13 hours ago · Individuals with intermediate stage with intrahepatic multifocal HCC benefit from liver-directed treatments, such as transcatheter arterial chemoembolization (TACE). Many transplant centers now accept patients with HCC patients who have been successfully down-staged by liver-directed therapy.36. Systemic therapy is recommended for advanced-stage HCC. >> Go To The Portal
Once the diagnosis of HCC is made and the patient is deemed to be a good candidate for transplant, the patient is immediately put on the list with exception points and offered treatment to slow down or halt the growth of the tumor while waiting for the MELD points to accrue (this can take between 9 and 15 months in New York State).
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Portal vein tumor thrombosis (PVTT) commonly occurs in patients with hepatocellular carcinoma (HCC). Patients with PVTT usually have an aggressive disease course, decreased liver function reserve, limited treatment options, higher recurrence rates after treatment, and, therefore, worse overall survival.
Who is a Liver Transplant Candidate? When you have end stage liver disease, and no longer see results with medical therapy, you may be eligible for a liver transplant at UPMC. At the UPMC Liver Transplant Program, we consider each person referred to our program – even if other centers have said that you are not a candidate.
According to the Scientific Registry of Transplant Recipients (commonly referred to as the SRTR), in 2019, HCC was the primary diagnosis for 10.6% of waitlist candidates. 4 The deceased-donor transplant rate for candidates with HCC exception points remained higher than those without HCC exception (94.3 vs. 58.3 per 100 waiting list-years).
The current Barcelona Clinic Liver Cancer staging system categorizes HCC patients with PVTT as advanced stage, for which the standard of care is targeted therapy with sorafenib. However, sorafenib is associated with only marginal benefits among patients with PVTT.
Objectives: Portal vein thrombosis is no longer a contraindication for liver transplantation. However, varied outcomes are still reported with regard to patients with complete portal vein thrombosis.
(See "Overview of treatment approaches for hepatocellular carcinoma".) Liver transplantation for treatment of HCC is attractive because resection of the malignant tumor can be achieved while also replacing the cirrhotic liver that remains at risk for the development of new lesions.
Patients diagnosed with HCC exceeding the Milan criteria can still be candidates for liver transplantation, depending on local or national allocation guidelines (Yao 2008; Grant et al....Table 2.Absolute contraindicationRelative contraindicationsUncontrolled/limiting medical conditionsSevere obesity/malnutrition3 more rows
Liver transplantation is the only curative treatment for patients with portal hypertension in end-stage liver dis- ease. Patients with good liver function despite portal hy- pertension may be managed satisfactorily without liver transplantation.
To this end, the optimal LT criteria for HCC must not only account for tumor size and number, but additional markers of tumor biology including alpha‐fetoprotein (AFP) and novel biomarkers, response to LRT, and 18F‐labeled fluoro‐2‐deoxyglucose positron emission tomography (18F‐FDG‐PET) imaging.
You may be disqualified from having a liver transplant if you have: Current alcohol or drug abuse problems. Uncontrolled infection that will not go away with a transplant. Metastatic cancer or bile duct cancer.
A liver transplant may be recommended if you have end-stage liver disease (chronic liver failure). This is a serious, life-threatening liver disease. It can be caused by several liver conditions. Cirrhosis is a common cause of end-stage liver disease.
The most common indications for liver transplantation in the United States are hepatitis C virus (30%) and alcoholic liver disease (18%). Other indications include the following: Idiopathic/autoimmune liver disease (12%)
Patients should be considered for liver transplantation if they have evidence of fulminant hepatic failure, a life-threatening systemic complication of liver disease, or a liver-based metabolic defect or, more commonly, cirrhosis with complications such as hepatic encephalopathy, ascites, hepatocellular carcinoma, ...
In adults with portal vein thrombosis, the 10-year survival rate has been reported to be 38-60%, with most of the deaths occurring secondary to the underlying disease (eg, cirrhosis, malignancy).
Portal hypertension is defined as the pathological increase of portal venous pressure, mainly due to chronic end-stage liver disease, leading to augmented hepatic vascular resistance and congestion of the blood in the portal venous system.
You can't reverse damage caused by cirrhosis, but you can treat portal hypertension. It may take a combination of a healthy lifestyle, medications, and interventions.
Most HCC patients undergoing transplant have “exception” MELD scores of around 30, but their true (or “biologic”) MELD scores are much lower. That means that most HCC patients are not terribly sick or may even feel completely healthy at the time of their transplant. HCC is almost always diagnosed with a CAT scan or MRI.
People infected with Hepatitis B or Hepatitis C viruses have an even higher risk. Although the presence of active cancer usually precludes the possibility of undergoing a transplant (because the immune suppressing drugs given afterwards can cause a cancer to grow uncontrollably), HCC can potentially be cured with liver transplant, and this is commonly practiced.
LT offers a successful therapy for early-stage HCC patients because it simultaneously removes the lesion(s) and the preneoplastic liver.6Ear ly records of post-LT outcome delineated high recurrence rates and were plagued with dismal patient survival.7,8Apart from tumor measurements, factors influencing recurrence include vascular invasion, histologic differentiation, previous response to local-regional therapy (LRT) and serum marker levels.9–12
TACE is the most frequently used palliative treatment technique in downstaging protocols, particularly for multifocal HCC.43The reported downstaging success rates with TACE (23.7–90%) are inconsistent and should be interpreted with caution.64Since the TACE mechanism of action targets the hepatic arterial supply, its efficacy depends on responsive HCCs with good blood supply and uptake. While TACE is not advised to be performed in the presence of portal vein thrombosis, transarterial radioembolization with Yttrium-90 (Y-90) beads is a safe alternative downstaging therapy.71,72Per available data there is no statistically significant difference between success rates of TACE and radioembolization for downstaging.65It is important to note the risk of inaccurate staging when relying on imaging results to gauge radiological response to TACE or radioembolization in terms of tumor size and viability. For example, tumor response to Y-90 typically evolves gradually and may require 3–6 months to exhibit an adequate response on triphasic computed tomography (commonly known as CT) or magnetic resonance imaging.73Therefore, timely intervals between treatment sessions and imaging are crucial to reduce confounding by image interpretation.
Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy. It is the sixth most common neoplasm and fourth cause of cancer-related mortality globally.1,2As the incidence of HCC is projected to increase in the USA as nonalcoholic fatty liver disease continues to increase exponentially and alcohol and hepatitis C remain public health issues, HCC has emerged as a leading indication for liver transplantation (LT).3–5
Hepatic resection is the preferred curative treatment for patients with small localized tumors and well compensated liver disease and is an option for downstaging.68Comprehensive pathological examination of resected specimens may facilitate the identification of patients with histological features of poor prognosis, for instance macrovascular invasion gone unobserved.69This significantly influences subsequent treatment choices during postoperative surveillance of tumor recurrence patterns. Although large lesion size is not an absolute contraindication to hepatic resection, portal hypertension and end-stage liver disease are major risk factors for postsurgical complications and death.70There is a subset of patients who require resection in conjunction with LRT to complete downstaging. However, surgical resection has been reported in a minority of studies as a downstaging modality so no statement can be made about its efficacy.
The primary aims of establishing criteria for LT are to select candidates with good post-LT prognoses and to exclude patients whose disease conditions are suitable for other therapies, such as resection or systemic therapy. The Milan criteria (MC) (a single nodule ≤5 cm, 2–3 nodules ≤3 cm), proposed in 1996, emerged as an international benchmark to select patients with HCC for LT. According to MC, post-LT 5-year survival in HCC is >70% with a recurrence rate <10–15%.13–15The American Association for the Study of Liver Disease (commonly known as AASLD) and Guidelines of the European Association for the Study of the Liver (commonly known as EASL) recommend LT for HCC patients within MC but unsuitable for resection.16,17
Nonetheless, MC remains the gold standard for HCC patient selection and prognostic evaluation in LT.28The adoption of extended selection criteria generates the dilemma of a sharp rise in HCC patients on the LT waitlist with unknown regional repercussions on non-HCC patients waiting for LT, while persistent shortages of donor organs highlight the fundamental challenge of maintaining equity in liver transplant allocation.
Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation ( LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.
Portal vein tumor thrombosis (PVTT) commonly occurs in patients with hepatocellular carcinoma (HCC). Patients with PVTT usually have an aggressive disease course, decreased liver function reserve, limited treatment options, higher recurrence rates after treatment, and, therefore, worse overall survival. Among untreated HCC patients with PVTT, the median overall survival has been reported as low as 2 to 4 months. Historically, many aspects of PVTT have impacted the theoretical and practical safety and efficacy of treatment, for example, disordered blood flow and associated impairment of liver function, heat-sink effects of blood flow in the area of the PVTT, and risk of recurrence due to tumor location in the blood vessel. The current Barcelona Clinic Liver Cancer staging system categorizes HCC patients with PVTT as advanced stage, for which the standard of care is targeted therapy with sorafenib. However, sorafenib is associated with only marginal benefits among patients with PVTT. First-line lenvatinib, which was shown to be noninferior to sorafenib, excluded patients with main portal trunk invasion. Regorafenib and nivolumab, an immune-based therapy, were recently approved in the United States for second-line therapy after sorafenib. Preliminary results for cabozantinib suggest a benefit in the second-/third-line after sorafenib failure. In addition, rapid advances in many fields (surgery, interventional radiology, nuclear medicine, and immunotherapy) have increased the potential treatment options for the management of this complex disease entity. A large portion of the emerging evidence focuses on the broader category of advanced HCC of which PVTT is a subgroup. While many of these studies show promising results, the efficacy among PVTT patients requires validation in prospective studies. Real-world data may help fill the evidence gap for patients not eligible for clinical trials due to common hepatic function requirements. The variety of new treatment advances for the heterogeneous and complex disease entity of HCC with PVTT means that personalized, multidisciplinary management may be necessary to achieve optimal outcomes. In this narrative review, we summarize the evolving management strategies for patients with HCC and PVTT.
First-line lenvatinib, which was shown to be noninferior to sorafenib, excluded patients with main portal trunk invasion. Regorafenib and nivolumab, an immune-based therapy, were recently approved in the United States for second-line therapy after sorafenib.
Hepatocellular carcinoma (HCC) with portal vein tumoral thrombosis (PVTT) represents a major concern especially in the field of deceased donor liver transplantation (DDLT).
All patients diagnosed with HCC and PVTT between May 2013 and November 2016 were evaluated to be enrolled into our “Superdownstaging” protocol.
During the study period, 17 patients were enrolled. Baseline characteristics of the overall population are shown in Table 1. Median age at the time of TARE was 53 years (range, 50-56 years). There were 15 males and 2 females.
This prospective pilot study showed that about 30% of HCC patients with PVTT were successfully downstaged and transplanted after TARE using deceased donors. OS and PFS were both significantly higher among those who received DDLT compared with those who were not transplanted.