected using a questionnaire, completed on the day of the anal swab testing. Patients with HR-HPV infection, abnormal cytology or both were subsequently sent for High Resolution Anoscopy (HRA).

Results

At present, we enrolled 150 MSM using PrEP and 107 MSMLWH. Quality of anal swabs was sufficient in respectively 95% (n=143) and 81% (n=87). HR-HPV prevalence in MSM using PrEP was comparable with HR-HPV prevalence in MSMLWH; respectively 74% (n=106) and 75% (n=65) tested positive for at least one HR-HPV (p=1.000). No significant difference in abnormal cytology was seen; 53% (n=76) of MSM using PrEP and 58% (n=51) of MSMLWH had either ASC-US, ASC-H, LSIL or HSIL (p=0.6). Until today, 58 MSM using PrEP and 31 MSMLWH underwent HRA. Biopsies were performed in 43 MSM using PrEP and 25 MSMLWH. Preliminary results on histology of lesions show presence of anal HSIL in 19% (n=11) and 32% (n=10) respectively (p= 0.706).

Conclusion

MSM using PrEP have a similar risk of HR-HPV infection and abnormal anal cytohistology as MSMLWH, which is higher than what has been reported in HIV-negative MSM not using PrEP (1). ANCHOR showed that treating anal HSIL reduces the incidence of anal SCC in people living with HIV (3), but the risk of progression to anal cancer and thus the need for screening and treatment is to be investigated in this immunocompetent population of MSM using PrEP.

References

1. Wei F, Gaisa M, Gypsyamber D et al. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021;8(9):531-43.
2. Machalek D, Poynten M, Jin F et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13(5):487-500.
3. Palefsky J, Lee J, Jay N et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 202;386(24):2273-82.