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Non-cirrhotic portal hypertension (NCPH) comprises a heterogeneous group of liver disorders causing portal hypertension without cirrhosis and carries a high risk of variceal bleeding. Recent guidelines, based largely on patients with viral cirrhosis, suggest low likelihood of high risk varices (HRV) in patients with a liver stiffness measurement (LSM) 150 × 109/L. In NCPH, LSM is often higher than healthy controls but lower than matched cirrhotic patients. The aim of this study was to assess whether LSM or other noninvasive assessments of portal hypertension could predict HRV in NCPH patients. Methods. Records of patients with NCPH seen at a single centre between 2007 and 2018 were reviewed retrospectively. Primary outcome measure was presence or absence of HRV at gastroscopy within 12 months of clinical assessment. Association of LSM or other clinical features of portal hypertension (spleen size, platelet count, platelet count/spleen length ratio (PSL), LSM-spleen length/platelet count ratio score (LSP)) with HRV and ability of these variables to predict HRV was analysed. Results. Of 44 patients with NCPH who met inclusion criteria, 34% (15/44) had HRV. In a multivariate model, spleen size and PSL correlated with HRV but platelet count, LSM, and LSP did not (spleen size: β = 0.35, p = 0.02; OR 1.42, 95% CI 1.06-1.92; PSL: β = -1.47, p = 0.02; OR 0.23, 95% CI 0.07-0.80). There was no significant difference between spleen size and PSL in predicting HRV (AUROC 0.81 (95% CI 0.66 – 0.91) versus 0.71 (95% CI 0.54 – 0.84), respectively, p = 0.400). Spleen size >17.2cm had sensitivity 78.6% and specificity 64.3% for prediction of HRV. Conclusions. In NCPH patients, spleen size may predict risk of HRV at gastroscopy within 12 months. LSM and platelet count are not useful to assess risk of HRV in NCPH.

Background. Rapid and early emergence of clinically significant LAM resistance is thought to be unlikely during the first year of treatment, and as a result LAM is thought to be a reasonable choice as a first line agent for prophylaxis during chemotherapy. Aim. To report fatal HBV reactivation despite appropriate LAM prophylaxis in two previously treatment-naive individuals undergoing R-CHOP chemotherapy. Case Presentation. Case 1 is a 65-year-old man with chronic HBV infection: HBeAg-negative, HBV DNA 6.65E5 IU/mL, ALT 43 IU/L, and Fibroscan 4.4 kPa, consistent with F0, who was diagnosed with lymphoma that was treated with R-CHOP and LAM prophylaxis. HBV DNA fell to 2.18E1 IU/mL within 2 months of starting LAM. Four months after chemotherapy, despite ongoing LAM of 7-month duration with confirmed adherence, severe asymptomatic hepatitis was noted during routine monitoring with ALT 1019 IU/L, HBeAg negative, HBV DNA 1.43E7 IU/mL, and genotyping confirmed L80I and M204I mutations. He died 14 days after flare diagnosis despite a switch to tenofovir (HBV DNA had fallen to 1.94E5 IU/mL 2 weeks after starting tenofovir). Case 2 is a 50-year-old man who was found to have HBeAg-negative hepatitis B, ALT 37 IU/L, and no clinical features of cirrhosis (platelets 283, APRI 0.19) after lymphoma diagnosis. Lymphoma was treated with R-CHOP and LAM prophylaxis. Pretreatment HBV DNA was not done but was 8.90E4 IU/mL 3 weeks after starting LAM and 3.96E3 IU/mL 3 months after starting LAM. Two months after chemotherapy, despite ongoing LAM of 7-month duration with confirmed adherence, severe symptomatic hepatitis presenting with jaundice, abdominal pain, and confusion was noted. ALT 902 IU/L, HBeAg negative, HBV DNA 1.02E8 IU/mL, and genotyping confirmed L80I, M80V, and M204V/S mutations. He died 3 days after flare diagnosis despite the addition of tenofovir. Conclusion. Lamivudine should not be used for prophylaxis of patients with chronic hepatitis B with detectable HBV DNA undergoing chemotherapy with rituximab containing cytotoxic chemotherapy even if they have never had exposure to lamivudine in the past. In this setting, lamivudine failure due to resistance can develop quickly leading to liver failure that cannot be salvaged with tenofovir. Whether LAM is safe for prophylaxis with rituximab-based cytotoxic chemotherapy for patients with undetectable HBV DNA is unknown, but agents with a high barrier to resistance may be preferable.