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C Liddle

Publications and source records attributed to C Liddle.

At least 37 records · Page 2Linked to original sources
PubMed1997

Barriers to hepatitis C transmission within breathing systems: efficacy of a pleated hydrophobic filter.

It has been suggested that breathing circuits contaminated with body fluids may provide a route of nosocomial patient-to-patient transmission of the hepatitis C virus. Thus, a number of authorities have recommended the use of breathing circuit filters to minimize such risks. The present study sought to simulate a humidified breathing circuit and evaluate two different designs of breathing circuit filters to determine their efficacy in preventing passage of the hepatitis C virus. A hydrophobic pleated-membrane filter consistently prevented the passage of hepatitis C virus while a large-pore "electret" filter design was ineffective. We conclude that not all filter types are equally suited to preventing the passage of viruses and we therefore consider it essential that, if filters are intended to prevent the passage of named pathogens in a humidified breathing circuit, they should be evaluated in a similar experimental system to that described in order to prove their efficacy.

Anesthesia, Closed-Circuit↗
PubMed1996

Effects of metyrapone on expression of CYPs 2C11, 3A2, and other 3A genes in rat hepatocytes cultured on matrigel.

Hepatocytes cultured on matrigel express many liver-specific functions, but the levels and activities of the predominant male-specific rat hepatic CYPs, 3A2 and 2C11, decline rapidly in culture. Metyrapone maintains the level of total cytochrome P450 of rat hepatocytes in primary culture, but the mechanism underlying this effect has not been completely elucidated. The present study sought to determine whether metyrapone acts solely to stabilise CYP proteins in rat hepatocytes cultured on matrigel, or whether it also influences mRNA levels of the encoding genes. Metyrapone maintained the level of total cytochrome P450 in cultured hepatocytes so that values were > 200% of those found in untreated control cells 24 hr after isolation. At this time, CYP3A2-mediated testosterone 6 beta-hydroxylation was approximately 7-fold higher in hepatocytes cultured in the presence of metyrapone than in control cells, and CYP2C11-dependent testosterone 2 alpha- and 16 alpha-hydroxylation activities were between 2 and 3-fold greater. The results inferred from catalytic activities were supported by immunoquantitation of CYP3A and 2C11 proteins. The trend of increased CYP protein levels in metyrapone-treated cells continued throughout the 48-hr culture period. In control cells, CYP3A2 and 2C11 mRNA levels fell abruptly in culture to reach values at 24 hr that were < 30% of those in freshly isolated cells; addition of metyrapone failed to arrest this fall. However, treatment of cells with metyrapone considerably elevated levels of one or more CYP3A subfamily mRNA species, as detected by a riboprobe based on the cDNA for CYP3A1 ("CYP3A1-like mRNA') that were demonstrated, by another riboprobe, not to be CYP3A2 or RNCYP3AM. RT-PCR of mRNA prepared from cultured hepatocytes, followed by restriction mapping of the cloned cDNAs was used to characterise the CYP3A induced by metyrapone. This revealed that elevated levels of the CYP3A1-like mRNA were attributable to induction of RL33/cDEX mRNA; there were no CYP3A1 cDNAs isolated from these cells. These data are interpreted as indicating that metyrapone stabilises the expression of cytochrome P450 in culture by both pre- and posttranslational mechanisms. The particular mechanism employed is gene-specific, whereby even the highly homologous genes CYP3A2, RL33/cDEX and, possibly, RNCYP3AM are subject to different types of regulation in the presence of metyrapone.

Animals↗
PubMed1996

Interferon gamma down-regulates cytochrome P450 3A genes in primary cultures of well-differentiated rat hepatocytes.

Administration of interferons of both the gamma and alfa/beta classes down-regulates hepatic cytochrome P450 (CYP) genes when administered to humans or rats. In male rats, interferons decrease expression of CYP3A2 at a pretranslational level, but because interferons also release other cytokines in vivo, it is unclear whether this is a direct effect on hepatocytes. We therefore examined the effects of rat recombinant interferon gamma (IFN-gamma) on CYP3A2, other 3A genes, and 2C11 in stable primary cultures of male rat hepatocytes. Hepatocytes were cultured on matrigel in Williams' E, and messenger RNAs (mRNAs) for 3A2, 3A1-like CYPs, and 2C11 mRNA were determined by RNase protection assays. CYP3A and 2C11 proteins were immunoquantified, and their catalytic activities were estimated by testosterone hydroxylation pathways. In control cells, 3A2 mRNA decreased initially but then recovered, and stable levels (15% of freshly isolated cells) were attained between days 3 and 7. Phenobarbital increased 3A2 mRNA to 60-120% values of freshly isolated cells, and mRNA for 3A1-like CYPs were increased 20-fold. In both control and phenobarbital-treated hepatocytes, rat recombinant IFN-gamma (33 U/mL) reduced mRNA for 3A2 and 3A1-like CYPs, as well as 3A protein and testosterone 6 beta-hydroxylase activity. Interferon had no effect on CYP2C11 at mRNA or protein levels in untreated cells, although a reduction in 2C11 protein was evident in phenobarbital-treated cultures. It is concluded that interferon directly alters expression of constitutive and inducible CYP3A genes in well-differentiated male rat hepatocytes in culture, but has no effect on constitutive expression of CYP2C11.

Animals↗
PubMed1996

Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis is morphologically identical to alcoholic hepatitis and has multiple etiologic associations and an unknown pathogenesis. The present study used a rat nutritional model of hepatic steatosis with inflammation to test the hypothesis that induction of the alcohol-inducible hepatic cytochrome P450 (CYP) 2E1 is associated with production of steatohepatitis. METHODS: Rats received a diet devoid of methionine-choline. CYP2E1 protein was detected in liver sections by immunohistochemistry and in hepatic microsomal fractions by immunoblotting; CYP2E1 activity was detected by N-demethylation of N,N-dimethylnltrosamine (NDMA). CYP2E1 messenger RNA was analyzed by Northern blotting and slot blot hybridization. RESULTS: After 4 weeks of methionine-choline devoid diet, macrovesicular steatosis and an inflammatory infiltrate were prominent in hepatic acinar zone 3. CYP2E1 immunostaining was increased and had a more extensive acinar distribution corresponding to that of the steatosis. Microsomal CYP2E1 protein, NDMA activity, and hepatic CYP2E1 messenger RNA levels were all correspondingly increased. CONCLUSIONS: CYP2E1 is induced, partly at a pretranslational level, in this experimental form of steatohepatitis. The finding of biochemical and histological similarities between this nutritional model of hepatic steatosis with inflammation and alcoholic hepatitis indicates possible clues to common pathogenetic mechanisms. The relevance of this finding to human nonalcoholic steatohepatitis remains uncertain and requires further investigation of human liver specimens.

Animals↗
PubMed1996

Virus and host factors are both important determinants of response to interferon treatment among patients with chronic hepatitis C.

Virus and host factors have both been linked to the response to interferon treatment among patients with chronic hepatitis C but their relative importance and potential interactions are unclear. Hepatitis C virus genotype and level of viraemia were determined in pretreatment sera from 65 Australian patients treated with interferon-alpha 2b (IFN-alpha 2b), 3 MU tiw for 6 months. Hepatitis C viraemia was quantitated by a competitive reverse transcription-polymerase chain reaction (RT-PCR) method and genotype was determined by a line probe assay. By univariate analysis, there were positive associations between initial (short-term) responses to IFN treatment and younger age (P = 0.004), absence of cirrhosis (P = 0.01), and injecting drug use as risk factor for infection (P = 0.05) but not gender, duration of infection, or level of viraemia. Genotype appeared to be important (P = 0.06) but failed to reach statistical significance. By multivariate analysis, absence of cirrhosis was the only significant independent predictor of treatment response (P = 0.01). Among initial responders, the factors associated with long-term response were the pretreatment HCV RNA titre and the duration of infection. There was a close association between viral genotype, but not viral load, and the severity of liver disease. An interplay of factors determines the outcome of a 6-month course of interferon treatment for hepatitis C. Severity of liver disease, but not the viral load, is the most crucial determinant of initial response to interferon, and histological severity appeared to be influenced by the viral genotype. The level of hepatitis C virus (HCV) viraemia and the duration of infection are independent determinants of long-term response by affecting the relapse rate after interferon treatment.

Chronic Disease↗
PubMed1996

Hepatitis C.

The hepatitis C virus (HCV) genome was isolated during the late 1980s using molecular cloning techniques. It is recognized as the cause of most cases of percutaneously transmitted non-A, non-B hepatitis. Prevalence of antibodies to HCV(anti-HCV) in the general Australian population is 0.3%. However, among regular intravenous drug users the prevalence exceeds 90%. The predominant risk factors for HCV are intravenous drug use, tattoos, exposure to blood products, occupational risk and ethnicity. In contrast to hepatitis B, sexual spread and vertical transmission of HCV from mother to neonate are relatively uncommon. The risk of acquiring HCV from a single HCV-contaminated needlestick accident is about 5%. Most cases of acute HCV infection are asymptomatic, but 50 to 80% progress to chronic disease. The percentage of those with chronic HCV progressing to cirrhosis is not accurately known, but is probably 20%. Treatment strategies for HCV, utilizing recombinant interferons, are proving useful in patients with mild to moderate liver disease, but fare less well in patients with cirrhosis. Currently, there is no vaccine for hepatitis C, so pre-exposure prophylaxis is not possible. Equally, no post-exposure intervention, for example with gamma globulin, has been shown to be beneficial, though there may be a role for early interferon therapy.

Australia↗
PubMed1996

Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man.

We used the antipyrine clearance test (APC) to examine the effect of growth hormone (GH) therapy on hepatic cytochrome P450 (CYP) enzyme activity. Eleven GH deficient adults were randomized to receive GH or placebo for 6 months, all subjects subsequently received GH. Before treatment, APC was below the normal range in six subjects. We found an increase in APC in the subjects randomized to receive GH compared to those on placebo (median change +0.14 ml/min/kg [range + 0.04 to + 0.20]vs -0.04 ml/min/kg [range -0.07 to + 0.04], p = 0.011). The stimulatory effect of GH on drug metabolism was confirmed by the data for 3 months GH treatment in all 11 subjects, with APC increasing from 0.33 ml/min/kg (range 0.22 to 0.69) to 0.50 ml/min/kg (range 0.27 to 0.83), p = 0.018). These data indicate that GH modulates hepatic CYP activity. This has important clinical implications, as the hepatic metabolism of drugs and hormones may be altered in patients undergoing GH therapy.

Adult↗
PubMed1995

Pre-translational regulation of cytochrome P450 genes is responsible for disease-specific changes of individual P450 enzymes among patients with cirrhosis.

We have recently reported that disease-specific differential alterations in the hepatic expression of xenobiotic-metabolizing cytochrome P450 (CYP P450) enzymes occur in patients with advanced liver disease. In order to determine whether the observed changes in CYP proteins are modulated at pre- or post-translational levels, we have now examined the hepatic levels of mRNA for CYPs 1A2, 2C9, 2E1 and 3A4 by solution hybridization in the same livers of 20 controls (surgical waste from histologically normal livers), 32 cases of hepatocellular and 18 of cholestatic severe chronic liver disease. CYP1A2 mRNA and CYP1A immunoreactive protein were both reduced in livers with hepatocellular and cholestatic types of cirrhosis. In contrast, CYP3A4 mRNA and protein were reduced only in livers from patients with hepatocellular diseases. For 1A2 and 3A4 there were significant correlations between mRNA species and the respective protein contents (rS1A2 = 0.74, rS3A4 = 0.64, P < 0.0001). CYP2C9 mRNA was reduced in patients with both cholestatic and hepatocellular types of liver disease, but 2C protein was reduced only in patients with cholestatic dysfunction. The correlation between CYP2C9 mRNA and protein, was also significant (rs = 0.36, P < 0.005) but mRNA levels accounted for only 13% of the variability in protein rankings. This is probably a consequence of other CYP2C proteins apart from 2C9 being detected by the anti-2C antibody. CYP2E1 mRNA and protein were reduced in patients with cholestatic liver disease, but in hepatocellular disease the expression of only CYP2E1 mRNA was decreased. CYP2E1 mRNA was significantly correlated with CYP2E1 protein but accounted for only 18% of the variability in protein rankings (rs = 0.43, P < 0.0005). Taken collectively these data indicate that the disease-specific alterations of xenobiotic-metabolizing CYP enzymes among patients with cirrhosis is due, at least in part, to pre-translational mechanisms. The lack of a strong correlation between CYP2E1 mRNA and protein suggests that this gene, like its rat orthologue, may be subject to pre-translational as well as translational and/or post-translational regulation.

Cytochrome P-450 Enzyme System↗
PubMed1995

Antipyrine clearance and response to interferon treatment in patients with chronic active hepatitis C.

To determine whether hepatic metabolic function affects the response to interferon treatment, we measured antipyrine clearance (APC) in 85 patients with chronic active hepatitis C and compared the results with treatment outcome. Among 55 patients who responded to interferon by normalization of alanine transaminase (ALT), median APC before treatment was 0.47 (range, 0.12 to 0.98; normal range, 0.34 to 1.02 mL/min/kg body wt), a value that was significantly greater than in 30 nonresponders (0.23; 0.08 to 0.67 mL/min/kg body wt, P < .001). APC was closely associated with response to interferon. The response rate among cases with values > 0.25 mL/min/kg body weight was 79%, the same as in cases without cirrhosis. Cases without cirrhosis and with APC of > 0.25 mL/min/kg body weight had an 85% chance of responding to interferon; this was unlikely a simple reflection of histological activity, because the correlation with Scheuer score was poor in this subgroup (r = -.31, P < .05). A second, independent group of 43 patients was used to test the predictive value of APC (using 0.25 mL/min/kg body wt as a cut-off) for response to interferon treatment. In this group, APC correctly predicted positive response to interferon in 75% of cases. APC was also used to measure the effects of treatment on hepatic metabolic function. Regardless of outcome, there was no change in APC at the end of a 6-month course of interferon treatment. Six months later, however, improvement in APC (14%; P < .05) was evident among responders but not in those who had failed to respond to interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Coinfection with hepatitis B and C or B, C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment.

Chronic coinfection with the hepatitis B (HBV) and hepatitis delta (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-alpha 2b (IFN-alpha) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied; 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheuer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-alpha 2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and delta coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Downregulation of male-specific cytochrome P450s 2C11 and 3A2 in bile duct-ligated male rats: importance to reduced hepatic content of cytochrome P450 in cholestasis.

The effects of bile duct ligation (BDL) on the activity and content of individual hepatic mixed-function oxidases (MFOs) was examined. Five days after BDL, hepatic microsomal total cytochrome P450 (CYP) content and NADPH-cytochrome P450-reductase (P450-reductase) activity were reduced to 56% and 57% of control, respectively. MFO activities attributable to the sexually undifferentiated CYPs 1A, 2A1, 2C6, and 2E1 were decreased to 32% to 52% of control, but the activities of two male sex-specific CYPs, 2C11 and 3A2, were reduced to a significantly greater extent (P < .05). The microsomal contents of CYP proteins 2C6 and 2E1 were decreased after BDL to 61% and 63% of control, whereas 2C11 and 3A2 proteins were 21% and 45% of control. Corresponding reductions of the messenger RNA (mRNA) species for CYP 2C11 (9% of control) and 3A2 (37%) were detected, whereas there was no reduction of 2C6 mRNA. These findings are consistent with downregulation of the CYP 2C11 and 3A2 genes. Nuclear run-on studies performed 3 days after BDL showed that there was a generalized impairment of gene transcription after BDL, but a disproportionate reduction in transcription of CYPs 2C11 and 3A2. A possible explanation for downregulation of CYP 2C11 and 3A2 was provided by the observation that serum estradiol concentrations were threefold greater in BDL male rats, while serum testosterone was reduced; estradiol is known to downregulate CYPs 2C11 and 3A2. It is concluded that male sex-specific CYP enzymes are decreased to a greater extent than other microsomal proteins in BDL male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hepatocellular carcinoma in western Sydney. Aetiology, changes in incidence, and opportunities for better outcomes.

OBJECTIVES: To examine the incidence of hepatocellular carcinoma (HCC) in western Sydney over the last 14 years, to assess risk factors for the disease among ethnic groups of Australian residents, and to consider the opportunities for improving its usually poor outcome. DESIGN AND SUBJECTS: Retrospective case-record review of clinical features in all (122) patients discharged from a 900-bed tertiary-referral teaching hospital with a diagnosis of HCC from January 1979 to March 1993. MAIN OUTCOME MEASURES: Annual number of new cases; risk factors according to birthplace; surgical resectability of tumours. RESULTS: New cases admitted each year at least doubled between 1979-1985 and 1986-1992. This apparent increase involved individuals born in Australia (50% of all patients) as well as immigrants. Cirrhosis was found in 93% at liver biopsy or autopsy. Excessive alcohol intake was an associated risk factor for 46% of Australian-born patients and for 13% of those born overseas. Among the latter, HCC was associated with markers of hepatitis B virus infection in 64%. Since hepatitis C virus (HCV) tests became available in 1990, five of nine patients tested were anti-HCV positive. Surveillance screening of patients known to have cirrhosis detected eight cases of early HCC. Seven of these had surgical resection and all are alive. CONCLUSIONS: New diagnoses of HCC have increased recently, irrespective of country of birth. In Australian-born patients alcoholic liver disease remains a major aetiological factor but the role of HCV requires further evaluation. Among immigrants, cirrhosis from chronic viral hepatitis accounts for most cases. We propose that prevention of cirrhosis caused by chronic viral hepatitis should have the greatest long-term impact on prevention of HCC in Australia. The role of surveillance of people with cirrhosis to detect small and potentially resectable tumours should be explored.

Adult↗
PubMed1993

Alpha-interferon 2b in the treatment of chronic hepatitis C: interim report of the first multicentre Australian trial.

Interferon has been shown to be effective in the treatment of chronic hepatitis C but the optimal treatment regime has not yet been defined. Studies using 3 million units (MU) of interferon thrice weekly (tiw) for 6 months have shown normalization of serum alanine aminotransferase (ALT) in about 50% of patients, but relapse occurs in at least 50% of responders after interferon is stopped. The aims of this study were to determine whether 5 MU of interferon tiw produces a higher response rate than 3 MU tiw and to examine if the higher dose results in more sustained remissions. In addition, factors that are associated with a more or less favourable response to interferon treatment were sought. Overall, 65% of patients responded and no advantage of the higher dose therapy was found, either in terms of response or relapse rate after treatment. The presence of cirrhosis on the pre-treatment liver biopsy was associated with a poor response rate to interferon and a trend towards a higher relapse rate. Risk factor for acquisition of disease was also related to likelihood of response but not relapse. We conclude that two thirds of Australian patients with chronic hepatitis C initially respond to interferon treatment. Positive predictors of response are intravenous drug use as a risk factor and histologically less severe liver disease. Relapse occurs in two thirds of all responders.

Australia↗
PubMed1992

The effects of partial hepatectomy on serum sex steroids in humans.

In both rats and humans, partial hepatectomy results in a substantial increase in serum estradiol concentrations. Because mammalian liver of both sexes contains estrogen receptor, it has been suggested that this surge in serum estrogen concentration may initiate or facilitate liver regeneration. We have reexamined the potential role of sex steroids in human liver regeneration by measuring serum estradiol and testosterone concentrations in men and postmenopausal women before and after hepatic resection. The results were compared with those obtained in patients subjected to other forms of major surgery. In both men and postmenopausal women, serum estradiol levels increased after partial hepatectomy. However, the magnitude of increase was not related to the amount of liver removed. Moreover, similar increases occurred in patients undergoing other major surgical procedures not involving the liver. Serum testosterone concentrations decreased in men and increased in postmenopausal women undergoing all forms of surgery. It is concluded that effects of partial hepatectomy on serum sex steroid levels are nonspecific and probably related to stress. These observations diminish the likelihood that such changes are an important factor in the control of liver regeneration in humans.

Abdomen↗
PubMed1992

Constitutive expression and hormonal regulation of male sexually differentiated cytochromes P450 in primary cultured rat hepatocytes.

Experiments, predominantly performed in vivo, have shown that the pattern of growth hormone (GH) release from the pituitary gland is a major regulator of sex-specific cytochromes P450 (P450) in rats and other rodents. However, difficulty in constitutively expressing male-specific forms of P450 using in vitro models, such as primary cell culture, has impeded efforts to examine the direct actions of hormones on these enzyme forms. In the present study mRNA species for the male-specific P450 2C11 and 2C13, but not 3A2, were successfully expressed in primary hepatocytes cultured on a laminin-rich extracellular matrix (matrigel) in a serum-free, chemically defined medium containing insulin as the only hormone. When cells were exposed to GH (100 ng/ml), 2C11 mRNA expression was virtually abolished and 2C13 expression decreased to approximately 50% of control values, demonstrating that the negative regulation of these P450 forms by GH is a direct action on hepatocytes. Dexamethasone (DEX, 10(-8) M) increased the expression of 2C11 to 195% while decreasing 2C13 expression to 25% of control values. When GH and DEX were administered concurrently 2C11 was downregulated, indicating that GH is the dominant regulatory hormone for this form. L-Triiodothyronine (T3) (10(-9) M) suppressed 2C11 (46% of control) but had no effect on 2C13 mRNA expression. The positive regulatory effect of glucocorticoids on 2C11 was also found to occur in vivo and demonstrated to operate predominantly at the transcriptional level. This study demonstrates that primary cultures of hypatocytes are a suitable in vitro model for studies on regulation of some male-specific P450 forms and that GH, DEX, and T3 act directly on hepatocytes at a pretranslational level to regulate these forms.

Animals↗
PubMed1992

Growth hormone regulation of hepatic cytochrome P450 expression in the rat.

GH by means of its sexually differentiated secretory pattern is the predominant regulator of the expression of cytochrome P450 enzymes responsible for a sexual dimorphism of hepatic steroid metabolism. Other hormones, such as gonadal, thyroid and glucocorticoid hormones, as well as insulin appear to modulate the sexually differentiated expression of these enzymes. The major constitutively expressed sex specific forms of P450, belonging to the P4502C-subfamily, have been shown to be regulated by GH at the level of transcription. However, the GH postreceptor events leading to increased or decreased transcriptional activity are essentially unknown. Neither is the functional role of the soluble GH binding protein yet resolved. On-going protein synthesis is a prerequisite for GH transcriptional activation of the female specific P4502C12 but not for all GH effects in the hepatocyte. With regard to signalling mechanisms PKC activity appears to be permissive for the GH induction of P4502C12 but some as yet unidentified factor/kinase(s) may also be activated. The transcriptional control exerted on the rat P4502C-gene subfamily by the pattern of GH secretion offers a versatile tool to elucidate the molecular mechanisms of GH regulation of cytochrome P450 expression.

Androgens↗
PubMed1990

Does hepatitis C virus play a role in "non-viral" chronic liver disease?

It has recently been suggested that the hepatitis C virus may play a significant role in chronic liver diseases, such as autoimmune chronic active hepatitis, which are usually attributed to non-viral causes. We tested for antibodies to hepatitis C virus (anti-HCV) in sera from 140 patients with well characterised "non-viral" chronic liver diseases as well as sera from 51 patients thought to have chronic non-A, non-B (NANB) hepatitis (acting as positive controls) and 25 patients with non-hepatic autoimmune disorders. As expected, 45 of 51 patients (88%) diagnosed as having chronic NANB hepatitis were anti-HCV seropositive. Among 26 patients with cryptogenic cirrhosis, 8 were anti-HCV seropositive; in 5 patients (22%) there was no apparent risk factor for parenteral transmission. In the remaining 114 patients with chronic liver disease, 10 patients (9%) were seropositive for anti-HCV. However, 5 of these patients had a significant risk factor for parenteral transmission of hepatitis C virus, leaving only 5 of 106 (4.7%) with unexplained positive anti-HCV test results. Among patients with high titres of circulating autoantibodies but no liver disease, no positive results occurred. It is concluded that hepatitis C virus infection may account for some cases of cryptogenic cirrhosis. Although anti-HCV occurs more commonly in patients with other "non-viral" chronic liver diseases than has been reported in the community (0.5%-1.2%), the low prevalence of the antibodies indicates that hepatitis C virus infection is unlikely to be important in the aetiology or pathogenesis of autoimmune chronic active hepatitis and other poorly understood chronic liver diseases.

Autoimmune Diseases↗