Forty patients with compensated chronic active hepatitis B and elevated aminotransferases who were HBsAg and HBeAg positive were randomised to a treatment group receiving recombinant interferon alpha-2b (rIFN alpha-2b) or no treatment as a control group. The treated patients were divided into 2 groups, group I (n = 12) received IFN in a dose of 5 MU/m2 thrice weekly by subcutaneous injection for 16 weeks, and group II (n = 8) received the same dose daily for the same duration. Patients were followed up for 12 months after therapy ended. Initiation of IFN therapy was associated with an increase in aminotransferases, reaching a peak at 4-6 weeks in most patients, associated with clearance of HBeAg. At end of follow-up, 81% of the treated patients had cleared HBeAg vs 33% of the control group (p less than 0.01). Changes in other HBV markers were more frequent in the treated patients, though insignificantly. The type of response to therapy was significantly related to the duration of illness, being shortest in those who cleared HBsAg. A complete response to therapy with loss of HBsAg was associated with marked reduction in biochemical and histological activity. A partial response with clearance of HBeAg was associated with moderate improvement in biochemical parameters and ongoing activity in liver histology; whereas persistence of HBeAg was associated with elevated aminotransferases and histological deterioration in most cases. The rise in aminotransferases during seroconversion was associated with hepatic decompensation and death on 3 occasions: one during spontaneous seroconversion, and the other 2 during IFN therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Experience with interferon in chronic hepatitis B in Egypt.

A 43-year-old man with common variable immune deficiency underwent liver transplantation for cirrhosis caused by hepatitis C virus (HCV). HCV had been acquired from a contaminated batch of immunoglobulin. He developed cirrhosis within 3 years of infection with the virus, then liver failure requiring liver transplantation. The immediate post-transplant course was uncomplicated. Five months after transplantation he developed liver failure, and the histological appearances were those of severe cholestatic hepatitis. Withdrawal of immunosuppression resulted in recovery from liver failure. Clearance of the HCV from serum was also observed and has been sustained during follow-up (despite the subsequent reintroduction of low-dose immunosuppression). The patient is alive and well more than 5 years after transplantation. His post-transplant course has been remarkable for the aggressive recurrence then clearance of the HCV.

Successful outcome of liver transplantation in a patient with hepatitis C and common variable immune deficiency.

Specific therapy for chronic hepatitis B virus (HBV) infection with a-interferon (a-IFN) has now become a possibility. These agents inhibit HBV replication and, in addition, appear to induce or amplify an immune response to HBV. Several shortcomings remain with this treatment, however: a-IFN requires parenteral administration, is not without side effects, and can be unpredictable in its effects. Treatment is made difficult by the fact that only 35-45% of patients respond to a-IFN, making selection of responsive patients complex.' However, the extensive data compiled during the evaluation of a-IFN therapy in controlled therapeutic trials of chronic HBV infection and parallel studies of the natural history of chronic HBV infection go some way toward providing predictive information to suggest which patients are more likely to respond to treatment. It is possible that some of the mechanisms operative in spontaneous clearance of replicative HBV infection and in IFN-induced clearance overlap, and the associated phenomena can be used to judge which patients are most likely to respond to treatment.

Alpha-interferon treatment of chronic hepatitis B infection: predictors of responsiveness.

OBJECTIVE: To identify the risk of hepatic failure in hepatitis B virus (HBV) carriers given intermittent immunosuppressive therapy. DATA SOURCES: The key words "immunosuppression" and "hepatitis B" were used to search MEDLINE for relevant articles in English published from 1970 to 1990; the bibliographies of these articles were reviewed for additional publications. Also included were articles published in 1991. STUDY SELECTION: Articles were included if they documented the use of immunosuppressive drugs to treat chronic hepatitis B or another condition in patients at high risk for the HBV carrier state. RESULTS: Long-term immunosuppressive therapy has not improved the survival of patients with chronic hepatitis B. The withdrawal of such therapy from HBV carriers has resulted in a flare-up of potentially fatal hepatitis in 20% to 50%, regardless of whether underlying liver disease was present. The presence of replicating viral DNA in the serum of HBV carriers may identify those who are at high risk of the deleterious effects of immunosuppressive therapy. CONCLUSIONS: Long-term immunosuppressive therapy is not advised for liver disease in HBV carriers. For other conditions in such people continuous rather than intermittent therapy is safer. Patients at high risk for hepatitis B should be screened for this virus when immunosuppressive therapy is contemplated.

Dangers of immunosuppressive therapy in hepatitis B virus carriers.

Although the North West Thames Region collects over 200,000 blood donations each year, less than four cases of post­ transfusion hepatitis B are reported to us annually (Barbara and Briggs 1981) presumably reflecting the exclusion of approximately 40 donors per annum found to be Hepatitis B surface antigen (HBsAg) positive. This study is the first step in the analysis of some of the unique data accumulated on these HBsAg-positive donations over an eighteen year period.

Routine HBsAg screening of all blood donations became mandatory in the U.K. by 1971. Since then, we at the North London Blood Transfusion Centre (NLBTC) have monitored as many HBsAg-positive donors as possible to obtain epidemiological data on HBsAg carriage and the prevalence of other hepatitis B virus (HBV) markers, and to examine ways of predicting the course of HBV infection, so that we can advise carriers concerning their level of infectivity and management of their infection in everyday life. The first section examines the role of HBV in the context of blood transfusion. The serological markers of HBV infection are described in detail, including viral subtypes and a description of mutant and defective strains. The HBV carrier state is then briefly described.

The second section describes current microbiological practices in blood transfusion including the present trend towards laboratory automation.

The third section details the serological assays available for the laboratory detection of HBV infection and an experimental evaluation defines the confidence we can place upon assay results.

Section four is a preliminary analysis of some of the epidemiological data accumulated at the NLBTC over 18 years. 286 HBsAg carriers have been followed up; with particular attention to their HBe antigen and antibody status as the markers most relevant to defining infectivity levels. Of the 35 carriers who were HBeAg-positive at the time of detection, 8 seroconverted from HBe antigen to anti-HBe during the follow-up period. HBeAg positivity was shown to be associated with raised liver function test (LFT) values. Those who seroconverted from HBe antigen to anti-HBe eventually developed normal LFT levels. My preliminary observations on the duration of HBsAg positivity and also on temporal changes in HBsAg titre will form the basis of further work. Although complete in itself, this study also serves as a pilot for a more comprehensive analysis of the wealth of material still to be examined.

Detailed follow-up of hepatitis B surface antigen positive blood donors.

Seventy-seven consecutive HBeAg-positive chronic hepatitis patients were studied from 1971 to 1983 to establish the seroconversion rate in the e system. Patients with less than a year of follow-up were not included in the study. Fifty-six patients with chronic active hepatitis (CAH) received immunosuppressive treatment (corticosteroids combined with azathioprine). The remaining twenty-one patients received no treatment, nine of them with chronic persistent hepatitis (CPH) and 12 with CAH. A retrospective study was performed with stored sera samples: HBeAg and anti-HBe were determined by RIA, and results were correlated with alanine aminotransferase (ALAT) levels in the same samples. The linearized seroconversion rate from HBeAg to anti-HBe was expressed as percent per patient-year. It was 9.6% in CPH patients and 8.8% in CAH patients without treatment. In CAH patients under immunosuppressive drugs it was as low as 1.1% and increased to 28.7% when treatment was withdrawn. ALAT levels were significantly lower in total seroconverted patients when compared with nonseroconverted (NS) patients, but no difference was found between partial seroconverted (PS) and NS patients. The results suggest that although immunosuppressive drug withdrawal may enhance seroconversion rate in type B CAH, delayed seroconversion and reported side effects during treatment stand against protracted usage of these drugs.

HBeAg/anti-HBe seroconversion during and after protracted immunosuppressive treatment in type B chronic hepatitis.

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/cld.840

Cuando la creación de un consorcio proporciona respuestas útiles: experiencia de la Latin American DILI network (LATINDILIN).

Drug-induced liver injury (DILI) is an uncommon event in clinical practice, which makes knowing its true incidence difficult. Prospective, retrospective and registry-based studies are the most important methods to obtain epidemiological data on DILI. Latin America (LA) has a historical lack of prospective studies on this topic. New definitions and the creation of hepatotoxicity registries have significantly improved the epidemiological understanding of hepatic drug reactions in several regions of the world. The Latin American DILI network, referred to as LATINDILI, has been created in 2011, and recently published its own DILI recommendations describing the most relevant issues on the management of hepatotoxicity in general, and those based on findings from our own LA experience in particular. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI. The joint work among researchers and the corresponding health and regulatory authorities should be stimulated due to the high impact that hepatotoxicity represents for public health.

Overview on drug-induced liver injury in Brazil.

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HBeAg/anti-HBe seroconversion during and after protracted immunosuppressive treatment in type B chronic hepatitis.

Cuando la creación de un consorcio proporciona respuestas útiles: experiencia de la Latin American DILI network (LATINDILIN).

Overview on drug-induced liver injury in Brazil.