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

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

Lactose intolerance and intestinal villi morphology in Thai people.

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

Problems and prevention of viral hepatitis in Thailand.

To this day, viral hepatitis remains a major public health problem in Thailand. Chronic infection with hepatitis B and C viruses are the leading causes of chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). Outbreaks of hepatitis A virus continue to occur in Thailand, even after several years of consistently declining prevalence rates. Also, the reduction in prevalence of hepatitis D virus infection has been observed among intravenous drug users over the past decade. Hepatitis E virus constitutes a rather unusual cause of sporadic acute hepatitis in Thailand. Highly effective vaccines are currently available for prevention of hepatitis A and B, however, as yet no effective vaccine for hepatitis C is imminent. Following rapid progress in the development of molecular techniques, several new hepatitis viruses have been identified. Among these, Hepatitis G, TT and SEN viruses have recently been described but their significance as to causation of human liver disease has yet to be established. This article reviews the current epidemiology, molecular biology, and strategies aimed at prevention and control of hepatitis virus infection in Thailand emphasizing new developments and recent data obtained from our research studies.

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.

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.

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

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

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.

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.

Serodiagnosis of Helicobacter pylori infection by immunoblot assay.

We compared a noninvasive serological test using a commercial immunoblot assay (Helicoblot 2.0) to tissue-based methods [rapid urease test (CLO test), histology and culture] in eighty Thai patients undergoing upper endoscopy. A true positive test was defined as at least two of the biopsy-related tests being positive. The CLO test was the most accurate test with sensitivity and specificity as high as 100%, whereas histology and culture had sensitivity of 100% and 72.2%, respectively, and the specificity of 72.7% and 96%, respectively. The serological test had a high sensitivity (97.2%) but exhibited an unsatisfactory specificity (40.9%). We concluded that the rapid urease test using multiple gastric biopsies was the most appropriate method for diagnosing H. pylori status. The role of immunoblot assay as a serological screening test in our population remains doubtful, but it may identify patients who have been infected with certain strains of H. pylori.

Short-term effects of branched-chain amino acids on liver function tests in cirrhotic patients.

A randomized study was conducted in 29 ambulatory cirrhotic patients to determine the short-term effects of branched-chain amino acids (BCAA) on nutritional status, biochemical liver function tests and caffeine clearance. Each patient received a 4-week period of isonitrogenous and isocaloric regimens, either a standardized diet contained 40 g protein with supplementation of BCAA 150 g daily (group I) or only a standardized diet contained 80 g protein daily (group II). At the end of treatment, only group I showed significant improvements in transaminase levels as well as the caffeine clearance test compared with those of the pre-treatment levels. Nonetheless, significant improvements in nutritional parameters and additional liver function tests were not yet detected. We conclude that the short-term nutritional supplementation of BCAA is well tolerated and leads to improvement in hepatic metabolic capacity assessed by the caffeine clearance test.

Fast liver alkaline phosphatase isoenzyme in diagnosis of malignant biliary obstruction.

Fast liver alkaline phosphatase isoenzyme was measured by cellulose acetate electrophoresis in the sera obtained from 84 patients with specific hepatobiliary diseases and 10 control subjects. The mean value of this isoenzyme in patients with malignant extrahepatic obstruction was 130.58 +/- 107.08 U/L, significantly higher than that of patients with benign extrahepatic obstruction (65.63 +/- 34.14 U/L), as well as patients with intrahepatic cholestasis and infiltrative liver cancers (65.31 +/- 38.11 U/L and 48.47 +/- 36.85 U/L, respectively). Furthermore, we could not detect this isoenzyme in normal individuals. When 100 U/L was used as a cut-off value to discriminate between patients with malignant extrahepatic obstruction and the remaining hepatobiliary disorders, the sensitivity, specificity and accuracy of the test were 63 per cent, 84 per cent and 80 per cent, respectively. It is concluded that the fast liver isoenzyme could be a useful marker in diagnosis of malignant extrahepatic obstruction.

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.

Prevalence of core promotor and precore mutants of hepatitis B virus in thailand by RFLP and sequencing.

Hepatitis B virus has been known to frequently undergo mutations of its genome at various sites, mostly due to it employing a reverse transcriptase devoid of proofreading capacity in the course of its replication. The purpose of the present study has been to screen 257 HBsAg-positive chronic liver disease patients, more specifically 78 cases chosen at random out of those negative for HBeAg and 33 of the HBeAg-positive cases serving as controls for three discreet point mutations in the precore/core region of hepatitis B virus. To that end, HBV DNA extracted from sera was amplified by polymerase chain reaction (PCR) using semi-nested primers and subsequently subjected to restriction fragment length polymorphism (RFLP) analysis, 36 HBeAg-negative versus 30 HBeAg-positive sera, respectively, as well as to direct sequencing in some samples randomly selected to corroborate the RFLP results. Our results showed double mutations at positions 1762 and 1764 of the core promoter in between 25/36 (69.4%) and 19/25 (76%) of the sera tested, a missense mutation of the start codon in between 8/36 (22.2%), and 5/25 (20%) and a mutation turning codon 1896 into a stop codon in between 9/36 (25%) and 6/25 (24%) determined by RFLP and sequencing, respectively. These data indicate the double mutation at positions 1762 and 1764 to be the most prevalent among HBeAg-negative chronic hepatitis patients in Thailand whereas, in contrast to reports from other Asian countries, the mutation at nucleotide 1896 occurred in a mere 25%, while on the other hand the mutation abolishing the start of protein synthesis was observed to occur at a higher frequency than determined in several other geographical areas.

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.

Caffeine clearance study in hepatocellular carcinoma.

The purpose of this study was to evaluate hepatic metabolic capacity in cirrhotic patients with hepatocellular carcinoma (HCC). We compared plasma caffeine clearance, calculated by two point analysis, between patients with cirrhosis alone and cirrhosis complicated with HCC. These two groups were comparable with regards to age, sex, and the severity of liver disease, graded by Child-Pugh score as compensated and decompensated cases. From our result, caffeine clearance in compensated cases was clearly higher than that of decompensated cases in both groups studied, particularly in the HCC group (p = 0.001). The mean value of caffeine clearance in HCC patients correlated well with the tumor staging as classified by Okuda's criteria. There was also a reversal correlation between tumor size and the clearance tested in compensated cases of HCC (p = 0.046), but this finding was not detected in decompensated cases (p > 0.05). We conclude that the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in cirrhotic patients complicated with HCC, and may be a useful predictor for survival outcome.

Alpha-L-fucosidase as a serum marker of hepatocellular carcinoma in Thailand.

To evaluate the role of serum alpha-L-fucosidase (AFU) in the diagnosis of hepatocellular carcinoma (HCC), we simultaneously studied both AFU activity and alpha-fetoprotein (AFP) level in 60 patients with HCC, 60 patients with cirrhosis and chronic hepatitis each, 30 patients with other liver tumors and 60 healthy subjects. Serum AFU activity in patients with HCC (1,418.62 +/- 575.76 nmol/ml/hr) was significantly higher than that found in cirrhosis (831.25 +/- 261.13 nmol/ml/hr), chronic hepatitis (717.71 +/- 205.86 nmol/ ml/hr) or other tumors (706.68 +/- 197.67 nmol/ml/hr) and in controls (504.18 +/- 121.88 nmol/ml/hr, p < 0.05). With 870 nmol/ml/hr (mean value of controls plus 3 standard deviations) considered as the cut-off point, AFU was more sensitive (81.7 vs 39.1%) but less specific (70.7 vs 99.3%) than AFP at a level of > 400 ng/ml as a tumor marker of HCC. With both markers combined, the sensitivity was improved to as much as 82.6%. AFU activity in HCC patients was correlated to tumor size (r = 0.3529, p = 0.006) but not associated with tumor staging classified by Okuda's criteria (p = 0.1). The AFU activity in the viral hepatitis group (hepatitis B or C) was also significantly higher than in the non-viral group (p = 0.0005). We conclude AFU to be a useful marker, in conjunction with AFP and ultrasonography, for detecting HCC, particularly in patients with underlying viral hepatitis and cirrhosis.

Current status of infection-related gastrointestinal and hepatobiliary diseases in Thailand.

The objective of this overview is to assess the present situation with regards to gastrointestinal and hepatobiliary diseases prevailing in Thailand. In that context, special emphasis has been put on those forms of viral hepatitis prevalent in the region, namely, hepatitis A the frequency of which has undergone a change from hyper- to hypoendemic with a resulting decline in naturally acquired immunity; hepatitis B with its tendency to cause chronic liver disease mainly due to asymptomatic infections during early childhood and the impact of mass vaccination programs on its endemicity; hepatitis C which can also lead to chronicity; hepatitis D solely found as a coinfection with hepatitis B; hepatitis E acute cases of which can sporadically be found; hepatitis G encountered in healthy subjects at a prevalence similar to that seen in patients with chronic liver disease and rather more prevalent among people at risk for contracting blood borne agents; finally the novel hepatitis TT virus with a distribution comparable to that of hepatitis G virus and a similarly unclear role as to the etiology of serious liver disease. Particularly in connection with hepatitis B we have examined the situation regarding hepatocellular carcinoma which represents one of the most common malignancies among the Thai population. Cholangiocarcinoma caused by the liver fluke Opisthorchis viverrini is the most common form of liver cancer in the northeastern part of Thailand where an estimated 70% of the population are infested with the parasite. Peptic ulcer caused by Helicobacter pylori constitutes another common gastrointestinal affliction with the overall prevalence of antibodies to the agent amounting to 63 to 74% in patients exhibiting gastroduodenal symptoms. The final part of the paper deals with HIV-related gastrointestinal and liver disease and with amebic and pyogenic liver abscesses.

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 GBV-C infection in intravenous drug users.

Our group has investigated 204 intravenous drug users for the presence of GBV-C-RNA by means of reverse transcriptase polymerase chain reaction (RT-PCR). The majority of the individuals tested were male, their age ranging from 16 to 63 years, and the duration of intravenous drug use from one to 40 years. We detected GBV-C-RNA in 46 of the 204 IVDUs (22.5%) with its prevalence peaking in the age group between 21 to 30 years while decreasing with advancing age. Similarly, its frequency was found in inverted relation to the duration of drug use. The present findings strongly hint at the host's immune system's capacity to clear hepatitis GBV-C as opposed to the other blood-borne hepatitis viruses. From the liver function tests performed we could not detect any statistically significant difference regarding ALT elevation observed in GBV-C-positive as compared to GBV-C-negative individuals. To date, GBV-C in most cases does not appear to cause any serious liver disease.