Variceal bleeding is aggravated by portal venous invasion of hepatocellular carcinoma: a matched nested case-control study

Abstract

Background We hypothesized that portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) increases portal pressure and causes esophageal varices and variceal bleedings. We examined the incidence of high-risk varices and variceal bleeding and determined the indications for variceal screening and prophylaxis. Methods This study included 1709 asymptomatic patients without any prior history of variceal hemorrhage or endoscopic prophylaxis who underwent upper endoscopy within 30 days before or after initial anti-HCC treatment. Of these patients, 206 had PVTT, and after 1:2 individual matching, 161 of them were matched with 309 patients without PVTT. High-risk varices were defined as large/medium varices or small varices with red-color signs and variceal bleeding. Bleeding rates from the varices were compared between matched pairs. Risk factors for variceal bleeding in the entire set of patients with PVTT were also explored. Results In the matched-pair analysis, the proportion of high-risk varices at screening (23.0% vs. 13.3%; P = 0.003) and the cumulative rate of variceal bleeding (4.5% vs. 0.4% at 1 year; P = 0.009) were significantly greater in the PVTT group. Prolonged prothrombin time, lower platelet count, presence of extrahepatic metastasis, and Vp4 PVTT were independent risk factors related to high-risk varices in the total set of 206 patients with PVTT (Adjusted odds ratios [95% CIs], 1.662 [1.151–2.401]; 0.985 [0.978–0.993]; 4.240 [1.783–10.084]; and 3.345 [1.457–7.680], respectively; Ps < 0.05). During a median follow-up of 43.2 months, 10 patients with PVTT experienced variceal bleeding episodes, 9 of whom (90%) had high-risk varices. Presence of high-risk varices and sorafenib use for HCC treatment were significant predictors of variceal bleeding in the complete set of patients with PVTT (Adjusted hazard ratios [95% CIs], 26.432 [3.230–216.289]; and 5.676 [1.273–25.300], respectively; Ps < 0.05). Conclusions PVTT in HCC appears to increase the likelihood of high-risk varices and variceal bleeding. In HCC patients with PVTT, endoscopic prevention could be considered, at least in high-risk variceal carriers taking sorafenib.

Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma – The Changing Tides

“…46 There is a positive association between the presence of the PVTT and hemorrhagic events in HCC patients. 47 A study reported that the estimated time for a tumor thrombus (TT) that is present in the 2nd portal branch to grow into the ipsilateral 1st portal branch and from the 1st portal branch to the main portal vein trunk was 8.2 and 11.5 days (median estimated time), respectively. 48 The extent of the PVTT itself is an independent risk factor for rapid progression of TT.…”

“… 46 There is a positive association between the presence of the PVTT and hemorrhagic events in HCC patients. 47 …”

Transarterial Chemoembolization Combined With Endoscopic Therapy Is Beneficial for Unresectable Hepatocellular Carcinoma With Esophagogastric Varices

“…Lim et al. ( 27 ) demonstrated that patients with PVTT had a higher proportion of high-risk varices (23.0 vs. 13.3%, p = 0.003) and cumulative variceal bleeding rate (4.5 vs. 0.4% at 1 year, p = 0.009) than those without, and Vp4 PVTT was an independent predictor for high-risk varices (aOR = 3.345, 95% CI: 1.457–7.680, p < 0.05). TACE may provide survival benefits for HCC patients with PVTT, and can be safely performed as long as liver function is good and collateral circulation around the embolization site is abundant ( 28 ).…”

Haemostatic alterations in patients with cirrhosis and hepatocellular carcinoma: laboratory evidence and clinical implications

“…However, given the relatively higher thrombotic tendency driven by HCC, it may be that the number of patients needed to treat to prevent one additional PVT is much lower than in patients without HCC. 103 Furthermore, prevention of PVT in these patients would not only reduce the risk of portal hypertension and portal-hypertension driven mortality [70][71][72][73] but is also important as complete thrombosis hampers the performance of trans-arterial chemoembolization to treat multifocal tumours. 12 Regarding direct oral anticoagulants, two placebo-controlled randomized clinical trials addressing the value of apixaban and rivaroxaban for the prophylaxis of VTE in cancer outpatients undergoing chemotherapy have been recently published.…”