High rate of core promoter and precore mutations in patients with chronic hepatitis B.

BACKGROUND: The prevalence of precore (PC) and core promoter (CP) mutations in patients with chronic hepatitis B virus (HBV) infection (CHB) and their impact on liver disease is incompletely defined in the United States. METHODS: A retrospective chart review using a cross-sectional approach of 1,186 CHB patients was conducted. RESULTS: Of 926 patients tested for HBV e antigen (HBeAg), 37% were HBeAg+. Of 194 patients tested for mutations, 80% had PC or CP mutations or both; 89% of HBeAg-negative and 56% of HBeAg+ patients had PC or CP mutations or both (p < 0.001). The mean log10 ALT was significantly lower in patients with both mutations compared to patients without mutations. The mean log10 HBV DNA was significantly lower in patients with only PC mutations (4.82) compared to patients without mutations (5.71, p = 0.019). With the study population divided into four subgroups based on ALT level at time of diagnosis, cirrhosis incidence was significantly higher in patients with ALT 1-2 × ULN and ALT > 2 × ULN compared to patients with ALT ≤ 0.5 × ULN. CONCLUSIONS: Our finding that PC and CP mutations may be associated with milder liver disease in some patients could serve as the basis for longitudinal studies to help delineate treatment need and duration in patients with these mutations. If confirmed, the finding of an association between ALT 1-2 × ULN and increased incidence of cirrhosis could call into question guidelines which only recommend treatment with ALT > 2 × ULN.

Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California.

BACKGROUND AND AIMS: With no report on the overall prevalence and ramifications of hepatitis Delta virus (HDV) infection in the United States for more than two decades, the characteristics of chronic hepatitis B virus (CHB) patients coinfected with HDV, including clinical presentation, rate of hepatitis C virus tri-infection, and HDV viral load, were assessed. METHODS: At California Pacific Medical Center, a retrospective chart review was conducted on all CHB patients. RESULTS: Of 1191 CHB patients, 499 had been tested for HDV, with 42 (8%) determined to be coinfected; half of these were also hepatitis C virus-infected. Cirrhosis was present in 73% of the coinfected, 80% of the tri-infected, but only 22% of the monoinfected. Twenty-nine patients (69%) were Caucasian non-Hispanic; 10 (24%) were Asians and Pacific Islanders. Of 39 patients for whom HBV-DNA quantification at time of HDV presentation was available, 22 (56%) had undetectable levels; four (10%) had levels > 100 000 IU/mL. CONCLUSIONS: HDV affects individuals of all ages and various ethnic groups. Although HBV viral loads are lower, rates of cirrhosis are higher in coinfected patients and higher still in the tri-infected. Our data support revising screening guidelines to advocate for all patients with HBV to be screened for HDV in order to both give the individual patient important information related to the possible need for treatment and to support the public health goal of reducing transmission by educating HDV-negative patients about the need for protection against superinfection and HDV-infected patients about the need to protect against transmission to others.

Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B.

BACKGROUND & AIMS: Tenofovir is a nucleotide reverse-transcriptase inhibitor approved for treatment of human immunodeficiency virus infection, as well as chronic hepatitis B (CHB). We evaluated nephrotoxicity among patients with CHB treated with tenofovir. METHODS: We performed a community-based, retrospective cohort study of 80 patients with CHB who received tenofovir, alone or in a combination regimen; they were matched for age and sex with 80 CHB patients who received only entecavir. Incidences of serum creatinine (SCr) increase ≥0.2 mg/dL and new SCr levels of 1.5, 2.0, or 2.5 mg/dL were assessed. Patients with an estimated glomerular filtration rate (eGFR) <60 mL/min, calculated using the Modification of Diet in Renal Disease or Cockcroft-Gault formula, or who had ≥20% decrease in eGFR were also recorded. RESULTS: More patients given entecavir had increases in SCr ≥2.5 mg/dL (1 vs 6; P = .053), whereas more patients given tenofovir had a new Cockcroft-Gault eGFR of <60 mL/min (15 vs 6; P = .022) and at least 1 dose adjustment (13 vs 4; P = .021). By multivariate analysis, the only significant factors associated with an increase in SCr were a history of organ transplantation (adjusted odds ratio, 6.740; 95% confidence interval, 1.799-28.250; P = .005) and pre-existing renal insufficiency (adjusted odds ratio, 10.960; 95% confidence interval, 2.419-48.850; P = .002). No factors, including therapy assignment, were associated with a new eGFR <60 mL/min. CONCLUSIONS: Markers of renal function indicated that patients who received tenofovir were no more likely to have changes in renal function than patients treated with entecavir. History of transplant and pre-existing renal insufficiency were the only factors independently associated with increases in SCr.