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.

Endoscopic management of cholangiocarcinoma.

Cholangiocarcinoma constitutes the second most common primary liver cancer after hepatocellular carcinoma. It is particularly prevalent in regions where liver flukes are hyperendemic. Obstructive jaundice is the most common presentation. To evaluate patients suspected for cholangiocarcinoma, endoscopy is becoming more popular. Endoscopy can provide important information especially cholangiogram and tissue diagnosis. Recently, the role of endoscopy has not only been used for diagnosis but also for treatment. In this article, the roles of endoscopy for diagnosis, therapy, and future modality of treatment for cholangiocarcinoma are provided.

Endoscopy in HIV infected patients.

HIV is a very common infection in Thailand, affecting about one million of the population already, with 99,555 persons with full blown AIDS at the end of 1999. The first case of AIDS was reported in Thailand in 1984. Gastrointestinal involvement is very common, the commonest presentations are diarrhea, esophageal symptoms, hepatobiliary symptoms, and weight loss. When the CD4+ T cell count falls below 200, the body becomes highly susceptible to opportunistic infections and neoplasms. Almost all AIDS patients will have GI symptoms at sometime during the course of their illness. This is because the GI tract contains an abundant quantity of lymphoid tissue and is likely to function as a reservoir of HIV infection. In chronic diarrhea cases, apart from other investigations, small bowel biopsy and aspiration may help to find the cause. If oral candidiasis is present, one should keep HIV in mind and look for oral hairy leucoplakia, dysphagia and odynophagia as one-third of patients with AIDS will develop dysphagia or odynophagia in the course of their disease. Those with esophageal candidiasis will usually have oral candidiasis and odynophagia while 18 per cent of the patients will not have oral thrush. CMV esophagitis and HIV ulcer (or idiopathic oesophageal ulcer) are also common. Upper gastrointestinal endoscopy and biopsy are helpful in finding the exact cause of the oesophageal symptoms. Hepatobiliary manifestations are present with jaundice, hepatomegaly, and pain. ERCP is very helpful in diagnosing and classifying these conditions. Papillary stenosis and dominant biliary stricture can be treated by endoscopy but long term results are still poor due to late manifestation of these conditions.

Eradication rates of Helicobacter pylori between metronidazole-sensitive and metronidazole-resistant strains with metronidazole containing regimen in Thai patients with peptic ulcer disease.

The results of the in vitro metronidazole resistance on Helicobacter pylori (H. pylori) eradication have been inconclusive. Metronidazole resistance varies among different geographical locations and a previous study from Thailand reported an in vitro metronidazole resistance of H. pylori of 51 per cent. This study was designed to investigate further the effect of the in vitro metronidazole resistance on the outcome of eradication of H. pylori in the Thai population. Fifty two patients with active gastric ulcer (GU) and duodenal ulcer (DU) who had positive culture for H. pylori were studied. All of these patients had positive rapid urease test (CLO test, Delta West, Australia) using gastric biopsy specimens from the antrum and body taken at the time of initial upper endoscopy. In vitro antimicrobial susceptibility test was performed using Epsilometer test (AB Biodisk, Solna, Sweden). All patients received a one-week triple regimen consisting of omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily. Patients with GU continued with another five weeks of omeprazole 20 mg twice daily and patients with DU received another three weeks of omeprazole 20 mg twice daily. Upper endoscopy was repeated at four weeks after the end of the treatment. Three antral and two body biopsy specimens were obtained for identification of H. pylori using CLO test, histology (modified Giemsa stain) and culture. All of these tests had to be negative to confirm a successful eradication. Metronidazole-resistant (MR) strains with MIC > or = 32 mg/l were identified in 27 of the 52 patients (51.92%), whereas, metronidazole-susceptible (MS) strains were isolated from 25 patients (48.08%). Five patients were lost to follow-up and one patient had drug allergy. Successful eradication as defined by negative CLO test, histology and culture was attained in 17/23 (73.91%) patients (GU = 6, DU = 16, GU and DU = 1) with MR strains. 20 out of 23 (86.96%) patients (GU = 9, DU = 12 GU and DU = 2) who had MS strains. The difference was not statistically significant in both groups (P > 0.05). The ulcer healing was, however, highly achieved in both groups (MS = 95.65%, MR = 91.30%, P > 0.05). In vitro metronidazole resistance was high in this population group although this does not predict the outcome of eradication in patients with GU and DU.

Adenocarcinoma of the pancreas: the clinical experience of 45 histopathologically proven patients, a 6 year study.

A retrospective study of 45 cases of adenocarcinoma of the pancreas at Chulalongkorn University Hospital from 1993 to 1998 was reviewed by clinical and histopathological criteria. Male and female ratio was 25:20. The mean age of the patients was 59.5 +/- 10.0 years. The common presenting symptoms and signs were epigastric discomfort (80.0%), weight loss (60.0%) and jaundice (51.1%). Twenty four patients (53.3%) were screened for a tumor marker (CA 19-9) and 87.5 per cent of these had high level of CA 19-9 (> 37 IU/ml). Thirty five patients (77.8%) had tumors located in the head of the pancreas. Most of the cases were investigated by using radiological imaging (ultrasonography or computerized tomography of the abdomen). Thirty five histopathological data (77.8%) were made by the operation, and the rest (22.2%) were performed by a fine needle aspiration from the pancreatic mass or liver metastasis. Whipple operation and the bypass procedure were the most common surgical procedures in our studies. Twenty five patients (55.6%) had post treatment complications from all modalities consisting of gastrointestinal bleeding, respiratory failure and infection. However, the mortality rate within 30 days postoperatively was 8.11 per cent which was due to blood loss during the operation and infections. The post treatment mortality rate from all modalities was 33.3 per cent. The average duration from the diagnosis until death was 82.3 days.

Current status of gastric cancer in Thai patients.

To determine the current status in various aspects of gastric cancer in Thai patients, we retrospectively reviewed the records of 119 patients with histologically proven gastric cancer in King Chulalongkorn Memorial Hospital during the five-year period from 1994 to 1998. There were 72 males (60.5%) and 47 females (39.5%) with ages ranging from 22 to 91 years (mean age 60.2+/-15.1 years). Among these, 20 patients (16.8%) were younger than 40 years. The duration of symptoms prior to first presentation averaged 20 weeks and dyspepsia and weight loss were the most common complaints. Lesion location was lower third in 40.3 per cent, middle third in 31.9 per cent, upper third in 15.1 per cent and entire stomach in 3.4 per cent of patients. Adenocarcinoma was the most common histological finding (91.6%), followed by lymphoma and leiomyosarcoma (3.4% each). Helicobacter pylori infection was detected in 17 of 25 (68%). The TMN staging was as follows: stage II, 5.9 per cent; stage III, 9.2 per cent; and stage IV, 68.9 per cent. (the stage was unknown in 16%). The overall 1-year, 2-year and 5-year survival rates were 51.6 per cent, 17.5 per cent and 4.4 per cent, respectively. Management was surgical treatment in 58.9 per cent (total gastrectomy 14.5%, subtotal gastrectomy 33.3% and palliative bypass surgery in 11.1%). Systemic chemotherapy was the primary modality of therapy in 16.8 per cent and was adjuvant therapy in 18.5 per cent. The median survival time of resectable cases was 1.00+/-0.53 years, significantly longer than that of unresectable cases (0.11+/-0.03 years) (p=0.0025). However, the administration of chemotherapy did not improve the survival rate. It is concluded that, in Thailand, gastric cancer continues to be an important health problem and is generally associated with a poor prognosis.

Hemobilia: four case reports and review of the literature.

In this report, we present four cases of hemobilia. Hemobilia occurs when conditions produce an abnormal communication between blood vessels and bile ducts. Although iatrogenic procedures as causes of hemobilia have been reported with increasing frequency, non-iatrogenic etiologies are still quite rare. We, therefore, report 4 cases of hemobilia secondary to different etiologies found in our institution from 1996 to 1998, that are non-iatrogenic. The first patient was a case of congenital aneurysm, the second pseudoaneurysm from trauma, the third cholangiocarcinoma and the fourth hepatocellular carcinoma. The classical triad consists of melena, jaundice and abdominal pain. Direct observation of blood flowing from the Ampulla of Vater by endoscopy was the initial diagnostic procedure in all four cases. Diagnosis was confirmed by ultrasonography, computerized tomography, angiography or surgery. Transcatheter selective embolization as a noninvasive treatment for hepatic aneurysm/pseudoaneurysm is emphasized.

Multicenter study of the efficacy and safety of fexofenadine 60 mg. twice daily in 108 Thai patients with chronic idiopathic urticaria.

Fexofenadine is a non-sedating antihistamine indicated for relieving symptoms from allergic conditions with a rapid onset of action without cardiotoxic risks. Controlled studies showed that fexofenadine 180 mg daily provides significant relief of symptoms of chronic idiopathic urticaria (CIU). The purpose of this study was to demonstrate the efficacy and safety of fexofenadine 60 mg twice daily in Thai patients with CIU in a multicenter trial. Patients were assigned to receive twice daily doses of fexofenadine 60 mg for 6 weeks. Patients rated symptom severity every night, investigators rated patients' signs and symptoms at recruitment and at 1, 3 and 6 weeks. Ninety eight out of 108 patient (90.7%) completed the study. The patients reported 95 per cent improvement and, of those, 91 per cent had very favorable responses (excellent 15%, very good 42%, good 30%, fair 8%). The objective assessment by their physicians paralleled those responses. Fexofenadine provided a rapid clinical response that was significantly superior to before treatment in relieving symptoms of CIU (p < 0.001). Adverse events occurred in 20 cases (18.5%), mostly mild headache and drowsiness. Fexofenadine 60 mg twice daily provides effective relief of the symptoms of CIU with minimal adverse events.

Clinical associations and prognostic significance of serum anti-p53 antibodies in Thai patients with hepatocellular carcinoma.

Mutations of the p53 gene have been reported to be of prognostic significance in hepatocellular carcinoma (HCC). However, the clinical associations and prognostic value of anti-p53 antibodies, known to be products of the host immune response to these mutations, have been controversial. Serum anti-p53 antibodies were measured in 121 Thai patients diagnosed with HCC using a specific enzyme-linked immunosorbent assay (ELISA) kit. The clinical/pathological characteristics of the patients were compared with respect to the presence of serum anti-p53 antibodies. Cox regression analysis was performed to assess factor interaction and association with survival. Anti-p53 antibodies were detected in 13.2% (16 of 121) of our patients. There were no differences between groups with regard to age, sex, viral markers (HBsAg or anti-HCV), severity of liver disease and tumor advancement. The median survival rates for patients positive and negative for anti-p53 antibodies were 4.0 and 3.0 months, respectively (p = 0.443, by log-rank test). Multivariate analysis demonstrated that an advanced Okuda stage, lack of therapy and presence of portal vein thrombosis were independent factors related to the prognosis of the patients. Nonetheless, the presence of anti-p53 antibodies did not constitute a predictive variable associated with a poorer prognosis. Serum assay of anti-p53 antibodies, although rapid and easily performed, may not be suitable as an alternative to molecular detection of mutations in assessing tumor advancement and prognosis of patients with HCC.

Prevalence and clinical relevance of serum anti-p53 antibodies in patients with cholangiocarcinoma.

Cholangiocarcinoma (CCA) constitutes carcinoma of the bile duct found at a high prevalence in northeastern Thailand. In the present study, we examined the sera of altogether 82 Thai CCA patients for the presence of anti-p53 antibodies in order to investigate a role of the tumor suppressor gene, p53 in the carcinogenesis. Our results revealed anti-p53 antibodies in 7.3% of the cases tested, which conforms to the prevalence rate of p53 gene mutation recently reported at 5% among Thai patients. With limited number of the patients, anti-p53 antibodies were rapidly detected more frequently among patients with peripheral tumors than those with central tumors. However, further studies is required to establish significance and prognostic value of the antibodies in the context of CCA.

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.

Eradication of Helicobacter pylori with lansoprazole based triple therapy in peptic ulcer disease.

Lansoprazole 30 mg, amoxicillin 1000 mg, and tinidazole 500 mg were given twice daily to 39 peptic ulcer patients (26 duodenal and 13 gastric ulcer, mean age 52.4 +/- 15.01) who had H. pylori infection for two weeks. Additional lansoprazole 30 mg daily was given to duodenal and gastric ulcer patients for another two and six weeks respectively. Follow-up gastroduodenoscope was performed at fourth and eighth week and eighth and twelfth week for all duodenal and gastric ulcer patients, respectively. H. pylori status was evaluated by rapid urease test (CLO test) and histology at first and last endoscope. The ulcers were healed at the last endoscopy in 11 (85%) gastric ulcer patients and 24 (92%) duodenal ulcers patients. H. pylori infection was eradicated in 31 patients (79%). Mild side effects were observed in 15 per cent. In conclusion, 2 week regimen of lansoprazole, amoxicillin, and tinidazole triple therapy resulted in a relatively high healing rate of peptic ulcer (90%) and an acceptable eradication rate of H. pylori infection (79%).

A risk scoring system to predict outcome of non-variceal upper gastrointestinal bleeding in Thai patients.

The purpose of this study was to determine the predictors for poor outcome in patients with upper gastrointestinal bleeding (UGIB) by constructing a risk-scoring system based on retrospective data analysis and validating the scoring system prospectively. In the first phase of the study, 264 patients with acute non-variceal UGIB were retrospectively reviewed, and likely predictors of poor outcome, including major re-bleeding, need for emergency surgery to control bleeding and hospital death, were ranked into a risk scoring system. In the second phase, this scoring system was prospectively validated in 107 patients. The characteristics of the retrospective and the prospective groups were not significantly different. Four predictors of outcome were found to be significant, namely concurrent illnesses, the presence of at least one disease (score 1), heart rate above 110 beat/min (score 1), blood transfusion over 6 units (score 2) and the presence of visible vessels on endoscopic examination (score 1). Patients with a total score of less than 2 had good outcome whereas scores of 2 or more were associated with a poor outcome. The accuracy of the test was 82.5 per cent. The positive and negative predictive values were 46.3 per cent and 92.7 per cent respectively. The likelihood ratio was 4.5. It is concluded that the risk scoring system constructed in this study represents a good predictor of poor clinical outcome in patients presenting with non-variceal UGIB.

Treatment of psoriasis vulgaris with topical vitamin D analogue (calcipotriol): open multicenter study.

Sixty-one psoriasis patients, 46 males and 15 females (mean age: 40 years, range: 20-70 years) with baseline PASI score of 7.16 (+/- 3.66 SD) were enrolled in the study. All subjects were advised to apply calcipotriol ointment twice daily for 6 weeks. Six patients dropped out, five after 2 weeks and one after 4 weeks of treatment. PASI scores of fifty five patients were reduced to 2.16 per cent, 46.78 per cent and 55.55 per cent by 2 weeks, 4 weeks and 6 weeks respectively versus the baseline. Overall clinical assessment showed remission in 7.27 per cent marked improvement 74.54 per cent and slight improvement 18.18 per cent. Mild erythema were observed in fourteen patients (22.95%) that were mostly transient except for one patient. Serum creatinine, calcium and phosphate were normal throughout the study.

Hepatitis viruses and chronic liver disease.

We have investigated several groups of Thai patients diagnosed with chronic liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma, as well as cholangiocarcinoma, for the prevalence of infection with either one of the hepatitis viruses B, C, G and the novel hepatitis virus TT (TTV). The 168 patients tested comprised 120 men and 48 women with their median age ranging from 42.3 to 62.3 years. Screening for antibodies to HBV and HCV was performed by a commercially available serological test kit, for the presence of HBV and TTV DNA by PCR, and of HCV and HGV RNA by RT-PCR, respectively. There was a clear two-fold higher prevalence of HBV (49%) over HCV (27%) infection and a four-fold higher frequency compared to HGV (13%) and TTV (11%) infection, respectively, in those individuals with chronic hepatitis, cirrhosis, and hepatocellular carcinoma, whereas all but one patient with cholangiocarcinoma the etiology of which has been ascribed to parasitic infestation, were free of all viral markers. In Thailand chronic HBV, and to a lesser extent, chronic HCV infection represent the two most common causes of hepatitis potentially proceeding to chronic liver disease, whereas the clinical significance pertinent to HGV and TTV remains to be elucidated.

Linear IgA bullous dermatosis of childhood: a long-term study.

BACKGROUND: Linear IgA bullous dermatosis (LAD) of childhood is a rare acquired subepidermal blistering disease of young children. Most of the studies were reported from the USA and European countries. METHOD: Twelve cases of Thai patients diagnosed as LAD of childhood were analyzed concerning clinical, histopathological, immunopathological findings including treatment responses and courses compared with those of Caucasians. RESULT: The mean age of onset was 5.1 years. The areas of common involvement were the perioral region, lower abdomen, perineum, buttock, inner thighs and extremities. Histopathology in half of the cases showed features of dermatitis herpetiformis or bullous pemphigoid. All patients had positive linear IgA band at the basement membrane zone (BMZ) by direct immunofluorescence. Only one patient had positive circulating anti BMZ antibody at the titer of 1:10. Most patients responded well to dapsone. The mean duration before remission was 1.9 years. CONCLUSION: Our study in Thai patients with LAD of childhood produced data similar to previous studies carried out in the Caucasian nations.