Nicole E. Rich

Hepatocellular carcinoma tumour markers: Current role and expectations

Tumour markers could be helpful along the continuum of care for patients with hepatocellular carcinoma; however, there is insufficient data for routine use of most current biomarkers in clinical practice. Therefore, the backbone of early detection, diagnosis and treatment response for hepatocellular carcinoma remains imaging-based. Alpha fetoprotein is the best studied of all biomarkers and may be of benefit for early detection when used in combination with ultrasound. Several other biomarkers, including AFP-L3, DCP, osteopontin, and GP73, are also being evaluated for early detection of hepatocellular carcinoma in phase III biomarker studies. Serum and tissue-based biomarkers and genomics may aid in HCC diagnosis, prognosis, and treatment selection; however, further studies are needed to better characterize their accuracy and potential role in clinical practice.

Malignant infiltration of the liver presenting as acute liver failure.

There have been few reports of acute liver failure (ALF), with encephalopathy and coagulopathy, caused by infiltration of the liver by malignant cells. We describe a case series of 27 patients with ALF caused by malignancy. We examined a large, multicenter ALF registry (1910 patients; mean age, 47.1 ± 13.9 y) and found only 27 cases (1.4%) of ALF attributed to malignancy. Twenty cases (74%) presented with abdominal pain and 11 presented with ascites. The most common malignancies included lymphoma or leukemia (33%), breast cancer, (30%), and colon cancer (7%); 90% of the patients with lymphoma or leukemia had no history of cancer, compared with 25% of patients with breast cancer. Overall, 44% of the patients had evidence of liver masses on imaging. Diagnosis was confirmed by biopsy in 15 cases (55%) and by autopsy for 6 cases. Twenty-four patients (89%) died within 3 weeks of ALF.

Racial and Ethnic Disparities in Nonalcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting 75–100 million Americans. However, the disease burden may not be equally distributed among races or ethnicities. We conducted a systematic review and meta‐analysis to characterize racial and ethnic disparities in NAFLD prevalence, severity, and prognosis. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases through August 2016 for studies that reported NAFLD prevalence in population‐based or high‐risk cohorts, NAFLD severity including presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis, and NAFLD prognosis including development of cirrhosis complications and mortality. Pooled relative risks, according to race and ethnicity, were calculated for each outcome using the DerSimonian and Laird method for a random‐effects model. RESULTS: We identified 34 studies comprising 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis. NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high‐risk cohorts (range 47.6%–55.5%) than population‐based cohorts (range, 13.0%–22.9%). Among patients with NAFLD, risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98–1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60–0.87) than Whites. However, the proportion of patients with significant fibrosis did not significantly differ among racial or ethnic groups. Data were limited and discordant on racial or ethnic disparities in outcomes of patients with NAFLD. CONCLUSIONS: In a systematic review and meta‐analysis, we found significant racial and ethnic disparities in NAFLD prevalence and severity in the United States, with the highest burden in Hispanics and lowest burden in Blacks. However, data are discordant on racial or ethnic differences in outcomes of patients with NAFLD.

Medical Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) typically occurs in patients with advanced liver disease, so therapeutic decisions must account for the degree of underlying liver dysfunction and patient performance status in addition to tumor burden. Curative treatment options, including liver transplantation, surgical resection, and local ablative therapies, offer 5-year survival rates exceeding 60% but are restricted to patients with early-stage HCC. Surgical resection and local ablative therapies are also limited by high recurrence rates, highlighting a need for adjuvant and/or neoadjuvant therapies. A majority of patients with HCC are diagnosed beyond an early stage, when the tumor is no longer amenable to curative options. For patients with liver-localized HCC in whom curative options are not possible, transarterial therapies, either chemoembolization or radioembolization, can prolong survival but are rarely curative. Sorafenib and regorafenib are the only approved first-line and second-line systemic therapies, respectively, with a survival benefit for patients with advanced HCC; however, the benefit is primarily observed in patients with intact liver function and good performance status. There are several ongoing phase II and III trials evaluating novel systemic therapies, including immunotherapies. Patients with poor performance status or severe hepatic dysfunction do not derive any survival benefit from HCC-directed therapy and have a median survival of approximately 6 months. These patients should be treated with best supportive care, with a focus on maximizing quality of life. Multidisciplinary care has been shown to improve appropriateness of treatment decisions and overall survival and should be considered standard of care for patients with HCC.

Systematic review with meta‐analysis: recurrence of hepatocellular carcinoma following direct‐acting antiviral therapy

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after direct‐acting antivirals (DAA), data are conflicting regarding HCC recurrence and aggressiveness in patients who have a history of HCC with complete response.

Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: A Potential New Challenge for Hepatocellular Carcinoma Surveillance

Marcia Cruz-Correa, Section Editor David Schwartz, Section Editor 65 66 STAFF OF CONTRIBUTORS 67 68 69 70 71 72 73 74 75 Joseph Anderson, White River Junction, VT Johanna L. Chan, Houston, TX Matthew A. Ciorba, St. Louis, MO Massimo Colombo, Milan, Italy Gregory A. Cote, Charleston, SC Evan S. Dellon, Chapel Hill, NC Alex Ford, Leeds, United Kingdom Lauren B. Gerson, San Francisco, CA David S. Goldberg, Philadelphia, PA Samir Gupta, San Diego, CA

Overdiagnosis: An Understudied Issue in Hepatocellular Carcinoma Surveillance

Overdiagnosis, the detection of clinically insignificant disease that would not otherwise impact the patients lifespan, is a phenomenon that has been described in several solid tumors, such as prostate, breast, thyroid, and lung cancers. Population-based efforts to reduce hepatocellular carcinoma (HCC) mortality in cirrhosis patients by screening and early detection may result in the overdiagnosis of HCC. One of the harms of overdiagnosis is subsequent overtreatment, which can result in increased costs, as well as physical side effects, psychological harms, and poorer quality of life. In this review, the authors explore the potential for overdiagnosis in HCC.

CON (“The window is closed”): In patients with cirrhosis with ascites, the clinical risks of nonselective beta‐blocker outweigh the benefits and should NOT be prescribed

Even though nonselective beta-blockers (NSBBs) have proven benefits in cirrhosis, some evidence suggests they may be harmful in a subset of patients with decompensated cirrhosis, in particular those with refractory ascites, baseline hypotension, or at high risk for infection. The decision to initiate a NSBB should be individualized; continuation of NSBB should be continually reassessed in decompensated patients with ascites. Consider decreasing or stopping the NSBB in patients with low mean arterial pressure (<80 mm Hg), hyponatremia, renal insufficiency, ongoing infection, or refractory ascites requiring frequent paracentesis.

Outcomes of simultaneous liver kidney transplantation in patients with hepatocellular carcinoma

Background The frequency of simultaneous liver kidney (SLK) transplantation has increased following the implementation of the model for end-stage liver disease system for liver transplantation (LT). There is a paucity of data evaluating SLK outcomes in patients undergoing LT for hepatocellular carcinoma (HCC). Our aim was to compare outcomes between patients with HCC who underwent SLK and those who received SLK for other indications. Methods We performed a retrospective analysis of adult recipients receiving SLK between 2002 and 2013 from the United Network for Organ Sharing registry. The primary outcome was posttransplant mortality. Patient survival was determined using Kaplan-Meier analysis and predictors of mortality were identified using proportional Cox hazard regression models. Propensity score matching was performed between SLK-HCC and SLK in the absence of HCC (SLK-A) groups to reduce confounding. Results Between 2002 and 2013, 186 HCC patients underwent SLK-HCC and 3599 patients underwent SLK-A. The 1-year and 3-year survival rates were 89.0% and 76.7% in the SLK-HCC group and 84.5% and 76.3% in the SLK-A group (P = 0.20). In multivariable Cox regression, HCC was not associated with post-LT survival among all patients (hazard ratio, 1.15; 95% confidence interval, 0.84-1.58) or the propensity score-matched cohort (hazard ratio, 0.97; 95% confidence interval, 0.64-1.47). SLK-HCC patients had similar rates of acute rejection (13.3% vs 10.5%, P = 0.36) and liver graft failure requiring re-transplantation (3.2% vs 2.3%, P = 0.44) compared with SLK-A patients. Conclusions Liver transplant candidates with advanced renal dysfunction and HCC may be considered for SLK.