The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

Transmission of hepatitis C virus in Asia: past and present perspectives.

Hepatitis C virus (HCV) infection is a major public health problem. The epidemiology of HCV infection in different parts of Asia is similar, with an average seroprevalence of hepatitis C antibody (anti-HCV) less than 2.5% in healthy adults. The infection is rarely seen in children. The major routes of HCV transmission in Asia during the past few decades have been through administration of therapeutic blood products and injecting drug use, similar to the pattern observed in other parts of the world. However, obvious parenteral routes of transmission only account for 30-60% of anti-HCV-positive cases, depending on the geographic area. Other inapparent parenteral or per-mucosal exposures, including medical intervention, tattooing, acupuncture, vertical and sexual transmission, accidental needlestick and household contact, are also possible routes of HCV transmission. Although screening of blood donors for anti-HCV and improvements in infection control have significantly decreased the exposure to HCV, it is believed that HCV is still spreading in some areas of Asia because of the lack of routine screening of donated blood, injecting drug usage, traditional medicine practices or medical treatment under suboptimal hygienic conditions that involve blood contamination, and tattooing. Accordingly, until effective and safe immunoprophylaxis is available, interruption of transmission routes, such as implementation of blood donor screening for anti-HCV, adequate sterilization of surgical instruments or the use of disposable medical instruments, especially needles and syringes, and avoidance of sharing personal grooming aids remains the mainstay to prevent HCV infection in Asia today.

Inhibition of the membrane translocation and activation of protein kinase C, and potentiation of doxorubicin-induced apoptosis of hepatocellular carcinoma cells by tamoxifen.

Hepatocellular carcinoma (HCC) is characterized by high drug resistance to currently available chemotherapeutic agents. In a prospective clinical study, we have demonstrated that high-dose tamoxifen significantly enhanced the therapeutic efficacy of doxorubicin in patients with far-advanced HCC. In a search for a possible mechanism, we found that tamoxifen at a clinically achievable concentration (2.5 microM) significantly enhanced doxorubicin-induced cytotoxicity and apoptosis of Hep-3B cells, a multidrug resistance (MDR)-1 expressing HCC cell line. This synergistic cytotoxic effect of tamoxifen, at this concentration, however, was not mediated by MDR inhibition. Instead, as evidenced by both western blot and immunofluorescence studies, tamoxifen inhibited the cytoplasmic-membrane translocation of protein kinase C (PKC)-alpha. 12-O-Tetradecanoylphorbol-13-acetate (TPA) restored the membrane translocation of PKC-alpha and abrogated the synergistic cytotoxicity of tamoxifen. We also showed that tamoxifen, at this concentration, did not directly affect the enzyme activity of PKC. Further, membrane translocation of other membrane-bound proteins, such as Ras protein, was similarly inhibited by tamoxifen, but could not be restored by the addition of TPA. Together, these data suggested that tamoxifen may act on the cytoplasmic membrane, and thereby inhibit PKC-alpha translocation to the membrane where it is activated. We hypothesize that high-dose tamoxifen may be an effective modulator of doxorubicin in the treatment of HCC, and suggest that biochemical modulation of PKC as a measure to improve systemic chemotherapy for HCC deserves further investigation.

Elucidation of Islamic drugs in Hui Hui Yao Fang: a linguistic and pharmaceutical approach.

Hui Hui Yao Fang, an Islamic formulary, was probably the official formulary of the Mongolian administration during the Yuan dynasty (13th-14th century) in China. In the three chapters of prescriptions that remain extant today, there are 517 Islamic drugs carrying Arabic or Persian names, each with its Chinese transliteration. Chapter 12 deals with the 'wind' diseases, containing 199 Islamic drugs. In this research, 129 items were identified, and each of which was assigned to a definite taxon; these are the most frequently cited drugs in the formulary. Identifications were corroborated by botanical, pharmacological and phonetic considerations. This exercise demonstrates the inherent affinity between Islamic and Chinese medicines. The reciprocal influence between them greatly enriched the content of these two important bodies of drug science, thus, setting a pattern for the synthesis of drug knowledge and the regulation of therapeutic substances. Recognition of different bodies of ethnomedicine is necessary in view of the fact that there is an increasing mobility of people today, who tend to bring with them their drug knowledge.

Absence of infection in breast-fed infants born to hepatitis C virus-infected mothers.

The role of breast-feeding in perinatal transmission of hepatitis C virus (HCV) was explored in 15 HCV-infected mothers and their infants. The 15 carrier mothers had anti-HCV titers ranging from 1:80 to 1:40,000 and also had HCV-ribonucleic acid with concentrations ranging from 10(4) to 2.5 x 10(8) copies/ml. Both anti-HCV antibody and HCV-ribonucleic acid were present in colostral samples in much lower levels, but none of the 11 breast-fed infants had evidence of HCV infection for up to 1 year of age. Thus breast-feeding seems safe for these infants.

Hepatitis B virus in the colostra of HBeAg-positive carrier mothers.

To investigate the amount of hepatitis B virus (HBV) in colostra of hepatitis B e antigen (HBeAg)-positive carrier mothers and the relationship of HBV amount between colostrum and maternal blood, 50 HBeAg-positive carrier mothers were recruited and studied for hepatitis B surface antigen (HBsAg) titer, HBeAg titer, and HBV-DNA concentration in their sera and colostra. According to the presence or absence of seral HBV-DNA determined by dot hybridization, these 50 HBeAg-positive carrier mothers could be divided into two groups: group 1 (n = 28, HBV-DNA < 0.04 ng/ml), and group 2 (n = 22, HBV-DNA > or = 0.04 ng/ml). The colostral HBsAg and HBeAg titers were both significantly higher in group 2 than in group 1. In addition, both colostral HBsAg and HBeAg titers had positive correlation with each corresponding maternal blood. Although the colostral HBV-DNA was undetectable by dot hybridization, all were positive by polymerase chain reaction with Southern blot hybridization. Because HBV-DNA can be detected in all HBeAg-positive carrier mother's milk, it reinforces the necessity of hepatitis B vaccination for the neonates born to these carrier mothers, particularly in countries with a high carrier rate.

Laserthermia for the treatment of small hepatocellular carcinoma: a preliminary study.

A newly designed interstitial probe (hybrid probe) was used to treat small hepatocellular carcinoma (HCC) with laserthermia. Before the human study, testing in normal rabbit liver was done to measure the thermal map. Laserthermia was then studied in human small HCC. The set condition was 43-45 degrees C in thermocouple and the duration of laserthermia was 20 minutes. On follow-up computed tomography and liver biopsies, laserthermia had tumorcidal effect. It is concluded that laserthermia may be helpful to patients with small HCC.

[Serum vitamin A levels of radar operators and effects of supplementary vitamin A].

This paper reports serum vitamin A (VA) content of 28 radar operators, and the effects of supplementation VA were studied by means of observing change of serum VA level and objective dark adaptation time. The results indicated, with respect to serum VA content, 14.3% of radar operators had a deficient level (less than 10 micrograms%), whereas 57.2% of radar operators had a low level (less than 20 micrograms%). There were 39.3% of radar operators who had a low level on nineteenth day and 92.9% of radar operators who had a acceptable value on twenty-eighth day after oral VA supplementation VA of 3,000 IU, suggesting that supplementation VA of 3,000 IU to radar operators with VA malnutrition for about one month is necessary. A certain correlation between serum VA level and objective dark adaptation time was also observed.