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Alcohol-Related Liver Cancer Diagnosed at Later Stages

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For patients with alcohol-related hepatocellular carcinoma (HCC), survival rates are poorer than for patients with HCC that is not alcohol related, primarily because they are diagnosed with late-stage disease, according to results from a new study.

The study was published online March 28 in Cancer.

Median overall survival was 9.7 months for patients with non-alcohol-related HCC compared to 5.7 months for patients with the alcohol-related HCC. However, when the authors reviewed each cancer stage individually, survival was similar, and the prognostic role of alcohol consumption disappeared.

"We show in the paper that when the stage at diagnosis is the same, the survival between patients with non-alcohol-related HCC and alcohol-related HCC is not different, meaning that the stage at diagnosis is driving the difference in survival observed in the global population," explained lead author Charlotte Costentin, MD, of Hôpital Henri-Mondor, Public Hospital System of Paris, Creteil, France.

 

"Therefore, patients with alcohol-related liver cancer do not need more aggressive treatment but better screening programs — both for underlying liver disease and liver cancer — to diagnose liver cancer early," she told Medscape Medical News.

Costentin explained that underlying liver disease was detected at the time that liver cancer was diagnosed more frequently in the group with alcohol-related HCC. "This underlies the need for improving identification of alcohol-related liver disease in order to implement alcoholism treatment and surveillance for liver cancer," she said.

These patients "also need better access to alcoholism treatment to improve liver function, a key component to be eligible for curative treatment," she added.

Alcohol-Related Disease Increasing

The authors note that globally, hepatitis B and C infections are the primary causes of HCC. Alcohol abuse and nonalcoholic fatty liver disease are the other dominant risk factors. But because treatment for hepatitis infections has improved and alcohol consumption is increasing in some regions, it is likely that alcohol consumption will become the leading cause of liver cancer.

They point out that currently, alcohol consumption is the primary cause of liver cancer in France.

In contrast, the American Cancer Society recently reported that 32% of cases of HCC in the United States are caused by metabolic disorders, including obesity. A smaller proportion of cases are linked to hepatitis C virus infection (21%), excessive alcohol intake (13%), and smoking (9%), as reported by Medscape Medical News.

However, the authors of this article note that the "real US figure" pertaining to alcohol is "likely higher as alcohol consumption is often underreported when another risk factor is present."

Late Diagnosis for Alcohol-Related HCC

To compare aspects of alcohol-related and non-alcohol-related liver cancer, Costentin and her colleagues used data from the CHANGH (Carcinomes Hepatocelulaires de l'Association des hépato-Gastroentérologues des Hôpitaux Généraux) cohort, a large, French, prospective, observational cohort study that collected data on the clinical features and treatment of patients with newly diagnosed HCC. In this group of patients, HCC related to alcohol consumption predominated.

A total of 894 patients were included in their analysis: 582 patients (65.1%) had alcohol-related HCC (group A), and 312 patients (34.9%) had non-alcohol-related HCC (group NA).

The median follow-up period was 5.7 months for group A and 8.3 months for group NA.

In the NA group, nonalcoholic fatty liver disease was responsible for 23.1% of cases, hepatitis C for 32.7%, hepatitis B for 23.1%, hemochromatosis for 4.5%, and other disorders, including autoimmune hepatitis and primary biliary cholangitis, for 16.7%. The median follow-up period was 5.7 months for group A and 8.3 months for group NA.

Patients in group A were less likely to receive treatment with curative intent (resection, ablation, or liver transplant) compared to group NA (16.3% vs 27.1%; P < .0001). The distribution of stages according to the Barcelona Clinic Liver Cancer (BCLC) scoring system differed between the two groups, but the overall comparison did not reach statistical significance (P = .06).

A total of 601 patients had died by the time of final analysis on October 31, 2014. Although survival was shorter in group A, it was comparable between both groups after stratification by BCLC stage.

Within group A, the authors also compared patients who had abstained from alcohol (n = 305) with those who were consuming alcohol (n = 244) at the time of their HCC diagnosis (33 patients were excluded from the analyses).

For patients who were nonabstinent, performance status was worse (Eastern Cooperative Oncology Group performance status >1, 51.7% vs 39.5%; P = .005). For nonabstinent patients, disease was diagnosed at a later BCLC stage (P = .01), and such patients were less likely to fulfill the Milan criteria for liver transplant (P = .04). The proportion of cancer cases diagnosed through a cirrhosis follow-up program was lower in the nonabstinent group than in the abstinent group (11.9% vs 28.4%; P < .0001).

Median overall survival was similar, however: 5.8 months for the abstinent group vs 5.0 months for the nonabstinent group (P = .09).

Importance of Cirrhosis Follow-up

The French team also evaluated the importance of participation in a cirrhosis follow-up program before cancer diagnosis. Patients who were diagnosed during a cirrhosis follow-up program (n = 190) were more likely to receive intent-to-cure treatments (15.4% vs 37.6%; P < .0001) than those who were not in such a program.

For the entire cohort, the lead time-adjusted median survival was 11.7 months among patients enrolled in a cirrhosis follow-up program vs 5.4 months for those diagnosed incidentally (P < .0001). Survival was shorter for patients with alcohol-related HCC than for those with non-alcohol-related disease (9.7 months vs 15.0 months; P = .042).

Costentin explained that despite guidelines recommending biannual screening, fewer than 30% of the patients in this study were involved in a cirrhosis follow-up program. The same figures have been reported in the United States.

"Patients with liver cancer diagnosed during a surveillance program had prolonged survival compared to patients diagnosed incidentally, and nonabstinent patients were less likely to be included in a surveillance program," she said. "Survival times in abstinent patients were comparable to nonalcohol patients and longer than in nonabstinent patients.

"Therefore, in order to improve the prognosis of HCC in the alcoholic population, efforts should be made to improve screening for cirrhosis, a goal that can be reach by increasing awareness among primary care practitioners towards the alcohol issue," Costentin continued.

Screening for liver cancer also needs improvement. In addition, physicians need to become more aware of the positive impact of liver cancer screening, as do patients with liver disease, she explained. Access to alcoholism treatment may also need to be facilitated.

"Altogether, these interventions should translate into a smaller tumor burden and better liver function at diagnosis, and ultimately into increased rates of patients with alcohol-related liver cancer amenable to curative treatment and improved prognosis," she added.

Alcohol Abuse and Biology of Cancer

"The take-home message is that patients with alcohol-related liver disease are less likely to be followed carefully by their physicians and less likely to be diagnosed with cirrhosis and are therefore less likely to be screened for liver cancer when they do have cirrhosis," commented Scott L. Friedman, MD, dean for therapeutic discovery, Fishberg Professor of Medicine, and chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai in New York City.

"One of the striking things about the data was that there was a much higher percentage in the alcoholic liver cancer patients who were not even aware that they had liver disease," he told Medscape Medical News. "To me, this is as much a reflection on the consequences of alcohol abuse as it is on the biology of cancer.

"Once they develop a tumor of specific size or stage, they do no worse than other patients with etiologies," Freidman continued. "But they are more likely to present at later stages, and they are much less likely to have follow-up care and much less likely to be aware that they have severe underlying liver disease."

He noted that the study was conducted in France, and although that does not mean that the study is not relevant to clinicians in the United States, alcohol-related liver disease is more prevalent in France. "A higher fraction of their liver transplants are for alcohol-related disease, so it is a more pervasive problem, but that doesn't diminish its importance in the US, or anywhere else, of identifying alcoholism and liver disease and screening those patients for cirrhosis and the risk of cancer," he said.

The study was supported by the Association Nationale des Hé pato-Gastroentérologues des Hôpitaux Généraux group and Roche Pharmaceuticals. Dr Costentin and Dr Friedman have disclosed no relevant financial relatinshiips. Several coauthors have disclosed relationships with industry, as noted in the original article.

Cancer. Published online March 28, 2018.

Ben Nguyen