A comparison of hepatitis B viral markers of patients in different clinical stages of chronic infection.

PURPOSE: Hepatitis B viral markers may be useful for predicting outcomes such as liver-related deaths or development of hepatocellular carcinoma. We determined the frequency of these markers in different clinical stages of chronic hepatitis B infection. METHODS: We compared baseline hepatitis B viral markers in 317 patients who were enrolled in a prospective study and identified the frequency of these tests in immune-tolerant (IT) patients, in inactive carriers, and in patients with either hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis or cirrhosis. RESULTS: IT patients were youngest (median age 27 years) and HBeAg-negative patients with cirrhosis were oldest (median age 58 years) (p = 0.03 to <0.0001). The male to female ratio was similar both in IT patients and in inactive carriers, but there was a male preponderance both in patients with chronic hepatitis and in patients with cirrhosis (p < 0.0001). The A1896 precore mutants were most prevalent in inactive carriers (36.4%) and HBeAg-negative patients with chronic hepatitis (38.8%; p < 0.0001), and the T1762/A1764 basal core promoter mutants were most often detected in HBeAg-negative patients with cirrhosis (65.1%; p = 0.02). Genotype A was detected only in 5.3% of IT patients, and genotype B was least often detected in both HBeAg-Positive patients with chronic hepatitis and cirrhosis (p = 0.03). The hepatitis B viral DNA levels were lowest in inactive carriers (2.69 log(10) IU/mL) and highest in IT patients (6.80 log(10) IU/mL; p = 0.02 to <0.0001). At follow-up, HBeAg-positive and HBeAg-negative patients with cirrhosis accounted for 57 of 64 (89.1%) liver-related deaths (p < 0.0001). CONCLUSION: Differences in baseline hepatitis B viral markers were detected in patients in various clinical stages of hepatitis B virus infection. HBeAg-positive and HBeAg-negative patients with cirrhosis accounted for the majority of the liver-related fatalities.

Surveillance for hepatocellular carcinoma improves survival in Asian-American patients with hepatitis B: results from a community-based clinic.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy in Asians with hepatitis B virus infection. HCC patients often present with poor liver function and large tumors resulting in rapid mortality. The impact of HCC surveillance and subsequent therapy on patient survival remain controversial. AIMS: We sought to determine if surveillance for HCC in a community-based clinic improve survival and, if so, identify factors that contribute to the benefit of early tumor detection. METHODS: From 1991 to 2008, alpha-fetoprotein and abdominal ultrasound examination were used as surveillance tests for HCC. The survival of HCC patients detected by surveillance was compared to patients who presented to the clinic with HCC (no surveillance). An adjusted lead-time bias interval was added to the survival time of patients who presented with HCC. RESULTS: During this period, 26 patients with surveillance developed HCC while 52 patients presented with HCC. More surveillance patients had normal levels of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase (p < 0.05-0.0001) and had tumors that were within Milan and University of California San Francisco (UCSF) criteria (p = 0.02-0.0001). The 1-, 3-, and 5-year survival rates were higher in surveillance patients and in those who received surgical or loco-regional therapies (p = 0.007-0.0001). On multivariate analysis, baseline independent factors predicting survival were single tumors (Hazard ratio [HR] 0.25, p = 0.0005), UCSF criteria (HR 0.29, p = 0.006), Child-Turcotte-Pugh class A (HR 0.45, p = 0.03), platelet counts per log(10) increase (HR 0.315, p = 0.04) and aspartate aminotransferase per log(10) increase (HR 5.7, p = 0.01). CONCLUSIONS: Surveillance for HCC identified patients with smaller tumor burdens and more adequate liver function who were able to receive more definitive therapies. HCC surveillance improves survival and should be included as standard of care for patients with hepatitis B.

Factors associated with progression to hepatocellular carcinoma and to death from liver complications in patients with HBsAg-positive cirrhosis.

BACKGROUND AND AIMS: Hepatitis B viral markers and liver tests were used as predictors for development of hepatocellular carcinoma and progression to end-stage liver disease in 128 cirrhosis patients with hepatitis B. RESULTS: During a median follow-up of 63.5 months, 28 patients (21.9%) developed HCC and 36 (28.1%) died from non-HCC liver deaths. By multivariate analysis, independent predictors of HCC development and their hazard ratios were high alfa-fetoprotein (HR2.83, 95% CI 1.60-5.00, P = 0.0003), negative HBeAg (HR2.33, 95% CI 1.04-5.29, P = 0.04), and low alanine aminotransferase value (HR1.42, 95% CI 1.08-1.89, P = 0.02). Independent predictors of non-HCC liver deaths were HBeAg positivity (HR3.39, 95% CI 1.16-9.93, P = 0.02), decrease albumin (HR1.61, 95% CI 0.99-2.63, P = 0.05), decrease platelet count (HR2.54, 95% CI 1.03-6.25, P = 0.04), high ALT value (HR1.22, 95% CI 1.03-1.43, P = 0.02), and onset of encephalopathy (HR3.34, 95% CI 1.21-9.27, P = 0.02). CONCLUSIONS: HBeAg negativity, elevated AFP, and low ALT values predicted HCC development, while HBeAg positivity, abnormal liver tests, and low platelet counts identified patients with non-HCC liver deaths.

Treatment recommendations for chronic hepatitis B: an evaluation of current guidelines based on a natural history study in the United States.

UNLABELLED: Current guidelines for treatment of chronic hepatitis B include hepatitis B e antigen (HBeAg) status, levels of hepatitis B virus (HBV) DNA, and serum alanine aminotransferase (ALT) values in the setting of either chronic hepatitis or cirrhosis. Based on findings from a prospective study of hepatitis B surface antigen (HBsAg)-positive patients, we determined whether these guidelines included patients who developed hepatocellular carcinoma (HCC) and who died of non-HCC liver-related complications. The criteria for treatment from four published guidelines were matched to a cohort of 369 HBsAg-positive patients enrolled in the study. During a mean follow-up of 84 months, 30 patients developed HCC and 37 died of non-HCC liver-related deaths. Using criteria for antiviral therapy as stated by the four guidelines, only 20%-60% of the patients who developed HCC, and 27%-70% of patients who died of non-HCC liver-related deaths would have been identified for antiviral therapy according to current treatment recommendations. If baseline serum albumin levels of 3.5 mg/dL or less or platelet counts of 130,000 mm(3) or less were added to criteria from the four treatment guidelines, then 89%-100% of patients who died of non-HCC liver-related complications, and 96%-100% of patients who developed HCC would have been identified for antiviral therapy. In addition, if basal core promoter T1762/A1764 mutants and precore A1896 mutants also were included, then 100% of patients who developed HCC would have been identified for treatment. CONCLUSION: This retrospective analysis showed that the current treatment guidelines for chronic hepatitis B excluded patients who developed serious liver-related complications.

The emerging importance of chronic hepatitis C infection in Asian Americans.

OBJECTIVES: To study the demographics, epidemiology, and natural history of chronic hepatitis C in Asian Americans. METHODS: This retrospective survey describes 260 Asian Americans with chronic hepatitis C referred to one tertiary center. RESULTS: Ninety-two percent of patients were born in Asia. Fifty-one percent reported a history of unsafe therapeutic injections, which was a risk factor only in those with exposure outside the United States (p < 0.0001). A history of transfusion was reported in 41% of patients and was more frequent in those with exposure within the Unites States (p < 0.0001). Only 3.8% reported a history of intravenous drug abuse, which was more frequent in those with exposure within the United States (p < 0.0001). Hepatitis C genotype 1 was detected in 64.2% of patients, genotype 2 in 18.3%, and genotype 6 in 11.3%. Genotype 1 had a significantly lower sustained virologic response rate (32.8%) to interferon treatment, compared with genotype 2 (77.8%) or 6 (69.2%). During a mean follow-up of 6 yr, 26 patients developed hepatocellular carcinoma (HCC). Logistic regression model revealed fibrosis stage 4 (odds ratio [OR] 8.87, 95% confidence interval [CI] 2.97-26.48, p < 0.0001), age at presentation (55 vs 35 yr--OR 3.45, 95% CI 1.22-9.75, p= 0.0194), and baseline albumin level (3.0 vs 4.0 mg/dL--OR 3.47, 95% CI 1.02-11.76, p= 0.0464) were independent predictive factors for HCC development. CONCLUSIONS: Asian Americans with a history of unsafe therapeutic injections must be screened for chronic hepatitis C. Antiviral treatment should be initiated prior to development of cirrhosis. Surveillance for HCC must be routinely performed in cirrhosis patients.