Point-of-care ultrasound to inform antiviral treatment initiation in chronic hepatitis B virus infection in low-resource settings - the PUSH protocol

Abstract

Background: Chronic Hepatitis B (CHB) is prevalent worldwide and most related deaths occur in low-resource settings. Antiviral treatment of CHB is indicated in those with significant liver disease and markers of viral replication. However, recommended diagnostics such as elastography (a non-invasive imaging measure of fibrosis/cirrhosis) or HBV viral load are often lacking in these settings, which creates barriers to treatment. Point-of-care clinical B-mode ultrasound (US) has potential to overcome implementation barriers in HBV care programs in low-resource settings.

Methods: We describe a Point-of-care US protocol for Hepatitis ("PUSH") to check for signs of cirrhosis and hepatocellular carcinoma in the liver of people with CHB. We performed a prospective observational study applying the protocol, first by trainee clinicians and then by trainers, in consecutive patients referred to our clinic for CHB treatment eligibility assessment. All patients additionally underwent physical examination, liver function tests (LFTs) and platelet counts. We describe the PUSH training approach and performance of the protocol.

Results: Four clinicians and 111 adult patients with HBV infection were included in the development of PUSH. Using US, liver complications of HBV were documented in 31 (27.9%) patients; including cirrhosis in 15 patients, HCC with cirrhosis in 13, and HCC without cirrhosis in 3. Patients with sonographic findings had significantly more clinical symptoms also their LFTs were higher and more frequently indicative for HBV treatment. Of 28 patients with sonographic diagnosis of cirrhosis, 23 (82.1%) showed a nodular liver surface, 24 (85.7%) a coarse echotexture, 20 (71.4%) scarce vessels, and 9 (32.1%) an enlarged caudate lobe. Overall concordance of the findings between assessment of trainees and experienced sonographers was high, ranging from 90 to 95%; trainees were not blinded to clinical and laboratory findings.

Conclusion: Ultrasound can facilitate same-day initiation of antiviral therapy for chronic HBV monoinfection in a resource-limited setting and a streamlined protocol-driven liver ultrasound can be feasibly used by front line clinicians managing HBV.

Keywords: Cirrhosis; HCC; Hepatitis B; Low-resource setting; Treatment indication; Ultrasound.

Fig. 1

Point-of-care UltraSound for hepatitis - the PUSH protocol

Fig. 2

Surface nodularity: While normal liver shows a smooth, straight surface, it becomes irregular and nodular in cirrhosis due to regenerative cirrhotic nodules located in the subcapsular area (arrows). It is particularly obvious when ascites is present but can also be seen otherwise

Fig. 3

Enlarged caudate lobe: (a) In the normal liver the caudate lobe is small and in the epigastric longitudinal scan the profile resembles a shark. In cirrhosis, the caudate lobe may enlarge due to redistribution of blood supply and consecutive hypertrophy; the “shark face” is distorted (b)

Fig. 4

Coarse texture: While normal liver tissue shows a smooth, velvet-like texture in US this changes in cirrhosis. The formation of nodules, especially of macro-nodules (>3 mm) induced by CHB, causes a coarse, nodular texture throughout the liver

Fig. 5

Reduced vascularity: (a) In the cirrhotic liver, the stiff tissue reduces the visibility of peripheral portal branches while at the same time the central portal vein may be enlarged due to portal hypertension. (b) Peripheral portal branches may show a tortuous course around regenerative nodules

Fig. 6

Hepatocellular carcinoma: Slightly hyperechoic, mosaic-like lesions which can show a hypoechoic halo and hypoechoic sinusoids in the tumor (s) as in this case are typical for HCC. In low-resource settings, HCCs are often large (~ 10 cm) at time of diagnosis