R. Palmer Beasley

PREVENTION OF PERINATALLY TRANSMITTED HEPATITIS B VIRUS INFECTIONS WITH HEPATITIS B IMMUNE GLOBULIN AND HEPATITIS B VACCINE

A randomised blind controlled trial of hepatitis B immune globulin (HBIG) plus hepatitis B vaccine for the prevention of the perinatally transmitted HBsAg carrier state was conducted in Taipei. Infants of e-antigen-positive HBsAg carrier mothers were given HBIG immediately after birth, and then one of three schedules of vaccination. There was no difference in efficacy between the three schedules; the combined efficacy was 94%, compared with that of HBIG alone (71%) or of vaccination alone (75%). Persistent HBs antigenaemia developed in only 9 (6%) of the 159 infants receiving prophylaxis, but in 88% of the controls. Antibodies developed in all those who did not become antigenaemic and presumably will provide long-term protection from hepatitis B virus infection. HBIG should be given as soon as possible after birth and need not be given again if the infant is subsequently vaccinated. With HBIG coverage from birth, the timing of the start of vaccination does not seem to be of importance within the first month of life, but to maximise compliance and minimise costs hepatitis B vaccination should be initiated during the confinement.

Institute of Medicine recommendations for the prevention and control of hepatitis B and C

Despite federal, state, and local public health efforts to prevent and control hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, these diseases remain serious health problems in the United States. About 1%‐2% of the U.S. population has chronic HBV or HCV infections, and each year about 15,000 people die from liver cancer or liver disease related to these preventable infections. The Institute of Medicine formed an expert committee to determine ways to reduce new HBV and HCV infections and the morbidity and mortality related to chronic viral hepatitis and released its findings in a report. The major factor found to impede current efforts to prevent and control HBV and HCV is lack of knowledge and awareness about these diseases among healthcare and social‐service providers, members of the public, and policy makers. Because the extent and seriousness of this public health problem is not appreciated, inadequate resources are being allocated to prevention, control, and surveillance programs. This situation has led to continued transmission of HBV and HCV and inadequate identification of and medical management for chronically infected people. Conclusion: To address the situation, the Institute of Medicine report makes recommendations in four areas: improved surveillance for HBV and HCV; improved knowledge and awareness among healthcare and social‐service providers and the public, especially at‐risk people; improved HBV vaccine coverage; and improved viral hepatitis services and access to those services. HEPATOLOGY, 2010

EVIDENCE AGAINST BREAST-FEEDING AS A MECHANISM FOR VERTICAL TRANSMISSION OF HEPATITIS B

A follow-up study of 147 babies born to mothers known to be carriers of hepatitis B surface antigen (HBsAg) revealed no evidence for a relationship between breast-feeding and the subsequent development of antigenaemia in the babies. All babies were tested at three or more months of age, and the mean age at last follow-up was eleven months with a mean of three serum specimens per baby (not counting cord-blood specimens). The frequency of acquisition of HBsAg and anti-HBs was almost identical among breast-fed and non breast-fed infants. The frequency of other variables known to influence the development of antigenaemia among infants of carrier mothers did not vary according to breast-feeding status: mothers HBsAg titre, HBsAg positivity rate in cord-blood specimens, and HBsAg prevalence among siblings. 32 breast-milk specimens from carrier mothers were all HBsAg negative.

HEPATITIS B IMMUNE GLOBULIN (HBIG) EFFICACY IN THE INTERRUPTION OF PERINATAL TRANSMISSION OF HEPATITIS B VIRUS CARRIER STATE: Initial Report of a Randomised Double-Blind Placebo-Controlled Trial

Abstract A randomised double-blind placebo-controlled efficacy trial of hepatitis B immune globulin (HBIG) for prevention of the vertically transmitted HBsAg carrier state was conducted in Taiwan where the carrier rate in the general population is 15-20%. HBIG was given immediately after birth to infants of e antigen positive HBsAg carrier mothers and all infants were followed for 15 months or more. Among 35 placebo-treated infants the carrier rate was 91%. This compares with the carrier rate of only 23% among 40 infants who received 0·5 ml HBIG at birth, three months, and six months and the 45% carrier rate among 42 infants receiving a single 10 ml dose of HBIG at birth only. Efficacy was 75% and 45% respectively for the two treatment schedules. Significantly, the most common response of HBIG-treated infants was passive-active immunisation.

Prognostic histologic features of resected small hepatocellular carcinoma (HCC) in Taiwan: a comparison with resected large HCC

The morphologic features and their prognostic significance were analyzed in 83 surgically resected hepatocellular carcinomas (HCC): 44 of them were of ⩽5 cm in diameter and 39 were larger. This study demonstrated a high prevalence of tumor capsule in both small and large HCCs, 86.4% and 84.6%, respectively. In small HCC, the capsule formation was significantly higher in the liver with cirrhosis (96.9%, or 31/32) than without (58.3%, or 7/12) (P < 0.003). In both small and large HCCs, the most important histologic parameter influencing the tumor recurrence was the liver invasion. In the small but not in the large HCC, the invasion through the capsule also correlated well with recurrence (P < 0.05). None of the 19 patients whose HCC were confined by a tumor capsule and did not invade the liver, had a recurrence during the 10 months or longer follow‐up period. The significantly more favorable outcome of smaller HCC was related to the lower frequencies of liver invasion (P < 0.001), portal vein involvement (P < 0.01), and satellite formation (P < 0.01). Tumor recurrence did not correlate with the tumor grading, presence of clear cells, liver cell dysplasia, or host inflammatory response. The HBsAg positivity in tumor cells was significantly higher in small (40.9%, or 18/44) than in large HCC (10.3%, or 4/39), suggestive of a gradual loss of the cytoplasmic expression of HBsAg in the tumor cells during the growth of HCC.

Hepatitis B Vaccination in High-Risk Infants: 10-Year Follow-Up

The long-term efficacy of hepatitis B vaccination among high-risk infants was determined in 805 vaccine responders, immunized at birth in Taiwan during 1981-1984 and followed to age 10 years, via life table survival and Cox multivariate analyses. At 10 years, cumulative persistence of antibody to hepatitis B surface antigen (anti-HBs) was 85%, and cumulative incidence of hepatitis B virus (HBV) infection was 15%. Three children became carriers. Twelve-month anti-HBs titer was the strongest predictor of efficacy. The higher the initial titer, the lower the risk of anti-HBs loss (relative risk [RR], 0.26 for titer of 100-999 mIU/mL; RR, 0.08 for titer >1000 mIU/mL; P<.001) and HBV infection (RR, 0.55 and 0.27; P<.05). Maternal hepatitis B e antigen positivity but not hepatitis B immunoglobulin dose or gender predicted greater antibody persistence to age 10 years. Because the level of antibody persistence remained high and few became carriers, booster revaccination within 10 years seems unnecessary.

Colorectal cancer in Egyptian patients under 40 years of age

Although colorectal cancer is not a common cancer in Egypt, the age distribution of the disease shows that a high proportion occurs in children and adults under 40 years of age. We reviewed the records of 1,608 colorectal cancer patients treated in 4 cancer hospitals in Egypt during a period of 3 to 10 years. The hospitals in which about 85% of all colorectal cancer cases in Egypt were seen included Egypts 2 major cancer centers, The National Cancer Institute (NCI) in Cairo and Tanta Cancer Center (TCC) in the mid‐Nile Delta region, and 2 major university hospitals, Assiut University in South Egypt and Ain Shams University in Cairo. Our review showed that patients younger than 40 years represented 35.6% of all patients in the 4 cancer hospitals, and that these rates were similar among the hospitals and for the years reviewed. The male‐to‐female ratio increased from 1.0 to 1.7 for the age groups ranging from 0–9 and 30–39 years, and increased from 1.0 to 1.5 for the age groups ranging from 40–49 to over 60 years. More than half of all patients had rectal tumors, and about 90% of the cancers were adenocarcinomas; 30.6% of patients younger than 40 years, compared with 13.8% of older patients, had mucin‐producing tumors. This study confirmed the occurrence of a high colorectal cancer rate in young Egyptians, and it opens the door to future epidemiologic studies to identify causes and risk factors of this disease pattern in Egypt. Int. J. Cancer, 71:26–30, 1997.

The role of hepatitis C in hepatocellular carcinoma: a case control study among Egyptian patients.

Background Egypt has one of the highest prevalence rates of hepatitis C virus (HCV) infection in the world; however, the risk and attribution related to HCV in Egyptian patients with hepatocellular carcinoma (HCC) remains unknown. Goals The current study was undertaken to estimate the risk of HCC in relation to HCV in Egypt. Study Thirty-three patients with HCC and 35 healthy controls who had a similar socioeconomic status were prospectively enrolled at the University of Cairo National Cancer Institute. Results Anti-HCV antibodies were present in 75.8% of the patients and in 42.9% of the controls (p = 0.01); hepatitis B surface antigen (HBsAg) was present in 15.2% of the patients and in 2.9% of the controls (p = 0.03). In addition, the sex-and age-adjusted odds ratio (OR) for anti-HCV antibodies was 5.1 (95% CI = 1.5–17.4) and for HBsAg was 13.2 (95% CI = 1.2–148.2). Concurrent Schistosoma mansoni and anti-HCV was associated with an OR of 10.3 (95% CI = 1.3–79.8), which was higher than that for anti-HCV (6.5; 95% CI = 1.6–26.6) and S. mansoni infection (0.2; 95% CI = 0.1–6.2) alone. Finally, we estimated the attributable fraction of HCC to HCV to be 64% in this study population and 48% in the general Egyptian population. Conclusions Both HCV and hepatitis B virus infection increase the risk of HCC in Egyptian patients, whereas isolated Schistosoma infection does not. Because of the very high prevalence rate of HCV in the general Egyptian population, it accounts for most HCC cases in Egypt.

Rocks Along the Road to the Control of HBV and HCC

Hepatitis B vaccine is one of the best human vaccines ever developed; it is safe, cheap, and highly immunogenic, stimulates long lasting protective efficacy, and is the first human cancer vaccine. Remarkably, HBV vaccine works even when administered to newborns, timing which is necessary because of mother to infant transmission. Countrywide HBV immunization programs were initiated in Taiwan and Thailand in the 1980s. HBV vaccine has been part of the WHO global immunization since 199x and with at-birth immunization programs in xxx countries resulting in major declines in acute sequelae of HBV infection. Of far greater significance, HBV vaccination prevents hepatocellular carcinoma (HCC) and its use is reducing mother to infant transmission, the driving force behind the HBV carrier state worldwide. These benefits are just being realized since decades elapse between perinatal transmission at birth and the onset of HCC decades later. Studies in Taiwan and Thailand are showing declines in HCC incidence as a result of country wide at-birth HBV immunization programs initiated in the 1980s. Many investigators from many countries have contributed to the understanding of HBV and its role as the major cause of HCC. This article briefly summarizes the work of my University of Washington laboratory in Taipei, Taiwan where I lived and worked from 1972 and 1986 because of the very high HBV carrier rates of HBV in Taiwan. During those 14 years we discovered vertical transmission, its timing and mechanism, and the predictive value of HBeAg. We went on to establish the efficacy of HBIG for prevention of vertical transmission. In later studies we established the efficacy and timing of HBV vaccine and HBIG and HBV vaccine in combination for optimum preventive efficacy. Of greatest significance, our studies showed that chronic HBV infection is the commonest cause of HCC. Worldwide, mothers are the driving force behind the infections that lead to HCC because the HBV carrier state is inversely proportional to the age of the infant when infected. We were able persuade WHO to adopt HBV as the 7th immunogen in the EPI, its global infant immunization program. In some ways enormous progress has been made but measured against its potential, progress in most countries, including the United States has been far too slow.

FAMILIAL AGGREGATION OF COLORECTAL CANCER IN EGYPT

We have investigated the familial aggregation of colorectal cancer and hereditary nonpolyposis colorectal cancer (HNPCC) in Egypt because of the high incidence of colorectal cancer in Egyptian children and young adults and the prevalence of consanguinity there. In a pilot study, we conducted detailed interviews with 111 Egyptian colorectal cancer patients and 111 healthy Egyptian controls about their family histories of colorectal cancer, and other cancers, consanguinity, age at diagnosis, symptoms and recurrence. Eight patients (7.2%) had one or more first‐ or second‐degree relatives under age 40 with colorectal cancer, suggestive of HNPCC by the Amsterdam criteria. One of these families had a typical history of HNPCC, with 4 relatives having colorectal cancer in 3 generations; 3 of these relatives were younger than age 45 at colon cancer diagnosis, and other relatives had extracolonic tumors. Another 14 patients (12.6%) had a first‐ or second‐degree relative with a family history of other neoplasms such as endometrial, urinary and hepatobiliary cancers that could also be related to HNPCC. Four patients with early‐onset colon cancer and a family history of other HNPCC‐related cancers reported that their parents were first‐degree cousins. Int. J. Cancer 77:811–816, 1998.© 1998 Wiley‐Liss, Inc.