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The purpose of this study was to investigate the relationship between perforated appendicitis and patient with diabetes using a population-based data set.This study used data from the Longitudinal Health Insurance Database 2005 in Taiwan. We identified 4,806 patients hospitalized with acute appendicitis. The independent variable was whether a patient had ever received a diagnosis of diabetes before the index hospitalization. We performed a conditional logistic regression model to explore the odds ratio and its corresponding 95% confidence interval of perforated appendicitis.Rates of perforated appendicitis for patients with and those without diabetes were 46.2% and 28.3%, respectively. A chi-square test revealed that there was a significant difference in rates of perforated appendicitis between patients with and those without diabetes (P.001). The conditional logistic regression model revealed that the adjusted odds ratio of perforated appendicitis for patients with diabetes was 1.35 (95% confidence interval = 1.11 to 1.65) compared with patients without diabetes.Our study demonstrated that a history of diabetes is an important factor with regard to the rate of perforated appendicitis.

This study demonstrates an association between sialolithiasis and nephrolithiasis. The results call for more awareness of this association among physicians and patients with nephrolithiasis.Very few empirical studies have been conducted to explore the potential association between sialolithiasis and nephrolithiasis. As such, the association between sialolithiasis and nephrolithiasis still remains unclear. This study aimed to explore the possible association between sialolithiasis and nephrolithiasis using a population-based dataset.Using data from the Taiwan Longitudinal Health Insurance Database 2005, this case-control study identified 966 patients with sialolithiasis as cases and 2898 sex- and age-matched subjects without sialolithiasis as controls. Conditional logistic regressions were conducted to examine the association of sialolithiasis with previously diagnosed nephrolithiasis.Out of 3864 sampled patients, 165 (4.27%) had prior nephrolithiasis. Using Chi-square test, it was found that there was a significant difference in the prevalence of prior nephrolithiasis between the cases and controls (10.25% vs 2.28%, p0.001). Moreover, by conditional logistic regression analysis, the odds ratio of prior nephrolithiasis for cases was 4.74 (95% CI = 3.41-6.58, p0.001) when compared to controls after adjusting for monthly income, geographic location, urbanization level of residence, diabetes, hypertension, heart failure, chronic renal disease, and tobacco use.

Objective: To determine whether hepatitis C virus (HCV) infection is a risk factor for developing Parkinson disease (PD). Methods: This nationwide population-based cohort study was based on data obtained from a dataset of the Taiwan National Health Insurance Research Database for the period 2000 to 2010. A total of 49,967 patients with viral hepatitis were included for analysis. Furthermore, 199,868 people without viral hepatitis were included for comparisons. Patients with viral hepatitis were further grouped into 3 cohorts: hepatitis B virus (HBV) infection, HCV infection, and HBV-HCV coinfection. In each cohort, we calculated the incidence of developing PD. A Cox proportional hazards model was applied to estimate the risk of developing PD in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The crude HRs for developing PD was 0.66 (95% CI = 0.55–0.80) for HBV infection, 2.50 (95% CI = 2.07–3.02) for HCV infection, and 1.28 (95% CI = 0.88–1.85) for HBV-HCV coinfection. The association between HCV and PD remained statistically significant after adjustments for age, sex, and comorbidities (adjusted HR = 1.29, 95% CI = 1.06–1.56). Conclusions: We conducted a large nationwide population-based study and found that patients with HCV exhibit a significantly increased risk of developing PD.

ObjectiveGastro-oesophageal reflux disease (GORD) is a common comorbidity among patients with rheumatoid arthritis (RA). While GORD has been attributed to the antirheumatic medications, no studies of human cohorts have investigated a link between GORD and RA. This study investigates whether GORD is associated with a subsequent RA diagnosis over a 5-year follow-up using a population-based dataset.SettingTaiwanParticipantsWe used data from the Taiwan Longitudinal Health Insurance Database. The study group consisted of 13 645 patients with an ambulatory claim showing a GORD diagnosis. We used propensity score matching to select 13 645 comparison patients (one per study patient with GORD).InterventionWe tracked each patient’s claims over a 5-year period to identify those who subsequently received a diagnosis of RA. Cox proportional hazard (PH) regression modelling was used for analysis.ResultsOver 5-year follow-up, RA incidence rate per 1000 person-years was 2.81 among patients with GORD and 0.84 among the comparison group. Cox PH modelling showed that GORD was independently associated with a 2.84-fold increased risk of RA (95% CI 2.09 to 3.85) over 5-year follow-up, after adjusting for the number of ambulatory care visits within the year following the index date (to mitigate surveillance bias).ConclusionsWe observed that GORD might associate with subsequent RA occurrence. Because current treatment guidelines for RA emphasise early diagnosis and prompt treatment, the observed association between GORD and RA may help acquaint clinicians to patients with GORD with higher RA risk and facilitate early diagnosis and treatment.

AIM: To investigate variations in the incidence of peptic ulcers (PUs) in Taiwan by day of the week within age subgroups. METHODS: Ambulatory care data were retrieved from the Longitudinal Health Insurance Database 2000. There were 7204 subjects ≥ 18 years-old with an emergency room admission claim for the treatment of PUs, resulting in a total of 9234 emergency room visits for PUs between 2009 and 2011. Data was divided into the seven days of the week and an additional variable for holidays. One-way analysis of variance was used to examine associations among the daily mean number of PU emergency room admissions and holidays/weekends/weekdays. RESULTS: One-way analysis of variance showed that there was a significant difference in emergency room admissions for PUs by the day of the week (P < 0.001), with admission more likely to occur on Sundays or holidays than weekdays within the total and working populations. The weekday patterns of admission were similar for the patients aged 18-64 years and ≥ 65 years of age. Holidays, followed by Sundays, had higher PU admissions than the mean daily PU emergency room admissions. Furthermore, inclusion of only those treated for PUs with hemorrhage or perforation, Sundays and holidays had higher mean emergency room admissions than other days. Inclusion of patients who diagnosed with Helicobacter pylori infection, only holidays had higher mean emergency room admissions than other days. Inclusion of patients who had been prescribed non-steroidal anti-inflammatory drugs (NSAIDs) for over 30 d, Sundays and holidays had higher mean PU ER admissions than other non-holiday weekdays. CONCLUSION: There is a higher incidence of emergency room admission for PUs on weekends than on weekdays for the total and working populations.

SummaryObjective Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with significant clinical diversity. However, the aetiology, pathogenesis and optimal treatment of UC remain unclear. The purpose of this case-control study was to investigate the association between previously diagnosed hyperthyroidism and UC using a large population-based data set in Taiwan. Methods The data for this population-based case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 2709 patients with UC as cases and 8127 sex- and age-matched patients without UC as controls. A conditional logistic regression analysis was conducted to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between UC and prior hyperthyroidism. Results We found that, in total, 327 of the 10 836 sampled patients (3.02%) had previously been diagnosed with hyperthyroidism. There was a higher proportion of prior hyperthyroidism among cases than controls (4.10% vs 2.66%, P

This retrospective cohort study examined the relationship between a cholecystectomy and the subsequent risk of peptic ulcers using a population-based database. Data for this study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. This study included 5209 patients who had undergone a cholecystectomy for gallstones and 15,627 sex- and age-matched comparison patients. We individually tracked each patient for a 5-year period to identify those who subsequently received a diagnosis of peptic ulcers. We found that of the 20,836 sampled patients, 2033 patients (9.76%) received a diagnosis of peptic ulcers during the 5-year follow-up period: 674 from the study group (12.94% of the patients who underwent a cholecystectomy) and 1359 from the comparison group (8.70% of the comparison patients). The stratified Cox proportional hazard regressions showed that the adjusted hazard ratio (HR) for peptic ulcers during the 5-year follow-up period was 1.48 (95% CI = 1.34~1.64) for patients who underwent a cholecystectomy than comparison patients. Furthermore, the adjusted HRs of gastric ulcers and duodenal ulcers during the 5-year follow-up period were 1.70 and 1.71, respectively, for patients who underwent a cholecystectomy compared to comparison patients. This study demonstrated a relationship between a cholecystectomy and a subsequent diagnosis of peptic ulcers.

Background This retrospective cohort study examined whether diabetic patients have a higher risk for recurrent appendicitis during a 1-year follow-up period after successful antibiotic treatment for patients with acute uncomplicated appendicitis than nondiabetic patients using a population-based database. Methods We included 541 appendicitis patients who received antibiotic treatment for acute appendicitis. We individually tracked each patient for a 1-year period to identify those who subsequently underwent an appendectomy during the follow–up period. Results Cox proportional hazard regressions suggested that the adjusted hazard ratio of an appendectomy during the 1-year follow-up period was 1.75 for appendicitis patients with diabetes than appendicitis patients without diabetes. We found that among females, the adjusted hazard ratio of an appendectomy was 2.18 for acute appendicitis patients with diabetes than their counterparts without diabetes. However, we failed to observe this relationship in males. Conclusions We demonstrated a relationship between diabetes and a subsequent appendectomy in females who underwent antibiotic treatment for noncomplicated appendicitis.

Appendicitis and gastroesophageal reflux disease (GERD) are both prevalent diseases and might share similar pathological mechanisms. The aim of this study was to investigate the association between GERD and appendicitis using a large population-based dataset. This study used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 7113 patients with appendicitis as cases, and 28452 matched patients without appendicitis as controls. This study revealed that GERD was found in 359 (5.05%) cases and 728 (2.56%) controls (p

Despite some studies having indicated a possible association between appendicitis and duodenal ulcers, this association was mainly based on regional samples or limited clinician experiences and as such, did not permit unequivocal conclusions. In this case-control study, we examined the association of acute appendicitis with peptic ulcers using a population-based database. We included 3574 patients with acute appendicitis as cases and 3574 sex- and age-matched controls. A Chi-squared test showed that there was a significant difference in the prevalences of prior peptic ulcers between cases and controls (21.7% vs. 16.8%, p p pared to controls. The results further revealed that younger groups demonstrated higher ORs for prior peptic ulcers among cases than controls. In particular, the adjusted OR for cases p

To evaluate whether the tumour suppressor gene, PPP2R1B, is involved in pathogenesis of hepatocellular carcinoma (HCC), reverse transcription-polymerase chain reaction (RT-PCR) and cDNA sequencing were performed. Eleven of 38 (29%) tumours and 1 of 34 (3%) corresponding non-tumour tissues showed coexpression of wild-type and aberrant mRNA. Various deletions were found in aberrant transcripts. Southern blot analysis did not show gene deletion in tumours, suggesting abnormal RNA splicing may be involved. These data suggest the possibility that aberrant transcripts of PPP2R1B might be associated with the development of HCC.

Background This study aimed to compare clinical outcome between laparoscopic and open right hemicolectomy. Methods The data were sourced from Taiwan’s National Health Insurance Research Database. This study included 14,320 and 1313 patients who underwent open and laparoscopic right hemicolectomies, respectively. The study outcome included “intensive care unit (ICU) admission,” “over 2 h of general anesthesia,” “use of mechanical ventilation,” “acute respiratory failure,” “in-hospital death,” and “hospitalization for pneumonia.” Separate conditional logistic regressions were performed for each clinical outcome. Results The results showed that patients who underwent an open right hemicolectomy had significantly higher likelihood of ICU admission (31.4 vs. 13.4 %, p

Background Prior studies indicate a possible association between depression and cholecystectomy, but no study has compared the risk of post-operative depressive disorders (DD) after cholecystectomy. This retrospective follow-up study aimed to examine the relationship between cholecystectomy and the risk of DD in patients with gallstones in a population-based database. Methods Using ambulatory care data from the Longitudinal Health Insurance Database 2000, 6755 patients who received a first-time principal diagnosis of gallstones at the emergency room (ER) were identified. Among them, 1197 underwent cholecystectomy. Each patient was then individually followed-up for two years to identify those who were later diagnosed with DD. Cox proportional hazards regressions were performed to estimate the risk of developing DD between patients with gallstone who did and those who did not undergo cholecystectomy. Results Of 6755 patients with gallstones, 173 (2.56%) were diagnosed with DD during the two-year follow-up. Among patients who did and those who did not undergo cholecystectomy, 3.51% and 2.36% later developed depressive disorder, respectively. After adjusting for the patient’s sex, age and geographic location, the hazard ratio (HR) of DD within two years of gallstone diagnosis was 1.43 (95% CI, 1.02–2.04) for patients who underwent cholecystectomy compared to those who did not. Females, but not males, had a higher the adjusted HR of DD (1.61; 95% CI, 1.08–2.41) for patients who underwent cholecystectomy compared to those who did not. Conclusions There is an association between cholecystectomy and subsequent risk of DD among females, but not in males.

Background Physicians are considered to be the most informed consumers in the use of medical services since they have more information about diseases or medical technology. However, although plenty of researchers have suggested that different medical seeking behavior exists among physicians, very few empirical studies have been conducted to investigate differences in medical utilization between physicians and the general population. Objective We explored differences in the utilization of healthcare services between physicians and the general population using a population-based dataset. Design A cross-sectional study. Participants Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included 1426 physicians and 1426 sex- and age-matched comparison subjects. Methods We used Wilcoxon-Mann-Whitney tests to explore differences in variables of healthcare resource utilization between physicians and comparison subjects. We further used Kruskal-Wallis tests to examine differences in variables of healthcare resource utilization between physician practice location and comparison subjects. Results We found that physicians had significantly fewer outpatient visits (13.2 vs. 15.7, p

Background Altered immune function after appendicectomy has been associated with autoimmune disease, even though the mechanisms are not clearly elucidated. This study aimed to investigate whether the frequency of new-onset type II diabetes was increased after appendicectomy in a case–control study. Methods This was a retrospective cohort study from the Taiwan Longitudinal Health Insurance Database 2000. The relative risk was compared with that in the general population using population-based data. Each patient was tracked for a 3-year interval to identify those who developed type II diabetes. Cox proportional hazard regression analysis was used to assess the risk of type II diabetes during follow-up. Results A total of 31 512 patients were included in the study, of whom 5252 had an appendicectomy (study cohort) and 26 260 were matched for comparison. Some 714 patients (2·3 per cent) developed type II diabetes during the 3-year follow-up, 161 in the study cohort (3·1 per cent) and 553 in the comparison cohort (2·1 per cent). The adjusted hazard ratio (HR) for type II diabetes in the study cohort was 1·45 (95 per cent c.i. 1·22 to 1·74). This increased risk was most pronounced in men (adjusted HR 1·47, 1·16 to 1·88) and in those with a perforated appendix (adjusted HR 2·28, 1·71 to 3·03), and applied only to patients younger than 65 years of age. Conclusion An increased risk of new-onset type II diabetes within 3 years after appendicectomy was found in patients aged less than 65 years. The risk was highest in men and in those with complicated appendicitis.

Many studies have reported a possible association of an appendectomy with rheumatoid arthritis (RA). However, findings of the relationship between an appendectomy and RA remain inconsistent. Furthermore, all such studies were conducted in Western societies, and relevant studies on the relationship between an appendectomy and RA in Asian countries are still lacking. In this study, we investigated the relationship between an appendectomy and the subsequent risk of RA using a population-based dataset. We retrieved data for this retrospective cohort study from the Taiwan “Longitudinal Health Insurance Database 2005”. We included 4,294 subjects who underwent an appendectomy in the study cohort and 12,882 matched subjects in the comparison cohort. We individually tracked each subject for a 5-year period from their index date to identify those who developed RA. A stratified Cox proportional hazard regression was performed to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI) for the subsequent development of RA during the 5-year follow-up period between subjects who underwent an appendectomy and comparison subjects. Of the sampled subjects, 93 (0.54%) received a diagnosis of RA during the 5-year follow-up period: 33 from the study cohort (0.77% of subjects who underwent an appendectomy) and 60 from the comparison cohort (0.47% of comparison subjects) (p

Aims The study was designed to survey the change of adiponectin levels before and after interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis B and C infections. Methods Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-alpha for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-alpha therapy. Insulin suppression test was conducted before and within 1 week after IFN-alpha therapy. Results The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-alpha treatment (-4.8+/-2.2 vs. 0.5+/-1.0 microg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-alpha (P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9+/-3.2 vs. 10.8+/-3.0 microg/ml, P=0.02, n=4) and HBV responders (17.7+/-4.1 vs. 9.2+/-1.0 microg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6+/-1.8-11.7+/-1.2 mmol/l, P=0.03), but not in non-responders (12.3+/-1.1-11.0+/-1.0 mmol/l, P=0.20), after IFN-alpha therapy. Conclusions IFN-alpha resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-alpha treatment, contributes to the lowering of adiponectin levels needs to be further investigated.

BackgroundPsoriasis is a prevalent autoimmune disorder. Various studies have reported on the relationship between psoriasis and chronic diseases but very few have explored the association between psoriasis and subsequent acute infection. This retrospective cohort study aimed to compare the risk of pneumonia between subjects with and those without psoriasis.MethodsThe medical records of 14,022 patients with psoriasis and 14,022 without psoriasis were obtained from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was followed-up for a three-year period. Cox proportional hazard regressions were performed to compare difference of subsequent pneumonia incidence between subjects with and those without psoriasis.ResultsThere were 206 (1.47%) subjects with psoriasis and 138 (0.98%) without psoriasis hospitalized for pneumonia. By Cox proportional hazard regressions analysis, the HR (hazard ratio) of pneumonia requiring hospitalization for patients with psoriasis was 1.50 (95% confidence interval [CI]: 1.21-1.86) compared to patients without psoriasis. The adjusted HR was 1.40 (95% CI: 1.12-1.73). The adjusted HR of pneumonia hospitalization for subjects with mild and severe psoriasis was 1.36 (95% CI: 1.09-1.70) and 1.68 (95% CI: 1.12-2.52), respectively, compared to those without psoriasis.ConclusionsPatients with psoriasis have significantly higher incidence of pneumonia compared to those without psoriasis.

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths in Taiwan. HCC with duodenal involvement are rare and are associated with a poor prognosis. The purpose of this retrospective study was to collect clinical information and data regarding survival following various treatments.Between 1996 and 2009, 21 cases (17 men) were diagnosed with HCC and duodenal invasion and metastases by diagnostic imaging, endoscopy with biopsy, or surgically collected specimens sent to pathology. The clinical course was analyzed from the patients' medical records.Gastrointestinal bleeding was reported in 18/21 patients. Diagnostic imaging showed that the majority of cases involved direct tumor invasion (predominantly from the right liver lobe) and six cases from metastasis. Tumor mass and ulcerations were the most common features noted on endoscopy. In addition to the component therapy and medication treatment, panendoscopic hemostasis, surgery, transcatheter arterial embolization, and radiotherapy were performed for the management of duodenal involvement and gastrointestinal bleeding. Survival duration after duodenal involvement ranged from 0.2 to 57.8 months (mean 10.5 months).Gastrointestinal bleeding in advanced HCC should raise suspicions of duodenal involvement. HCC can involve the duodenum by direct invasion (from either the left or right liver lobes) or metastasis. The prognosis for HCC patients with duodenal involvement is poor, but is improved by supportive care and application of various treatment modalities.

Liver progenitors, so-called oval cells, proliferate remarkably from periportal areas after severe liver injury when hepatocyte regeneration is compromised. These cells invade far into the liver parenchyma. Molecular mechanisms underlying these behaviors of oval cells remain poorly understood. In this study, we treated rats with 2-acetylaminofluorene/carbon tetrachloride to induce hepatic oval cells. By expression microarray analysis, we investigated global gene expression profiles in liver tissue, with an emphasis on adhesion molecules, extracellular matrix proteins, matrix metalloproteinases (MMPs), growth factors/cytokines, and receptors that might contribute to the distinct behaviors of oval cells. Genes upregulated at least twofold were selected. We then performed immunostaining to verify the microarray results and identified expression of MMP-7 and CD44 in oval cells. Staining of cytokeratin (CK)-19, an oval-cell marker, was similar between oval cells located next to periportal areas and those located far within the parenchyma. In contrast, CD44 staining was more intense in the parenchyma than in periportal areas, suggesting a role of CD44 in oval-cell invasion. Moreover, newly differentiated CK-19+ hepatocytes within foci did not show CD44 staining, suggesting that CD44 is related to the undifferentiated oval-cell phenotype. We then investigated oval-cell reactivity in CD44-deficient mice fed an oval cell-inducing diet of 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Results showed significantly reduced oval-cell reactivity in CD44-deficient mice. Thus, oval cells express MMP-7 and CD44, and CD44 appears to play critical roles in the proliferation, invasion, and differentiation of hepatic oval cells in rodents.

The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown.Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to receive lamivudine (100 mg per day) or placebo for a maximum of five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive placebo. The primary end point was time to disease progression, defined by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or death related to liver disease. An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data.We randomly assigned 651 patients (98 percent Asian and 85 percent male) to receive lamivudine or placebo. The study was terminated after a median duration of treatment of 32.4 months (range, 0 to 42) owing to a significant difference between treatment groups in the number of end points reached. End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo (hazard ratio for disease progression, 0.45; P=0.001). The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo (hazard ratio, 0.45; P=0.02), whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group (hazard ratio, 0.49; P=0.047). Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine, and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine (7 percent vs.1 percent). Overall, 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events.Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.

Serial serum samples from 35 patients with posttransfusion non-A, non-B hepatitis in a prospective study were tested for antibody to hepatitis C virus (HCV) by a multiple recombinant antigen based immunoassay [anti-HCV (2nd); Abbott], Of them, 23 were positive for anti-C100, and 27 were positive for HCV RNA by polymerase chain reaction. By anti-HCV (2nd), 28 patients were positive, and all except 1 of the 28 patients were positive for HCV RNA. A total of 24 patients, who became HCV RNA positive at the acute stage and who were negative for both anti-C100 and anti-HCV (2nd) before transfusion, were considered to have posttransfusion hepatitis C. The mean time to seroconversion for anti-HCV (2nd) was 7.5 or 12.1 weeks after the onset of hepatitis or the date of transfusion, respectively, and was generally 6 weeks earlier than that detected by anti-C100. However, seroconversion was delayed in 2 hepatitis B surface antigen carriers as compared with anti-C100. The anti-C100 assay detected 20 (83%) and the anti-HCV (2nd) all 24 patients with documented posttransfusion hepatitis C. The second-generation test is, therefore, better than conventional anti-C100 for the early diagnosis of HCV infection.

Cellular and nuclear DNA content was measured by flow cytometry and the fraction of binucleated cells by fluorescence microscopy in normal adult human livers, hepatocellular carcinomas, cirrhotic livers surrounding tumors, and in some benign liver conditions. In five normal livers about one-half of the hepatocytes were polyploid; the majority of these were binucleated tetraploids containing two diploid nuclei. Thus, polyploidization in human liver does not progress as far as, for example, in the rat, where 80%-90% of adult hepatocytes are polyploid, mostly with tetraploid or octoploid nuclei. In five human euploid hepatocellular carcinomas and one investigated case of focal nodular hyperplasia, the percentage of polyploid cells was significantly reduced. Four other carcinomas exhibited a prominent aneuploid (hypotetraploid) peak in addition to the diploid peak. An abnormally low fraction of binucleated cells was also indicated in these tumors. Liver tissue surrounding the tumors had a ploidy distribution similar to that of normal liver. The results suggest that, like in several models of experimental hepatocarcinogenesis, human hepatocellular tumor growth is associated with a decreased polyploidization tendency and a corresponding increase in diploid, divisional growth, which may give the tumors a growth advantage relative to the surrounding liver.

The growth rate of 31 asymptomatic hepatocellular carcinomas (diameter less than or equal to 5 cm) discovered in 28 patients by a prospective screening program was determined by real-time ultrasonography over 36-860 days. Except for one tumor that shrank on follow-up, the doubling time ranged from 29 to 398 days, with a median of 117 days, an arithmetic mean of 136 days, and a geometric mean of 110 days. In 17 tumors with more than two measurements, the growth rate remained exponential in nine, declined in growth in seven, and showed an initial lag period in one. Doubling time correlated with initial tumor diameter but was independent of the patient's age, sex, hepatitis B surface antigen status, tumor location, liver function tests, stage of liver cirrhosis, histologic type, or grade of malignancy. Although initial alpha-fetoprotein levels did not correlate well with growth rate, in 14 patients with an exponential increase of serum alpha-fetoprotein, the alpha-fetoprotein doubling time was closely related to the tumor doubling time. Based on the above data, the median detectable subclinical period of hepatocellular carcinoma was deduced to be 3.2 yr, and the suitable screening interval for its early detection in our area was 4-5 mo.