Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis.

BACKGROUND AND RATIONALE: Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. MATERIAL AND METHODS: A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. RESULTS: Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. CONCLUSION: In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

There is no difference in hepatic fibrosis rates of patients infected with hepatitis C virus and those co-infected with HIV

Some studies have suggested that human immunodeficiency virus (HIV) infection modifies the natural history of hepatitis C virus (HCV) infection, accelerating the progression of fibrosis and the development of cirrhosis. Our objective was to evaluate the fibrosis progression rate (FPR) in HCV/HIV-co-infected patients, and to identify factors that may influence it. HCV-mono-infected and HCV/HIV-co-infected patients with a known date of HCV infection (transfusion or injection drug use) and a liver biopsy were included. The FPR was defined as the ratio between the fibrosis stage (Metavir score) and the estimated length of infection in years and the result was reported as fibrosis units per year. The factors studied were gender, age at infection, consumption of alcohol, aminotransferase levels, histological activity grade, HCV genotype and viral load, CD4 cell count, HIV viral load, and the use of antiretroviral therapy. Sixty-five HCV-infected (group 1) and 53 HCV/HIV-co-infected (group 2) patients were evaluated over a period of 19 months. The mean FPR of groups 1 and 2 was 0.086 ± 0.074 and 0.109 ± 0.098 fibrosis units per year, respectively (P = 0.276). There was a correlation between length of HCV infection and stage of fibrosis in both groups. The age at infection, the aspartate aminotransferase level (r = 0.36) and the inflammatory activity grade were correlated with the FPR (P < 0.001). No difference in FPR was found between HCV-mono-infected and HCV/HIV-co-infected patients.

There is no difference in hepatic fibrosis rates of patients infected with hepatitis C virus and those co-infected with HIV.

Some studies have suggested that human immunodeficiency virus (HIV) infection modifies the natural history of hepatitis C virus (HCV) infection, accelerating the progression of fibrosis and the development of cirrhosis. Our objective was to evaluate the fibrosis progression rate (FPR) in HCV/HIV-co-infected patients, and to identify factors that may influence it. HCV-mono-infected and HCV/HIV-co-infected patients with a known date of HCV infection (transfusion or injection drug use) and a liver biopsy were included. The FPR was defined as the ratio between the fibrosis stage (Metavir score) and the estimated length of infection in years and the result was reported as fibrosis units per year. The factors studied were gender, age at infection, consumption of alcohol, aminotransferase levels, histological activity grade, HCV genotype and viral load, CD4 cell count, HIV viral load, and the use of antiretroviral therapy. Sixty-five HCV-infected (group 1) and 53 HCV/HIV-co-infected (group 2) patients were evaluated over a period of 19 months. The mean FPR of groups 1 and 2 was 0.086 +/- 0.074 and 0.109 +/- 0.098 fibrosis units per year, respectively (P = 0.276). There was a correlation between length of HCV infection and stage of fibrosis in both groups. The age at infection, the aspartate aminotransferase level (r = 0.36) and the inflammatory activity grade were correlated with the FPR (P < 0.001). No difference in FPR was found between HCV-mono-infected and HCV/HIV-co-infected patients.

The emergence of YMDD mutants precedes biochemical flare by 19 weeks in lamivudine-treated chronic hepatitis B patients: an opportunity for therapy reevaluation

Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine (LMV) and the availability of new alternative treatments for chronic hepatitis B patients, early detection of viral genotypic resistance could allow the clinician to consider therapy modification before viral breakthrough and biochemical relapse occur. To this end, 28 LMV-treated patients (44 ± 12 years; 24 men), on their first therapy schedule, were monitored monthly at four Brazilian centers for the emergence of drug resistance using the reverse hybridization-based INNO-LiPA HBV DR assay and occasionally sequencing (two cases). Positive viral responses (HBV DNA clearance) after 6, 12, and 18 months of therapy were achieved by 57, 68, and 53 percent of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53 percent of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35 percent of patients at 6, 12, and 18 months, respectively. The emergence of these variants was not associated with viral genotype, HBeAg expression status, or pretreatment serum alanine aminotransferase levels. The detection of resistance-associated mutations was observed before the corresponding biochemical flare (41 ± 14 and 60 ± 15 weeks) in the same individuals. Then, if highly sensitive LMV drug resistance testing is carried out at frequent and regular intervals, the relatively long period (19 ± 2 weeks) between the emergence of viral resistance and the onset of biochemical relapse can provide clinicians with ample time to re-evaluate drug therapy.

The emergence of YMDD mutants precedes biochemical flare by 19 weeks in lamivudine-treated chronic hepatitis B patients: an opportunity for therapy reevaluation.

Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine (LMV) and the availability of new alternative treatments for chronic hepatitis B patients, early detection of viral genotypic resistance could allow the clinician to consider therapy modification before viral breakthrough and biochemical relapse occur. To this end, 28 LMV-treated patients (44 +/- 12 years; 24 men), on their first therapy schedule, were monitored monthly at four Brazilian centers for the emergence of drug resistance using the reverse hybridization-based INNO-LiPA HBV DR assay and occasionally sequencing (two cases). Positive viral responses (HBV DNA clearance) after 6, 12, and 18 months of therapy were achieved by 57, 68, and 53% of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53% of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35% of patients at 6, 12, and 18 months, respectively. The emergence of these variants was not associated with viral genotype, HBeAg expression status, or pretreatment serum alanine aminotransferase levels. The detection of resistance-associated mutations was observed before the corresponding biochemical flare (41 +/- 14 and 60 +/- 15 weeks) in the same individuals. Then, if highly sensitive LMV drug resistance testing is carried out at frequent and regular intervals, the relatively long period (19 +/- 2 weeks) between the emergence of viral resistance and the onset of biochemical relapse can provide clinicians with ample time to re-evaluate drug therapy.

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

Hepatitis C virus (HCV) infection is a serious public health problem, since 80 percent to 85 percent of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81 percent from public and 19 percent from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62 percent) and white patients (80 percent). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64 percent) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65 percent of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8 percent and 13.6 percent of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65 percent of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil.

Hepatitis C virus (HCV) infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62%) and white patients (80%). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64%) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65% of the patients weighed less than 77 kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

[Experimental cirrhosis induced by carbon tetrachloride inhalation: adaptation of the technique and evaluation of lipid peroxidation]. / Cirrose experimental induzida pela inalação de tetracloreto de carbono: adaptação da técnica e avaliação da peroxidação lipídica.

BACKGROUND: Long-term administration of carbon tetrachloride is an accepted experimental model to produce hepatic fibrosis. Oxidative stress has been postulated as a major molecular mechanism involved in carbon tetrachloride hepatotoxicity, where the reactive oxygen species play an important role in the pathogenesis of liver fibrosis. AIMS: This study was conducted to evaluate the effectiveness of an experimental model of hepatic cirrhosis induced by carbon tetrachloride inhalation as well as the importance of lipid peroxidation and the characteristics of the ascitic fluid in this model. METHODS: At first the hepatic histologic findings were assessed using the hematoxilineosin technique in different moments of carbon tetrachloride inhalation (5th, 7th, 9th, 12th weeks). Later, at the end of 15 weeks of the study the rats were divided in three groups (control; control + phenobarbital; and carbon tetrachloride + phenobarbital) for lipid peroxidation, ascitic fluid and histologic characteristics evaluation. For the lipid peroxidation analysis, thiobarbituric acid and QL techniques were used. Cytologic and bacteriologic parameters were analysed in the ascitic fluid. RESULTS: Cirrhosis was established in 100% of carbon tetrachloride rats between the 12th and 15th weeks with an elevation in the lipid peroxidation carbon tetrachloride rats' livers. Ascitic fluid infection was observed in one of seven rats who has developed ascites. CONCLUSIONS: The carbon tetrachloride inhalation method developed in this study is effective in cirrhosis induction and ascites formation, and the carbon tetrachloride cirrhosis physiopathogenesis is probably related to the oxidative stress installation.

Flow cytometry in the diagnosis of peritoneal carcinomatosis.

OBJECTIVES: Peritoneal carcinomatosis is the second major cause of ascites. Because of its frequency and poor prognosis, it is important to establish an accurate diagnosis. The aim of this study was to analyze the use of a DNA index, detemined by flow cytometry in the differential diagnosis of ascites, and to compare it to the cytopathological examination. METHODS: A prospective analysis was carried out on 67 patients (39 female, 28 male; mean age, 53+/-14 yr [range, 5-82]) with ascites of various etiologies. Peritoneal carcinomatosis was detected in 21 patients, whereas in 46 the ascites was of noncarcinomatosis origin. RESULTS: The sensitivity of the cytopathological examination for the diagnosis of peritoneal carcinomatosis was 42.9%, and the specificity was 100%. The mean DNA index determined by flow cytometry was similar for peritoneal carcinomatosis and noncarcinomatosis patients, being 1.28 versus 1.01, respectively, in the preparations without control lymphocytes and 1.28 versus 1.04, respectively, when control lymphocytes were added. The sensitivity of DNA index cytometry was 57.1% and specificity, 93.5%. The combined use of the DNA index and cytopathological examination did not show an advantage over the use of any of the tests individually, although the DNA index was able to detect half of the cases of peritoneal carcinomatosis in which cytopathological examination was negative. Although the sensitivity was higher when the parameters were associated, the DNA index did not offer a statistically significant advantage over the use of cytopathological examination alone, which in turn had higher specificity. CONCLUSION: The DNA index presented lower sensitivity for the diagnosis of peritoneal carcinomatosis when used alone, showing no advantage over conventional cytopathological examination. However, the DNA index was able to detect 50.0% of peritoneal carcinomatosis cases whose conventional cytopathological examinations were negative, and could be valuable in these situations.

The value of serum-ascites albumin gradient for the determination of portal hypertension in the diagnosis of ascites.

BACKGROUND/AIMS: The aim of the present study was to evaluate the correlation between serum-ascites albumin gradient and portal pressure gradient in a population with ascites related to multiple conditions. METHODOLOGY: Thirty-seven patients were divided into two groups: group 1: 30 patients with cirrhosis as the cause of ascites, and group 2: 7 patients with ascites due to other causes. All patients were submitted to paracentesis and blood examination to determine the serum-ascites albumin gradient and the hepatic venous pressure gradient was measured. RESULTS: Mean serum-ascites albumin gradient was 2.0 g/dL in group 1 and 0.6 g/dL in group 2. Mean hepatic venous pressure gradient was 14.7 mm Hg in group 1 and 1.3 mm Hg in group 2. CONCLUSIONS: There was a significant correlation between the serum-ascites albumin gradient and the hepatic venous pressure gradient (r = 0.502), indicating the reliability of the serum-ascites albumin gradient in demonstrating the presence of portal hypertension and its relationship with the origin of ascites.

[Sclerotherapy versus somatostatin in the treatment of upper digestive hemorrhage caused by rupture of esophageal varices]. / Escleroterapia versus somatostatina na hemorragia digestiva alta por ruptura de varizes esofágicas.

The aim of this study was to compare the efficacy of somatostatin versus endoscopic sclerotherapy in the management of digestive bleeding caused by rupture of esophageal varices. Forty patients were evaluated; 21 were randomly assigned to receive somatostatin (initial 250 micrograms followed by a 48-hour continuous infusion of 250 micrograms/h and 250 micrograms 6/6 h bolus in the first 24 hours) and 19 to receive endoscopic sclerotherapy with ethanolamine oleate 5%. The patients were evaluated after 48 hours and after 7 days of treatment. Both groups of patients were similar in sex, age, gravity of the hemorrhage and liver dysfunction. Therapeutic failure occurred in 26.3% and 35.7% in the group of endoscopic sclerotherapy (48 h and 7 days respectively), and in 23.8% and 21.4% in the group of somatostatin. The need of blood transfusion (3.38 U in the group of endoscopic sclerotherapy and 2.42 U in the group of somatostatin) and the mortality rate (31.6% in the group of endoscopic sclerotherapy and 28.6% in the group of somatostatin) were also similar (P > 0.05). The authors conclude that somatostatin is as effective as endoscopic sclerotherapy and that it should be considered in the treatment of acute esophageal variceal bleeding.

Endoscopic dilation of benign esophageal strictures: report on 1043 procedures.

OBJECTIVE: Endoscopic dilation is considered the best treatment for most cases of benign esophageal stricture, although the best dilation technique and the kind of stricture is the most amenable to treatment is still controversial. We report on our experience on a large series of patients treated by dilation without the aid of fluoroscopy and compare the results of this therapy among patients with strictures from different causes. METHODS: Between 1992 and 1997, we performed 1043 dilation sessions on 153 patients. Treatment was considered adequate if the esophageal lumen could be dilated up to the size of a 42F catheter. If the stricture recurred after initial successful treatment, the stricture was dilated again up to a 42F catheter. RESULTS: One hundred forty patients (96 men, 44 women; mean age, 54.1 yr) were followed-up for a mean of 20.5 months (4 to 62 months). Stricture's etiology was postsurgical in 80 patients, peptic in 37, caustic in 12, and from other causes in 11 patients. Adequate dilation was achieved in 93.5% of the patients (131 of 140). Patients with peptic strictures needed a median of three sessions to be adequately dilated during follow-up in comparison to five sessions among patients with postsurgical or caustic strictures (p = 0.07). There were four perforations, with one death (2.8% and 0.7% per patient and 0.4% and 0.1% per session, respectively). CONCLUSIONS: Endoscopic dilation without the aid of fluoroscopy is safe and effective in relieving dysphagia caused by benign strictures of different causes, although repeated sessions are necessary because of stricture recurrence.