Serum hepatitis B surface antigen monitoring in long-term lamivudine-treated hepatitis B virus patients.

Serum hepatitis B virus surface antigen (HBsAg) levels have been suggested to predict interferon response in chronic hepatitis B. A few data are available on the role of HBsAg measurement in nucleos(t)ide analogues (NA) treatment. We retrospectively investigated the relation between HBsAg changes and main treatment outcomes during long-term lamivudine treatment in hepatitis e antigen (HBeAg)-negative chronic hepatitis B. A total of 42 HBeAg-negative patients were consecutively enrolled in an open-label study on long-term lamivudine monotherapy (150 mg/die). Serum HBsAg levels were quantified every 6 months by Architect assay (Abbott Diagnostics). HBV-DNA was quantified quarterly by real-time PCR (Roche Diagnostics). The median duration of lamivudine treatment was 66 months (20-153). One patient (2%) was a primary nonresponder, 35 (83%) developed virological breakthrough (VB) and the remaining six patients (14%) were classified as long-term on-treatment responders. During treatment, HBsAg levels decreased only in long-term on-treatment responders, while no changes were observed in resistant patients. Failure to achieve a decrease of 0.7 log(10) IU/mL in serum HBsAg at month six of lamivudine had a positive predictive value of developing VB of 90% and a negative predictive value of 100%. These high predictive values were also maintained in the subgroup of patients negative for HBV-DNA at month six. The results of this study with a small sample size suggest a role of on-treatment HBsAg quantification in the management of lamivudine-treated patients. If validated prospectively in a larger patient cohort, HBsAg measurements would be a useful adjunct to optimize antiviral therapy.

Immunological modifications during treatment with thymosin alpha1 plus antiviral therapy in chronic hepatitis C.

The current standard therapy for the treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin, although many patients fail to clear the virus and their retreatment options are still unsatisfactory. Thymosin alpha1 (Talpha1) is an immunomodulating agent that has been proposed as complementary therapy for chronic HCV, especially in the setting of difficult-to-treat patients. The aim of this study was to evaluate, in patients nonresponsive to previous Peg-based therapy, the effect of standard antiviral therapy with or without Talpha1 on peripheral lymphocyte subsets. Twenty-four patients, 12 receiving Talpha1 and 12 standard therapy, were enrolled. Peripheral subpopulations were analyzed by flow cytometry. Although the addition of Talpha1 did not seem to significantly modify the T-lymphocyte subpopulations, as comparable behaviors were observed in the CD4 and CD8 longitudinal evaluation, Talpha1 produced an earlier increase of natural killer cells. An accurate selection of HCV patients who can benefit from immunomodulation is needed.

Pharmacokinetics and efficacy of intravenous or intramuscular hepatitis B immunoglobulins in prophylaxis of hepatitis B after liver transplantation.

AIM: The use of hepatitis B immunoglobulin (HBIg) combined with nucleos(t)ide analogues (NUCs) has improved outcomes in post-hepatitis B (PHB) liver transplant (LT), reducing the 1-year recurrence rate below 10%. The aim of this study was to evaluate efficacy and pharmacokinetics of prophylaxis with NUC(s) and intravenous (iv-) or intramuscular (im-) HBIg in 33 PHBLTs, transplanted for more than 1 year. METHODS: During the first six months of the study, 18 subjects received 5000 IU of iv-HBIg every four weeks and 15 patients 2160 IU/12 mL of im-HBIg every two weeks. In the following six months, 31 subjects were switched to two different concentrations of im-HBIg, 2160/12 mL (16 patients) or 2000 IU/6 mL every two weeks (15 patients). RESULTS: All patients remained HBsAg-negative and 30/31 maintained anti-HBs >100 IU/L. Overall mean anti-HBs titer during treatment was 363 IU/mL. Mean HBIg half-life was 21.4, 27.3 and 26 days with intravenous, diluted or concentrated im-preparations, respectively. CONCLUSION: These results confirm an analogue efficacy and tolerance of iv- and im-HBIg combined with antivirals in prophylaxis of hepatitis B after LT. Anti-HBs titers three times higher than aimed and four weeks mean half-life could suggest the reduction of doses and the elongation of the interval of administration of im-HBIg.

Hepatitis C Virus-related chronic liver disease in elderly patients: an Italian cross-sectional study.

Chronic hepatitis C virus (HCV) infection has been poorly investigated in the elderly. The aim of this study was to identify the age-specific characteristics of chronic hepatitis C by comparing patients > or =65 years with those <65 years. A cross-sectional study was performed on data collected from consecutive outpatients referred for the first time to two tertiary outpatient clinics for liver diseases located in Bologna (Northern Italy) and Paola, Cosenza (Southern Italy) over a two-year period. A total of 560 anti-HCV and HCV-RNA positive patients were enrolled, of whom 174 (31%) were 65 years or older. The proportion of older patients was significantly higher in the Southern Italy centre, accounting for more than 40%. Comparison of younger and older groups showed that 51% patients > or =65 years had advanced liver disease (liver cirrhosis or hepatocellular carcinoma) compared with 26% younger patients (P < 0.0001). About half of the patients > or =65 years were not aware of their anti-HCV positive status, even if they tended to be more symptomatic than the younger group. By multivariate analysis, age > or = 65 years, alcohol consumption and diabetes were independently associated with advanced liver disease. Overall, 34 out of 174 patients (20%) > or =65 years had received antiviral treatment compared with 122 out of 386 (32%) younger patients (P = 0.003). Our results further emphasize the notion that chronic hepatitis C is becoming a disease of the elderly and that elderly patients with chronic HCV infection often have severe and underestimated disease.

Early discontinuation of ribavirin in HCV-2 and HCV-3 patients responding to Peg-interferon alpha-2a and ribavirin.

Guidelines for the treatment of patients infected with hepatitis C virus of genotypes 2 and 3 (HCV-2 and HCV-3, respectively) recommend a 24-week course of Peg-interferon (Peg-IFN) alpha-2a combined with ribavirin, despite 50% of patients in registration trials attaining a sustained virologic response (SVR) following Peg-IFN alpha-2a monotherapy. The aim of this study was to delineate patient characteristics that might help to identify individuals likely to benefit from ribavirin discontinuation. One hundred and forty-four HCV-2- and HCV-3-infected patients initiated Peg-IFN alpha-2a (180 microg/week) and ribavirin (1000 or 1200 mg/day); those with viral clearance at week 4 were randomized to either Peg-IFN alpha-2a monotherapy (n = 59) or continuing combination therapy (n = 61) until week 12. Overall, all but one patient with a rapid virologic response (RVR) responded by the end of therapy and the overall SVR rates were lower after discontinuation of ribavirin (54%vs 82%; P < 0.001). In RVR patients who discontinued ribavirin, low baseline viraemia helped predict SVR (odds ratio 11.2, 95% CI 2.7-47.1). SVR rates were similar in patients receiving mono- or combination therapy with low (< or =300,000 IU/mL) and intermediate viraemia (86%vs 81% and 70%vs 71%, 86% refers to low viraemic patients receiving monotherapy and 81% to those receiving combination therapy. Similarly, 70% refers to patients with intermediate viraemic levels receiving monotherapy and 71% to those receiving combination therapy), but different in those with high (>700,000 IU/mL) viraemia (37%vs 88%; P = 0.004). Thus in HCV-2- and HCV-3-infected patients, withdrawal of ribavirin and continuation of Peg-IFN alpha-2a monotherapy may be appropriate to attain an SVR, providing viraemia is cleared early during therapy and associated with low baseline viral load. These results warrant future investigations, as discontinuing ribavirin could lead to considerable savings in cost and quality of life related to over-treatment.

In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with eAg-negative chronic hepatitis B.

Thymosin alpha-1 (Talpha1) has been shown to be effective in chronic hepatitis B treatment. This study investigated the effect of Talpha1 and interferon-alpha (IFNalpha) on cytokine production by peripheral blood mononuclear cells (PBMCs) of 12 patients with eAg-negative chronic hepatitis B (HBV). We evaluated the effect of incubation with Talpha1, IFNalpha or both on the synthesis of T-helper 1 (Th1) cytokines [interleukin-2 (IL-2), IFNgamma] and Th2 cytokines (IL-4, IL-10) and of antiviral protein 2',5'-oligoadenylate synthetase (2',5'-OAS) in patients and in a group of 10 healthy controls. Concerning Th1 profile, controls showed lower IL-2 synthesis than HBV patients. In HBV setting, IFNalpha/Talpha1 combination was able to increase IL-2 production significantly, when compared with baseline condition. About the Th2-cytokines, controls showed statistically lower synthesis of IL-4 and higher production of IL-10, than HBV patients. In these latter, IFNalpha increased the synthesis of IL-10 compared with baseline. Interestingly, both Talpha1 alone and the IFNalpha/Talpha1 combination reversed this effect. Finally, compared with baseline, the synthesis of 2',5'-OAS was significantly higher in the presence of Talpha1 and IFNalpha alone, and in the presence of IFNalpha/Talpha1 association, while no differences were found between controls and HBV patients. In conclusion, in PBMCs from eAg-negative HBV patients, Talpha1 alone was able to increase the antiviral protein synthesis, while in association with IFNalpha, it stimulated the IL-2 synthesis and inhibited the IFN-induced IL-10 production. These results need further investigations, but reinforce the idea of an immunotherapeutic approach for chronic hepatitis B.

Pegylated interferon plus ribavirin for recurrent Hepatitis C infection after liver transplantation in naïve and non-responder patients on a stable immunosuppressive regimen.

BACKGROUND: Hepatitis C virus recurrence after liver transplantation is universal, leading to chronic hepatitis and cirrhosis. AIMS AND PATIENTS: We evaluated the efficacy and safety of pegylated interferon and ribavirin in 20 patients with recurrent Hepatitis C virus after liver transplantation (10 naïve and 10 non-responders to a previous interferon course). METHODS: Treatment consisted of pegylated interferon alfa-2b (1.0 microg/kg once weekly) and ribavirin (600 mg/daily) for at least 6 months. Therapy continued for an additional 6 months only in patients with undetectable serum Hepatitis C virus-RNA or >2 log drop from baseline levels. RESULTS: Eleven out of 20 patients (55%) completed 1 year of treatment. Nine patients (45%) had undetectable Hepatitis C virus-RNA at the end of treatment, six of them were naïves and three non-responders. In all of them, virological response persisted 6 months after discontinuation of therapy, so the sustained virological response rate was 60% in naïve patients and 30% in non-responders. CONCLUSIONS: Our results suggest that pegylated interferon plus ribavirin combination therapy may be effective in patients with post-liver transplantation recurrent chronic Hepatitis C, even in those previously non-responders to interferon plus ribavirin. These results need to be confirmed by large studies.

Cytokine profile of peripheral blood mononuclear cells from patients with different outcomes of hepatitis C virus infection.

SUMMARY: The relationship between the balance of helper T-cell type 1 (Th1) or type 2 (Th2) cytokines and the clinical course of hepatitis C virus (HCV) infection is unclear. We evaluated Th1 [interleukin (IL)-2, interferon-gamma (IFN-gamma)] and Th2 cytokine (IL-4, IL-10) and 2,5-oligoadenylate synthetase (OAS, an IFN-induced antiviral protein) production by peripheral blood mononuclear cells from 10 healthy anti-HCV-positive individuals (group A), 10 HCV-RNA-positive with persistently normal alanine aminotransferase (ALT) levels (group B), 10 HCV-RNA-positive with abnormal ALT (group C) and 10 uninfected healthy controls. IL-2 production was significantly increased in group B when compared with all the other groups. No difference was found for IFN-gamma. IL-4 was significantly higher in group C than in both group B (P = 0.0006) and controls (P = 0.004). Compared with controls, IL-10 was significantly decreased in group A (P = 0.013) and B (P = 0.004). The production of 2,5-OAS was significantly higher in group B than in A (P = 0.04) and in C (P = 0.004). Finally, in all HCV-RNA-positive patients, a significant correlation was found between ALT and both IL-2 (r = -0.78; P = 0.0008) and IL-4 (r = 0.75; P = 0.0008). IN CONCLUSION: (i) subjects who cleared HCV showed a cytokine profile similar to controls; (ii) a preferential shift towards a Th1 profile seems associated with a more favourable clinical outcome in chronic hepatitis C; and (iii) a prevalent Th2 profile seems implicated in HCV pathogenesis and severity of liver disease.

High risk of hepatocellular carcinoma in anti-HBe positive liver cirrhosis patients developing lamivudine resistance.

The emergence of drug-resistant virus in hepatitis B virus patients treated with lamivudine is well documented. However, its clinical impact in the long-term treatment of anti-HBe positive compensated cirrhotic patients is not well known. In this study, we treated 22 consecutive patients with anti-HBe compensated cirrhosis with lamivudine for a median period of 42 months. All patients responded to lamivudine, but viral breakthrough occurred in 13 patients (59%) between 9 and 42 months of therapy due to the emergence of a mutant strain. During the follow-up, 11 developed hepatocellular carcinoma. Of these, 10 occurred soon after the emergence of viral resistance, generally showing aggressive behaviour, and one in the nine long-term responder patients (P = 0.013). Lamivudine resistance was the only independent predictor of hepatocellular carcinoma development (risk ratio: 10.4; 95% CI: 1.3-84.9). Our study suggests that the occurrence of lamivudine resistance increases the risk of hepatocellular carcinoma in anti-HBe positive cirrhosis and warrants further research.

Thymosin-alpha 1 plus interferon-alpha for naive patients with chronic hepatitis C: results of a randomized controlled pilot trial.

In this pilot study, we evaluated the efficacy of interferon-alpha (IFN) plus Thymosin-alpha 1 (TA1) to that of IFN alone in naive patients with chronic hepatitis C. Twenty-two patients were randomized to receive interferon-alpha 2b (3 million units three times a week) plus thymosin-alpha l (900 microg/m2 body surface area) and 19 received interferon-alpha 2b alone at the same dose. Patients were treated for 6 months and followed up for another 6 months. Biochemical (alanine aminotransferase values) and virological (hepatitis C virus-RNA) responses to treatment were determined. Combination treatment showed significantly higher efficacy than monotherapy in achieving virological end-of-treatment response (P = 0.03). At 6-month follow up, the sustained biochemical and virological response was not different between the two groups. Our results indicate that the immune modulator TA1 may enhance the end-of-treatment response in naive patients with chronic hepatitis C. Higher doses and/ore more prolonged courses as well as the association with new interferon formulation such as pegylated interferons could improve the sustained response rates to this treatment.

Interferon-alpha combined with ketoprofen as treatment of naïve patients with chronic hepatitis C: a randomized controlled trial.

In this randomized controlled study, we evaluated the efficacy and safety of interferon-alpha combined with ketoprofen to that of interferon-alpha alone in naïve patients with chronic hepatitis C. Forty patients were randomized to receive Interferon-alpha2a (3 million units three times a week) and ketoprofen (150 mg twice a day) and 40 to receive only interferon-alpha2a at the same dose. Patients were treated for 6 months and followed up for 6 months. Response was defined by undetectable HCV-RNA in serum at the end-of-treatment and after 6 months from the completion of therapy (long term response). At the end of treatment the response was similar in the two group. However, combination treatment showed significantly higher efficacy than monotherapy in achieving long term response (10%vs 32.5%; P = 0.014). Overall adverse events were similar in the two groups. 'Flu-like syndrome was significantly less common in the ketoprofen plus interferon group which experienced a significantly higher incidence of epigastric pain'. Our results indicate that the combination of ketoprofen plus interferon is significantly more effective than interferon alone in the treatment of naïve patients with chronic hepatitis C and is well tolerated. However this combined treatment appears to be less effective than the association of pegylated IFN and ribavirin which represent the current standard treatment. Thus, the role of ketoprofen in the treatment of chronic hepatitis C needs to be further evaluated against such a treatment.

Impact of interferon therapy on the natural history of hepatitis C virus related cirrhosis.

BACKGROUND: The role of interferon treatment on the natural history of hepatitis C virus related cirrhosis is under debate. AIM: To evaluate the effect of interferon on the clinical course of compensated hepatitis C virus related cirrhosis. PATIENTS AND METHODS: Seventy two cirrhotic patients treated with interferon and 72 untreated controls matched treated patients with for quinquennia of age, sex, and Child-Pugh's score were enrolled in a prospective non-randomised controlled trial. Treated patients received leucocytic interferon alfa, with an escalating schedule for 12 months. The incidence and risk (Cox regression analysis) of clinical complications (hepatocellular carcinoma, ascites, jaundice, variceal bleeding, and encephalopathy) and death were calculated. RESULTS: Over median follow up periods of 55 months for treated and 58 for untreated subjects, seven and nine patients, respectively, died, and 20 and 32, respectively, developed at least one clinical complication (ns). Hepatocellular carcinoma developed in six treated and 19 untreated patients (p=0.018). Seven treated patients showed sustained aminotranferase normalisation and none died or developed complications. Clinical complications were significantly associated with low albumin, bilirubin, and prothrombin activity while hepatocellular carcinoma was significantly related to no treatment with interferon, oesophageal varices, and high alpha fetoprotein levels. By stratified analysis, the beneficial effect of interferon was statistically evident only in patients with baseline alpha fetoprotein levels > or =20 ng/ml. CONCLUSIONS: Interferon does not seem to affect overall or event free survival of patients with hepatitis C virus related cirrhosis while it seems to prevent the development of hepatocellular carcinoma. Patients who achieved sustained aminotransferase normalisation survived and did not develop any complications during follow up.

In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C.

Current evidence suggests that increased expression of Th1-associated cytokines is important for immune-mediated eradication of hepatitis C infection, while an increase in Th2-associated cytokines is associated with persistence of infection. In this study we evaluated the effects of thymosin-alpha1 (TA1), a naturally occurring thymic peptide, and interferon-alpha (IFN-alpha) on cytokine production in peripheral blood mononuclear cells from untreated patients with chronic hepatitis C. We examined the effect of incubation with TA1, IFN-alpha, or both, on production of Th1-associated cytokines (IL-2, IFN-gamma), Th2-associated cytokines (IL-4, IL-10), and synthesis of the antiviral protein 2',5'-oligoadenylate synthetase. TA1 treatment induced a significant increase in production of IL-2 and 2',5'-oligoadenylate synthetase. Smaller increases were also seen after treatment with IFN-alpha, while incubation with TA1 and IFN-alpha together led to an additive or synergistic effect. Incubation with TA1 resulted in a decrease in IL-4 and IL-10, whereas IFN-alpha increased these cytokines. The addition of TA1 to IFN-alpha significantly reversed this IFN-alpha-induced increase. Hence, TA1 treatment could benefit patients with hepatitis C infection by increasing the Th1-type response, fundamental for sustained clearance of hepatitis C; and by decreasing the Th2-type response, associated with persistence of viraemia.

Vitamin E as treatment for chronic hepatitis B: results of a randomized controlled pilot trial.

BACKGROUND AND AIMS: Interferon-alpha treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases. METHODS: We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months. RESULTS: The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls (P=0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively (P=0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls (P=0.0019). CONCLUSION: Vitamin E supplementation might be effective in the treatment of chronic hepatitis B.

Interferon-alpha plus ribavirin and amantadine in patients with post-transplant hepatitis C: results of a pilot study.

BACKGROUND: Recurrence of hepatitis C after liver transplantation is almost constant and may lead to graft loss. The results of treatment with interferon and/or other agents have been controversial. AIMS: To evaluate the efficacy and safety of combination therapy with interferon-alpha2b (3 MU, 3 times weekly), ribavirin (600 mg daily) and amantadine (100 mg daily) in post-transplant hepatitis C. PATIENTS AND METHODS: Enrolled in the study were 9 liver transplant recipients with histologically proven recurrent hepatitis C. Patients were treated for 12 months and followed up for 6 months after treatment. RESULTS: Treatment was not tolerated: only one patient completed the planned course, two stopped therapy within the first 3 months and 6 needed a change. However, mean alanine aminotransferase levels significantly decreased during treatment and were significantly lower than baseline at the end of follow-up. One patient out of 9 (11%) achieved a biochemical and virological sustained response. Control liver biopsy showed improvement in 2/7 patients, no change in 3 and worsening in 2. CONCLUSIONS: In recurrent post-transplant hepatitis C, antiviral treatment with interferon, ribavirin and amantadine seems to be poorly tolerated. However further studies are needed before expressing any conclusion on this potentially important option.

Soluble CD30 serum level in HCV-positive chronic active hepatitis: A surrogate marker of disease activity?

In the present study, high levels of CD30s, a glycoprotein preferentially expressed and released by T lymphocytes producing Th(2)-type cytokines, were seen in the sera of patients with chronic hepatitis C, and a correlation with histological activity of the disease was found. CD30s levels were assayed in the sera of 29 HCV RNA-positive patients with histologically proven chronic active hepatitis and in 30 healthy blood donors. Thirteen of 29 (45%) HCV patients had CD30s serum levels above the normal range (>20 U/ml). Mean CD30s serum levels were significantly higher in HCV patients than in controls (P<0.0005). A positive correlation was found between serum CD30s levels and both the histological activity index (r=0.59, P=0.001) and ALT serum levels (r=0.5; P=0.006). The raised CD30s level found in more severe HCV liver disease indirectly suggests activation and expansion of Th(2)cells. CD30s levels could represent a useful surrogate marker of activity in chronic HCV infections.

Interferon-alpha plus ribavirin in chronic hepatitis C resistant to previous interferon-alpha course: results of a randomized multicenter trial.

BACKGROUND/AIMS: Interferon-alpha plus ribavirin seem to be more efficacious than interferon monotherapy in chronic hepatitis C. In a multicenter randomized trial, we evaluated the efficacy of this association for interferon-alpha resistant chronic hepatitis C. METHODS: Fifty patients who were non-responders to recombinant or lymphoblastoid interferon-alpha were randomized to receive either ribavirin (800 mg/day) plus leucocytic interferon-alpha (3 mega units thrice weekly) or the same dose of interferon-alpha alone, for 6 months. Effects of therapy were evaluated by serum aminotransferase and hepatitis C virus RNA levels and control liver biopsies. RESULTS: At the end of treatment, aminotransferase levels become normal in 9/26 patients receiving combination therapy (35% [confidence interval, 16% to 53%]) and in 2/24 receiving interferon-alpha alone (8% [confidence interval, -3% to 19%]) (p = 0.03). Aminotransferase normalization was never associated with hepatitis C virus RNA clearance. All patients with normal aminotransferase relapsed after discontinuation of therapy. At the end of treatment, mean hepatitis C virus RNA levels significantly decreased only in the group receiving combination therapy, but returned to pretreatment values 6 months thereafter. No histological improvement was observed in either group. CONCLUSIONS: There is no indication for treatment with interferon-alpha at the dose of 3 mega units thrice weekly plus 800 mg/day of ribavirin for 6 months in chronic hepatitis C resistant to interferon-alpha.

Serum pancreatic enzyme concentrations in chronic viral liver diseases.

Serum amylase and lipase concentrations were determined in 78 patients with chronic liver diseases [26 chronic active hepatitis (CAH) and 52 liver cirrhosis] and in 15 healthy subjects. Pancreatic isoamylase concentrations and macroamylase complexes were assayed in hyperamylasemic sera. Serum amylase levels were abnormally elevated in 27 patients (35%; 22 liver cirrhosis, 5 CAH), whereas serum lipase levels were elevated in 16 patients (21%; 15 liver cirrhosis, 1 CAH). In 9 of the 27 hyperamylasemic patients, the hyperamylasemia was of pancreatic type. Macroamylasemic complexes were not detected in hyperamylasemic sera. Patients with liver cirrhosis had serum levels of amylase and lipase significantly higher than both the healthy subjects and the patients with CAH, while no significant differences were found in serum levels of these enzymes in patients with CAH as compared to the healthy subjects. A decreased liver metabolism of serum amylase and lipase in patients with chronic infective liver disease, especially in those having liver cirrhosis, may lead to an accumulation of these enzymes in the blood.