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Biomedical subjects

S J Hadziyannis

Publications and source records attributed to S J Hadziyannis.

At least 19 recordsLinked to original sources
PubMed2006

A partially overlapping treatment course with lamivudine and interferon in hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND: Treatment of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHBe-) with interferon or lamivudine alone is inefficient and reports of combination treatment with both drugs, equivocal so far. AIM: To investigate the efficacy of a lamivudine-interferon combination therapy in 36 patients HBeAg-negative CHBe-. METHODS: Lamivudine was administered from 1 to 12 months and interferon-alpha2b from 7 to 18 months. A historical control group of 36 CHBe- patients, matched for age and sex and treated with the same dosage of interferon-alpha2b was used. All patients were followed up for > or =12-month post-treatment. RESULTS: The biochemical response rate at the end of treatment was 78% in lamivudine-interferon and 52.8% in interferon-control group (P = 0.026) and at 12-month post-treatment 38.9% and 22.2%, respectively (P = 0.125). Alanine aminotransferase normalization and serum HBV-DNA levels < or =30 000 cp/mL were observed in 50.0% of lamivudine-interferon-treated and 30.6% of interferon-treated patients at the end of treatment (P =0.093) and in 22.2% and 13.9% of patients, respectively, at 12-month post-treatment (P = 0.358). Moreover, alanine aminotransferase normalization and undetectable serum HBV-DNA (<400 cp/mL) was observed in 30.6% of lamivudine-interferon-treated and 8.3% of interferon-treated patients at the end of treatment (P = 0.017) and in 8.3% and 0% of patients, respectively, at 12-month post-treatment (P = 0.076). CONCLUSIONS: In CHBe-, 12 months after ending a lamivudine-interferon partially overlapping 18-month combination course, 22% of patients still maintain normal alanine aminotransferase and HBV-DNA levels < or =30 000 cp/mL. However, a 12-month interferon monotherapy course may achieve similar responses.

Adolescent↗
PubMed2005

Changes in epidemiological patterns of HCV infection and their impact on liver disease over the last 20 years in Greece.

SUMMARY: The aim of this study was to investigate the relative frequency of hepatitis C virus (HCV) genotypes in Greek patients with chronic infection as well as possible secular changes in their distribution in relation to modes of transmission, age and time at acquisition of the infection and other variables. We evaluated 434 unselected patients, 241 males and 193 females with a median age of 46.2 years (18-75), with chronic HCV infection presenting during the period 1996-2000. HCV infection was confirmed by the detection of HCV-RNA by polymerase chain reaction (PCR), while HCV genotyping was performed by the Inno-LiPA assay. Liver biopsies were evaluated according to Ishak's scoring system. Of 434 patients, 167 had a history of blood transfusion [post-transfusion hepatitis (PTH)], 80 were i.v. drug users and in 187 the route of infection remained unknown. The overall distribution of HCV genotypes 1, 2, 3 and 4 was 47, 8.3, 27 and 15.2%, respectively. Genotype 3 was common in younger adults and i.v. drug users, whereas genotype 1 predominated in older people and PTH patients (P < 0.001 for both). Infection acquired before 1981 (group A) was related to transfusion and genotype 1, while after 1981 (group B) with i.v. drug use and genotype 3 (P < 0.01). Biopsy was available in 369 (85%) patients, of whom 22.5% had cirrhosis; 29.8% in group A and 9.9% in group B. In a multivariate analysis, cirrhosis was strongly associated with the duration of infection (P = 0.013). Our study revealed a change of HCV genotype distribution in the last 20 years among Greek patients with chronic HCV infection as a result of epidemiological changes in HCV transmission. The presence of cirrhosis was associated only with the duration of infection. These observations have impact both on prevention and treatment.

Adult↗
PubMed2004

Review article: current management of chronic hepatitis B.

Chronic hepatitis B can be diagnosed in patients with increased aminotransferases, hepatitis B virus viraemia and necroinflammation with fibrosis on liver biopsy. Although, ideally, all patients with chronic hepatitis B should be treated, therapeutic intervention is currently recommended for cases with a relatively satisfactory likelihood of response and/or advanced disease. A realistic therapeutic approach aims to sustain hepatitis B e antigen (HBeAg) loss and hepatitis B e antibody (anti-HBe) seroconversion in HBeAg-positive chronic hepatitis B and to sustain biochemical and virological remission in HBeAg-negative chronic hepatitis B. Currently, three drugs are licensed for chronic hepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. In patients with HBeAg-positive chronic hepatitis B, all of these drugs achieve HBeAg loss (24-33%) and anti-HBe seroconversion (12-30%) rates significantly superior to those observed in untreated placebo controls. In patients with HBeAg-negative chronic hepatitis B, the sustained off-therapy response rate is 20-25% after a > or =12-month course of interferon-alpha and minimal (<10%), if any, after a 12-month course of lamivudine or adefovir. Long-term lamivudine induces an initial response in 70-90% of patients, but only 30-40% of patients remain in remission after the third year due to progressively increasing viral resistance. Long-term adefovir achieves a response in approximately 70% of patients at 12 months, which is maintained at 24 months with rare (<2%) drug resistance. Adefovir is also effective against lamivudine-resistant strains. Many other anti-viral agents, immunomodulatory approaches and combination therapies are currently being evaluated in chronic hepatitis B.

Antiviral Agents↗
PubMed2003

Thrombotic risk factors and extent of liver fibrosis in chronic viral hepatitis.

BACKGROUND AND AIMS: Thrombosis of the small intrahepatic veins has been suggested to trigger liver tissue remodelling. We evaluated the prevalence of multiple thrombotic risk factors and their association with the extent of fibrosis in chronic viral hepatitis. METHODS: Ninety consecutive patients with chronic hepatitis B or C without malignancy, a history of venous thrombosis, or antiviral/immunosuppressive therapy within the last six months were included. Thrombophilic and coagulation factors were evaluated on the liver biopsy day. RESULTS: One or more thrombotic risk factors were found in 68% and > or =2 factors in 37% of patients. Higher necroinflammatory activity was independently associated with higher prothrombin time (p=0.003), alanine aminotransferase level (p=0.011), and histological staging (p=0.018). Patients with staging scores of 4-6 compared with those with scores of 0-3 more frequently had deficiency of protein C (24% v 3%; p=0.007), antithrombin III (28% v 5%; p=0.005), and plasminogen (19% v 2%; p=0.03), and a trend for more frequent activated protein C resistance (8% v 0%; p=0.075). The presence of > or =1 significant thrombotic risk factor was observed in 11/25 (44%) patients with staging scores of 4-6 and in 6/65 (9%) patients with scores of 0-3 (p<0.001), being the only variable independently associated with advanced staging (odds ratio 2.4, p=0.02). CONCLUSIONS: Thrombotic risk factors are frequently detected in patients with chronic viral hepatitis and the presence of > or =1 significant factor is associated with more advanced fibrosis. Whether the association of such thrombophilic conditions with advanced fibrosis is a primary or secondary phenomenon and whether their development in combination with local inflammation accelerate the progression of liver fibrosis need further evaluation.

Adult↗
PubMed2001

Immunopathogenesis of hepatitis B e antigen negative chronic hepatitis B infection.

Hepatitis B e antigen (HBeAg) negative chronic hepatitis B represents currently the predominant form of chronic hepatitis due to the hepatitis B virus (HBV) in several parts of the world. In this review, recent data regarding the process of HBeAg negative HBV strain selection during the course of chronic HBV infection are presented and the potential virus and/or host-mediated mechanisms that lead to chronic liver necroinflammation, i.e. chronic hepatitis are outlined.

Hepatitis B e Antigens↗
PubMed2001

The long-term outcome of interferon-alpha treated and untreated patients with HBeAg-negative chronic hepatitis B.

BACKGROUND/AIMS: This study aimed to evaluate the effect of interferon-alpha therapy on the long-term outcome of HBeAg-negative chronic hepatitis B. METHODS: A cohort of 209 interferon-alpha treated and 195 untreated patients with histologically documented HBeAg-negative chronic hepatitis B were closely followed for a mean of 6 (1-13.5) years. Patients with decompensated liver disease and/or hepatocellular carcinoma at presentation were excluded. RESULTS: Survival and complication (liver decompensation and/or hepatocellular carcinoma) -free survival were significantly worse in patients with compared to those without baseline cirrhosis and in patients older compared to those younger than 45 years (P < 10(-4)). Sustained biochemical remission was achieved in 57 treated patients. Sustained responders had significantly better survival and complication-free survival than non-sustained responders (P = 0.027 and P = 0.019, respectively) or than untreated patients (P = 0.048 and P = 0.012, respectively). Multivariate analysis showed that absence of baseline cirrhosis, younger age, and sustained biochemical remission were independently associated with an improved outcome. CONCLUSION: In patients with HBeAg-negative chronic hepatitis B, sustained biochemical remission induced by interferon-alpha is associated with improved long-term outcome, even in the presence of cirrhosis and old age, both known factors associated with worse survival. Therefore, long-term biochemical remission appears to represent a satisfactory therapeutic target in this setting.

Adolescent↗
PubMed2001

Induction interferon therapy in naïve patients with chronic hepatitis C: increased end-of-treatment virological responses but absence of long-term benefit.

BACKGROUND AND AIMS: The low efficacy of interferon monotherapy and data from viral kinetic studies led us to evaluate the efficacy of interferon administered daily in chronic hepatitis C. PATIENTS AND METHODS: Thirty-eight naïve patients with chronic hepatitis C and active liver disease randomly received 3 or 5 MU IFN-alpha daily for 1 month, followed by the same dose three times a week for 11 months. Results were compared to a three-times-a-week scheme of 3 MU IFN-alpha for 1 year. RESULTS: At the end of the induction period, 27 out of 38 (71%) patients had cleared HCV-RNA with a significantly higher rate in the 5 MU than in the 3 MU group (17 out of 18 or 94% vs. 10 out of 20 or 50%, P=0.003). The end-of-treatment virological response rate was 66% (25 out of 38) in the induction groups and 40% (10 out of 25) in the control group (P=0.04). Six months after completion of therapy, the sustained response rate dropped to 29% (11 out of 38) compared to 28% (7 out of 25) in the standard regimen. CONCLUSIONS: In chronic hepatitis C, treatment with 5 or 3 MU IFN-alpha daily during the first month of a standard IFN regimen leads to significantly increased end-of-treatment virological responses, but long-term responses are similar to those of standard IFN monotherapy.

Adult↗
PubMed2001

Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta-analysis.

BACKGROUND: The role of interferon in the prevention of hepatocellular carcinoma remains controversial. AIM: In this meta-analysis we evaluated the hepatocellular carcinoma incidence in interferon-treated and -untreated patients with hepatitis C virus-related cirrhosis. METHODS: Eleven studies with 2178 patients were found to fulfil our inclusion criteria. The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated from the raw study data. RESULTS: Hepatocellular carcinoma development was significantly more frequent in untreated (21.5%) than in interferon-treated patients (8.2%; OR: 3.0, 95% CI: 2.3-3.9). In the five studies reporting hepatocellular carcinoma incidence in patients with and without sustained response to interferon, hepatocellular carcinoma was detected at a much higher rate in patients without (9%) than with a sustained response (0.9%; OR: 3.7, 95% CI: 1.7-7.8). Moreover, hepatocellular carcinoma developed significantly more frequently in the untreated patients than in the non-sustained responders (OR: 2.7, 95% CI: 1.9-3.9). The benefit from interferon on hepatocellular carcinoma incidence was not influenced by the study type (prospective or retrospective), the follow-up duration, or the study origin. CONCLUSIONS: Interferon therapy significantly reduces the hepatocellular carcinoma risk in patients with hepatitis C virus cirrhosis. Hepatocellular carcinoma development becomes almost negligible among sustained responders, but a reduction in hepatocellular carcinoma incidence is also achieved even in the non-sustained responders.

Antineoplastic Agents↗
PubMed2001

Diagnosis and management of pre-core mutant chronic hepatitis B.

Chronic hepatitis due to pre-core hepatitis B virus (HBV) mutants presents as hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). HBeAg-negative CHB represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti-HBe. It is usually associated with pre-core stop codon mutation at nucleotide 1896 (mainly selected in non-A HBV genotypes), but also with other pre-core changes or with mutations in the basic core promoter region (mainly in HBV genotype A). In chronic HBV infections, pre-core mutants can be detected both in patients with HBeAg-negative CHB and in inactive hepatitis B surface antigen (HBsAg) carriers. The diagnosis of HBeAg-negative CHB is based on HBsAg positivity, HBeAg negativity, and mainly on increased alanine aminotransferase (ALT) and serum HBV-DNA levels and exclusion of other causes of liver disease. The differential diagnosis between patients with CHB and inactive HBsAg carriers can be made only by close follow-up of aminotransferase activity and viraemia levels, although the cut-off level of serum HBV DNA has not been definitely determined. IgM anti-HBc levels have also been suggested as an index that increases the diagnostic accuracy for transient hepatitis flares, while liver biopsy confirms the diagnosis and evaluates the severity of the liver disease. Interferon-alpha (IFN-alpha) and lamivudine are the two drugs that have been tried, mainly in the management of HBeAg-negative CHB. A 12-month course of IFN-alpha achieves sustained biochemical remission in about 20% of patients, which has been associated with improvement in the long-term outcome of this subset. A 12-month course of lamivudine is rather ineffective, maintaining remission in less than 15% of patients after cessation of therapy. Long-term lamivudine is associated with progressively increasing rate of virological and subsequent biochemical breakthroughs due to YMDD mutants, with approximately 30% of patients remaining in remission in the third year of therapy. Several other antiviral agents are currently being evaluated in this setting with combined regimens being the most reasonable step for the near future.

Antiviral Agents↗
PubMed2001

Interferon alpha treatment and retreatment of hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND AND AIMS: In hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHBe-), interferon (IFN) achieves very low biochemical sustained response rates. No information exists on retreatment. METHODS: Two hundred sixteen CHBe- patients treated for 5 or 12 months with 3 MU IFN-alpha2b thrice weekly and retreated (51 patients, 60 courses) because of no response or relapse were retrospectively analyzed. RESULTS: After 7.0 years of median follow-up, 39 naive patients (18.1%) were still in biochemical and virologic remission after a single IFN course. Longer treatment and a biochemical response within 4 months were significant predictors, inversely related to relapse by multivariate analysis (relative hazard [RH], 0.611; 95% confidence interval [CI], 0.448-0.834 and RH, 0.290; 95% CI, 0.192-0.438, respectively). Retreatment resulted in 18.4% sustained response by intention-to-treat (18 of 98 patients). Patients with sustained response had persistently normal alanine aminotransferase levels, undetectable hepatitis B virus (HBV) DNA by molecular hybridization, and significant improvement of histologic grade, and 32% of them lost hepatitis B surface antigen. In sustained responders, serum HBV DNA was undetectable or very low at the end of treatment and at the end of follow-up (median 3934 and 903 copies/mL, respectively) by quantitative polymerase chain reaction. CONCLUSIONS: IFN induced long-term biochemical and virologic remission in approximately 18% of naive or retreated patients with CHBe-. Sustained responders exhibited significant histologic improvement and a high rate of HBsAg loss.

Adult↗
PubMed2001

Autoimmune hepatitis associated with the antiphospholipid syndrome.

The antiphospholipid syndrome has rarely been described in patients with autoimmune hepatitis. Two cases with type I autoimmune hepatitis and antiphospholipid syndrome are presented. The first case is that of a 53-year-old Caucasian female with a history of arterial thrombosis and fetal loss who was submitted to clinical and laboratory testing due to persistent transaminasaemia and was found to have autoimmune hepatitis. Antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) were positive. The second case is that of a 31-year-old Caucasian woman with a history of autoimmune hepatitis who was submitted to laboratory testing due to a second-trimester fetal death, revealing an increased activated partial thromboplastin time and positive antiphospholipid antibodies. In conclusion, secondary antiphospholipid syndrome may accompany autoimmune hepatitis.

Adult↗
PubMed2000

Complex management issues: management of HCV in the atypical patient.

Some patients with chronic hepatitis C virus (HCV) infection demonstrate atypical features of presentation and clinical course. These features may be due to direct or indirect effects of the underlying HCV infection or may be part of a separate clinical syndrome. Patients that can be categorized as 'atypical' include immunosuppressed individuals (hypogammaglobulinaemic, co-infected with human immunodeficiency virus, recipients of solid organ or haematopoietic cell transplants, those with associated disease requiring chronic immunosuppressive therapy and patients with chronic renal failure on haemodialysis) as well as patients with various extra-hepatic (HCV-associated mixed cryoglobulinaemia, membranoproliferative glomerulonephritis etc) or autoimmune manifestations. Since many of these patients have been excluded from the large trials evaluating the efficacy of interferon-alpha alone or in combination with ribavirin, data regarding management are limited. In this chapter, the available information regarding the treatment of these patients is reviewed and the frequently encountered therapeutic dilemmas discussed. Finally, some reasonable therapeutic approaches are suggested while the need for controlled studies for these groups of patients is emphasized.

Agammaglobulinemia↗
PubMed2000

Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B.

We evaluated the safety and efficacy of long-term lamivudine monotherapy in a group of 25 patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Lamivudine was administered in a daily dose of 150 mg for a mean of 26 +/- 7 months and was well tolerated. No patient lost hepatitis B surface antigen (HBsAg). The rate of initial biochemical response increased from 88% at 6 months to 96% at 12 months of therapy, but it progressively decreased thereafter; the biochemical remission rate was 68% at 18 months, 59. 5% at 24 months, and 42.5% at >/=30 months. Alanine transaminase (ALT) increased to higher than the baseline levels in 8 of the 11 patients with a biochemical breakthrough reaching acute hepatitis levels in 6 of them. Acute icteric hepatitis developed in one patient. The virologic remission rate assessed by a sensitive quantitative polymerase chain reaction (PCR) assay was 68% at both 6 and 12 months, decreasing thereafter to 52% at 18 months and to 41. 6% at both 24 and >/=30 months. Virologic breakthroughs were always persistent and preceded ALT elevations by a median of 4 (3-24) months. YMDD mutants were detected in all patients with a virologic breakthrough. In conclusion, in patients with HBeAg-negative chronic hepatitis B, long-term lamivudine therapy is safe and is associated with high biochemical and virologic response rates at the end of the first year. However, response rates tend to decrease with time and breakthroughs due to YMDD mutants accumulate. ALT activity during breakthroughs often exceeds the baseline and may reach even acute hepatitis levels.

Adult↗
PubMed2000

Gliclazide-induced acute hepatitis.

There are few reports in the literature related to sulfonylurea-induced hepatotoxicity. We describe the case of acute hepatitis induced by gliclazide, a second generation sulfonylurea. A 60-year-old woman with diabetes mellitus (type 2) developed an acute icteric hepatitis-like illness 6 weeks after the initiation of gliclazide therapy. Other causes of acute hepatocellular necrosis were excluded. Liver histology showed marked portal inflammation with lymphocytes, monocytes and eosinophils, associated with lobular inflammation (indicative of a histological pattern consistent with drug-induced hepatitis). The drug was immediately withdrawn and the patient was given glibenclamide. The patient recovered clinically and, in less than 4 weeks, her serum bilirubin and aminotransferases returned to normal levels. We believe that this is the first description of acute hepatitis caused by an idiosyncratic adverse reaction to gliclazide or to one of its metabolites. In conclusion, this case strongly suggests that gliclazide can induce acute icteric liver necro-inflammation which may be misdiagnosed clinically as acute viral hepatitis. In patients who show abnormal liver function tests, the immediate discontinuation of gliclazide is recommended.

Chemical and Drug Induced Liver Injury↗
PubMed2000

Epidemiology of hepatitis C virus infection in seven European Union countries: a critical analysis of the literature. HENCORE Group. (Hepatitis C European Network for Co-operative Research.

Hepatitis C is now recognized as the most common infection causing chronic liver disease in the European population. Our aim was to assess the prevalence of the antibody to hepatitis C virus (HCV), and the incidence of HCV seroconversion in the general population and the main risk groups, namely intravenous drug users, haemodialysis and transfused patients, in seven countries of the European Union, by carrying out a critical analysis of the literature. Data sources used were the Medline database and a manual search using the key words: hepatitis C, prevalence, incidence, transmission, risk factors and epidemiology. Articles published between January 1990 and March 1997 were reviewed. Articles were reviewed according to a critical analysis method regarding title, type of article, study design, period and population, tests, results and their consistency with data. The tests performed were mainly second- or third-generation serological tests. The average prevalence rate in blood donors was 1%, with a north-south gradient ranging from 0.04% to 2%. Prevalence varied from 20% to 30% in haemodialysis patients. The incidence in transfused patients was less than 1% after 1991. The prevalence in intravenous drug users was about 80%. Multicentre studies conducted in larger samples are needed to obtain more accurate and reliable results, in particular. However, the epidemiological studies available allowed us to assess the magnitude of HCV infection in Europe.

Europe↗