COMMENTARY

Viral Hepatitis: Five Highlights From the Liver Meeting

William F. Balistreri, MD

Disclosures

November 29, 2018

In This Article

Hepatitis B Virus (HBV)

Is the Incidence of HBV Rising?

There has been a well-documented increase in HCV infections among women of childbearing age and young children, especially in the central Appalachian region of the United States. Kushner and colleagues[9] set out to evaluate whether there has been a similar increase in HBV in these populations. They interrogated the Quest Diagnostics national laboratory database to determine national and state‐by‐state prevalence of HBV. Although the national prevalence of new diagnoses of chronic HBV decreased significantly (from 0.83% to 0.19%) during the period of 2011 to 2017, the trend was reversed in Kentucky, Mississippi, and West Virginia. The national prevalence rate of acute HBV (0.03%) was unchanged in all states; however, the rates were increased in Alabama, Indiana, and Kentucky. In children aged 0‐2 years, 90% had immunity to HBV, and acute and chronic diagnoses of HBV remained stable at a mean level of 0.22% and 0.01%, respectively. These data highlight the impact of the opioid epidemic and associated injection drug use on new HBV infections. Immunity acquired from HBV birth‐dose vaccination waned over time. Whether this is associated with increasing rates of exposure over time or booster vaccine doses (especially in high‐risk patient populations) should be further investigated. The investigators suggest repeat HBV serologic testing and booster HBV vaccines in high-risk groups such as injection drug users.

Chronic HBV Treatment and Outcomes

Tenofovir disoproxil fumarate (TDF) is approved for use in patients aged 12 years and older. Chang and colleagues[10] evaluated the safety and efficacy of TDF compared with placebo in children aged 2 to <12 years with ≥10 kg body weight. Children with HBV DNA levels ≥105 copies/mL, alanine aminotransferase (ALT) levels ≥1.5 times the upper limit of normal, and creatinine clearance ≥80 mL/min/1.73m2 were randomized to receive either TDF (8 mg/kg) or matching placebo once daily for 48 weeks, after which all patients received open-label TDF up to week 192. At week 48, 77% of the TDF and 7% of the placebo recipients had HBV DNA <69 IU/mL; a higher proportion of TDF, compared with placebo recipients, had ALT normalization (TDF 52% vs 18%), whereas the rate of HBeAg seroconversion was similar. Grade 3 or 4 adverse events and serious adverse events related to the study drug were similar for TDF vs placebo recipients. At week 48, greater median declines in estimated glomerular filtration rate were seen with TDF compared with placebo (-8.7 vs -0.1 mL/min/1.73m2). No HBV resistance was observed. Thus, although TDF was safe and well tolerated, increases in bone mineral density were smaller in those receiving TDF treatment.

Hepatocellular Carcinoma Surveillance After HBV Therapy

Papatheodoridis and colleagues[11] assessed predictors of the development of hepatocellular carcinoma after year 5 of entecavir or TDF therapy in 1951 patients with chronic HBV. Hepatocellular carcinoma (HCC) was diagnosed in 2.3% of patients overall, with cumulative incidences of 0.7%, 1.8%, 2.4%, 3.2%, and 3.8% at years 6, 7, 8, 10, and 13, respectively. In multivariable Cox regression analysis, only age and the presence of cirrhosis were independently associated with the development of HCC. After year 5, HCC developed only in patients older than 50 years (3.3%). Cirrhosis at baseline was present in 15% of patients aged 50 years and younger and in 32% of patients aged older than 50 years. The 6-, 8-, and 10-year incidence of HCC was lower in patients without cirrhosis at baseline (0.6%, 1.7%, and 2.0%) than in patients with cirrhosis reversion at year 5 (1.0%, 5.1%, and 8.0%) or patients who maintained cirrhosis (1.5%, 7.0%, and 7.0%). If cirrhosis was not considered, the development of HCC was associated with age and platelet counts <150 x 109/L at year 5. The investigators conclude that HCC after the first 5 years of entecavir or TDF therapy seems to develop exclusively in patients older than 50 years. Elastographic reversion of cirrhosis at 5 years does not appear to decrease the risk for HCC. Platelet counts were not useful for excluding patients from HCC surveillance after year 5. The investigators suggest that surveillance for HCC should continue in all treated patients older than 50 years and in those with cirrhosis aged 50 years and younger.

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