Treatment of hepatitis B e antigen-negative chronic hepatitis B with lamivudine.
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Drug Administration Schedule↗
Biomedical subjects
Mario Rizzetto
Publications and source records attributed to Mario Rizzetto.
Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study.
BACKGROUND/AIMS: This study assess prevalence, risk factors, and clinical and virological features of dual hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. METHODS: We evaluated 837 hepatitis B surface antigen positive patients, prospectively enrolled in 14 Italian units. RESULTS: Anti-HCV was present in 59 cases (7%); age specific prevalences were 4.5% (0-30 years), 4.4% (>30-50) and 14% (>50). Independent predictors of dual infection were age >42 years, history of I.V. drug use (IDU), blood transfusion and residence in the South of the country. The strength of the association with IDU was high, but this exposure accounted for five coinfection cases only. Cirrhosis was present in 107 of the 709 patients with HBV alone (15.1%), in 30 of 69 with hepatitis D virus coinfection (43%) and in 17 of 59 with HCV coinfection (28.8%); a light alcohol use was marginally associated with cirrhosis. Of 36 B/C coinfected patients, 16 (44.4%) had only HBV-DNA in serum, (median age=47.5 years) five (13.9%) had both HBV-DNA and HCV-RNA (age=53), nine (25%) had HCV-RNA alone (age=59) and six (16.7%) tested negative for both. CONCLUSIONS: This study depicts the epidemiological and clinical burden of dual HBV/HCV infection in Italy.
Adult↗
Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis.
The relations of dietary habits to insulin sensitivity and postprandial triglyceride metabolism were evaluated in 25 patients with nonalcoholic steatohepatitis (NASH) and 25 age-, body mass index (BMI)-, and gender-matched healthy controls. After a 7-day alimentary record, they underwent a standard oral glucose tolerance test (OGTT), and the insulin sensitivity index (ISI) was calculated from the OGTT; an oral fat load test was also performed in 15 patients and 15 controls. The dietary intake of NASH patients was richer in saturated fat (13.7% +/- 3.1% vs. 10.0% +/- 2.1% total kcal, respectively, P =.0001) and in cholesterol (506 +/- 108 vs. 405 +/- 111 mg/d, respectively, P =.002) and was poorer in polyunsaturated fat (10.0% +/- 3.5% vs. 14.5% +/- 4.0% total fat, respectively, P =.0001), fiber (12.9 +/- 4.1 vs. 23.2 +/- 7.8 g/d, respectively, P =.000), and antioxidant vitamins C (84.3 +/- 43.1 vs. 144.2 +/- 63.1 mg/d, respectively, P =.0001) and E (5.4 +/- 1.9 vs. 8.7 +/- 2.9 mg/d, respectively, P =.0001). The ISI was significantly lower in NASH patients than in controls. Postprandial total and very low density lipoproteins triglyceride at +4 hours and +6 hours, triglyceride area under the curve, and incremental triglyceride area under the curve were higher in NASH compared with controls. Saturated fat intake correlated with ISI, with the different features of the metabolic syndrome, and with the postprandial rise of triglyceride. Postprandial apolipoprotein (Apo) B48 and ApoB100 responses in NASH were flat and strikingly dissociated from the triglyceride response, suggesting a defect in ApoB secretion. In conclusion, dietary habits may promote steatohepatitis directly by modulating hepatic triglyceride accumulation and antioxidant activity as well as indirectly by affecting insulin sensitivity and postprandial triglyceride metabolism. Our findings provide further rationale for more specific alimentary interventions, particularly in nonobese, nondiabetic normolipidemic NASH patients.
Adult↗
Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome.
Nonalcoholic fatty liver disease (NAFLD) has been associated with the insulin-resistance syndrome, at present defined as the metabolic syndrome, whose limits were recently set. We assessed the prevalence of the metabolic syndrome in 304 consecutive NAFLD patients without overt diabetes, on the basis of 3 or more criteria out of 5 defined by the U.S. National Institutes of Health (waist circumference, glucose, high-density lipoprotein [HDL]-cholesterol, triglycerides, and arterial pressure). The prevalence of the metabolic syndrome increased with increasing body mass index, from 18% in normal-weight subjects to 67% in obesity. Insulin resistance (Homeostasis Model Assessment method) was significantly associated with the metabolic syndrome (odds ratio [OR], 2.5; 95% CI, 1.5-4.2; P <.001). Liver biopsy was available in 163 cases (54%). A total of 120 patients (73.6%) were classified as having nonalcoholic steatohepatitis (NASH); 88% of them had a metabolic syndrome (vs. 53% of patients with pure fatty liver; P <.0001). Logistic regression analysis confirmed that the presence of metabolic syndrome carried a high risk of NASH among NAFLD subjects (OR, 3.2; 95% CI, 1.2-8.9; P =.026) after correction for sex, age, and body mass. In particular, the syndrome was associated with a high risk of severe fibrosis (OR, 3.5; 95% CI, 1.1-11.2; P =.032). In conclusion, the presence of multiple metabolic disorders is associated with a potentially progressive, severe liver disease. The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension, and ultimately the metabolic syndrome puts a very large population at risk of forthcoming liver failure in the next decades.
Adult↗
Helicobacter pylori and coronary heart disease: which directions for future studies?
Classical risk factors explain the pathogenesis of coronary heart disease (CHD) in only a proportion of cases; therefore, the need to investigate the possible role of "new" agents has incited intense research. Since 1994, a number of studies regarding the possible involvement of Helicobacter pylori (H. pylori) have been published with conflicting results. Establishing a causal link between this infection and CHD would be of major public health importance, since the eradication of the bacterium is easy and much less expensive than long-term treatment of the other risk factors. The main cause of this discordance was the vast heterogeneity of such studies: sufficiently powerful design was found only in few investigations, CHD was defined with a low degree of homogeneity, biases were obvious in the control groups, thus giving room for large variation in the adjustment of potential confounding factors. The present paper attempts to highlight the future directions towards which research should be headed in this area to establish a causal role of H. pylori infection in the pathogenesis of CHD. Future research should take three directions: 1) prospective population-based studies in which the incidence or the recurrence of CHD be evaluated in correlation with H. pylori status, 2) intervention trials, focusing separately on the chronic and acute phases of coronary heart disease and, 3) studies of physiopathology (both in the animal model and humans) to understand the potential biological plausibility.
Animals↗
Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations.
Aceruloplasminemia is a recessive disorder characterized by anemia, iron overload, and neurodegeneration, caused by the absence of ceruloplasmin (Cp), a multicopper oxidase important for iron export. Few patients homozygous for loss of function mutations of the Cp gene have been reported. We describe a 62-year-old white woman with heavy liver iron overload, diabetes, anemia, and neurologic symptoms. She was compound heterozygote for 2 novel mutations that result in the absence of hepatocyte Cp: an adenine insertion at nucleotide 2917 causing a truncated protein and a C-G transversion causing a glutamine-->glutamic acid substitution at position 146. Although rare in whites, aceruloplasminemia should be considered in the differential diagnosis of unexplained anemia associated with iron overload, because these features anticipate progressive neurologic symptoms. We propose that anemia, secondary to the impaired macrophage iron release, plays a major role in hepatic iron overload through increased absorption mediated by the erythroid regulator.
Anemia↗
Progress in the prevention and control of viral hepatitis type B: closing remarks.
Hepatitis type B remains an important disease globally. Rapid advances have been made during the last two decades in the understanding of the biology of HBV, the complex interaction between the virus and the host, and the pathology and the clinical aspects of infection. Mass vaccination has been shown to be a safe and highly effective means for the control and prevention of hepatitis B. The presence of a large worldwide reservoir of carriers requires a continuous effort to develop new drugs for the treatment of persistent HBV infection. Efforts to sustain immunization programs and to make vaccines and drugs available to countries with limited resources, are the main challenges to the eradication of hepatitis B in the next few decades.
Adult↗
Treatment of recurrent hepatitis C in liver transplants: efficacy of a six versus a twelve month course of interferon alfa 2b with ribavirin.
BACKGROUND/AIMS: Interferon (IFN) with ribavirin combination therapy (CT) was proposed for the treatment of hepatitis C recurring in liver transplants. We assessed the efficacy of two protocols of CT in transplanted patients with recurrent severe hepatitis C virus (HCV) hepatitis. METHODS: Fifty-seven patients (68% genotype 1b) were treated with IFN alfa-2b 3 million units three times weekly and oral ribavirin 800mg/die for 6 or 12 months. Study end-points were the end of treatment (ETVR) and the 12-month post-therapy sustained virologic response (SVR; negative HCV-RNA). RESULTS: ETVR was induced in 9/27 (33%) and in 7/30 patients (23%) treated, respectively, for 6 and 12 months (P=0.4); a SVR was induced in six (22%) of the former and five (17%) of the latter (P=0.4). HCV genotype non-1 patients responded better than genotype 1 (SVR: 43% in genotype non-1 versus 12% in genotype 1, P: 0.02). In ETV responders the hepatitis activity index improved by >2 points in biopsies taken after therapy compared to pre-therapy biopsies. Anemia and leukopenia required reduction of therapy in 51% of the patients. CONCLUSIONS: CT is efficacious in controlling HCV disease in about 20% of transplants with recurrent hepatitis C. Six months of therapy are as efficacious as 12 months.
Adult↗
Helicobacter pylori seroprevalence in patients with autoimmune hepatitis.
Autoimmune hepatitis is characterized by a continuing hepatocyte necrosis that usually progresses to liver cirrhosis. Autoimmunity is also a feature of chronic infection by Helicobacter pylori, a gram-negative bacterium involved in the pathogenesis of peptic ulcer and upper gastrointestinal bleeding, with both events frequently occurring in patients with chronic liver disease. A newly described pathogenetic mechanism for chronic hepatitis and hepatocellular carcinoma in the mouse is linked to Helicobacter spp. infection. A high prevalence of H. pylori infection was demonstrated in patients with viral-related cirrhosis but never studied in cases of autoimmune hepatitis. In a case-control study, we examined 31 consecutive patients (25 women and 6 men, age range 20-66, mean age 46 +/- 4.3 years) suffering from autoimmune hepatitis and 62 sex- and age-matched blood donors (50 women, 12 men, age range 20-65, mean age 46 +/- 5.4 years) resident in the same area. Antibodies to H. pylori were present in 20 of 31 (64.5%) autoimmune patients compared to 33 of 62 (53.2%) controls (P = 0.3, odds ratio 1.60, 95% CI 0.60-4.28). The difference was not statistically significant either in female or male patients. In conclusion, the prevalence of H. pylori infection in patients and controls was similar in our study of patients with chronic autoimmune hepatitis.
Antibodies, Bacterial↗
Efficacy of irbesartan, a receptor selective antagonist of angiotensin II, in reducing portal hypertension.
The use of angiotensin II antagonists in the treatment of portal hypertension remains controversial. Our aims were to assess the effect of Irbesartan on portal pressure and to evaluate its safety in cirrhotic patients with portal hypertension. Twenty-five cirrhotic patients were treated in a pilot study with Irbesartan 300 mg orally once daily for 60 days. Hemodynamic evaluations and biochemical tests were performed before therapy and after two months of treatment. Three patients (12%) discontinued treatment for symptomatic arterial hypotension (mean arterial pressure -26.% +/- 3.1 versus basal). In the 18 responders, the hepatic venous pressure gradient diminished by a mean of 18.1% +/- 10.5 from baseline (p = 0.02); the gradient decreased by 20% or more in only 5 patients (23%). The mean arterial pressure decreased significantly during therapy (92 +/- 7 vs 109 +/- 25 mm Hg, P < 0.001). In conclusions, Irbesartan induced a marginal reduction in portal pressure and its safety was limited by the pronounced effects on arterial pressure.
Angiotensin Receptor Antagonists↗
Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma.
BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis; whether NASH plays also a role in the development of hepatocellular carcinoma (HCC) is unknown. METHODS: Among 641 cirrhosis-associated HCCs, we retrospectively identified 44 patients with cryptogenic cirrhosis (CC). Of these, 23 were actively followed up and were compared in a case-control study with viral- and alcohol-associated HCC. Family and personal history of diabetes, hypertension, coronary heart disease, dyslipidemia, obesity, and biochemical data were compared between groups. Iron status and presence of mutations in the HFE gene of familiar hemochromatosis were also determined. RESULTS: Family history was not different in relation to etiology. The prevalence of obesity and diabetes was significantly higher in patients with CC. Although liver function was similar, CC patients had higher glucose, cholesterol, and triglyceride plasma levels, increased parameters of insulin resistance, and lower aminotransferase levels. Iron status and prevalence of mutations in the HFE gene did not differ. Logistic regression analysis identified in sequence hypertriglyceridemia, diabetes, and normal aminotransferases as independent factors associated with HCC arising in CC. CONCLUSIONS: Features suggestive of NASH are more frequently observed in HCC arising in patients with CC than in age- and sex-matched HCC patients of well-defined viral or alcoholic etiology. HCC may represent a late complication of NASH-related cirrhosis.
Aged↗
Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association.
This study aims to determine the presence of the components of the metabolic syndrome in primary nonalcoholic steatohepatitis (NASH) and to assess the role of liver disease in the genesis of peripheral hyperinsulinemia. Nineteen patients (18 men and 1 woman; mean age, +/- SD, 38 +/- 10 years; body mass index [BMI], 26 +/- 2 kg/m(2)) with histologic evidence of NASH were enrolled; 19 age- and sex-matched normal subjects were investigated as controls. Plasma glucose, insulin, and C-peptide levels were measured during an oral glucose tolerance test, and a frequently sampled intravenous glucose tolerance test (FSIGT), analyzed by minimal modeling technique, was performed. Compared with controls, the NASH group had lower insulin sensitivity (3.84 +/- 2.44 vs. 7.48 +/- 3.01 10(-4) x min(-1)/microU/mL; P =.0003) and higher total insulin secretion (21 +/- 13 vs. 10 +/- 3 nmol/L in 240 minutes; P =.001). Hepatic insulin extraction was similar in both groups (69.8% +/- 16.1% vs. 70.2% +/- 18.3%; P =.854). According to the results of the oral glucose tolerance test, no patient was classified as diabetic, 5 were classified as glucose intolerant, and 1 was classified as having impaired fasting glycemia. Nine patients (47%) had at least the 2 minimum criteria required to define the metabolic syndrome according to the European Group for the Study of Insulin Resistance (EGIR). In conclusion, hyperinsulinemia and insulin resistance occur frequently in patients with NASH; these conditions do not stem from a reduced hepatic insulin extraction but from an enhanced pancreatic insulin secretion compensatory to reduced insulin sensitivity. The derangement of insulin regulation, often associated with the metabolic syndrome, may play a causal role in the pathogenesis of NASH.
Adult↗
A randomized 4-arm multicenter study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C relapsing after interferon monotherapy.
To determine whether a higher dosage of interferon (IFN) and/or a prolonged time of administration may improve the efficacy of combination therapy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C relapsing after 1 or more previous treatment courses with IFN monotherapy. Group A (n = 70) received 3 MU IFN alfa-2b 3 times per week plus ribavirin 1,000 mg/d for 12 months; group B (n = 70) received 5 MU 3 times per week plus ribavirin for 12 months; group C (n = 82) received 3 MU 3 times per week plus ribavirin for 6 months, and group D (n = 73) received 5 MU 3 times per week plus ribavirin for 6 months. The primary end point was the clearance of viremia at the end of 6-month follow-up: test results for hepatitis C virus (HCV)-RNA were negative in 54% of group A, 56% of group B, 40% of group C, and 49% of group D patients (P = NS). Among patients with genotype 1 and 4, the sustained response was significantly higher in groups A and B than in group C (45%, 49% vs. 22%, P =.03; group D = 33%, P = NS). In patients with genotype 2 and 3, the sustained virologic response was not affected by the different regimens (group A = 69%, group B = 68%, group C = 62%, group D = 71%, P = NS). In conclusion, duration of therapy rather than IFN dosage is more important in increasing the sustained virologic rate among HCV-positive patients with genotype 1 and 4 relapsing after IFN monotherapy; patients with genotypes 2 and 3 can be effectively retreated with a 6-month course of combination therapy, avoiding unnecessary side effects and waste of resources.
Adult↗
Spectral electroencephalogram analysis in hepatic encephalopathy and liver transplantation.
The aim of this study is to evaluate the role of spectral electroencephalogram (EEG) analysis ((S)EEG) in quantitating brain dysfunction in cirrhotic patients, showing conditions of minimal hepatic encephalopathy (HE), and determining the impact of orthotopic liver transplantation (OLT) on its correction. (S)EEG was compared with visual EEG ((V)EEG) in 44 cirrhotic patients waiting for OLT and 44 healthy controls. Eighteen patients had overt HE, and 26 patients had no apparent HE. Twenty-one transplant recipients were reexamined 6 months after OLT. Computerized (S)EEG was performed by mean dominant frequency (MDF) and the occipital alpha-theta ratio, expressed as its logarithmic transformation (LogR). All patients underwent psychometric assessment. MDF and LogR correlated significantly with Child-Pugh score (P <.05) and the presence of HE (P <.0001). (S)EEG and (V)EEG determined minimal HE in 8 (31%) and 6 (23%) of 26 patients without overt HE, respectively. (S)EEG did not correlate with age, sex, cause of liver disease, portal hypertension, or psychometric test results. MDF and LogR improved in many transplant recipients. LogR was significantly lower in OLT candidates who died before OLT compared with OLT survivors. In conclusion, (S)EEG provides reliable quantitative information to evaluate the degree of HE and appears more sensitive than (V)EEG to discriminate a subclinical stage of HE. The improvement in (S)EEG results observed in transplant recipients confirms the reversibility of bioelectric brain dysfunction with restoration of liver functions.
Adolescent↗
Successful closure of a postsurgical benign esophagomediastinal fistula by temporary placement of a polyester, expandable stent: Case report and review.
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Adenocarcinoma↗
High-grade B-cell lymphoma arising in mucosa-associated lymphoid tissue of the duodenum.
Duodenal mucosa-associated lymphoid tissue lymphoma is a rare neoplasm. We report a case of a 70-year-old man with non-Hodgkin's lymphoma located in the descending duodenum that was not associated with Helicobacter pylori infection of the stomach. A surgical resection due to obstruction of the bowel lumen above the ligament of Treitz was performed. No invasion into the adjacent structure was confirmed at surgery. The pathological examination showed an infiltration of the duodenal mucosa and submucosa with B lymphocytes. Monoclonal proliferation of the lymphoid tissue was demonstrated by polymerase chain reaction. The histological appearance and the demonstration of monoclonality fulfilled the criteria for malignant high-grade B-cell lymphoma arising from mucosa-associated lymphoid tissue.
Aged↗
Renal failure in cirrhotic patients: role of terlipressin in clinical approach to hepatorenal syndrome type 2.
OBJECTIVES: Renal failure secondary to hepatorenal syndrome or to organic renal disease occurs frequently in cirrhotic patients with portal hypertension. The present prospective study investigates the usefulness of terlipressin in both the diagnostic and the therapeutic approach to cirrhotics with renal failure. PATIENTS AND METHODS: Sixteen patients were studied: 11 with hepatorenal syndrome type 2 (group 1) and five with organic renal disease (group 2). All received terlipressin (1 mg/4 h intravenously) for 7 days. Subsequently, 12 patients (nine from group 1 and three from group 2) underwent a transjugular intrahepatic portosystemic shunt. RESULTS: Terlipressin significantly improved renal function (serum creatinine, 1.8 +/- 0.8 versus 2.4 +/- 0.9 mg/dl; blood creatinine clearance, 53 +/- 8 versus 21.3 +/- 8.7 ml/min; P < 0.05) in group 1 [8/11 patients (73%) versus 1/5 (20%) of group 2; P < 0.05]. The only patient in group 2 who responded to terlipressin had a mixed renal dysfunction. Renal function improved significantly after transjugular portosystemic shunt in all patients who responded to terlipressin. CONCLUSIONS: Terlipressin administration significantly improves renal function in cirrhotic patients with hepatorenal syndrome type 2 but not in organic kidney failure. By providing the critical information that a patient's kidney function is (or is not) reversible, a trial with terlipressin may be useful when selecting cirrhotic patients with renal failure as candidates for a transjugular intrahepatic portosystemic shunt or liver transplantation.
Female↗
Re-treatment with interferon-beta of patients with chronic hepatitis C virus infection.
OBJECTIVE: To evaluate the efficacy of interferon-beta (IFN-beta) in the re-treatment of patients with chronic hepatitis C who did not respond to IFN-alpha monotherapy. PATIENTS AND METHODS: Thirty patients (24 men and six women; mean age, 41 +/- 13 (SD) years; range, 23-62 years), with chronic hepatitis C that was non-responsive to a standard course of IFN-alpha therapy, were re-treated with recombinant human IFN-beta-1a. All patients received IFN-beta, 12 MIU subcutaneously, three times weekly for 3 months, after which time patients' responses were evaluated. Responders (normal alanine aminotransferase, and negative for serum hepatitis C virus RNA) continued to receive IFN-beta, 12 MIU, for a further 3 months. Non-responders had their dose increased to 18 MIU for the remaining 3 months of treatment. After 6 months of treatment, therapy was stopped and patients were followed-up for a further 6 months. RESULTS: Overall, six (20%) of the 30 patients exhibited a response at the end of treatment. One patient (3.3%) maintained a sustained virological response at the end of post-treatment follow-up. CONCLUSIONS: Treatment with recombinant IFN-beta, at doses of up to 18 MIU for 6 months, is safe and well tolerated. However, the results of the trial do not support the use of IFN-beta monotherapy in patients with chronic hepatitis C that is resistant to IFN-alpha.
Adult↗