Coinfections with hepatitis g and/or c virus in hepatitis B-related chronic liver disease.

Concurrent infections with HGV and/or HCV (HGV/HCV) were investigated in 196 patients with HBV-related chronic liver disease (115 chronic hepatitis, 31 liver cirrhosis, 50 hepatocellular carcinoma), and in 100 HBsAg carriers. Coinfections were detected in 18 (9.2%) patients with HGV (10) or HCV (5) or both agents (3), but in none of the HBsAg carriers. Patients with coinfection were more frequently exposed to blood transfusions (55.6% vs 5.6%) and also were more commonly anti-HBe positive. Serum levels of HBV-DNA were lower in patients with HCV coinfection than in those coinfected with HGV. Interferon was administered to 39 patients with chronic active hepatitis including 7 patients with HGV/HCV coinfection. Sustained clearance of HBV-DNA was observed in 10 (25.6%) patients who were solely infected with HBV. These patients were significantly younger and had much lower histological scores than non-responders. Patients with HCV coinfection had significantly higher pre-treatment histological scores than those without HCV. After interferon treatment, a significant reduction in histological scores was observed in all patients except those coinfected with HGV/HCV. None of the 7 patients with coinfection had sustained clearance of HBV-DNA or HCV-RNA, and only one had cleared HGV-RNA. These results suggest that parenteral exposure is a risk factor for HGV/HCV coinfection in chronic HBV infection. HGV infection shows no significant impact on chronic HBV infection. HCV coinfection appears to inhibit HBV replication, but causes more severe chronic hepatitis and increases resistance to interferon therapy.

Susceptibility to hepatitis A virus infection among chronic liver disease patients and healthy blood donors in Thailand.

Due to improvements in socio-economic and sanitation conditions, Thailand has undergone a change from hyperendemicity to intermediate endemicity for hepatitis A virus infection, leaving a large part of the adult population without immunity. At the same time, the country is still highly endemic for hepatitis B and especially in the northeast, hepatitis C virus infection both of which when acquired during infancy or early childhood exhibit a strong tendency to turn towards chronic liver disease, although in particular with hepatitis B virus the asymptomatic carrier state is also rather common. As no cross-immunity exists between any of these viruses, double or triple infections do occur, a situation where previously acquired immunity to HAV becomes crucial as double infections have been shown to take a more severe or even fatal course. In the present study, we investigated 820 HBV- and/or HCV-related chronic liver disease (CLD) patients and 195 blood donors, both groups divided by 10-year age intervals, for the prevalence of anti-HAV. The results showed the same age dependence of immunity for all groups tested as can be expected for an area of intermediate endemicity, in that approximately 50% of those between 21 and 30 years of age had acquired anti-HAV. These findings indicate the immune response to HAV infection not to be altered by chronic infection with either HBV or HCV. Hence, vaccination against HAV should be considered, particularly in anti-HAV-negative patients with CLD.

Genotypes and subtypes of hepatitis B virus in Thailand.

Hepatitis B virus exhibits considerable variability evident in its various antigenic subtypes, which complicates the characterization of epidemiological factors, particularly in areas endemic for hepatitis B. Our group investigated the genotypes and subtypes prevalent in Thailand employing nested PCR and sequencing of the a determinant, as well as the sub-determinants located on the S gene. The sera examined originated from a mixed range of HBV-infected individuals. The results were mostly consistent with those reported for Southeast Asia in that genotype C (54.4%) dominates over genotypes A (22.1%) and B1 (23.5%). Regarding the subtypes, we have exclusively found adw2 (45.6%) and adr (54.4%) as expected for this area, with one case of subtype adw representing the exception. While genotype and/or subtype of HBV do not predispose to clinical disease, they nevertheless may account for those few cases reported in which a mutation, particularly within the a determinant of the S gene, causes evasion of routine detection by commercial kits, particularly as long as the respective individuals remain asymptomatic carriers solely expressing anti-HBc.

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.

Fever, skin rash, jaundice and lymphadenopathy after trichloroethylene exposure: a case report.

Trichloroethylene, a chlorinated hydrocarbon has been reported to cause many adverse health effects. This paper describes a female patient presenting with rather unusual manifestation secondary to trichloroethylene (TCE) exposure, i.e. hepatitis and generalized dermatitis. The diagnosis was confirmed by positive skin patch testing with 50 per cent TCE solution. After withdrawal from the exposure site, her symptoms improved and liver function test returned to baseline level after a three-months period of follow-up. TCE induced immunologic reaction has been postulated as the pathological process of this illness.

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.

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.

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.

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.

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)

Hepatitis B problem in Thailand.

HBV infection is hyperendemic in Thailand. Approximately 5 million Thais are chronic HBV carriers. The prevalence of HBV markers in general population varies from 40-60%. Approximately 10-20% of children between the ages 1-5 years have serologic evidence of HBV infection and this prevalence increases with age reaching a plateau of 40-60% by age 20. High risk groups are household contacts of HBsAg carriers and babies born to HBsAg positive mothers. Approximately 75% of the babies born to HBsAg & HBeAg positive mothers become HBsAg positive at 3 months after birth. A few studies showed that the HBV prevalence of hospital personnel and other high risk groups is similar to that of the general population. The prevalence of chronic HBsAg carrier varies from 5-10% and is highest among age groups 10-30 years. Primary hepatocellular carcinoma (PHC) is the first and third most common cancer among Thai males and females, respectively. Approximately 35%-75% of PHC in adults are HBsAg positive. Histological studies showed that 47.3% of cryptogenic cirrhosis, 58%-66% of PHC and 35%-85% of cryptogenic cirrhosis with PHC were HBsAg positive. Studies on Hepatitis B immune globulin and Hepatitis B vaccine revealed a 70% and 56%, respectively, reduction in the HBsAg prevalence of infants born to HBsAg and HBeAg positive mothers. More epidemiologic, clinical and laboratory studies on HBV infection are being carried out by groups of scientists and investigators in the Ministry of Public Health and many medical schools. A national committee has been appointed to plan strategy for controlling HBV.