Genetic regulation of autoimmune disease: BALB/c background TGF-beta 1-deficient mice develop necroinflammatory IFN-gamma-dependent hepatitis.

Autoimmune hepatitis (AIH) in humans arises spontaneously in genetically susceptible individuals and is associated with the presence of Th1 cells in the liver. The understanding of AIH has advanced more slowly than that of other organ-specific autoimmune diseases, however, largely because of the lack of an appropriate animal model. We now describe a new mouse model characterized by spontaneous development of necroinflammatory hepatitis that is restricted by genetic background. Mice deficient in the immunomodulatory cytokine TGF-beta1 were extensively back-bred to the BALB/c background. The BALB/c background dramatically modified the phenotype of TGF-beta1(-/-) mice: specifically, BALB/c-TGF-beta1(-/-) mice developed a lethal necroinflammatory hepatitis that was not observed in TGF-beta1(-/-) mice on a different genetic background. BALB/c background TGF-beta1(-/-) livers contained large numbers of activated CD4(+) T cells that produced large quantities of IFN-gamma, but little IL-4, identifying them as Th1 cells. BALB/c background TGF-beta1(-/-)/IFN-gamma(-/-) double knockout mice, generated by cross-breeding, did not develop necroinflammatory hepatitis, demonstrating that IFN-gamma is mechanistically required for its pathogenesis. This represents the first murine model of hepatitis that develops spontaneously, is restricted by genetic background, and is dependent upon the Th1 cytokine IFN-gamma, and that thus recapitulates these important aspects of AIH.

Local radiotherapy with or without transcatheter arterial chemoembolization for patients with unresectable hepatocellular carcinoma.

PURPOSE: To evaluate the treatment outcome, patterns of failure, and prognostic factors for patients with unresectable hepatocellular carcinoma (HCC) treated with local radiotherapy alone or as an adjunct to transcatheter arterial chemoembolization (TACE). METHODS AND MATERIALS: From March 1994 to December 1997, 25 patients with unresectable HCC underwent local radiotherapy to a portion of the liver. Twenty-three patients were classified as having cirrhosis in Child-Pugh class A and 2 in class B. Mean diameter of the treated hepatic tumor was 10.3 cm. Mean dose of radiation was 46.9 +/- 5.9 Gy in a daily fraction of 1.8-2 Gy. Sixteen patients were also treated with Lipiodol and chemotherapeutic agents mixed with Ivalon or Gelfoam particles for chemoembolization, either before and/or after radiotherapy. Percutaneous ethanol injection therapy (PEIT) was given to one patient. All patients were monitored for treatment-related toxicity and for survival and patterns of failure. RESULTS: In a median follow-up period of 23 months, 11 patients were alive and 14 dead. The median survival duration from treatment was 19.2 months with a 2-year survival of 41%. Only 3 of 25 patients had local progression of the treated hepatic tumor. The recurrences were seen within the liver or extrahepatic. The 2-year local, regional, and extrahepatic progression-free survival rates were 78%, 46%, and 39%, respectively. The local control ranked the highest. Patients with Okuda Stage I disease had significantly longer survival than those with Stage II and III (p = 0.02). Patients with T4 disease (p = 0.02) or treated with radiotherapy alone (p = 0.003) had significantly shorter survival. T4 disease (p = 0.03) and pretreatment alpha-fetoprotein level of more than 200 ng/ml (p = 0. 03) were associated with significantly worse regional progression-free survival. A significant difference was observed in both regional progression-free survival (p = 0.0001) and extrahepatic progression-free survival (p = 0.005) between patients with and without portal vein thrombosis before treatment. The presence of satellite nodules had a significantly worse impact on regional progression-free survival (p = 0.04) and extrahepatic progression-free survival (p = 0.03). Patients with hepatic tumor more than 6 cm in diameter or portal vein thrombosis tended to have shorter survival. Radiation-induced liver disease (RILD) and gastrointestinal bleeding were the most common treatment-related toxicities. CONCLUSION: Radiotherapy is effective in the treatment of patients with unresectable HCC. Its effect appeared to be more prominent within the site to which radiation was given. The combination of TACE and radiation was associated with better control of HCC than radiation given alone, probably due to the selection of patients with favorable prognosis for the combined treatment. A dose-volume model should be established in the next phase of research in the treatment of unresectable HCC.

A pilot study of three-dimensional conformal radiotherapy in unresectable hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to determine the potential role of three-dimensional (3-D) conformal radiotherapy (RT) in treatment of unresectable hepatocellular carcinoma (HCC). METHODS: Thirteen patients were included in this study, which was conducted between 1993 and 1996. Nine patients (group A) were treated with 3-D conformal RT alone because of main portal vein thrombosis, inferior vena cava thrombosis, obstructive jaundice and failure of previous transcatheter arterial chemoembolization (TACE) to control the disease. The remaining four patients (group B) were treated with a combination of TACE and 3-D conformal RT. RESULTS: The greatest dimension of the main tumour in the whole group of patients ranged from 6 to 25 cm (median 15 cm). The radiation dose ranged from 40 to 60 Gy. The tumour response was evaluated by computed tomography scans of the liver 6-8 weeks after completion of radiotherapy. Partial response was observed in 58% of the patients (seven of 12) and minimal response in another 25% of patients (three of 12). One patient could not be evaluated because of the development of hepatic failure 1 month after completion of RT. All patients in group B lived for more than 1 year (range 16-40 months). In group A, one patient who had a large tumour (11 x 10 x 21 cm) with portal vein thrombosis was converted to become resectable after 45 Gy of radiation. The resection specimen revealed no residual cancer cells. This patient is alive longer than 15 months after treatment without the evidence of disease. CONCLUSIONS: Our experience indicates that HCC is more radiosensitive than it was traditionally expected. Three-dimensional reconstruction of tumour and surrounding organs helps to avoid excessive exposure of the liver and adjacent organs to RT and makes it a safer treatment modality for unresectable HCC. Our preliminary data show promise and are worthy of further study to explore the potential role of radiotherapy in the treatment strategy for HCC at various stages of involvement.

Preoperative concurrent chemotherapy and radiotherapy in rectal cancer patients.

The management of rectal cancer has changed significantly in recent years. The key end-point is no longer survival but rather preservation of sphincter function with improved quality of life. Preoperative radiation can not only render a low-lying rectal tumor amenable to sphincter-preserving surgery but has also been reported to give better local control and lower toxicity than postoperative radiotherapy. From October 1991 through July 1996, 46 patients with local advanced or low-lying rectal cancer were treated with preoperative high-dose radiotherapy and concurrent chemotherapy. All patients underwent pelvic radiotherapy with 5,000 to 5,400 cGy in 25 to 27 fractions. Chemotherapy was given concomitantly and consisted of two courses of 5-fluorouracil (5-FU) at 1,000 mg/m2 for 4 days in week 1 and week 5 plus mitomycin C 10 mg/m2 single bolus on day 1 of week 1. In 30 patients, postoperative adjuvant chemotherapy with 5-FU and levamisole weekly was also given, for a total of 12 months. The most common acute toxicity was grade 1 to 2 diarrhea and tenesmus during radiation or soon afterward. Only five of the 46 patients experienced symptomatic grade 3 acute toxicity. Forty-two patients underwent subsequent surgery 6 to 8 weeks after concurrent chemoradiotherapy. Pathologic examination disclosed complete tumor regression in eight patients and microscopic residual disease in 13 patients after preoperative chemoradiation. Of the 42 patients who completed the intended treatments, only one had local recurrence. The sphincter was preserved in 21 of the 26 patients in whom the tumor was located within 5 cm above the anal verge. Twelve of the 16 evaluable patients had good to excellent sphincter function. The 2-year overall survival rate was 93% and the disease-free survival was 81%. Our findings indicate that preoperative concurrent chemoradiotherapy not only allows low-lying rectal tumors to be resected while preserving sphincter function but also results in good local control and acceptable toxicity.

Prevention of hepatitis B and C virus infection for prevention of cirrhosis and hepatocellular carcinoma.

In Taiwan, cirrhosis and hepatocellular carcinoma (HCC) have been common in medical practice since the 1960s. In 1969, Taiwan was shown to be a hyperendemic area of hepatitis B virus (HBV) infection with a high rate of hepatitis B surface antigen (HBsAg) positivity, 19% of the population being infected before the fourth decade of life. There is evidence indicating that more than 80% of chronic hepatitis, cirrhosis and HCC are the sequelae of chronic HBV infection. In 1984, after 3 years of preparation, a programme to control cirrhosis and HCC began. All neonates born to HBsAg+ mothers were given Pasteur plasma-derived vaccine 5 micrograms i.m. at 1, 5 and 9 weeks with a booster at 12 months. In 1986, all neonates were included in this programme. In addition, beginning in 1987, all non-vaccinated preschool children were also immunized and susceptible medical personnel and people from HBsAg+ households were recommended to receive the vaccine. Using data obtained from the 7-year evaluation study on the efficacy of this vaccine and some historical data, the HBsAg positivity rate in people born in the first few years after 1986 was estimated to be 2.6%. This rate is expected to decrease to 0.2% in those born after around 1990. In July 1992, an anti-hepatitis C virus (HCV) test was included in blood donor screening tests. This was followed by a decrease in the incidence of post-transfusion hepatitis (PTH) from 13 to 2.5% and there have been no anti-HCV+ PTH cases since. However, without immunization, the prevalence of HBsAg decreased among children in Taipei in 1989. This coincided with the widespread use of disposable syringes and needles and an improvement in the sterilization of medical instruments. Therefore, it is likely that HCV infection may also decrease as a result of these practices. Through the use of immunization and improved medical procedures, chronic hepatitis, cirrhosis and HCC may decrease in Taiwan by around 95%.

Colonoscopic screening for families of patients with colorectal cancer.

We conducted a prospective study using primary colonoscopy in the families of patients with surgically treated colorectal cancer (CRC) to evaluate its feasibility as a screening method for CRC. The presumed detection sensitivity of sigmoidoscopy in this group was also evaluated. Over a 3-year period, 142 first-degree relatives (73 men and 69 women) of 117 patients with CRC participated in this colonoscopic screening study. The average age at presentation for examination was 49.1 years (range, 31-79 yr). Forty-nine patients had adenomatous polyps (AP) and four patients had cancer, yielding a frequency of 37% (53/142). Thirty-six family members were under 40 years of age, eight of whom had AP. In total, there were 111 AP and four invasive cancers; 42% (48/111) of AP and 75% (3/4) of cancers were beyond the reach of conventional flexible sigmoidoscope. Of 53 patients with AP or cancer in the large bowel, 36 had AP or cancer in the distal colon (rectosigmoid region and descending colon), 15 (42%) of whom were found to have at least one AP or cancer in the proximal colon (proximal to the descending colon). The remaining 17 patients' lesions were confined to the proximal colon, and would not have been detected with a flexible sigmoidoscope. Sigmoidoscopy in high-risk patients with neoplasm in the large bowel has a sensitivity of 68%. We conclude that a vigorous surveillance program using primary colonoscopy should be set up for those who are first-degree relatives of patients with CRC. Routine examination should start at the age of 40, and the entire colon should be evaluated.

A program for eradication of hepatitis B from Taiwan by a 10-year, four-dose vaccination program.

Approximately 15 percent of the Taiwanese population are chronic carriers of hepatitis B virus (HBV), among the highest rates in Asia. In July 1984, the Taiwanese government initiated a nationwide HBV-vaccination program. The program began with educational efforts and voluntary prenatal screening for HBsAg. Infants of HBsAg-carrier mothers received a four-dose regimen of hepatitis B vaccine. Those born to highly infectious mothers also received a dose of hepatitis-B immune globulin within 24 hours after birth. Seroepidemiologic studies were conducted using a random sample of infants. Serum samples were collected at 18, 24, 36, and 48 months and analyzed via radioimmunoassay for HBsAg, anti-HBs, and anti-HBc. Infants of highly infectious mothers had HBsAg positivity rates of 14.2 percent (vaccine plus HBIG) and 19.7 percent (vaccine only) when on schedule, and 17.0 percent when off schedule. Infants of moderately infectious mothers had an HBsAg positivity rate of 3.0 percent when on schedule and 6.4 percent when off schedule. These low positivity rates persisted throughout the 48-month follow-up period. This represents a dramatic improvement upon the 40 to 96 percent vertical transmission rate seen before the program implementation. This program demonstrates that mass immunoprophylaxis for HBV is feasible, and provides practical strategies for other Asian countries.

A clinicopathologic study of chronic non-A, non-B (type C) hepatitis in Taiwan: comparison between posttransfusion and sporadic patients.

To elucidate the clinicopathological course and the role of hepatitis C virus in posttransfusion and sporadic chronic non-A, non-B hepatitis in Taiwan, we retrospectively studied 85 histologically confirmed patients with long-term follow up. Antibodies against hepatitis C virus (anti-HCV) by a second-generation assay were positive in 81% of the patients: 88% in the posttransfusion group and 76% in the sporadic group. Clinical manifestations were generally mild, and were noted in only half of the patients. During follow up, 33% (28 of 85 patients) had episodes of acute exacerbation of chronic liver disease and 24% (20 of 85) had normalized liver tests. Patients with normalized liver tests were usually anti-HCV negative (55% vs. 8%, p < 0.001). In 34 patients who had had blood transfusions, initial liver biopsies revealed chronic active hepatitis in 41%, active cirrhosis in 6%, and inactive cirrhosis in 9%. Follow-up biopsies in eight patients in this group showed histological progression in three after an average of 40.6 months. In the 51 sporadically infected patients, initial work-up revealed chronic active hepatitis in 37%, active cirrhosis in 4%, and inactive cirrhosis in 14%. Among the nine who underwent repeated biopsies, only one (11%) had progression. Patients above age 40 displayed more severe histologic activity than those below 40 (p < 0.005). Three patients, all with cirrhosis, died of hepatocellular carcinoma 7 to 12 years after follow up. Further genotyping study of hepatitis C virus in 28 patients showed that type II virus was most predominant in Taiwan and histologic severity was similar among patients infected with different genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of T Cell Clones Specific to a Determinant of Hepatitis B Virus Core and e Antigens in Chronic Type B Hepatitis: Implication for a T Cell Mechanism of HBV Immunopathogenesis.

T cell clones specific for hepatitis B core (HBcAg) and e (HBeAg) antigens of hepatitis B virus (HBV) were generated from liver infiltrates of HBeAg-positive patients. Analyzed with a panel of overlapping synthetic peptides spanning the complete sequences of HBcAg and HBeAg, eight clones responded specifically to the e2 peptide (PAYRPPNAPIL; amino acid residues 130-140 of HBcAg and HBeAg), which was doubly restricted by class I and II molecules. A preferential usage of the T cell receptor (TCR) alpha chain variable (V(alpha)) gene was found: V(alpha)12.1 for five HLA-Cw9(3)-restricted cytotoxic T lymphocyte (CTL) clones, and V(alpha)7.1 for three other HLA-DRw52-restricted type 1 helper T cell (Th1) clones. Although heterogeneous in the usage of TCR alpha chain joining region (J(alpha)) segments, their junctional-region sequences revealed conserved hydrophilic serine residues in seven of the eight e2-specific T cell clones. Single alanine substitution of the centrally located and the only hydrophilic asparagine residue of e2 peptide abrogated T cell responsiveness. The nonstimulatory e2 analogue could competitively inhibit e2-specific responses. These results demonstrate that both CTL and Th1 clones recognizing a determinant of HBcAg and HBeAg are present in the liver of chronic hepatitis B patients. The preferential V(alpha) gene usage and the expression of conserved residues in junctional-region sequences of TCRalpha chains by viral-peptide-specific, intrahepatic T cells may provide a T cell mechanism of HBV immunopathogenesis. Copyright 1994 S. Karger AG, Basel

Double-blind comparison of omeprazole 20 mg OM and ranitidine 300 mg NOCTE in duodenal ulcer: a Taiwan multi-centre study.

Two hundred and twenty-six patients with endoscopically confirmed duodenal ulcers > or = 5 mm in diameter entered a double-blind randomized trial comparing 20 mg omeprazole administered once daily in the morning with 300 mg ranitidine administered once daily at night. The patients were assessed endoscopically and symptomatically after 2 weeks, and those whose ulcers had healed terminated the study. Patients with unhealed ulcers continued treatment for a total of 4 weeks. Omeprazole produced significantly higher healing rates than ranitidine at both 2 weeks (57 vs 28%, P < 0.0001) and 4 weeks (93 vs 80%, P = 0.006). Similarly, significantly higher 'effective healing rates' (defined on the criteria established by the Japanese Society of Digestive Endoscopy) were observed with omeprazole compared with ranitidine at 2 and 4 weeks. After 2 weeks, there were significantly fewer reports of both day-time and night-time epigastric pain by omeprazole-treated patients compared with ranitidine-treated patients (22 vs 44%, P < 0.0001 for day-time pain; 24 vs 35%, P = 0.025 for night-time pain). Both drugs were well-tolerated and no major adverse effects were recorded during either treatment. In conclusion, 20 mg omeprazole administered once daily was superior to 300 mg ranitidine administered once daily for duodenal ulcer healing and symptom relief.

Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion.

T cell proliferative responses to hepatitis B virus-encoded envelope antigen (S + preS2 + preS1), recombinant core antigen (HBcAg), and natural hepatitis B e antigen (HBeAg) were examined in 22 HBeAg-positive patients with chronic type B hepatitis and 17 healthy hepatitis B surface antigen (HBsAg) carriers. The results showed that HBeAg-positive patients had (a) higher levels of T cell responses to HBcAg/HBeAg than those of healthy HBsAg carriers (P less than 0.001 and P less than 0.01, respectively); (b) a further increase in these T cell responses during acute exacerbations (P less than 0.05 and P less than 0.05, respectively); (c) subsidence in the T cell responses to HBcAg/HBeAg after recovery from acute exacerbations and HBeAg seroconversion, whereas the responses would persist at high levels if the patients did not enter a clinical remission; and (d) low levels of T cell responses to S + preS2 + preS1 either before or after HBeAg seroconversion. The appearance of increasing T cell responses to HBcAg/HBeAg usually occurred in the early phase of acute exacerbations. These findings imply that HBcAg/HBeAg-specific T cells play an important role in the exacerbations of chronic hepatitis B and in HBeAg seroconversion. HBcAg/HBeAg-specific precursor T cell frequencies were serially studied in selected cases by limiting dilution assay. Elevation (two- to fourfold) of HBcAg/HBeAg-specific precursor T cell frequencies contributed to the increase of HBcAg/HBeAg-specific T cell proliferation during acute exacerbations.

Therapeutic effect of ursodeoxycholic acid on early-stage primary biliary cirrhosis.

Primary biliary cirrhosis is a rare chronic liver disease in Taiwan, which eventually causes mortality. As yet, no safe and effective treatment has been found. To investigate the safety and therapeutic efficacy of recently introduced ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis, an uncontrolled trial was conducted in 6 patients in the early stages (I-II) and 5 patients in the late stages (III-IV). Five patients in stage I and one patient in stage II were treated with 10-15 mg/kg/day UDCA for a mean administration period of 13 +/- 9 months. Levels of laboratory tests including serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) improved significantly within one month and were sustained at the new lower levels for the period of observation. The symptoms of one patient with pruritus were reduced after long-term therapy. No major side effects were found during the treatment period. In contrast to early-stage patients, patients with late-stage primary biliary cirrhosis who received UDCA therapy for a mean duration of 25 +/- 5 months showed no beneficial effects either clinically or biochemically. From these preliminary results, UDCA appears to be safe and effective in the treatment of early-stage primary biliary cirrhosis, although further controlled clinical trials in conjunction with histological follow-up are mandatory to evaluate the critical role of UDCA in primary biliary cirrhosis.

Hepatitis C virus infection in Taiwan.

To investigate the epidemiology of HCV in Taiwan, anti-HCV was studied by radioimmunoassay or enzyme immunoassay in patients with chronic liver disease, healthy adults, and subjects at risk. The anti-HCV prevalence was 0.95% in 420 volunteer blood donors, 90% in 100 hemophiliacs and 81% in 58 parenteral drug abusers. Anti-HCV was present in 6 (7.7%) of 78 HBsAg-positive and 28 (65%) of 43 HBsAg-negative patients with chronic hepatitis, 3 (10%) of 31 HBsAg-positive and 13 (43%) of 30 HBsAg-negative cirrhotics, and 7 (17%) of 42 HBsAg-positive and 15 (63%) of 24 HBsAg-negative patients with HCC. An outbreak of non-A, non-B hepatitis revealed 18% of 57 patients to be positive for anti-HCV. In a prospective study of PTH, 37 or 13% patients contracted hepatitis and 22 (60%) were due to HCV, and at least 17 (77%) of them became chronic. Cloning of HCV genome in a Taiwanese patient with acute posttransfusion non-A, non-B hepatitis by using reverse transcription polymerase chain reaction was performed, and partial characterization of the nucleotide sequences showed 80% and 92% homology as compared to HCV sequences from Chiron and one of the published Japanese isolates, respectively. It is concluded that HCV infection plays a relatively minor role in HBsAg-positive liver decrease in Taiwan, but is strongly associated with HBsAg-negative chronic liver disease and HCC. It is also important in PTH, and the infection is extremely common in hemophiliacs and parenteral drug abusers. The Taiwanese strain of HCV seems more similar to that from Japan, as revealed by nucleotide sequences.

Recombinant immunoblot assay for hepatitis C antibody in patients with posttransfusion non-A, non-B hepatitis.

In a prospective study of 287 patients who received blood transfusion, 26 who were found positive for hepatitis C antibody (anti-HCV) by an enzyme-linked immunosorbent assay (ELISA) were studied by a recombinant immunoblot assay (RIBA). Nineteen of the 26 patients had posttransfusion non-A, non-B (NANB) hepatitis. Sixteen (84.2%) of the 19 patients with hepatitis had positive results by RIBA, 2 had indeterminate results, and 1 was negative. By contrast, five of the 7 recipients without hepatitis were negative, 1 indeterminate, and 1 positive by RIBA. Those with negative RIBA results had significantly lower optical density (OD) readings by ELISA than those with positive RIBA tests. Therefore, patients without hepatitis or lower OD value have a higher false-positive rate in anti-HCV ELISA than did those with a high OD value or with evidence of hepatitis.

A prospective study of posttransfusion hepatitis in Taiwan.

In a follow-up study of 6 months or more of two hundred and ninety-six patients who had received blood transfusion, 37 (12.5%) developed acute posttransfusion hepatitis. Patients with posttransfusion hepatitis had significantly higher donor numbers and transfusion amounts than patients without hepatitis. Frequency was not related to the age, sex or hepatitis B carriage of recipients. There were no cases of fulminant hepatitis. Of 37 patients with hepatitis, 36 were diagnosed as non-A, non-B hepatitis and one as hepatitis B. Twenty-two (59.5%) of the 36 patients with non-A, non-B hepatitis seroconverted to hepatitis C antibody. Two of these were positive for hepatitis C antibody before transfusion and 12 were negative for hepatitis C antibody. Thirty-three of the 36 patients were followed-up for more than 6 months after the onset of hepatitis. While 13 of the 33 patients recovered, the remaining 20 (60.6%) patients still had persistent liver test abnormalities 6 months after the onset of hepatitis. Seventeen (85%) of the 20 patients who developed chronic hepatitis were hepatitis C antibody positive. In contrast, only four (30%) of the 13 patients who recovered after acute hepatitis were positive for the hepatitis C antibody. Chronicity rate was not related to the patient's sex, age, transfusion amount or donor number. Our results suggest a high frequency of posttransfusion hepatitis C in Taiwan and that the infection has a high risk of chronicity.

Early predictor of the efficacy of immunoprophylaxis against perinatal hepatitis B transmission: analysis of prophylaxis failure.

To research early predictors of the efficacy of the ongoing mass immunoprophylaxis against perinatal hepatitis B virus (HBV) transmission in Taiwan and to analyse the possible causes of immunoprophylaxis failure, 52 hepatitis Be antigen (HBeAg)-positive carrier mothers were recruited for the study. Maternal blood samples were taken at the first and third trimesters and delivery. Umbilical blood was collected and venous blood samples were taken at 4, 7, 11 and 14 months of age. Serum hepatitis B surface antigen (HBsAg) and antibody titres, HBeAg titre and HBV-DNA concentration were analysed. All the umbilical cord blood samples were negative for HBsAg. Among the 52 vaccinated infants, four were poor responders (anti-HBs less than 10 mIU ml-1 before vaccine booster). Another five infants became HBsAg-positive by 4 months of age and remained carriers. All these five carrier mothers were HBV-DNA-positive and three of them had risk factors related to maternal-fetal haemorrhage during pregnancy or delivery. The remaining 43 infants showed protective anti-HBs level (greater than 10 mIU ml-1) by 4 months of age. Three mothers out of these 43 cases also had the same haemorrhage risk factors during pregnancy or delivery, but were HBV-DNA-negative. Therefore, the anti-HBs level at 4 months is a predictor of the success of immunoprophylaxis. It may be helpful to distinguish HBV-DNA-positive carrier mothers among HBeAg-positive ones, to avoid inducing more maternal-fetal haemorrhage in such cases during pregnancy or delivery. Otherwise, additional hepatitis B immune globulin may be indicated in such cases to raise the successful prevention rate.

Seroprevalence of hepatitis B virus infection in children in Taipei, 1989: five years after a mass hepatitis B vaccination program.

A nationwide hepatitis B vaccination program was launched in Taiwan in 1984. To study the impact of this ongoing program on hepatitis B virus (HBV) infection, a follow-up seroepidemiologic study was carried out in 1989 in a Taipei district where pre-vaccination seroepidemiology had been studied. HBV markers were studied in 1134 apparently healthy children (619 boys and 515 girls) under 13 years of age between March and July 1989. The prevalence of hepatitis B surface antigen (HBsAg) in children under 5 years of age decreased from 9.3% in 1984 to approximately 2% in 1989. A significant decrease in HBsAg prevalence and hepatitis B core antibody in 5- to 8-year-old children who were not immunized against HBV showed that horizontal infection among the older children had also decreased. Thus, this program not only protected vaccinated subjects; the reduction in numbers of highly infectious young HBV carriers also contributed to a lower prevalence of hepatitis B infection and carrier rates in some older children. This study demonstrates that hepatitis B vaccination is effective in protecting the majority of children in hyperendemic areas from HBV infection and from becoming chronic carriers.

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.

The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers.

Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasma-derived vaccines. However, its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemic area. We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen (HBsAg) carrier mothers in a study of recombinant vaccine efficacy. They were randomized into 2 groups, A (54 infants) and B (56 infants), to receive 4 doses of vaccine, containing 20 or 10 micrograms of surface antigen, respectively, at 0, 1, 2 and 12 months of age. An additional 60 high risk infants were recruited later (Group C) and received three 20-micrograms doses of vaccine at 0, 1 and 6 months of age. All infants also received a dose (145 IU) of hepatitis B immunoglobulin soon after birth. Sera were collected at 0, 1, 2, 3, 6, 12 and 14 months of age to assay HBsAg and anti-HBs. At 12 months of age the HBsAg carrier rates were 7.4 and 1.8%, in Groups A and B, respectively. In Group C the HBsAg-positive rate was 3.3%. HBsAg was invariably first observed between 0 and 2 months of age. Virtually all noncarrier infants developed substantial titers of anti-HBs at 12 months of age. No serious adverse effect was observed after vaccination.