Associations Among Cardio-Ankle Vascular Index, Carotid Intima-Media Thickness, and Fibroblast Growth Factor-21 Levels in Kidney Transplant Patients.

BACKGROUND: Cardiovascular disease is the major cause of death in patients with chronic kidney disease, even after renal transplantation. Cardio-ankle vascular index (CAVI) provides an indicator of arterial stiffness, whereas fibroblast growth factor-21 (FGF-21) levels may provide a biomarker for atherosclerotic disease. We investigated the association between CAVI and FGF-21 and their relationships to carotid intima-media thickness (IMT) and other cardiovascular risk factors. METHODS: This study included 90 renal transplant patients. Data on CAVI, echocardiograms, homocysteine, high-sensitivity C-reactive protein, carotid IMT, FGF-21, and incidence of cardiovascular disease were collected and correlations were analyzed statistically. RESULTS: The mean CAVI was 7.51 ± 1.69. CAVI was significantly higher in older patients (mean age, 51.54 ± 9.92 vs 42.92 ± 11.20 years, P < .001) and was positively correlated with carotid IMT (r = 0.214, P = .050) and negatively with hemoglobin (r = -0.219, P = .044). There was no association between CAVI and FGF-21 or other parameters. FGF-21 was positively correlated with high-sensitivity C-reactive protein and negatively with renal function. The mean carotid IMT score was 0.57 ± 0.18. Scores were significantly higher in patients >60 years of age, with low cholesterol and high-density lipoprotein and high body mass index. Higher body mass index (P = .013) and carotid IMT (P < .001) were associated with more frequent cardiovascular events. Mean homocysteine levels remained >15 µmol/L and did not differ in those with or those without cardiac events. CONCLUSIONS: This study demonstrates that cardiovascular risk factors remain after renal transplantation, despite normal arterial stiffness. Close cardiac monitoring and risk-factor modification are therefore recommended, even after successful renal transplantation.

Hepatitis G infection and therapeutic response to interferon in HCV-related chronic liver disease.

Circulating HGV-RNA was determined in 117 patients with HCV-related chronic liver disease and in 200 healthy blood donors. The patients, aged 50.8+/-13.8 years, were classified as chronic hepatitis (CH; n = 82), liver cirrhosis (n = 25) and hepatocellular carcinoma (HCC; n = 10). HGV-RNA was detected in 5 (4.3%) patients, all with CH and in 10 (5%) of blood donors. The majority of all groups (52% to 70%) were infected with HCV genotype II/1b, including 4/5 patients with HGV co-infection. Of 5 patients with HGV co-infection, 4 were positive for anti-HBs and anti-HBc and none exhibited jaundice. A 24-week course of interferon treatment with 12-month follow-up was achieved in 27 patients with chronic active hepatitis, including 3 with HGV co-infection. Of these, 55.6% responded to the therapy, but only 6/27 (22.2%) patients were sustained responders. The majority of sustained responders were HCV genotype III/2a (4/6) while genotype II/1b was found in the majority of patients with relapse (7/9) and non-responders (9/12). At the 48- month follow up, 2/6 sustained responders (one with HGV co-infection) became HCV RNA positive. These results show that the prevalence of HGV infection in HCV-related chronic liver disease is low, as in the general population, and is found in younger patients with chronic hepatitis. HGV coinfection does not interfere with clinical severity, disease progression or response to interferon in patients with HCV-related chronic liver disease. The favorable factors ofinterferon treatment for HCV infection are young age, low HCV-RNA levels and HCV genotype III/2a.

Herpes simplex virus type-2, cytomegalovirus and Epstein-Barr virus infection in acute non A to E hepatitis Thai patients.

A significant number of acute non A to E hepatitis cases are reported in Thailand every year, and the etiologies of these cases are unknown. Members of the herpesviridae family have been reported to cause either a self limited or fatal hepatitis in a small proportion of patients in other parts of the world. To determine whether herpesviruses may play a role in acute non A to E hepatitis, sera from 32 acute hepatitis patients without markers for acute hepatitis A to E virus infection were examined for IgM to herpesvirus type 2 (HSV-2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) using commercially available assays. IgM to HSV-2 was detected in four sera, IgM to CMV was detected in one serum, and IgM to EBV was detected in one serum. All of the acute non A to E hepatitis patients recovered and none had underlying conditions associated with impaired immunity. These results suggest that herpesviruses should be considered in the differential diagnosis for Thai patients with hepatitis.

Etiology of acute non-A, B, C hepatitis in Thai patients: preliminary study.

To better characterize the etiology of acute non-A, B, C hepatitis, 24 sera from 50 acute hepatitis without acute markers for hepatitis A, B, and C were examined for acute markers for the hepatitis E virus (HEV), cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2), and Epstein-Barr virus. Immunoglobulin M (IgM) specific for HEV, HSV-2, and CMV was detected using ELISA and total Ig specific to EBV was determined by standard indirect immunofluorescence. IgM to CMV was not observed in sera from any of the patients; whereas, IgM to HEV was detected in sera from 2 patients and IgM to HSV-2 was detected in 5 of 24 acute hepatitis patients. In addition, high titer of antibody was found in 2 of the patients. This results indicate that HSV-2 and HEV circulate in Thailand and are responsible for a small proportion of non-A, B, C hepatitis in Thailand.

Haemostatic abnormalities in patients with liver disease associated with viral hepatitis.

Clinical and laboratory findings were studied in 56 patients with liver disease (10 acute hepatitis, 10 fulminant hepatitis and 36 cirrhosis). Spontaneous bleeding occurred in 19 patients (8 fulminant hepatitis, 11 cirrhosis) and another 8 cirrhotic patients had variceal bleeding. There were 22 deaths (36%), 12 of these patients had spontaneous bleeding. Depletion of antithrombin III (AT III) occurred in fulminant hepatitis (mean +/- S.D. = 27 +/- 16%) and cirrhosis (49 +/- 23%) but thrombin-antithrombin III complexes (TAT) were significantly higher in the former (45 +/- 22 vs 8.6 +/- 7.0 ng/ml; p = 0.006). Within subgroups of cirrhosis (with or without spontaneous bleeding or with variceal bleeding), there were no significant differences in levels of AT III or TAT. Of all patients, those with spontaneous bleeding had persistently lower AT III levels but had variable changes of other coagulation parameters (PT, PTT, TT, FDP, fibrinogen and platelet counts). This study showed that coagulopathic consumption is an important cause of AT III deficiency in fulminant hepatitis but not in cirrhosis. Serial changes in AT III levels correlated with bleeding risk in patients with liver disease.

Serum trace metal levels in patients with acute hepatitis B.

This study was conducted to determine serum levels of trace metals in young adult patients in the early icteric phase of acute hepatitis B virus infection. There were 15 patients (10 males, 5 females) and 15 healthy volunteers (11 males, 4 females). The age distribution of both groups ranged from 15-40 years and were comparable [mean (SD) = 28(6) vs 31(7) years; p = 0.12]. Compared to the healthy controls, the patients had significantly decreased serum zinc but elevated serum copper levels [means (SD) of zinc = 118(22) vs 97(20) micrograms/dl, p = 0.012; and of copper = 82(15) vs 135(40) micrograms/dl, p < 0.001]. The overall serum levels of calcium, magnesium and phosphorus in the studied patients were within normal ranges. Serum zinc concentrations of these patients correlated with albumin (r = 0.69, p = 0.005) and their serum calcium correlated with alkaline phosphatase (r = 0.61, p = 0.015). These results demonstrate that alterations of zinc and copper metabolism occur early during the acute icteric phase of uncomplicated hepatitis. These changes may be of pathophysiological significance in acute hepatitis, in particular in patients with pre-existing zinc deficiency.

Hepatitis B virus strains in Thailand: genomic variants in chronic carriers.

Genetic heterogeneity of the hepatitis B virus (HBV) has been shown to influence the serological pattern and clinical picture in HBV infection. Thailand has a high transmission rate of HBV, but the molecular epidemiology of HBV strains circulating in this region was hitherto unknown. In this study, the HBV strains from 34 Thai HBsAg-positive patients were investigated. In a proportion of these samples, an antigenically important region of the S gene (n = 18), and the pre-S2 and precore genes (n = 15) were sequenced after PCR amplification. Four strains had in-frame deletions of an upstream region of the pre-S2 gene, with all deletions ending at the same nucleotide. In one of three anti-HBe positive strains without a translational stop at codon 28 of the precore gene, there was a one nucleotide insertion in the precore gene. This insertion would cause a frame shift and result in a nonsense protein being expressed, thus providing one explanation for the lack of HBeAg in this patient. Several rare or unique amino acid changes in the region between residues 120 and 161 of the S protein were found. Glycine 145 was changed to alanine in one strain, and this position showed an apparent mixture of glycine and arginine in another. In total, 10 strains displayed unexpected changes that were not related to the normal variability between subtypes or genetic subgroups. It is concluded that there is considerable heterogeneity in HBV strains in Thailand and that this could have clinical and epidemiological importance in a region with high HBV transmission rates.

Helicobacter pylori prevalence in northeastern Thailand.

Helicobacter pylori is distributed worldwide and has been demonstrated in Thailand. However, no study has been conducted so far in northeastern Thailand. The objective of this study was to find the prevalence of H. pylori in patients undergoing upper gastrointestinal endoscopy in northeastern part of Thailand. One hundred and twenty-six patients undergoing surgery between November 1992 and January 1993 were studied. Biopsies were done at antrum, corpus, and other positive lesions. Diagnostic tests of H. pylori by using CLO test, microbiological tests (Gram stain and culture), and histological examination (hematoxylin and eosin) were carried out. The prevalence of H. pylori by CLO test, Gram stain, culture, and histology were 49.2%, 61.9%, 22.2%, and 45.2% respectively. The overall prevalence of H. pylori by all diagnostic tests was 73.8% (95% confidence interval = 66.1-81.5%). This study revealed a high prevalence rate of H. pylori in patients which should alert clinicians who practice in this geographical area.

Inferior vena cava stenosis and pancreatic ascites complicating chronic calcific pancreatitis: a case report.

A 19-year-old Thai male, who was a regular drinker, presented with massive ascites, back pain and leg edema for four months. On examination there was obvious clinical evidence of an inferior vena cava obstruction. Inferior vena cavography showed narrowing of the hepatic portion of IVC with collateral circulation. Surgical dilatation of the inferior vena cava was performed. The ascites were diagnosed four months later as pancreatic ascites with a very high ascitic amylase level. Computerised axial tomography and endoscopic retrograde pancreatography showed evidence of chronic calcific pancreatitis and pseudocyst. After further medical treatment, ascites and inferior vena cava stenosis subsided which was confirmed by repeated vena cavography, computerised axial tomography and magnetic resonance imaging. The cause of inferior vena cava stenosis and clinical obstruction in this case most likely resulted from phlebitis secondary to pancreatitis. The etiology of chronic calcific pancreatitis in this case might be alcoholic abuse and/or nutritional tropical pancreatitis. Inferior vena cava stenosis and associated pancreatic ascites complicating chronic calcific pancreatitis has not been previously reported in Thailand.

Immunoproliferative small intestinal disease (IPSID) in Thailand.

Immunoproliferative small intestinal disease (IPSID) is prevalent in the Mediterranean region and in many Third World countries but is rare in Southeast Asia. Between 1980-1990, 4 cases of IPSID were admitted to Ramathibodi Hospital, Bangkok. Three were males and the mean age was 32 +/- 20.2 years. All patients presented with chronic diarrhea of 7 months to 6 years duration, and weight loss of 15 to 31 kg. All were malnourished, three cachectic, and one patient showed growth retardation. Intestinal parasites were found in all cases: two had multiple infections and three had uncommon protozoal infections (coccidium, cryptosporidium). Barium radiographs revealed intestinal mucosal fold thickening with malabsorption pattern in all cases. Alpha chain IgA was detected in one patient. The remainder underwent exploratory laparotomy and the histological finding was of plasma lymphocytic infiltration of the small intestinal mucosa. All patients responded to oral tetracycline with complete remission occurring in one case. During the follow-up period, 3 cases had progressive retractable clinical courses but all died 2 to 5 years after the diagnosis. The causes of death in these patients were secondary bacterial infection (1 case), intestinal tuberculosis (1 case), fungal infection (1 case) and immunoblastic sarcoma in another case. The results of this study confirm the occurrence of IPSID in Thailand. IPSID responds to oral antibiotic therapy and complete remission may be achieved during the early reversible benign phase, thus an awareness of its occurrence is of clinical importance.

Predisposition to reinfection by intestinal helminths after chemotherapy in south Thailand.

Rates of reinfection by the intestinal helminths hookworm, Ascaris lumbricoides and Trichuris trichiura after chemotherapy were studied in two villages in Phang-Nga Province, southern Thailand. It was found that intensity of infection levels attained after reinfection correlated positively with pretreatment intensities of infection for all parasites. This implies that certain persons in the community are predisposed to receiving high numbers of worms, due either to environmental or personal risk factors. Therefore, it would be advantageous to identify such persons and treat them preferentially. Targeted chemotherapy, however, should be combined with efforts to identify the risk factors that vary within the community and direct educational efforts or environmental intervention towards the section of the community most affected by the parasites.

Prevalence of anti-HCV antibody in family members of anti-HCV-positive patients with acute and chronic liver disease.

Presence of circulating anti-hepatitis C antibody (anti-HCV) was screened in 201 Thai patients with acute and chronic liver disease who presented to Ramathibodi and Phya Thai Hospitals during 1984-1990. Of these, 29 patients (14.4%) were positive for anti-HCV. Circulating anti-HCV was determined in 92 family members (20 spouses, 72 household contacts) of these index cases and was detected in 5 contacts (2 spouses, 2 daughters and 1 mother) of 3 index cases. The overall prevalence of anti-HCV among the contacts was 5.4% (5/92) and it was higher in sexual partners (2/20, 10.0%) compared to other household contacts (3/72, 4.2%) but this was not statistically significant (p = 0.297). The anti-HCV-positive contacts were significantly older (mean +/- SD = 61.4 +/- 14.4) than the other contacts either comparing within the same families (26 +/- 16.5; p = 0.012) or all studied families (25.1 +/- 13.3; p = 0.006). One anti-HCV-positive contact had hepatocellular carcinoma, one had unexplained elevation of serum aminotransferase and the remaining 3 had no clinical or laboratory evidence of liver disease. All of the 3 index cases with anti-HCV-positive contacts, had chronic liver disease (2 cirrhosis, 1 chronic persistent hepatitis) and the prevalence of anti-HCV in these families (8/13, 61.5%) was significantly higher than the remaining 26 families (26/108, 24.1%) (p = 0.008). The results of this study suggest that sexual and other intrafamilial personal contact may be important for HCV transmission. Duration of close contact and family relationships appear to determine this mode of HCV transmission.

Prevalence and outcomes of HBV and anti-HCV seropositive patients with chronic liver disease and hepatocellular carcinoma.

The prevalences of serological markers of hepatitis B virus (HBV) and antibody to hepatitis C virus (anti-HCV) were determined in 168 patients (135 males and 33 females), aged 19-79 years (mean = 50.8) in Thailand. Of these, 33 had chronic persistent hepatitis, 35 chronic active hepatitis, 50 cirrhosis and 50 hepatocellular carcinoma (HCC). Seromarkers for either HBV or anti-HCV or both were detected in 140 (83.3%), 3 (1.8%) and 18 (10.7%) patients, respectively, but 7 (4.2%) were sero-negative for both viruses. The overall prevalence of anti-HCV was 12.5% but was significantly lower in HCC (2%) compared to the other 3 groups of liver disease (12-21.5%, p less than or equal to 0.05) and in HBsAg positive (5%) compared to HBsAg negative (30%) patients (p less than 0.001). After 0.5-9 years follow-up of all anti-HCV positive patients, 2 died and another 6 had progressive liver disease. The prevalence of coexistent HBV seromarkers was similar in patients with a progressive (87.5%) and a stable clinical course (92.3%) (p = 0.62). A higher proportion of the anti-HCV-positive patients with a progressive course had a history of blood transfusion [75.0% vs 46.1% (p = 0.20)]. These findings suggest that HBV is the most important etiologic virus associated with chronic liver disease and HCC in Thailand, but HCV may play a role particularly in HBsAg-negative patients.

Cholangiocarcinoma masquerading as liver abscess.

A 60-year-old man from Eastern Thailand was admitted to hospital because of right upper quadrant abdominal pain and fever. Ultrasonographic examination revealed two cavitary lesions in the right lobe of the liver. Needle aspiration obtained 110 ml of anchovy sauce-like pus which showed no bacteria on gram stain and routine culture. Serological test for E. histolytica antibody was negative. Initially, the patient responded well to metronidazole. Two weeks later, the symptoms recurred and sonography revealed one large cavitary lesion with three adjacent locules in the right lobe of the liver. Repeated needle aspiration again showed anchovy sauce-like pus which grew Enterobacter agglomerans. O. viverrini ova were detected in the stool. Laparotomy revealed histologically proven cholangiocarcinoma. This report indicates that O. viverrini infection associated with CCC can masquerade as liver abscess.

Prevalence, incidence, intensity and associated morbidity of intestinal helminths in south Thailand.

Intensive surveys for Ascaris lumbricoides, Trichuris trichiura and hookworm were carried out in two villages in Phang Nga Province, southern Thailand, in order to measure prevalence, estimate incidence and determine the relation between intensity of infection and morbidity before and after chemotherapy. The study populations were a small upland village community (Nai Tone) and a grade school in a small coastal village (Boh Saen). About half of the Nai Tone villagers were given a broad spectrum antihelminthic (albendazole), and the Boh Saen students were all treated successively with three drugs: piperazine citrate to treat for Ascaris, pyrantel pamoate to treat for hookworm, and mebendazole to treat for Trichuris. Stool examinations were made using the quick Kato smear technique, questionnaires were administered concerning a variety of possible symptoms, and anthropometric and blood biochemical parameters were measured both before and after treatment. The prevalence of Ascaris was 31.0 and 22.6%, hookworm was 89.1 and 88.0% and Trichuris was 59.7 and 77.8% in the Nai Tone and Boh Saen study populations, respectively. Average intensity of Ascaris was highest in the 0-9 year age class (greater than 32,000 epg) in Nai Tone Village. Hookworm intensity of infection was higher in males than in females in all age classes, and in Nai Tone Village at least 25% of males and 20% of females had 8000 or more epg of faeces. Trichuris intensity of infection was highest between 5 and 10 years of age in both populations. The only signs or symptoms showing a significant (P less than 0.05) difference between high and low classes of intensity of infection and a significant improvement (P less than 0.01) after drug treatment, were headache and flatulance in the case of hookworm infection in Boh Saen School. The presence of multiple infections made testing of hypotheses concerning particular parasite species difficult.

Pancreatitis: an analysis of 106 patients admitted to Ramathibodi Hospital during 1969-1984.

In analysing 106 patients with pancreatitis admitted to Ramathibodi hospital from 1969 to 1984, 71 were males and 35 females. Their ages ranged from 8-83 years. Of the 106 patients, 92 were diagnosed as acute, and 14 as chronic pancreatitis; 49(46.2%), 48(45.3%), and 9(8.5%) had mild, moderately severe, and fulminant disease, respectively. Etiologically, chronic alcoholism, biliary tract stones, and unknown cause were found associated in 33.0, 24.5 and 22.6 per cent, of the total cases respectively. Relapsing pancreatitis occurred in 35 patients (33.0%), 27(77.1%) of whom were chronic alcoholic. Five (62.5%) of the 8 patients with traumatic induced pancreatitis were children. Among the more common clinical symptoms and findings: abrupt epigastric pain occurred in 76 patients (71.7%), localized abdominal tenderness in 59(55.7%), generalized abdominal tenderness in 33(31.1%), nausea and vomiting in 34(32.0%), fever of over 38 degrees C in 20 (18.8%), palpable mass in 17(16.0%), and ascites in 8(7.5%). Laboratorically, elevated serum amylase was the most useful single diagnostic test, i.e. it was elevated in 100(94.3%) of the 106 patients. Pseudocyst, pancreatic abscess, and GI hemorrhage with liver failure occurred in 10 (9.4%), 2(1.8%), and 3(2.8%) patients, respectively. Sixty-six patients were treated medically and 40 patients were subjected to surgery. Regardless of whether they were treated medically or surgically, 7 of the 9 patients with fulminating pancreatitis died, and another 2 remaining patients were taken home in moribund state.

Omeprazole or cimetidine once daily for the treatment of duodenal ulcers?

Thai patients (n = 257) entered a double-blind randomized trial to compare omeprazole, 20 mg once daily, and cimetidine, 800 mg once daily for treatment of duodenal ulcer. The healing rates observed in the omeprazole and cimetidine groups were 65% versus 45% (P less than 0.01) at 2 weeks and 97% versus 85% (P less than 0.01) at 4 weeks. At the end of 4 weeks' treatment, omeprazole achieved equal healing rates (97%) for both large (greater than 10 mm) and small ulcers, whilst cimetidine healed large ulcers at a lower rate than that observed for small ulcers (71% versus 89%). There were significantly fewer reports of daytime epigastric pain after 2 weeks of omeprazole compared with cimetidine (P less than 0.01). No major clinical side-effects or changes in laboratory variables were detected during or after treatment with either drug. In conclusion, omeprazole (20 mg) was found to be superior to cimetidine (800 mg) administered once daily for the treatment of duodenal ulcer as measured by ulcer healing and pain relief.

Histological, biochemical and clinical findings in hepatitis B carriers undergoing elective abdominal surgery.

Prospective surveillance for serum Hepatitis B surface Antigen (HBsAg) was performed in 255 patients undergoing elective abdominal surgery at Ramathibodi Hospital during 1984-1987. HBsAg was detected in 13 patients (5.0%), 11 of whom gave consent for serial evaluation of liver histology and laboratory findings. There were eight males and three females aged 20-75 years (mean = 43.4 years). Nine of the eleven patients had wedge liver biopsies taken at operation and two patients had percutaneous biopsies performed. All patients were followed up at 3-6 month intervals and after 20-36 months, follow-up liver biopsies by the percutaneous route were performed in the nine cases who gave consent. The histological findings of initial and follow-up biopsies from these patients were all abnormal, ranging from reactive hepatitis to chronic active hepatitis. During the follow-up study, none of the patients lost their HBs antigenemia and orcein staining of liver biopsies for HBsAg was positive in all ten cases tested. In the nine cases who underwent follow-up liver biopsy, progression of liver pathology was found in seven, although none of these patients showed clinical deterioration or had significant rise in HBsAg titre or SGOT/SGPT levels. The mean age of the five cases who progressed to CAH (51.2 years) was higher than that of the remaining four cases (32.5 years) who had no or minor changes in liver histology, although the difference was not significant. Of the five cases with progression to CAH, four cases were more than 40 years old. None of the conventional clinical or laboratory parameters correlated with the progression of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)