Noninvasive Models for Predicting Liver Fibrosis in Individuals with Hepatitis D Virus/Hepatitis B Virus Coinfection in the Brazilian Amazon Region.

Hepatitis D virus (HDV) genotype III is endemic in the western Amazon basin and is considered to cause the most severe form of chronic viral hepatitis. Recently, noninvasive fibrosis scores to determine the stage of liver fibrosis have been evaluated in individuals positive for HDV genotype I, but their utility in HDV genotype III-positive patients is unknown. In this retrospective study conducted in an outpatient viral hepatitis referral clinic in the Brazilian Amazon region, the aspartate aminotransferase (AST) to Aspartate aminotransferase to Platelet Ratio Index (APRI) and Fibrosis Index for Liver Fibrosis (FIB-4) values were calculated and compared with histological fibrosis stages. Among the 50 patients analyzed, the median age at liver biopsy was 35.6 years, 66% were male, and all had compensated liver disease. Histological staging revealed fibrosis stages 0, 1, 2, 3, and 4 in four (8%), eight (16%), 11 (22), 11 (22%), and 16 (32%) patients, respectively. The area under the receiver operating curve (AUROC) of AST-to-alanine aminotransferase (ALT) ratio, APRI, and FIB-4 for detection of significant fibrosis (F ≥ 2) was 0.550 (P = 0.601), 0.853 (P < 0.001), and 0.853 (P < 0.0001), respectively. Lower AUROC values were obtained for cirrhosis: the AST-to-ALT ratio was 0.640 (P = 0.114), APRI was 0.671 (P = 0.053), and FIB-4 was 0.701 (P = 0.023). The optimal cutoff value for significant fibrosis for APRI was 0.708 (sensitivity 84% and specificity 92%) and for FIB-4 was 1.36 (sensitivity 76% and specificity 92%). Aspartate aminotransferase to Platelet Ratio Index and FIB-4 were less useful to predict cirrhosis. In contrast to recent reports from Europe and North America, both APRI and FIB-4 may identify significant fibrosis in HDV-III-infected patients from northwestern Brazil.

A pilot study of 2 years of interferon treatment in patients with chronic delta hepatitis.

High dose interferon treatment for 1 year is the only established treatment for chronic hepatitis D, but it is associated with a high relapse rate after treatment discontinuation. In this study, patients were treated with 10 MU interferon alpha 2b, thrice weekly for 2 years. Twenty-three patients were recruited and 15 completed the 2-year treatment and 6 months follow-up periods. Treatment response was assessed biochemically [normal alanine aminotransferase (ALT)], virologically (undetectable hepatitis D virus RNA) and histologically (at least 2 point decrease in the Knodell score) at the end of treatment (EOT) and at the end of follow-up. Out of 15 patients who finished the 2-year treatment period, seven patients (47%) had a biochemical response but only two (13%) had a normal ALT after follow-up. ALT decreased from the baseline value of 143.1 +/- 121.7 (mean +/- SD) to 39.7 +/- 20.6 (P < 0.01) at EOT. Virological response was observed in six patients at EOT and in two patients at follow-up. Two patients lost hepatitis B surface antigen. Of the 12 patients with paired liver biopsies, a histological improvement was observed in eight patients. Interferon treatment leads to a complete or partial response in a substantial number of patients but 2 years of treatment does not appear to increase sustained response rates over 1 year treatment.

Chronic hepatitis C virus infection after treatment for pediatric malignancy.

Sera of 658 patients who had completed treatment for pediatric malignancy were analyzed by a second-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay test to assess the prevalence of hepatitis C virus (HCV)-seropositivity. All HCV-seropositive patients underwent detailed clinical, laboratory, virologic, and histologic study to analyze the course of HCV infection. One hundred seventeen of the 658 patients (17.8%) were positive for HCV infection markers. Among the 117 anti-HCV+ patients, 41 (35%) were also positive for markers of hepatitis B virus infection with or without delta virus infection markers, 91 (77.8%) had previously received blood product transfusions, and 25 (21.4%) showed a normal alanine aminotransferase (ALT) level during the last 5-year follow-up (11 of them never had abnormal ALT levels). The remaining 92 patients showed ALT levels higher than the upper limit of normal range. Eighty-one of 117 (70%) anti-HCV+ patients were HCV-RNA+, with genotype 1b being present in most patients (54%). In univariate analysis, no risk factor for chronic liver disease was statistically significant. In this study, the prevalence of HCV infection was high in patients who were treated for a childhood malignancy. In about 20% of anti-HCV+ patients, routes other than blood transfusions are to be considered in the epidemiology of HCV infection. After a 14-year median follow-up, chronic liver disease of anti-HCV+ positive patients did not show progression to liver failure.

Long-term follow-up of hepatitis B virus-infected recipients after orthotopic liver transplantation.

The outcome after OLT was studied in 53 patients with chronic hepatitis B virus (HBV)* infection, 15 of whom had, in addition, evidence of hepatitis delta virus (HDV) superinfection. Nine of 53 patients received short-term immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulin up to 1 week after OLT and 44 of 53 patients received long-term unlimited immunoprophylaxis. Eight of 9 (89%) patients with short-term immunoprophylaxis showed reactivation of replication with HBV DNA in serum > 10 pg/ml independently of the preoperative HBV DNA level and HBsAg reappeared in all cases. Four (44%) patients in this group lost their graft because of fulminant hepatitis or cirrhosis and required retransplantation, and 2 patients (22%) died after reinfection in the second graft. Nineteen of 44 (43%) patients with long-term immunoprophylaxis developed HBV values > 10 pg/ml after transplant and 12 of 44 (27%) became HBsAg+ again. Most of them had quantifiable HBV DNA levels before OLT. Retransplantation was required in 5 of 44 (11%) patients and 4 of them died after HBV recurrence. The frequency of HBV reactivation and the development of viral hepatitis after OLT were associated with the preoperative presence of HBV, as determined by the molecular hybridization assay. With nested polymerase chain reaction, all 53 patients were HBV-DNA+ in the serum before and after OLT. with just one exception, none of the patients with HDV superinfection died, in spite of increased HDV replication after OLT. The data indicate that long-term immunoprophylaxis with anti-HBs hyperimmunoglobulin after OLT improves the prognosis in HBV-infected patients. The preoperative detection of HBV DNA in serum by molecular hybridization assay is correlated with graft infection and represents a prognostic parameter. The presence of HDV may have a protective effect after OLT.

Treatment of chronic hepatitis D with interferon alfa-2a.

BACKGROUND AND METHODS: Chronic hepatitis D is a severe and rapidly progressive liver disease for which no therapy has been proved effective. To evaluate the efficacy of treatment with interferon, we studied 42 patients with chronic hepatitis D who were randomly assigned to receive either 9 million or 3 million units of recombinant interferon alfa-2a (three times a week for 48 weeks) or no treatment. RESULTS: By the end of the treatment period, serum alanine aminotransferase values had become normal in 10 of 14 patients receiving 9 million units (71 percent), as compared with 4 of 14 treated with 3 million units (29 percent, P = 0.029) and 1 of 13 untreated controls (8 percent, P = 0.001). Seven patients treated with the higher dose of interferon (50 percent) had a complete response (normal levels of alanine aminotransferase and no detectable serum hepatitis delta virus [HDV] RNA), as compared with three of those who received the lower dose (21 percent, P = 0.118), and none of the controls (P = 0.004). Treatment with 9 million units of interferon was associated with a marked improvement in the histologic findings (reduced periportal necrosis and portal and lobular inflammation), whereas in the untreated controls there was considerable histologic deterioration. In 5 of the 10 patients treated with 9 million units of interferon whose alanine aminotransferase values became normal, the biochemical responses persisted for up to 4 years (mean, 39 months), but the effects of treatment on viral replication were not sustained. In contrast, none of those who received 3 million units and none of the untreated controls had a sustained biochemical or virologic response. CONCLUSIONS: In about half the patients with chronic hepatitis D treated with high doses of interferon alfa-2a (9 million units three times a week for 48 weeks), the serum alanine aminotransferase level becomes normal, HDV RNA becomes undetectable in serum, and there is histologic improvement. However, a relapse is common after treatment has been stopped.

[Enzyme activity of interferon system in virus diseases]. / Aktivnost' fermentov sistemy interferona pri virusnykh zabolevaniiakh.

The enzymes activities of interferon system at viral infections of different etiology/influenza, parainfluenza, hepatitis B with delta infection and urticaria chronica with respiratory and herpes infection/has been studied and evaluation of the noted changes in the enzymes activity is discussed. It is shown that the same pathological changes in enzymes activities of interferon system were observed at different viral infections.

[Liver morphology in delta virus hepatitis]. / Morfologiia pecheni pri del'ta-virusnom gepatite.

Biopsy material from two groups of patients with liver diseases is studied. 12 patients with a high titer of total anti-delta (D)-antibodies are included into the 1st group. In this group, among patients with total antibodies to D-infection D-antigen in the liver tissue is found in 6 cases with a pronounced chronic aggressive hepatitis (CAH) and active liver cirrhosis (ALC). The 2nd group consisted of 30 patients with CAH and ALC and D-antigen was observed in 10 cases. Hepatocyte degeneration and pronounced lobular infiltration were the only distinctive feature of liver morphology in D-positive cases as compared to the D-negative ones. The presence of D-antigen always correlated with an active inflammatory process.

Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis.

The ratio of the serum aspartate to alanine amino-transferase levels (AST/ALT) is often used as a clue to the etiology of the underlying liver disease. This ratio is usually greater than 2.0 in alcoholic liver disease and less than 1.0 in patients with chronic hepatitis and chronic cholestatic syndromes. We analyzed the AST/ALT ratio in 177 patients with various forms of nonalcoholic chronic liver disease who underwent medical evaluation and percutaneous liver biopsy. In the majority of cases of chronic viral hepatitis, the AST/ALT ratio was less than 1.0. However, there was a statistically significant correlation between the AST/ALT ratio and the presence of cirrhosis. Among 100 patients with chronic type B hepatitis, the mean AST/ALT ratio was 0.59 in those without cirrhosis and 1.02 in those with cirrhosis. Furthermore, the AST/ALT ratio often rose to greater than 1.0 when cirrhosis first became manifest. Thus, the finding of an AST/ALT ratio of greater than 1.0 in a patient with nonalcoholic liver disease should suggest the presence of cirrhosis. In addition, the use of the AST/ALT ratio as a means of separating alcoholic and nonalcoholic liver disease must be tempered with the knowledge that this ratio may be less helpful in the presence of cirrhosis.

Infection with hepatitis delta virus in patients with fulminant hepatitis B and chronic HBsAg carriers in Bulgaria.

To evaluate the prevalence and clinical significance of delta infection in a Bulgarian population, 105 HBsAG positive patients with chronic liver diseases, and 42 patients who had died of fulminant hepatitis B were studied. Delta antigen was detected by direct immunofluorescence in the liver of 9 patients with chronic HBV infection (8.6%), and in 3 patients with fulminant hepatitis (7.14%). All chronic HBsAg carriers with delta superinfection had chronic active hepatitis or active liver cirrhosis. They were predominantly anti-HBe (+) in the serum. The mean age and the mean values of serum transaminase did not differ in delta antigen positive and negative patients with chronic liver diseases. A history of parenteral manipulations directly before the hepatitis was present in patients with delta antigen positive fulminant hepatitis. These results indicate a relatively low incidence of delta infection in our population, but it is invariably associated with severe liver disease.