Estrategias para la detección de infección por virus de la hepatitis C en población general / Strategies for the detection of hepatitis C viral infection in the general population

Objetivo: Evaluar cual de las 3 estrategias ensayadas es más efectiva para detectar nuevos casos de infección por virus de la hepatitis C (VHC) en atención primaria. Métodos: Estudio observacional, prospectivo y multicéntrico. Se evaluaron 3 estrategias: Estrategia 1: carta explicativa dirigida a personas adultas adscritas a 2 equipos de atención primaria (EAP), invitándoles a realizar un examen serológico. Estrategia 2: colocación en los EAP de pósteres y dípticos explicativos, ofreciendo la posibilidad de realizar un examen analítico. Estrategia 3: revisar el resultado de anti-VHC en los pacientes con hipertransaminasemia detectada en los últimos 2 años mediante la historia electrónica y efectuar determinación del anti-VHC en los casos en quienes no se había determinado. Resultados: Participaron 598 personas (51% mujeres con una media de edad de 50,6±13 años). Con la estrategia 1 se captaron 238 personas (4,1% de participación), con la estrategia 2, 69 personas (0,3%) y con la estrategia 3, 291 pacientes (100%). La detección de VHC oculto fue de un caso en las estrategias 1 y 2, representando una prevalencia del 0,4 y 1,4%, respectivamente, y de 2 casos en la estrategia 3 lo que representa una prevalencia de 0,7%. Conclusiones La búsqueda activa de casos ocultos de infección por VHC ha sido poco efectiva con los métodos ensayados, atendiendo al coste y esfuerzo que comportan (AU)

Objective: To evaluate which of the three studied strategies is the most effective to detect new cases of Hepatitis C virus (HCV) infections in primary care. Methods: This is an observational, prospective, and multicentre study evaluating three strategies. Strategy 1: provide an explanatory letter to adults assigned to two primary care teams (PCTs), inviting them to have a blood test. Strategy 2: place posters and leaflets in PCTs advertising the possibility of laboratory tests. Strategy 3: reexamine HCV antibody test results in patients with hypertransaminasemia diagnosed within the last two years through electronic records, and determine anti-HCV status in undiagnosed cases. Results: There were a total 598 participants (51% female with an average age of 50.6±13 years). There were 238 people (4.1% of letters sent) in Strategy 1, 69 people (0.3% of potential participation) in Strategy 2, and 291 people (100% participation) from Strategy 3. One new case of HCV was found in both Strategy 1 and Strategy 2, representing a prevalence of 0.4 and 1.4%, respectively. Two new cases of HCV were found in Strategy 3, representing a prevalence of 0.7%. Conclusions: The three studied strategies for detecting new cases of HCV infection are ineffective, especially in regards to their cost and effort (AU)

Strategies for the detection of hepatitis C viral infection in the general population.

OBJECTIVE: To evaluate which of the three studied strategies is the most effective to detect new cases of Hepatitis C virus (HCV) infections in primary care. METHODS: This is an observational, prospective, and multicentre study evaluating three strategies. Strategy 1: provide an explanatory letter to adults assigned to two primary care teams (PCTs), inviting them to have a blood test. Strategy 2: place posters and leaflets in PCTs advertising the possibility of laboratory tests. Strategy 3: reexamine HCV antibody test results in patients with hypertransaminasemia diagnosed within the last two years through electronic records, and determine anti-HCV status in undiagnosed cases. RESULTS: There were a total 598 participants (51% female with an average age of 50.6 ± 13 years). There were 238 people (4.1% of letters sent) in Strategy 1, 69 people (0.3% of potential participation) in Strategy 2, and 291 people (100% participation) from Strategy 3. One new case of HCV was found in both Strategy 1 and Strategy 2, representing a prevalence of 0.4 and 1.4%, respectively. Two new cases of HCV were found in Strategy 3, representing a prevalence of 0.7%. CONCLUSIONS: The three studied strategies for detecting new cases of HCV infection are ineffective, especially in regards to their cost and effort.

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Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis.

OBJECTIVES: The prevalence of hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC) is not well established, as some reports suggest a low risk, whereas others indicate that HCC may be no less frequent than in other types of cirrhosis. METHODS: We compared the incidence of HCC in a series of 140 patients with PBC (five men, 135 women, mean age 54 +/- 1.6 yr) followed-up for a mean of period of 5.6 +/- 0.4 yr with a group of patients with cirrhosis related to hepatitis C virus (HCV) who were matched for age, sex, and follow-up period. In all patients, HCC was prospectively screened by clinical, laboratory, and ultrasound procedures. RESULTS: Five patients with PBC (3.6%) developed HCC. All were in stage IV of the disease. The incidence of HCC in the 45 patients with late stages of the disease (III or IV) was 11.1%, similar to that found in patients with HCV-related cirrhosis, which was 15.0%. The relative risk for HCC in late stages of PBC was of 0.812 (95% CI, 0.229-2.883) with respect to HCV-related cirrhosis. The probability for developing HCC was significantly higher in patients with HCV-related cirrhosis than in PBC patients overall (p = 0.001), but was similar in patients with HCV-related cirrhosis and in patients with PBC in stages III and IV (p = ns). CONCLUSION: The risk for HCC in patients with late stages of PBC is similar to that in patients with HCV-related cirrhosis.

Collagen type Ialpha1 and vitamin D receptor gene polymorphisms and bone mass in primary biliary cirrhosis.

The potential influence of two gene polymorphisms, vitamin D receptor gene (VDR) and the gene encoding collagen type Ialpha1 (COLIA1) Sp1 polymorphisms, in the reduced bone mass observed in patients with primary biliary cirrhosis (PBC) was assessed in 61 women with PBC (age, 54.1 +/- 1.1 years) by restriction enzyme digestion of polymerase chain reaction (PCR)-amplified DNA extracted from whole blood. Bone mineral density (BMD) of the lumbar spine (L2-L4) and proximal femur were measured by X-ray absorptiometry. The severity of liver disease and cholestasis was also evaluated, and changes in BMD were calculated after a mean period of 2.9 +/- 0.3 years in 41 patients. Sixteen patients (26 %) had the BB, 20 the bb (33 %), and 25 Bb (41%) VDR genotypes. There were no significant baseline BMD differences among the 3 VDR genotypes. Forty-one patients (68%) had the SS, 16 the Ss (27%), and 3 the ss (5%) COLIA1 genotypes. The baseline lumbar BMD was significantly lower in patients having the s allele than in the homozygote SS patients (Z-score, -0.76 +/- 0.24 vs. -0.10 +/- 0.17, P =.02). The severity of cholestasis was not related to the VDR or COLIA1 1 polymorphisms. Lumbar bone loss was independent of VDR and COLIA1 genotypes, but it was associated with cholestasis. In conclusion, the COLIA1 but not VDR polymorphism is a genetic marker of peak bone mass in patients with PBC, although the severity of cholestasis is the main factor for osteoporosis since it is associated with the rate of bone loss.

[Prevalence and factors associated to the presence of fatty liver in apparently healthy adult men]. / Prevalencia y factores asociados a la presencia de esteatosis hepática en varones adultos aparentemente sanos.

BACKGROUND: Alcohol intake in one of the factors associated with fatty liver, although its contribution as well as other factors have not been completely established. Therefore the aim of this study was to assess the prevalence and associated factors for fatty liver diagnosed by ultrasonography. SUBJECTS AND METHODS: 1,801 presumably healthy male workers (age range 18-60 years). A complete physical and laboratory investigations, including HBsAg and anti-HCV antibodies, a detailed interview on alcohol intake, and an abdominal ultrasound examination were performed in all cases. Diagnosis of fatty liver was based on defined ultrasonographic criteria. RESULTS: Eighty eight cases were excluded because of the HBsAg or anti-HCV positivity or incomplete ultrasonography. Among the remaining 1,713 cases, 236 (13.8%; 12.2-15.4) had fatty liver. Logistic regression analysis disclosed age (RR: 1.04; CI 95%; 1.03-1.05), ethanol intake > 40 g/d (2.19; 1.81-2.65), gamma-glutamyl-transferase > 40 U/l (3.51; 2.95-4.18), body mass index > 30 (3.87; 3.22-4.66) and glycemia > 120 mg/dl (2.69; 1.85-3.90) as the risk factors for fatty liver. Fatty liver was present in 8.8% of cases who did not have obesity, diabetes or hypercholesterolemia. When the subjects with obesity, hyperglycemia or hypercholesterolemia were excluded, regression analysis confirmed age, ethanol intake and gamma-glutamyl-transferase as independent factors associated with fatty liver. CONCLUSIONS: Age, alcohol intake, obesity, and increased serum levels of glucose, cholesterol and gammaglutamyl transferase are the main factors associated with fatty liver in presumably healthy adult men.

Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver.

BACKGROUND/AIM: The aim of this study was to assess the efficacy of ursodeoxycholic acid (UDCA) for primary biliary cirrhosis in a randomized, double-blind placebo-controlled trial. METHODS: Consecutive patients (n=192) were randomized to receive 14-16 mg UDCA/kg/day or placebo. Patients underwent a complete history, physical examination, liver chemistries, immunological determinations and liver biopsy at entry and at the end of the trial, which lasted for at least 2 years. Patients were seen every 3 months and the median follow-up was 3.4 years (range 0.3 to 6.1 years). RESULTS: Patients receiving UDCA (99) or placebo (93) were comparable with regard to age, sex, biochemical parameters and liver histology. UDCA treatment was associated with decreases in alkaline phosphatase, gammaglutamyl transferase, alanine aminotransferase, and cholesterol levels, effects which were conspicuous after 3 months of treatment and remained similar during the follow-up. During the study 31 patients (10 receiving UDCA and 21 placebo) discontinued the trial because of noncompliance (n=11), voluntary withdrawal (n=19) or adverse effects (n=1). Treatment failure (death or liver transplantation) was observed in 17 patients receiving UDCA and in 11 patients receiving placebo. Times to death or liver transplantation and to clinical complications were not significantly different in patients receiving UDCA or placebo. Histological analysis indicates that UDCA improved portal inflammation and prevented histological stage progression. By contrast, histological stage as well as ductular proliferation and ductopenia progressed in patients receiving placebo. CONCLUSIONS: Although UDCA treatment did not significantly affect time to death or liver transplantation and to clinical complications, the effects on both cholestasis and liver histology suggest that UDCA is safe and may be useful for preventing the progression of primary biliary cirrhosis.

S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial.

BACKGROUND/AIM: The efficacy of S-adenosylmethionine (AdoMet) in the treatment of liver cell injury has been demonstrated in several experimental models. The aim of this study was to investigate the effects of AdoMet treatment in human alcoholic liver cirrhosis. METHODS: A randomized, double-blind trial was performed in 123 patients treated with AdoMet (1200 mg/day, orally) or placebo for 2 years. All patients had alcoholic cirrhosis, and histologic confirmation of the diagnosis was available in 84% of the cases. Seventy-five patients were in Child class A, 40 in class B, and 8 in class C. Sixty-two patients received AdoMet and 61 received placebo. RESULTS: At inclusion into the trial no significant differences were observed between the two groups with respect to sex, age, previous episodes of major complications of cirrhosis, Child classification and liver function tests. The overall mortality/liver transplantation at the end of the trial decreased from 30% in the placebo group to 16% in the AdoMet group, although the difference was not statistically significant (p = 0.077). When patients in Child C class were excluded from the analysis, the overall mortality/liver transplantation was significantly greater in the placebo group than in the AdoMet group (29% vs. 12%, p = 0.025), and differences between the two groups in the 2-year survival curves (defined as the time to death or liver transplantation) were also statistically significant (p = 0.046). CONCLUSIONS: The present results indicate that long-term treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic liver cirrhosis, especially in those with less advanced liver disease.

HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations.

The association of primary sclerosing cholangitis (PSC) to HLA class II genes was studied by comparing patients from five different European populations. Deduced HLA-DRB1, DQA1, DQB1 haplotypes of 256 PSC patients from England, Italy, Norway, Spain and Sweden were compared to those observed in 764 ethnically-matched controls. Increased frequencies of the DRB1*03, DQA1*0501, DQB1*02 (RR=3.0, P<0.00001) and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes (RR=2.4, P<0.0001) were observed in all five patient groups. A total of 16% of the PSC patients were homozygous for the DRB1*03, DQA1*0501, DQB1*02 haplotype compared to 1% of the controls (RR=20, P<0.0001). The DRB1*04, DQA1*03, DQB1*0302 haplotype was significantly reduced in frequency(RR=0.4, P<0.00001). Among Norwegian, Swedish and British patients that did not carry neither the DRB1*03, DQA1*0501, DQB1*02 nor the DRB1*13, DQA1*0103, DQB1*0603 haplotype, an increased frequency of the DRB1*15, DQA1*0102, DQB1*0602 haplotype was observed (RR=2.0, P<0.0001). Thus, PSC was found to be positively associated to three different HLA class II haplotypes (i.e. the DRB1*03, DQA1*0501, DQB1*02, the DRB1*15, DQA1*0102, DQB1*0602 and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes) and negatively associated to one HLA class II haplotype (i.e. the DRB1*04, DQB1*0302 haplotype).

[Autoimmune hepatitis. Clinical characteristics and response to treatment in a series of 49 spanish patients]. / Hepatitis autoinmune. Características clínicas y respuesta al tratamiento de una serie de 49 pacientes españoles.

The clinical and evolutive characteristics and the response to treatment of a series of 49 patients with autoimmune hepatitis (AIH) diagnosed in the Liver Unit of a tertiary hospital from 1979 to 1996 and followed over 5.6 +/- 0.7 years were reviewed. Forty cases (80.4%) were AIH type 1 (ANA/AML positive), 7 (14%) type 2 (ALKM positive) and 2 (5%) of an undetermined type (absence of detectable antibodies). In 13 (26.6%) the disease presented as acute hepatitis and 16 (32%) presented extrahepatic manifestations. The AIH type 2 was observed in younger patients with the debut being more acute than in AIH type 1, but no significant differences were observed between the two groups with regard to the results of laboratory tests, frequency of a systemic manifestations and histologic lesions. Immunosuppressive treatment was effective in 90% of the cases, but 11 (30%) out of 37 relapsed on suppression of prednisone or reduction of the dosis. All showed response on reinitiation or an increase in the dosis of prednisone. Progression to cirrhosis was observed in 17% of the patients without cirrhosis at the time of diagnosis despite biochemical remission induced by treatment. No patient died during the follow up but 4 required liver transplantation.

Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver.

BACKGROUND/AIMS: Our aim was to investigate the effectiveness of metadoxine (pyridoxol L, 2 pyrrolidone-5-carboxylate) in the treatment of alcoholic fatty liver. METHODS: A double-blind randomized multicenter trial involving 136 chronic active alcoholic patients diagnosed with fatty liver by clinical, biochemical and ultrasonographic criteria was performed. Patients were treated with 1500 mg/day of metadoxine (n = 69) or placebo (n = 67) for 3 months. Patients were clinically and biochemically evaluated every month. Ultrasonography was performed before and after treatment. RESULTS: At the end of the study there was a significant improvement in the liver function tests in both groups. However, the changes were more rapid and greater in patients treated with metadoxine, in whom significant changes in serum levels of bilirubin, aminotransferases and gammaglutamyl transpeptidase were already observed after 1 month of treatment, and normalization of these parameters was observed at the end. After treatment, the percentage of patients with ultrasonographic signs of steatosis was significantly lower in the metadoxine group (28% vs 70%, p < 0.01) and the degree of steatosis was also lower in this group. Sixteen patients treated with metadoxine and 15 with placebo continued drinking. Alcohol intake was lower than initially, and similar in both groups. In the metadoxine group, the biochemical changes were similar in both the abstinent and the nonabstinent patients. In contrast, in the placebo group the improvement in the liver function tests was significantly higher in abstinents. Among patients who continued drinking, the prevalence (45% vs 92%, p < 0.05) and the degree of steatosis were also significantly lower in patients treated with metadoxine. CONCLUSIONS: In patients with alcoholic fatty liver, metadoxine accelerates the normalization of liver function tests and the ultrasonographic changes, even in those who do not completely abstain from alcohol intake. Thus, metadoxine could be useful in the treatment of the early stages of alcoholic liver disease.

Carbohydrate-deficient transferrin as a marker of alcohol consumption in male patients with liver disease.

Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of alcohol abuse. However, its value in patients with associated liver disease is still controversial. The aim of the study was to investigate the usefulness of CDT as a marker of alcohol consumption in patients with liver disease. We measured serum levels of CDT and those of commonly used hematological and biochemical markers, mean corpuscular volume (MCV), transaminases (AST and ALT), and gamma-glutamyltransferase in 179 male subjects divided into four groups: 45 active drinkers (13 with normal liver, 21 with fibrosteatosis, and 11 with liver cirrhosis), 45 abstinent chronic alcoholics (18 with and 27 without liver disease), 58 patients with nonalcoholic liver disease, and 31 healthy controls. Serum CDT in active alcoholics was 37.5 +/- 3.6 units/liter, being significantly higher than that of abstinent alcoholics (20.3 +/- 1.5 units/liter), patients with nonalcoholic liver disease (18.1 +/- 1.1 units/liter), and controls (13.1 +/- 0.8 units/liter). Contrary to the other markers, no significant differences were observed in CDT values in relation with the presence and severity of liver disease in either the active drinkers or in the abstinent alcoholics. The sensitivity and specificity of CDT as a marker of alcoholism in the series as a whole was 64% and 82%, respectively, similar to the best conventional marker, MCV (64 and 82%). In patients with liver disease, CDT maintained good sensitivity (72%) and specificity (83%). Receiver operating characteristic analysis confirmed that CDT had a similar diagnostic value to that of MCV, but better than gamma-glutamyl-transferase and transaminases for the detection of alcohol abusers. The good diagnostic efficacy of CDT remained unchanged when analyzing only patients with liver disease. We conclude that serum CDT is a good marker of alcoholism and is less influenced than the currently used biochemical markers for associated liver disease. Thus, CDT is an effective laboratory test to detect alcohol abuse regardless of the presence of alcoholic liver disease.

[Class I and II histocompatibility antigens and severity of the alcoholic liver lesion]. / Antígenos de histocompatibilidad de clases I y II y gravedad de la lesión hepática alcohólica.

The association between the class I and class II histocompatibility antigens (HLA) and the severity of alcoholic liver disease was studied in 102 alcoholic patients (64 males and 38 females) with liver disease. According to histologic diagnosis 41 patients had a mild hepatic lesion (12 with minimum changes, 15 with steatosis and 14 with fibrosis) and 61 patients had severe hepatic lesion (13 with alcoholic hepatitis, 35 with cirrhosis and 13 with cirrhosis and alcoholic hepatitis). No differences were found between the two groups in regards to sex, quantity and length of alcohol consumption, although the patients with mild hepatic lesion were younger than those with severe hepatic lesion (41.2 +/- 8.2 and 47.8 +/- 11.6 years, respectively). The prevalence of the A30, B16, B47, Bw56, Cw1, Cw5 and Cw7 antigens was higher in the alcoholics than in the controls, although only the A30 (12.7% vs. 4.4%, p < 0.04) and the Bw56 antigens (3.9% vs 0.1%, p < 0.001) remained significant when the p value was corrected by the number of antigens studied. These differences were due to a greater prevalence of the A30 antigens (17.0% vs. 4.4%, p < 0.001), B16 (24.3% vs. 7.5%, p < 0.01) and Bw56 (7.3% vs 0.1%, p < 0.001) in patients with mild hepatic lesion versus the controls. In contrast, these antigens were present in similar numbers in patients with severe hepatic lesion and in the controls. On the other hand, no differences were observed regarding the prevalence of the class II HLA antigens between the alcoholics and the controls, or between the two alcoholic groups. These data suggest that the alcoholics with A30, B16 and Bw56 antigens are less susceptible to developing severe liver disease.

[Autoimmune cholangitis or primary biliary cirrhosis without antimitochondrial antibodies?]. / Colangitis autoinmune o cirrosis biliar primaria sin anticuerpos antimitocondriales?

The term cholangitis or autoimmune cholangiopathy is applied to patients with a disease similar to primary biliary cirrhosis because of its clinical and histologic characteristics but in whom there is a repeated absence of antimitochondrial antibodies and, by the contrary, the presence of antinuclear antibodies. The initial description of these cases was carried out in 1987. Good response was observed to treatment with glucocorticoids in these first cases and others described later. A series of 13 female patients with features of autoimmune cholangitis diagnosed from 1987 to 1993 in the Hospital Clinic i Provincial from Barcelona, Spain, is retrospectively reviewed. These patients were compared with 13 patients with primary biliary cirrhosis diagnosed on the basis of clinical and histologic criteria and the presence of antimitochondrial antibodies. No relevant clinical or histological differences were observed between the two groups of patients. Six patients with autoimmune cholangitis underwent treatment with glucocorticoids with unequal response, and in 5 cases ursodeoxycholic acid was administered with a slight analytical improvement being observed. According to these results and the current data of these patients, autoimmune cholangitis should be considered as a variety of primary biliary cirrhosis, the main characteristic of which would be the absence of antimitochondrial antibodies more than that of being a specific, independent disease.

Zinc administration improves gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol in alcohol-fed rats.

The effects of zinc on first-pass metabolism (FPM) of ethanol and gastric and hepatic alcohol dehydrogenase (ADH) activities have been investigated in two groups of male Wistar rats fed a liquid ethanol diet with normal zinc content (7.6 mg/liter), or zinc supplemented (76 mg/liter), for 21 days, and in two pair-fed groups receiving the same diets without ethanol. Alcoholic rats with normal dietary zinc had lower FPM (1.64 +/- 0.25 vs. 2.43 +/- 0.20 mM x hr, p < 0.05) and gastric ADH activity (184 +/- 7 vs. 335 +/- 41 micromol/min/mg protein, p < 0.01) than control rats. Zinc supplementation did not produce any change in FPM or in gastric ADH activity in control rats. By contrast, in alcoholic rats, the zinc supplement increased gastric ADH activity (247 +/- 31 vs. 184 +/- 7 micromol/min/mg protein, p < 0.05) and decreased the areas under the curve of blood ethanol concentrations after the intragastric administration of 0.25 g/kg of body weight of ethanol (0.78 +/- 0.07 vs. 1.71 +/- 0.24 mM x hr, p < 0.05), thereby increasing the FPM. In conclusion, in alcohol-fed rats, the administration of zinc supplements restores gastric ADH activity and improves the FPM of ethanol. These effects may be one of the mechanisms in which zinc has a beneficial role in preventing the development of alcoholic hepatic lesions.

Serum hyaluronate reflects hepatic fibrogenesis in alcoholic liver disease and is useful as a marker of fibrosis.

The high levels of hyaluronic acid (HA), a glycosaminoglycan of the liver extracellular matrix, which is synthesized and degraded in the liver sinusoidal cells, have been related with a decreased function of the endothelial sinusoidal cells. The relevance of HA in alcoholic liver disease has not been sufficiently evaluated, and therefore the current study was addressed to assess whether serum HA reflects the severity of liver fibrosis and fibrogenesis as well as the potential usefulness of hyaluronic acid as a marker of early fibrosis in alcoholics with liver damage. Serum HA and aminoterminal propeptide of collagen III (PIIIP) levels, a marker of liver fibrogenesis in alcoholics with liver disease, were assessed in 45 chronic alcoholic patients (31 men and 14 women, age: 44.1 +/- 1.5 years) (normal liver = 7; fatty changes = 8; fibrosis = 7; alcoholic hepatitis = 6; cirrhosis = 6; and cirrhosis plus alcoholic hepatitis = 11). The severity of liver inflammation and fibrosis were scored in liver specimens as: 0, no lesion; 1+ mild; 2+ moderate; and 3+ severe. Twenty-seven patients (60%) had HA above normal values (1 patient with fatty changes, 3 patients with fibrosis, and all patients with alcoholic hepatitis or cirrhosis). Hyaluronic acid and (PIIIP) levels increased in parallel with the severity of liver damage. Hyaluronic acid levels were higher in those patients with more liver inflammation (0, 128 +/- 38; 1+, 553 +/- 141; 2+, 668 +/- 259; 3+, and 1,073 +/- 419 microg/L; P = .004) and of fibrosis (0, 79 +/- 32; 1+, 156 +/- 70; 2+, 219 +/- 105; and 3+, 695 +/- 114 microg/L; P < .001). Procollagen III peptide levels were related with fibrosis (0, 17 +/- 1; 1+, 25 +/- 6; 2+, 47 +/- 13; 3+, and 55 +/- 9 ng/mL; P = .002) but not with inflammation (0, 29 +/- 7; 1+, 45 +/- 7; 2+, 54 +/- 9; 3+, and 66 +/- 30 ng/mL, P: not significant). Moreover, a direct linear correlation was observed between HA and PIIIP (r = .72, P < .001). A receiver operating characteristic (ROC) curve analysis revealed that HA was similar to PIIIP levels in discriminating between alcoholics without fibrosis and those with fibrosis (area under the ROC curves) .913 +/- .042 vs. .867 +/- .054; P: n.s). In conclusion, serum HA reflects the severity of liver inflammation, fibrosis, and fibrogenesis in patients with alcoholic liver disease and is useful as a marker of precirrhotic and cirrhotic stages.

Hepatitis C virus antibodies in chronic alcoholic patients: association with severity of liver injury.

The prevalence of hepatitis C virus antibody and its relationship to the severity of liver disease in chronic alcoholic patients has been assessed, using a recently developed enzyme immunoassay and confirmed by a recombinant immunoblot assay, in 144 patients (mean age +/- S.D. = 44.4 +/- 11.3 yr) who had consumed greater than 80 gm/day ethanol for greater than 5 yr. Hepatic disease was evaluated by clinical and biochemical studies and by liver biopsy when appropriate. In addition, 76 liver biopsy specimens from these patients were analyzed to determine whether liver lesions were similar in alcoholic patients with and without hepatitis C virus antibodies. According to clinical and histological features alcoholic patients were divided into five groups: normal liver (45 patients), fibrosteatosis (20 patients), alcoholic hepatitis (14 patients), cirrhosis (61 patients) and chronic hepatitis (4 patients). Hepatitis C virus antibodies were present in 35 alcoholic patients (24.3%). The prevalence of hepatitis C virus antibodies correlated with the severity of liver injury: 2.2% in patients without liver disease, 20% in those with fibrosteatosis, 41.4% in those with alcoholic hepatitis and 42.6% in those with cirrhosis. Hepatitis C virus antibodies were found in one of the four patients with chronic hepatitis (p less than 0.001). Furthermore, patients positive for hepatitis C virus antibodies with normal liver or fibrosteatosis showed higher serum bilirubin and gamma-globulin concentrations and lower aminopyrine breath test scores than did patients negative for hepatitis C virus antibodies with normal liver or fibrosteatosis. Similar differences between patients with and without hepatitis C virus antibodies were observed in patients with alcoholic hepatitis or cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)