OBJECTIVE:To estimate the cost for the management of chronic hepatitis C (CHC) and related morbidities by using a payer perspective in Thailand.METHODS:Data elements were extracted from medical records of 542 patients newly diagnosed with CHC in five tertiary care hospitals across Thailand. All patients were divided into five health states: noncirrhotic CHC, hepatitis C virus (HCV)-related compensated cirrhosis, HCV-related decompensated cirrhosis, HCV-related hepatocellular carcinoma, and HCV-related liver transplantation. Resource utilization data for each patient during a 12-month follow-up study period were compiled, and reference prices published by the Thai government were used to estimate the cost for each health state. The average cost was calculated and categorized into various groups, for example, laboratory and diagnostic tests, procedures, medication, and hospitalization.RESULTS:The average number of outpatient visits per patient was approximately six visits in all cohorts. The HCV-related hepatocellular carcinoma and liver transplantation cohorts had a higher average number of inpatient admissions per patient. The average number of days per admission varied from fewer than 3 days to 1 week or more across all the health states. The average annual total cost per patient varied across all health states from approximately 170,000 to 600,000 baht, and medication cost was the largest portion in every cohort, except the HCV-related liver transplantation cohort in year 1. Among all medications, the average annual antiviral medication cost per patient was the largest portion in the noncirrhotic CHC and HCV-related compensated cirrhosis cohorts.CONCLUSIONS:CHC was a costly disease in Thailand. The average annual medication cost was the largest portion in every health state, except HCV-related liver transplantation.

Summary Background : There is a high prevalence of peptic ulcer in cirrhotic patients, but the pathogenesis of peptic ulcer in cirrhosis remains inconclusive. Aim : To investigate factors associated with peptic ulcer and to evaluate peptic ulcer prevalence in asymptomatic cirrhotic patients. Methods : A total of 130 cirrhotics were recruited into the study for endoscopic screening. Data were collected and biochemical tests were done. Doppler ultrasound was used to assess the portal vein velocity and size. Patients underwent endoscopy for the presence of varices and peptic ulcer. Helicobacter pylori infection was confirmed by urease test, histology and 14 C‐urea breath test. Statistical analysis was performed. Results : Peptic ulcer was detected in 50 (39%) cases. Between peptic ulcer and non‐peptic ulcer groups, there were no significant differences in age, sex, alcoholic drinking, smoking, non‐steroidal anti‐inflammatory drug use, portal vein velocity and size, except for H. pylori infection ( P = 0.006), serum albumin ( P =0.02) and Child‐Pugh score ( P = 0.03). By multivariate analysis, H. pylori infection (OR: 3.26; 95% CI: 1.49–7.13; P = 0.003), Child‐Pugh classes B (OR: 2.48; 95% CI: 1.04–5.91; P = 0.04) and C (OR: 3.26; 95% CI: 1.2–8.81; P = 0.02) were independently associated with peptic ulcer. Conclusion : H. pylori infection and advanced cirrhosis are important factors associated with active peptic ulcer.

A number of studies have suggested that the clinical course of hepatitis A virus (HAV) infection is more severe in patients with chronic liver disease (CLD). A study was undertaken to determine the impact of acute HAV in asymptomatic hepatitis B surface antigen (HBsAg) carriers (n = 20) and patients with hepatitis B virus (HBV)‐(n = 8) or hepatitis C virus (HCV)‐related (n = 4) CLD. Disease progression was compared with that in 100 patients with isolated HAV infection. No patient with HAV infection alone developed complications, and all recovered fully. Fulminant or submassive hepatitis occurred in 55% of HBsAg carriers and 33% of patients with HBV‐ or HCV‐related CLD. The mortality rate in HBsAg carriers (25%) was not significantly different from that in the patients with CLD (33%). The seroprevalence of anti‐HAV immunoglobulin G in 820 individuals was also determined. Approximately 50% of the individuals had acquired HAV infection between the ages of 21 and 30 years. It was demonstrated that HAV infection may have a more severe clinical course in patients with underlying CLD, particularly among older individuals. Vaccination for such patients should be considered.

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.

The impact of acute super-infection with hepatitis A virus (HAV) was determined in 20 asymptomatic carriers of the surface antigen (HBsAg) of hepatitis B virus (HBV), eight patients with HBV-related chronic liver disease (CLD), and four patients with CLD related to hepatitis C virus (HCV). For comparison, 100 patients with isolated HAV infection were also studied. The HBsAg carriers and patients with CLD related to HBV or HCV were significantly older than the patients with isolated HAV infection, with mean (S.D.) ages of 43.9 (14.1), 46.4 (16.0), 52.5 (8.6) and 28.4 (10.7) years, respectively (P < or = 0.02). There were no significant between-group differences in the baseline serum concentrations of alanine aminotransferase. All the patients with isolated HAV infection fully recovered. Fulminant or submassive hepatitis occurred in 11 (55%) of the HBsAg carriers and four (33%) of the 12 patients with CLD related to either HBV or HCV. Nine of the 15 patients with severe hepatitis died and the mortality rate among the HBsAg carriers was not significantly different from that among the CLD patients (25% v. 33%; P = 0.15). These fatal cases were all aged > 50 years and were significantly older [59.0 (2.1) years] than the six severe cases who recovered [43.2 (10.7) years] as well as the remaining 17 uncomplicated cases with CLD or HBsAg [40.3 (13.0) years] (P < or = 0.001). The results indicate that acute HAV is rarely fatal in young adults but may be severe and potentially fatal in patients with underlying chronic HBV or HCV infection, especially among the elderly. Vaccination against HAV should be considered for the patients at high risk who are negative for anti-HAV.

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.

Typhoid fever is often associated with abnormal liver biochemical tests, but severe hepatic involvement with a clinical feature of acute hepatitis is a rare complication. There have been more than 150 cases of salmonella hepatitis reported from both developed and developing countries. The documented incidence varies widely from less than 1% to 26% of patients with enteric fever. The possible associated factors for development of salmonella hepatitis are virulence of the organisms, delayed treatment and poor general health of the patients. The pathogenesis of severe hepatic involvement in salmonella infection may be multifactorial and includes endotoxin, local inflammatory and/or host immune reactions. Clinical jaundice in salmonella hepatitis usually occurs within the first 2 weeks of the febrile illness. Hepatomegaly and moderate elevation of transaminase levels are common findings. Extreme hepatic dysfunction with hepatic encephalopathy is a rare coexisting complication in salmonella hepatitis. A positive culture for salmonella from blood or stool is essential to differentiate salmonella hepatitis from other causes of acute hepatitis. Hepatic pathology is characterized by the presence of typhoid nodules with marked hyperplasia of reticuloendothelial cells. The prognosis is usually good as salmonella hepatitis responds well to a specific antibiotic therapy and jaundice resolves with clinical improvement. The clinical course can be severe with a mortality rate as high as 20%, particularly with delayed treatment or in patients with other complications of salmonella infection. As enteric fever is a common infection, the recognition of salmonella hepatitis is of clinical importance.

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.

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.

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.

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.

This study was conducted to determine and compare serum trace metal levels in viral hepatitis-associated chronic liver disease. Of 98 patients aged 43 (± 13) [mean (± SD)] years, 83 (85%) were seropositive for hepatitis B surface antigen (HBsAg) and 15 (15%) were seropositive for anti-hepatitis C virus (HCV). Twenty-five patients had chronic persistent hepatitis, 32 chronic active hepatitis, 21 post-necrotic cirrhosis, and 20 hepatocellular carcinoma. Determination of fasting serum trace metal levels (zinc, copper, calcium, magnesium, and phosphorus) was performed after the patients had been on a 2-day diet containing 10–12 mg zinc/day. Compared to healthy volunteers (n=30), serum zinc levels were significantly decreased in patients with chronic active hepatitis, cirrhosis, and hepatocellular carcinoma (P≤0.0001), and copper levels were significantly elevated only in patients with hepatocellular carcinoma (P<0.0001). The overall serum levels of calcium, magnesium, and phosphorus were within normal ranges, and levels of calcium and magnesium correlated with serum zinc (P=0.01–0.03). Serum zinc levels correlated with bilirubin, albumin, and cholesterol (P=0.0004≤0.0001), but not with daily urinary zinc excretion. Serum copper levels correlated with alkaline phosphatase and gamma-glutamyltransferase (P=0.008–0.0001). These results suggested that changes in liver cell pathology compounded by functional impairment may alter the metabolism of trace metals, in particular, zinc and copper. The possible relationship of these changes to the pathogenesis of chronic liver disease is discussed.

The mechanisms involved in the activation of the coagulation cascade in severe falciparum malaria were studied in 22 adult patients (19 male, three female) aged 18-45 (mean +/-SD 31 +/- 11) years. Of these, nine had multiple vital organ dysfunction, and bleeding occurred in four patients, two of whom died. During acute illness the reduction in plasma antithrombin III (AT III) concentrations and elevation in thrombin-AT III complexes were associated with significant reductions in factor XII and prekallikrein activities, and an increase in the C1 inhibitor antigen/activity ratio. Serial plasminogen activity remained within the normal range in all patients while protein C activity was significantly reduced. All patients had markedly elevated plasma polymorphonuclear leucocyte elastase (PMN-elastase) levels with mild depletion of alpha-2 macroglobulin but normal concentrations of alpha-1 antitrypsin. There was no correlation between PMN-elastase concentrations and any of the coagulation parameters or concentrations of proteinase inhibitors. These results suggest that the intrinsic pathway of the clotting cascade is activated in severe malaria. This may cause activation of the complement system and release of bradykinin and PMN-elastase and could contribute to the pathogenesis of severe malaria.

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.

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.

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.

Sixty-one patients with falciparum malaria were studied prospectively to determine the plasma concentrations of the lysosomal proteinase, polymorphonuclear leucocyte elastase (PMN-elastase) and their relationship to disease severity. The patients were divided into 3 groups; severe (parasitaemia >5%) or vital organ dysfunction (n=23), moderate (parasitaemia 1%-5% without complications) (n=15), and mild (parasitaemia <1%)(n=23). The mean plasma PMN-elastase level in 10 healthy Thai volunteers was 49.5 (SD=21.6) ng/ml (range 33-65 ng/ml). Plasma PMN-elastase concentrations on admission were elevated (>2xSD above normal) in all patients with severe malaria and were above 100 ng/ml in 86.6% and 65% of the moderately severe and mild patients respectively. PMN-elastase levels during the first 3 hospital days were significantly higher in severe malaria compared with the other 2 groups (P=<0.001-0.013). The levels decreased as the patients became afebrile and aparasitaemic. Admission plasma concentrations of PMN-elastase correlated directly with bilirubin (r(s)=0.50, P<0.001), serum glutamic oxalacetic transaminase (r(s)=0.54, P0.001), parasite count (r(s)=0.62, P<0.001), blood urea nitrogen (r(s)=0.54, P<0.001) and inversely with antithrombin III activity (r(s)=0.54, P<0.001) and the platelet count (r(s)=0.58, P<0.001). Polymorphonuclear leucocyte activation may contribute to the pathogenesis of severe malaria.

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.

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.

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)