Long-term effect of interferon therapy on incidence of cirrhosis and hepatocellular carcinoma in Thai patients with chronic hepatitis B.

The aim of this study was to assess the long-term effects of interferon (IFN) therapy on the incidence of disease progression to cirrhosis and hepatocellular carcinoma (HCC) in Thai patients with chronic hepatitis B. Sixty-seven patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who received IFN therapy were retrospectively analyzed. The average duration of follow-up was 59.4+/-30.9 months (ranging from 20 to 119 months). Seventy-two untreated patients with comparable clinical data and mean duration of follow-up served as a control group. During follow-up, 24 (35.8%) treated and 7 (9.7%) untreated patients had a sustained loss of HBeAg. However, none of the treated patients or controls became negative for hepatitis B s antigen (HBsAg). Among treated patients, the response was independent of type and dose of IFN, as well as the presence of steroid priming. In addition, 1 of 24 (4.2%) sustained responders and 6 of 43 (14%) non-responders progressed to cirrhosis whereas 16 of 72 (22.2%) in the control group progressed to such sequelae. The overall incidence of new cirrhosis in sustained responders was significantly lower than in the control group (p=0.04). HCC appeared in 11 cirrhotic patients: 9 (12.5%) in the control group and 2 (4.7%) of the non-responders, whereas none of the sustained responders developed HCC. The average period to detection of HCC was 70.5+/-12.4 months for non-responders and 65.3+/-27.6 months for the control group, with no significant differences between these groups. In conclusion, our data suggest that IFN therapy might prevent the progression of cirrhosis and the development of HCC in patients with chronic hepatitis B. These beneficial effects were particularly observed in those who achieved a sustained virological response to treatment.

Lactose intolerance and intestinal villi morphology in Thai people.

OBJECTIVE: To study the relationship of lactose intolerance and intestinal villi morphology in Thai people. MATERIAL AND METHOD: Subjects for this study were patients with functional dyspepsia who had no history of milk allergy and underwent gastroduodenoscopy. Two mucosal biopsy specimens were taken from beyond the distal end of the second part of the duodenum. The specimens were carefully orientated and were graded according to the following scheme: group I: finger shaped villi; group II: mixed finger and leaf shaped villi; group III: clubbing or blunting shaped villi. All subjects were tested for lactose malabsorption by breath hydrogen analysis after consuming 50 gram lactose. Breath hydrogen concentration was analyzed in samples collected intermittently by end-expiratory technique. A rise in breath hydrogen concentration of 20 PPM over baseline was considered evidence of lactose malabsorption. RESULTS: The twenty-five subjects were twenty females (80.0%) and five males (20.0%) who ranged in age from 18 to 53 years (mean 31 +/- 8.29). Sixteen subjects belonged to the finger shaped villi group (64.0%), five to the mixed finger and leaf shaped villi, group (20.0%) and four to the clubbing or blunting shaped villi group (16.0%). Results of breath hydrogen excretion test identified the prevalence of lactose intolerance in 68 per cent of the subjects: 15/16 (93.75%) of group I; 1/5 (20.0%) of group II and 1/4 (25%) of group III respectively (P<0.001). The symptom of diarrhea after lactose loading was correlated well in patients who had positive breath hydrogen analysis. CONCLUSION: As shown in this study, the lactose intolerance is not related to intestinal villi morphology. It is implied that primary lactase deficiency is more common in Thai people than secondary lactase deficiency.

Core promoter and precore mutants of hepatitis B virus: prevalence and clinical relevance in chronic hepatitis patients.

The present study was conducted to determine prevalence and exact type, as well as nucleotide position of the precore/core mutations of hepatitis B virus found in Thai patients diagnosed with chronic hepatitis and/or cirrhosis in relation to the clinical parameters established with the respective patients. To that end, 24 HBeAg-positive and 56 HBeAg-negative individuals were selected at random from a cohort of altogether 256 chronic liver disease patients. DNA was extracted from their blood sera, amplified by polymerase chain reaction using semi-nested primers and subjected to direct sequencing. Clinically, the HBeAg-positive chronic hepatitis patients displayed significantly higher transaminase levels than those negative for HBeAg. Our results showed 2 of the 7 (28.6%) PCR-positive HBeAg-positive sera displaying double mutations in the core promoter region at position 1762/64. The nucleotide sequences obtained from the 24 PCR-positive HBeAg-negative sera revealed 18 (75%) mutations in the core promoter region (1762/64), and/or 7 (29.2%) mutations at position 1753, and/or 6 (25%) mutations of the start codon (1814), and/or 8 of (33.3%) nucleotide 1896 turning codon 28 into a stop codon and one sample (4.2%) displaying a deletion between nucleotides 1758-1772. It is suggested that the mutations observed have an impact on the DNA secondary structure in such a way that successful transcription of the HBeAg gene is rendered impossible. To what extent this mutation influences the severity of chronic liver disease remains to be elucidated.

Pseudomelanosis duodeni: association with hypertension and chronic renal failure: case report.

We present the first reported case with typical endoscopic and histological findings from Thailand. An 80-year-old man presented with chronic periumbilical abdominal pain for 3 months and melena for one week. He had had hypertension for 17 years, chronic renal failure for 4 years and gouty arthritis for 3 years. Panendoscopy was done and showed diffusely scattered small black and brown pigmentation over the stomach and duodenum. Tissue biopsies from the black pigmented lesions were taken for further microscopic and histochemical evaluation. Histological finding and special histochemical stains, Fontana stain, revealed mild chronic inflammation with accumulation of hemosiderin pigment in the lamina propria of the stomach and duodenal villi. This condition is called Pseudomelanosis duodeni. The literature of this condition was also reviewed.

Fibrolamellar hepatocellular carcinoma in a Thai man who presented with hypoglycemia: case report and review of literature.

We present a case of fibrolamellar hepatocellular carcinoma (FLHCC) in a 22 year old Thai man whose presenting symptom was hypoglycemic coma with right hemiparesis. The serum marker for hepatitis B virus (HBsAg) was positive and serum AFP was very high (over 100,000 IU/ml). The abdominal ultrasonography revealed a solitary heterogenic mass, size 5.5 x 6.5 cm in the right lobe. Chest X-ray showed multiple lung metastases. Ultrasound-guided needle liver biopsy was performed and typical histologic features of FLHCC in non-cirrhotic liver were diagnosed. The patient's comatose state and neurological deficits recovered rapidly after glucose administration. Unfortunately, the tumor mass could not be resected on account of far-advanced stage with metastases. Here, we also review of the literature concerning FLHCC in many aspects.

Serum interleukin-6 and interferon-gamma levels in patients with hepatitis B-associated chronic liver disease.

Hepatitis B virus (HBV) infection can elicit a variety of clinical sequelae ranging from acute self-limited hepatitis to hepatocellular carcinoma, which are not attributable to a direct cytopathic effect of the virus but rather to the individual host's immune response. Cytokines, low-molecular-weight proteins with a broad range of activity, have been shown to be involved in the regulation of hepatocyte functions, as well as in the pathogenesis leading to liver damage. In the present study, we investigated the correlation between serum interleukin 6 (IL-6) and interferon gamma (IFN-gamma) in altogether 75 patients chronically infected with HBV. They comprised 15 asymptomatic carriers, 15 chronic persistent hepatitis (CPH) and 15 chronic active hepatitis (CAH) patients, 15 cases of cirrhosis and 15 patients with hepatocellular carcinoma (HCC) previously diagnosed by serology and histology, respectively. IL-6 and IFN-gamma levels in their sera were determined using a commercially available kit. Our results showed various concentrations of serum IL-6 detectable in 6.7% of asymptomatic carriers, 13.3% of patients with CPH, 20% of patients with CAH, 33.3% in cirrhotic patients and 66.7% in HCC. In contrast, serum IFN-gamma was only found in 13.3% of asymptomatic carriers and CAH, but could not be detected in the other groups. Our data demonstrated a positive correlation between serum IL-6 and clinical severity of chronic HBV infection, whereas the IFN-gamma levels appeared not to be correlated. From this we conclude that among chronic hepatitis patients IFN-gamma is mostly not expressed at a level detectable by serology, whereas according to other authors it is involved in the immediate immune response triggered by acute hepatitis. IL-6 on the other hand, might rather be responsible for liver inflammation and regeneration in chronic liver disease.

Efficacy and safety of twice daily administration of cefpirome in the empiric treatment of sepsis.

Cefpirome is a fourth-generation cephalosporin with good activity against both gram-positive and gram-negative bacteria. A multicentre trial was performed to study the efficacy and safety of cefpirome 2 g twice daily in the treatment of sepsis. Sixty-three cases were recruited from 10 hospitals from April 1996 to January 1998. Fifty seven cases could be evaluated according to the protocol. The APACHE II score was used to measure severity of illness, with 46.9 per cent of patients having APACHE II score more than 10 and two patients more than 20; both were cured. The most common pathogens were gram-negative bacteria with E. coli predominating 16/40 (40.0%), followed by Klebsiella 8/40 (20.0%). The overall clinical success rates were 54 out of 57 patients (94.7%). In patients with positive blood culture, the clinical cures were achieved for 20/22 (90.9%). Cefpirome showed good efficacy and safety in the empirical treatment of suspected bacteremia or sepsis.

Non-cirrhotic portal fibrosis associated with pulmonary arteriovenous communication and pulmonary arterial hypertension.

A case of non-cirrhotic portal fibrosis associated with pulmonary arteriovenous communication and pulmonary arterial hypertension is reported. The patient was a 7-year old boy who presented with hematemesis, cyanosis, hypoxemia and orthodeoxia. His liver pathology was compatible with non-cirrhotic portal fibrosis. His pulmonary angiography showed arteriovenous shunting and pulmonary arterial hypertension (mean pulmonary artery pressure 34 mmHg). His sister also had non-cirrhotic portal fibrosis with neither hypoxemia nor orthodeoxia. This report raises the possibility of non-cirrhotic portal fibrosis having a genetic etiology.

Helicobacter pylori infection in Thai children with recurrent abdominal pain.

Sixty-five children with recurrent abdominal pain underwent gastrointestional endoscopy which showed Hp gastritis without duodenal ulcer in 16.9 per cent of cases. The prevalences of infection in recurrent abdominal pain and asymptomatic children were not different. Either urease test or histological method was appropriate for diagnosis of this infection. Triple therapy including bismuth subcitrate, amoxicillin and metronidazole improved abdominal pain symptom in 72.7 per cent without any side effect.

Empirical antibiotic therapy in febrile neutropenic patients with single-daily dose amikacin plus ceftriaxone.

Hematologic malignancies and cancer patients who become neutropenic as a result of disease or myelosuppressive cytotoxic therapy are at a high risk of developing life-threatening infections, and hence empirical antibiotic therapy is administered promptly. We investigated once daily regimen of amikacin, for dose-dependent bactericidal activity and post-antibiotic effects, plus ceftriaxone, with a long-half life to maximise time-dependent bactericidal activity. Microbiologically proven septicemia were 11 out of 49 febrile episodes (22.5%) and 10 (91%) of these were due to gram-negative bacilli, mostly Enterobacteriaceae. The overall success of the regimen was 63.3 per cent of patients, with no significant toxicity. In conclusion, our findings suggest that once-daily administration of amikacin plus ceftriaxone in the initial treatment of febrile episodes in neutropenic patients produces satisfactory results and more cost-effective compared with other antibiotic regimens requiring 3-4 doses a day.

Prolactin cell carcinoma of the pituitary.

Two patients with malignant prolactinoma are reported. The diagnosis of malignancy depends on the demonstration of invasion of brainstem and subarachnoid space and on the presence of marked cellular pleomorphism and mitotic activity. Review of the literature revealed that such malignant tumors were more common in men than in women. The most frequency intracranial sites of metastases were frontal and occipital lobes, and cerebellum. The possibility of radiation-induced carcinomatous transformation is discussed.

Effect of a selective restriction policy on antibiotic expenditure and use: an institutional model.

Strictly enforced antibiotic formulary restriction in combination with formulation of agreed guidelines for antibiotic use in common infection problems such as septicemia, febrile neutropenia, urinary tract infection, biliary sepsis, liver abscess, peritonitis, nosocomial pneumonia, soft tissue infection and purulent meningitis, generated a combined savings of 307,748.5 bahts or 13.5 per cent cost reduction over a 6 month period, and improved quality of use, appropriate 54.8 vs 67.5 per cent, statistically significance (P less than 0.002). Although this saving was offset in part by increased spending of unrestricted antibiotics, such as Penicillin and Gentamicin, an overall cost saving remained. In the months during the restrictions, no significant changes occurred regarding patients response and mortality. However, after the onset of the controls, it was revealed that antibiotics were more appropriately used afterwards. This study has shown, most importantly, that savings were achieved with no negative effect on good patient care. Moreover, the antibiotic use control was operationally successful, most house-staff and attending physicians, not only antibiotic evaluating team, have accepted the program in a very positive way. Overall, this program successfully achieved its initial goal, cost saving without compromising good medical practice. We are now continuing our program and also trying to modify so that it will be useful to all departments in the hospital.