Strategies to reduce hepatitis C virus recurrence after liver transplantation

Abstract

Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not retransplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pretransplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of posttransplant HCV recurrence and strategies to reduce its impact on our patients.

Hyperpolarized [1,3‐13C2]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer

“…Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized 13 C-MR marker. This could be appreciated by the signal-tonoise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state-of-the-art hyperpolarized substrate, [1][2][3][4][5][6][7][8][9][10][11][12][13] C]pyruvate. Also, the contrast-to-noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1- Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer.…”

“…With this hyperpolarized substrate it was shown how a liver cancer implanted in rat could be detected due to a higher substrate-to-product ratio in the cancer tissue compared with the surrounding healthy tissue. The signal-tonoise ratio (SNR) in the images, was comparable to the SNR obtained in a reported liver cancer study using hyperpolarized [1][2][3][4][5][6][7][8][9][10][11][12][13] C]pyruvate, 16 the most widely used d-DNP-MR substrate. 17 is a popular animal model.…”

“…Under these conditions a build-up is observed for hyperpolarized [1-13 C 1 ]acetoacetate in rat whole blood. The percentage of acetoacetate signal relative to the substrate signal is 3.6 6 0.4% (ratios taken from spectrum with highest product signal), whereas no conversion of hyperpolarized [1][2][3][4][5][6][7][8][9][10][11][12][13] C 1 ]ethyl acetoacetate was measured in human whole blood, as expected from literature. 21 To evaluate a possible contribution in the CSI images coming from acetoacetate produced in rat blood the total amount of acetoacetate relative to the total available substrate over 40 sec was compared in isolated blood (1% conversion) with signal from healthy rat liver (100% conversion) and tumor (52% conversion).…”

“…CSI data: Chemical Shift Imaging (CSI) maps were acquired on an 8 mm coronal slice placed in the abdominal region of the rat. The in plane field of view was set to 40 3 55 mm 2 and the corresponding matrix size was 14 3 14, reconstructed as a 32 3 32 matrix. Remaining acquisition parameters were set as follows: RF flip angle 5 5 , Repetition Time 5 105 ms.…”

“…This is the underlying reason for a strong correlation seen between an increasing incidence of HCC and a large number of patients infected with hepatitis C several decades ago, which now present complications of cirrhosis. 2 Due to the cirrhotic environment of most HCC, a common treatment of this disease is liver transplantation. This treatment is seen as the modality of choice because it removes the tumor along with the diseased liver.…”