In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.

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The incidence and contributing factors of cirrhosis developing in patients with chronic type B hepatitis were assessed prospectively in 684 clinicopathologically verified patients, of which 509 were HBeAg positive and 175 were anti-HBe positive at entry into the study. During an average follow-up period of 35.3 months, cirrhosis occurred 6 to 64 months after entry in 35 HBeAg-positive and 7 anti-HBe positive patients with a calculated annual incidence of 2.4 and 1.3%, respectively (p greater than 0.05). The incidence increased significantly with the increasing age at entry. Patients who had experienced (a) hepatic decompensation, (b) repeated episodes of severe acute exacerbation (with alpha-fetoprotein greater than 100 ng per ml and/or bridging hepatic necrosis), (c) severe acute exacerbation not accompanied by subsequent HBeAg seroconversion and (d) hepatitis B virus reactivation (particularly those with HBeAg reappearance) were found to develop cirrhosis much more frequently (p less than 0.001). Contrary to general belief, patients who had hepatitis delta virus superinfection and patients with chronic active hepatitis were not particularly prone to develop cirrhosis. We conclude that in addition to age factor, the extent, severity, duration, frequency and etiology of the hepatic lobular alterations are important factors for the development of cirrhosis in patients with chronic type B hepatitis.

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Although cancer cell secretome profiling is a promising strategy used to identify potential body fluid-accessible cancer biomarkers, questions remain regarding the depth to which the cancer cell secretome can be mined and the efficiency with which researchers can select useful candidates from the growing list of identified proteins. Therefore, we analyzed the secretomes of 23 human cancer cell lines derived from 11 cancer types using one-dimensional SDS-PAGE and nano-LC-MS/MS performed on an LTQ-Orbitrap mass spectrometer to generate a more comprehensive cancer cell secretome. A total of 31,180 proteins was detected, accounting for 4,584 non-redundant proteins, with an average of 1,300 proteins identified per cell line. Using protein secretionpredictive algorithms, 55.8% of the proteins appeared to be released or shed from cells. The identified proteins were selected as potential marker candidates according to three strategies: (i) proteins apparently secreted by one cancer type but not by others (cancer type-specific marker candidates), (ii) proteins released by most cancer cell lines (pan-cancer marker candidates), and (iii) proteins putatively linked to cancer-relevant pathways. We then examined protein expression profiles in the Human Protein Atlas to identify biomarker candidates that were simultaneously detected in the secretomes and highly expressed in cancer tissues. This analysis yielded 6 -137 marker candidates selective for each tumor type and 94 potential pan-cancer markers. Among these, we selectively validated monocyte differentiation antigen CD14 (for liver cancer), stromal cell-derived factor 1 (for lung cancer), and cathepsin L1 and interferon-induced 17-kDa protein (for nasopharyngeal carcinoma) as potential serological cancer markers. In summary, the proteins identified from the secretomes of 23 cancer cell lines and the Hu-

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The baseline alanine aminotransferase (ALT) level was reported to have prognostic value in chronic hepatitis B virus (HBV) infection, during which ALT may change over time. Instead of baseline ALT, this study aimed to study the prognostic value of the height of ALT during the course of chronic HBV infection. A total of 4376 asymptomatic hepatitis B e antigen (HBeAg) negative, surface antigen (HBsAg) carriers with baseline ALT less than 2 times the upper limit of normal (ULN) were monitored with ALT measurement and ultrasonography every 3 to 12 month for over 3 years. Maximal ALT levels during follow-up were correlated with long-term outcomes using morbidity and mortality data from hospital records, cancer registration, and national mortality database. Baseline ALT level was normal in 3673 subjects and increased to abnormal level in 1720 (46.8%) during a mean follow-up period of 13.4 ؎ 5.2 (3.0-28.7) years. The incidence of liver cirrhosis, hepatocellular carcinoma (HCC), and mortality increased with increasing maximal ALT level during follow-up, especially in those with maximal ALT of at least 2 times ULN, as compared with those who maintained normal ALT. Cox regression analysis indicated that age at entry, sex, and maximal ALT level during follow-up were significant independent factors associated with the development of cirrhosis, HCC, and mortality whereas cirrhosis was also an independent factor for HCC development and mortality. Conclusion: Persistently normal ALT was associated with excellent long-term prognosis, whereas increasing ALT levels of at least 2 times ULN during follow-up was associated with increasing morbidity and mortality. ALT of at least 2 times ULN is therefore an appropriate threshold for anti-HBV therapy, whereas those with ALT 1 to 2 times ULN require liver biopsy for decision. (HEPATOLOGY 2009;49: 1859-1867.) C hronic hepatitis B virus (HBV) infection is one of the major causes of liver morbidity and mortality. 1,2 Recent community-based studies involving a large number of hepatitis B surface antigen (HBsAg) positive subjects, mainly (Ͼ85%) hepatitis B e antigen (HBeAg) negative, have shown that baseline age, sex, HBeAg serostatus, and serum HBV-DNA level are factors associated with hepatocellular carcinoma (HCC) development and liver-related mortality. 3,4 Abnormal alanine aminotransferase (ALT) at entry was also found to be associated with cirrhosis development and liver-related mortality. 5,6 All HBV treatment guidelines of major liver associations also recommend that patients with active HBV replication and an ALT level greater than 2 times Abbreviations: AFP, alpha-fetoprotein; ALT, alanine aminotransferase; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDV, hepatitis D virus; maxALT, maximal alanine aminotransferase; PNALT, persistently normal alanine aminotransferase; ULN, upper limit of normal; US, ultrasonography.