Wang Th

Small Hepatocellular Carcinoma—A Clinicopathological Study in Thirteen Patients

Abstract To investigate the diagnosis and clinicopathological features of hepatocellular carcinoma at its early stage, 13 patients with carcinoma ≤3.0 × 3.0 cm in size (small hepatocellular carcinoma) were studied with radionuclide scan, celiac arteriography, computed tomography, ultrasonography, and peritoneoscopy. Most of the patients were found from prospective studies in hepatoma high-risk subjects and were asymptomatic, with liver tests showing only mild abnormalities. Hepatitis B surface antigen was positive in all except one who was hepatitis B core antibody positive. Serum α-fetoprotein level was normal in 3 patients and in the remaining patients it increased to an extent far lower than in patients with advanced hepatocellular carcinoma. For detecting small tumors, ultrasonography, computed tomography, and celiac arteriography were superior to radionuclide scan or peritoneoscopy (detection rate: 95%, 94%, 89% vs. 16%, 12%, respectively). Small hepatocellular carcinoma was characterized as a hypoechoic shadow with weak internal echoes on ultrasonography, hypodense lesion on computed tomography, and hypervascular stain in angiography. None of these three examinations detected all the tumors in every patient and thus at least two of the three examinations should be done to avoid missing any tumor. Among them, the real-time ultrasonography was most practical for localizing small hepatocellular carcinoma and the diagnosis could be confirmed by ultrasound-guided biopsy. Ultrasonography was indispensable for identifying the small tumor during laparotomy in 3 patients. Ten patients had a single tumor. The small tumors were resected successfully in 10 patients. The tumor was frequently surrounded by a thin fibrous capsule and the most common cell type was of the trabecular pattern.

Viral factors correlate with hepatitis B e antigen seroconverson in patients with chronic hepatitis B

Abstract: Background/Aims: Seroconversion (SC) from hepatitis B envelope antigen (HBeAg) to anti‐HBe usually indicates lower viral loads, resolved hepatitis activity and improved long‐term outcomes. However, the role of viral factors in the development of SC remains largely unknown. We thus comprehensively studied these factors in 25 patients with sustained HBeAg SC and seven control patients with sustained loss of HBeAg.

Superinfection by homotypic virus in hepatitis C virus carriers: Studies on patients with post‐transfusion hepatitis

Although heterotypic superinfection and mixed infections of hepatitis C virus (HCV) may be possible for hepatitis flares in chronic hepatitis C, the possibility of homotypic HCV superinfection in HCV carriers with post‐transfusion hepatitis has not been explored. Six HCV carriers with post‐transfusion non‐A, non‐B hepatitis found in a prospective study of post‐transfusion hepatitis were included. Serum samples before transfusion and during hepatitis were selected to determine genotypes of HCV and nucleotide sequences of the hypervariable region (HVR). The genotypes identified before and after transfusion were concordant in all. There were four with type 1b and one each with type 2a and type 2b. Amplified nucleotide sequences of the HVR before transfusion and during hepatitis were compared in four patients, and a, >95% homology was observed in three, suggesting persistence of original viruses. In contrast, only a 51% homogeneity was seen in a given patient, suggesting a homotypic HCV superinfection. Phylogenotic tree analysis validated further these findings. This study implies that HCV carriers can be reinfected by homotypic HCV, and this may contribute to hepatitis flares in chronic hepatitis C. These findings also confirm a weak or inadequate protective immunity in HCV infection and justify protection from reinfection of HCV of patients with chronic hepatitis C.

Prevalence and infectivity of hepatitis G virus and its strain variant, the GB agent, in volunteer blood donors in Taiwan.

BACKGROUND: The prevalence of hepatitis G virus (HGV) and its strain variant, the GB agent (GBV‐C) is high in non‐virus‐inactivated plasma products, but, persistent infection in recipients is relatively low. STUDY DESIGN AND METHODS: Stored samples from transfusion donors and recipients in a prospective study of posttransfusion hepatitis were tested for HGV RNA and antibody to the E2 protein (anti‐E2). RESULTS: Thirty‐two (2.1%) of the 1500 qualified donors were positive for HGV RNA. Twenty‐four persons had received a transfusion of blood from one of these 32 viremic donors. Of these 24 recipients, 3 were positive for HGV RNA before transfusion. Of the remaining 21 recipients, 8 became viremic after transfusion, while the other 13 were not infected. Four of the eight infected recipients were persistently positive for HGV RNA, while four became negative in 1 to 3 years. Three of the four patients with HGV clearance seroconverted to anti‐E2 positivity. Comparison of the viral titer, viral sequences at E2, storage period of blood donations, and clinical data in the infected and noninfected recipients revealed no significant differences. However, the noninfected recipients seemed to have a higher prevalence of anti‐E2 before transfusion. CONCLUSION: The prevalence of HGV viremia in volunteer blood donors in Taiwan is 2.1 percent, and blood from 0.6 percent of them actually causes HGV infection in the recipients. In half of infected recipients, clearance of HGV occurs. Anti‐E2 appears in most recipients whose viremia is cleared.

Incidence and clinical presentation of posttransfusion TT virus infection in prospectively followed transfusion recipients: emphasis on its relevance to hepatitis

BACKGROUND: A novel transfusion‐transmissible human DNA virus, TT virus (TTV), has been discovered recently. An attempt was made to determine the incidence and clinical outcome of TTV infection in recipients of blood transfusion.

Hepatitis B e antigen and antibody in asymptomatic Chinese with hepatitis B surface antigenemia in Taiwan

SummaryTwo hundred and twenty two asymptomatic carriers of hepatitis B surface antigen (HBsAg) with age between 4 months and 68 years, 172 healthy persons with antibody to HBsAg (anti-HBs) and 85 healthy persons seronegative for both HBsAg and anti-HBs were studied by double immunodiffusion for the evaluation of the meaning of hepatitis B e antigen (HBeAg) and its antibody (anti-HBe). In 222 asymptomatic carriers, HBeAg was detected in 32.4% and anti-HBe in 31.5%. The geometric titer of HBsAg was 1:2159 in the HBeAg positive and 1:149 in the anti-HBe positive persons. Frequencies of HBeAg and anti-HBe in asymptomatic carriers of HBsAg correlated closely with age. The highest frequency of HBeAg was found in the first decade in 64%, decreasing steadily to 20.8% in the fourth and then suddenly down to 4.1% in the fifth decade. A reverse trend was observed in anti-HBe frequency. From our analysis, it is likely that the high frequency of HBeAg in serum of Chinese, especially in females of fertile age, might be an important contributing factor for the high rates of hepatitis B virus (HBV) infection and HBsAg carrier in Taiwan. The presence of HBeAg/anti-HBe system is not only a marker of infectivity and prognosis but also a chronologic marker of HBV infection.

Absence of extensive genetic heterogeneity of hepatitis C virus in antibody-negative chronic hepatitis C

Hepatitis C virus (HCV) carriers usually have antibodies to HCV; however, there are viremic individuals without these antibodies. To investigate whether variations of the viral genome are responsible for this discrepancy, the nucleotide and deduced amino acid sequences of HCV capsid and nonstructural regions obtained from 15 viremic patients were examined. These 15 patients were infected with type 1b HCV, and 10 did not have antibody to HCV assayed with second‐generation tests. The nucleotide homology of the 5 seropositive and 10 seronegative patients with the HCV prototype sequence were 91.6% and 91.9%, respectively, in the capsid region. There was no apparent difference in the deduced amino acid sequences between the two groups of patients studied (94% vs. 95%). The nucleotide and amino acid sequences of a part of the nonstructural region 3 also showed similar results. These findings suggest that absence of antibodies against both capsid and nonstructural peptides in HCV carriers is not caused by genetic heterogeneity of the viral epitopes.

Pegylated IFN-α suppresses hepatitis C virus by promoting the DAPK-mTOR pathway.

Significance Death-associated protein kinase (DAPK) regulates several important biological functions through a diverse range of signal transduction pathways, including cell growth, the immune response, apoptosis, and autophagy, but its antiviral activity has not been explored. Our data provide evidence that DAPK is one of the major regulators for the pegylated IFN-α–induced antiviral activity against hepatitis C virus, suggesting that DAPK may serve as a novel antiviral target and also a new biomarker to predict the therapeutic efficacy of pegylated IFN-α and other antiviral agents. Death-associated protein kinase (DAPK) has been found to be induced by IFN, but its antiviral activity remains elusive. Therefore, we investigated whether DAPK plays a role in the pegylated IFN-α (peg-IFN-α)–induced antiviral activity against hepatitis C virus (HCV) replication. Primary human hepatocytes, Huh-7, and infectious HCV cell culture were used to study the relationship between peg-IFN-α and the DAPK-mammalian target of rapamycin (mTOR) pathways. The activation of DAPK and signaling pathways were determined using immunoblotting. By silencing DAPK and mTOR, we further assessed the role of DAPK and mTOR in the peg-IFN-α–induced suppression of HCV replication. Peg-IFN-α up-regulated the expression of DAPK and mTOR, which was associated with the suppression of HCV replication. Overexpression of DAPK enhanced mTOR expression and then inhibited HCV replication. In addition, knockdown of DAPK reduced the expression of mTOR in peg-IFN-α–treated cells, whereas silencing of mTOR had no effect on DAPK expression, suggesting mTOR may be a downstream effector of DAPK. More importantly, knockdown of DAPK or mTOR significantly mitigated the inhibitory effects of peg-IFN-α on HCV replication. In conclusion, our data suggest that the DAPK-mTOR pathway is critical for anti-HCV effects of peg-IFN-α.