In Older Hep B Patients, Carcinoma Surveillance Is Advised

Laird Harrison

November 15, 2018

SAN FRANCISCO — Surveillance for hepatocellular carcinoma (HCC) should continue in patients older than 50 years, even after they have undergone 5 years of therapy for chronic hepatitis B, according to an analysis of the PAGE-B cohort.

But the risk for the cancer is low enough in younger patients — except for those with cirrhosis — that surveillance might not be warranted, said George Papatheodoridis, MD, PhD, from Athens University Medical School in Greece.

"It will save monitoring in some patients," he told Medscape Medical News.

Long-term monotherapy with entecavir (Baraclude, Bristol-Myers Squibb) or tenofovir disoproxil fumarate (Viread, Gilead) suppresses the hepatitis B virus and improves liver lesions, so the survival rate in patients without compensated cirrhosis is comparable to that in the general population, Papatheodoridis explained here at The Liver Meeting 2018.

Still, the risk for HCC is significantly elevated in patients with chronic hepatitis B. It is the only factor that affects liver-related mortality in this population. Most data available on HCC risk in such patients come from studies with an average duration of less than 5 years.

So Papatheodoridis and his colleagues analyzed the need for HCC surveillance in their 10-center PAGE-B cohort.

They identified 1427 patients with no hepatitis C, hepatitis D, or HIV, who had not undergone liver transplantation, and who had a follow-up of more than 5 years.

At baseline, average age was 51 years, 77% of the cohort was male, 6% reported a history of alcohol abuse, and 8% had diabetes mellitus. In addition, 27% had cirrhosis diagnosed with biopsy. The cirrhosis status of 2% of the cohort was unknown.

After 5 years of therapy, patients underwent transient elastography (FibroScan, EchoSens), a type of ultrasound, to assess cirrhosis. With a liver stiffness cutoff of 12 kPa, 8.4% of the study population was determined to have cirrhosis.

The team used ultrasound and alpha-fetoprotein levels at least every 6 months to screen for HCC. Patients were followed for up to 12 years (mean, 8.4 years) and, during the follow-up period, 2.3% of patients were diagnosed with HCC.

On Cox regression analysis, there was a significant association between the development of HCC and cirrhosis at baseline, high baseline alanine aminotransferase levels, low baseline platelet counts, detectable hepatitis B DNA at baseline, nucleos(t)ide analogs before entecavir or tenofovir therapy, starting hepatitis B therapy after the age of 50 years, being older than 50 years after 5 years of therapy, and liver stiffness at year 5.

There was no significant association between risk for HCC and sex, body mass index, or hepatitis B e-antigen status.

On multivariable Cox regression analysis, only age, cirrhosis at baseline, and liver stiffness of at least 12 kPa at year 5 remained independently associated with the development of HCC in years 5 to 13.

But the liver stiffness measurement was ambiguous. The difference in HCC risk between patients with no cirrhosis at baseline and those with liver stiffness below 12 kPa at 5 years was significant (P = 0.001).

However, there was no significant difference between patients with liver stiffness above or below the cutoff of 12 kPa (P = .657).

Table. Risks for HCC During the Follow-up Period
Measure Year 6, % Year 8, % Year 10, %
No cirrhosis at baseline (n = 658) 0.6 1.7 2.0
Liver stiffness <12 kPa at year 5 (n = 206) 1.0 5.1 8.0
Liver stiffness ≥12 kPa at year 5 (n = 66) 1.5 7.0 7.0

Only one patient younger than 50 developed HCC. After the first 5 years of drug therapy, HCC seems to develop almost exclusively in patients older than 50 years, Papatheodoridis and his colleagues conclude.

Platelets are not useful for excluding patients from HCC surveillance after 5 years of therapy because the risk for HCC in all the subgroups was more than 0.2%, "the threshold for cost-effective," the researchers write in their abstract.

Surveillance should continue in all patients who are at least 50 years old after 5 years of therapy, they recommend. The risk associated with liver stiffness measured by transient elastography needs further study, but surveillance should continue "probably in the few cirrhotics" who are younger than 50 years.

The surveillance can be done with ultrasound, with alpha-fetoprotein levels as an optional addition.

Results from this analysis of patients from Greece, Germany, Italy, the Netherlands, Spain, and Turkey should be confirmed in other cohorts, Papatheodoridis pointed out.

The ambiguity of the transient elastography finding prompted questions from the audience. One person wondered if some aspect of liver damage other than stiffness persists after drug treatment. Another suggested that MRI would be more accurate for the detection of cirrhosis.

The correlation between cancer and baseline cirrhosis stood out for session moderator Kimberly Brown, MD, from the Henry Ford Health System in Detroit.

"What is important is that the risk continued even in patients whose cirrhosis improved once they were on treatment," she told Medscape Medical News. "This tells us that in patients on treatment for hepatitis B, we really need to screen both the older patients over time, regardless of the degree of their cirrhosis, and patients who had any indication of cirrhosis before starting treatment."

Papatheodoridis reports financial relationships with MSD, AbbVie, and Gilead. Brown reports financial relationships with Gilead, Merck, and Pfizer.

The Liver Meeting 2018: American Association for the Study of Liver Diseases (AASLD): Abstract 0017. Presented November 12, 2018.

Follow Medscape Gastroenterology on Twitter @MedscapeGastro and Laird Harrison @LairdH

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