Natural history of compensated cirrhosis in the Child-Pugh class A compared between 490 patients with hepatitis C and 167 with B virus infections

Natural histories of compensated cirrhosis in the Child-Pugh class A were compared between the 490 patients infected with hepatitis C virus (HCV) and 167 patients with hepatitis B virus (HBV) who were followed for more than 1 year up to 20 years without antiviral treatment. Patients with HCV were older (median age: 59 vs. 45 years), less predominantly male (59.0% vs. 76.0%), transfused more frequently (49.2% vs. 9.0%), and had higher aminotransferase as well as lower albumin levels and fewer platelets (P < 0.001 for all). Death was commoner (55.1% vs. 35.9%, P < 0.001) and hepatocellular carcinoma developed more often (53.9% vs. 28.7%, P < 0.001) in patients with HCV than HBV. In multivariate analysis, low albumin levels (hazard ratio: 1.65), alpha-fetoprotein (1.55), alcohol consumption (1.49), age >55 years (1.47), and retention of indocyanine green (1.39) were independent risk factors for the survival in patients with HCV, while male gender (4.43), age >45 years (2.24), retention of indocyanine green (2.14), hepatitis B e antigen (2.11), and low platelet counts (1.91) were in those with HBV. Chances for survival was significantly different (P < 0.001) among patients with HCV having low (number of factors: 0-1), medium (2-3), and high risks (4-5), as well as in those with HBV having low (0-1), medium (2-4), and high risks (5-6). In conclusion, survival and development of hepatocellular carcinoma, and factors for survival, are considerably different between patients with compensated cirrhosis infected with HCV and HBV, which would need to be taken into consideration in their management and planning treatment strategies.     

Prediction of compensated liver cirrhosis by ultrasonography and routine blood tests in patients with chronic viral hepatitis

Background/Aims

Liver biopsy is a standard method for diagnosis of liver cirrhosis in patients with chronic hepatitis. Because liver biopsy is an invasive method, non-invasive methods have been used for diagnosis of compensated liver cirrhosis in patients with chronic hepatitis. The current study was designed to evaluate the usefulness of ultrasonography and routine blood tests for diagnosis of compensated liver cirrhosis in patients with chronic viral hepatitis.

Methods

Two hundred three patients with chronic viral hepatitis who underwent liver biopsy were included in this study and ultrasonography and routine blood tests were analyzed retrospectively. Ultrasonographic findings, including surface nodularity, parenchyma echogenecity, and spleen size, were evaluated. The diagnostic accuracy of ultrasonography and routine blood tests were examined.

Results

Discriminant analysis with forward stepwise selection of variables showed that liver surface nodularity, platelet count, and albumin level were independently associated with compensated liver cirrhosis (p<0.05). Cross-tabulation revealed that the following 4 variables had >95% specificity: platelet count <100,000 /uL; albumin level <3.5 g/dL; INR >1.3; and surface nodularity. If at least one of the four variables exists in a patient with chronic viral hepatitis, we can predict liver cirrhosis with 90% specificity and 61% sensitivity.

Conclusions

These results suggest that four variables (platelet count <100,000 /uL, albumin level <3.5 g/dL, INR >1.3, and surface nodularity) can be used for identification of liver cirrhosis in patients with chronic viral hepatitis with high specificity.     

Mortality for liver disease in patients with HIV infection: a cohort study

We undertook this study to assess the association between the various potential causes of liver disease in HIV-seropositive patients and mortality due to liver failure. Three hundred and eight in-hospital deaths were observed from 1987 to December 1995 in a prospectively followed cohort of 1894 HIV-seropositive patients. For each study subject, clinical data were evaluated to assess whether liver failure had substantially contributed to mortality. A case control study nested in the cohort was then performed, which compared demographic and clinical variables observed at enrollment and during follow-up between patients who died for liver disease as the main or concurrent cause of death (cases) and those who died as a result of illness related to AIDS or other causes (controls). Among 308 in-hospital deaths, liver failure was found the cause of death in 35 patients (12%); in 16 cases, it was the primary cause and in 19 cases it was concurrent. Multivariate analysis showed that in-hospital liver-disease-related mortality was independently associated with hepatitis B surface antigen reactivity (odds ratio [OR], 9; 95% confidence interval [CI], 3.8-21.7) and history of alcohol abuse (OR, 2.3; 95% CI, 1-5.2). Prevention and treatment of hepatitis B virus infection and alcohol intake are management priorities in HIV-seropositive patients.     

Natural history of HIV-1 infection and predictors of survival in a cohort of HIV-1 seropositive injecting drug users.

Injecting drug users represent a pivotal and increasing component of acquired immunodeficiency syndrome (AIDS) case reporting in the United States. This article describes the natural history of human immunodeficiency virus (HIV) disease in a New York City cohort of 328 HIV-infected injecting drug users. The study sample of nearly two-thirds men (predominately African Americans and Latino Americans) underwent follow-up from December 1988 through December 1993. Male injecting drug users reported a longer injecting drug use history and were more likely to share needles/works than female injecting drug users. Eighty-nine of 328 study subjects died during the 5 years of observation. Comparing African Americans and Latinos, race/ethnicity was not related to survival. Survival was related to baseline CD4 count and hemoglobin level. Zidovudine use and PCP prophylaxis did not predict survival. Because of the continuing and increasing impact of HIV disease on injecting drug users and communities of color, there remains an unquestionable need to develop effective prevention programs, to understand the natural history of HIV disease, and to develop appropriate therapeutic interventions to treat those with HIV disease.     

Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study

Niemann-Pick disease type C (NP-C) is a devastating genetic disorder characterised by progressive neurological deterioration. However, data on the progression of neurological manifestations, particularly across different patient age-of-disease onsets, are limited. This is an observational retrospective cohort study designed to assess the progression of neurological disease in patients with NP-C. Physicians were asked to retrospectively complete a web-based questionnaire for each patient, at diagnosis and at up to three follow-up visits. An NP-C-specific disability scale was used to measure disease progression. The scale comprised four key parameters of neurological disease progression; ambulation, manipulation, language and swallowing. Disease progression was evaluated based on the annual rate of change in each parameter and the composite score using a linear mixed model analysis, and by classifying patients according to the number of worsened parameters during the observation period. Data were collected from 57 patients. The rate of deterioration was similar across the four individual parameters of the disability scale. The mean (95% CI) annual disease progression was +0.12 (0.09, 0.15) units. Among patients with a time interval of at least 1 year between diagnosis and last visit (n = 49), 42 (86%) patients had progressed disease and 7 (14%) patients had stable disease. Disease progression was consistently more rapid in patients diagnosed in early childhood, compared with those diagnosed in late childhood, or with juvenile or adult presentation. In conclusion, our findings showed a progression in all four parameters of the disability scale, representing a continuous, unbroken progression of neurological manifestations.     

Impact of circulating bacterial DNA in long-term glucose homeostasis in non-diabetic patients with HIV infection: cohort study

In HIV-infected patients, the damage in the gut mucosal immune system is not completely restored after antiretroviral therapy (ART). It results in microbial translocation, which could influence the immune and inflammatory response. We aimed at investigating the long-term impact of bacterial-DNA translocation (bactDNA) on glucose homeostasis in an HIV population. This was a cohort study in HIV-infected patients whereby inclusion criteria were: patients with age >18 years, ART-naïve or on effective ART (<50 HIV-1 RNA copies/mL) and without diabetes or chronic hepatitis C. Primary outcome was the change in HbA1c (%). Explanatory variables at baseline were: bactDNA (qualitatively detected in blood samples by PCR [broad-range PCR] and gene 16SrRNA - prokaryote), ART exposure, HOMA-R and a dynamic test HOMA-CIGMA [continuous infusion of glucose with model assessment], hepatic steatosis (hepatic triglyceride content - 1H-MRS), visceral fat / subcutaneous ratio and inflammatory markers. Fifty-four men (age 43.2 ± 8.3 years, BMI 24.9 ± 3 kg/m², mean duration of HIV infection of 8.1 ± 5.3 years) were included. Baseline HbA1c was 4.4 ± 0.4% and baseline presence of BactDNA in six patients. After 8.5 ± 0.5 years of follow-up, change in HbA1c was 1.5 ± 0.47% in patients with BactDNA vs 0.87 ± 0.3% in the rest of the sample p < 0.001. The change in Hba1c was also influenced by protease inhibitors exposure, but not by baseline indices of insulin resistance, body composition, hepatic steatosis, inflammatory markers or anthropometric changes. In non-diabetic patients with HIV infection, baseline bacterial translocation and PI exposure time were the only factors associated with long-term impaired glucose homeostasis.     

Natural anti-TNP antibodies from rainbow trout interfere with viral infection in vitro

Normal and viral-infected rainbow trout (RT) were tested for serum antibody activity against self and nonself antigens. Particularly high titres of anti-trinitrophenyl (TNP) antibodies were noted, as in other fish species. To analyse this, the anti-TNP antibodies were isolated by affinity chromatography and their capacity to interfere with viral infection in vitro was studied. We selected RT fibroblasts as target cells, and two common pathogenic viruses in trout, a rhabdovirus, viral haemorrhagic septicaemia virus (VHS) and a birnavirus, the infectious pancreatic necrosis virus (IPN). Anti-TNP antibodies were examined for their capacity to neutralize VHS and IPN viruses. Data obtained show that the anti-TNP antibodies, even at high concentrations, only partially neutralized virus. In contrast, when anti-TNP antibodies were assayed for their protective activity using RT fibroblast cells infected with VHS or IPN viruses, results showed high protective activity, regardless of serum origin or of the virus used, when the antibodies were added to the cell culture after viral infection. Therefore, our experiments indicate that the protective activity does not seem to be due to a direct interaction of the antibodies with the viruses. It is suggested that virus-modified cell surface self structures exhibit new epitopes which interact with the anti-TNP antibodies. Such an interaction would allow anti-TNP antibodies to participate in a non-specific defence mechanism against viral infection.     

Natural killer activity in patients with acute viral hepatitis.

Using the natural killer (NK) sensitive K562 cell line, enhanced NK cell cytotoxicity was demonstrable early in the course of acute hepatitis B while normal values were obtained in patients studied during convalescence. No evidence of enhanced NK activity was instead obtained in the course of acute non-A, non-B hepatitis. Serum levels of alpha-interferon, as determined by radioimmunoassay (RIA), were significantly increased in patients with acute hepatitis B showing enhanced NK cell activity but not in those with acute non-A, non-B hepatitis and normal NK cell activity. These results suggest that natural cytotoxicity may play a role early in the course of acute hepatitis type B, before antigen-specific T lymphocytes become fully operative.     

Hemostatic disorders in patients with HIV infection]

Impaired hemostasis was studied in 50 adult patients with HIV infection. The blood coagulative potential, the number and functional activity of platelets were examined. Platelet aggregation and secretion were shown to change earlier than thrombocytopenia developed and clinical signs of HIV infection appeared. The disturbance in the plasma section of hemostasis are due to concurrent opportunistic diseases and infections.     

Managing cardiovascular risk in patients with HIV infection

Highly active antiretroviral therapy (HAART) improves the survival of patients with HIV infection; however, several observational studies have described associations between HIV infection, HAART, and cardiovascular disease. Important limitations of these studies included a low incidence of cardiovascular events, short duration of HAART exposure, and retrospective design. Nevertheless, the weight of evidence from observational and surrogate end point studies suggests that the dyslipidemia and other metabolic changes that are common in patients with HIV infection and those using HAART may be associated with increased cardiovascular risk. The Infectious Disease Society of America/Adults AIDS Clinical Trials Group guidelines for the evaluation and management of dyslipidemia recommend target lipid levels and treatment of dyslipidemia in patients with HIV infection. Although practitioners should consider dyslipidemia and cardiovascular risk when making plans for initiating or altering HAART therapy, maintaining viremic control should be the overriding factor, because short-term absolute rates of cardiovascular disease are significantly lower than death rates from AIDS in inadequately suppressed patients. This article reviews the cardiovascular risks in patients receiving HAART and discusses the implementation of the new guidelines.     

Delta infection in patients with chronic viral hepatitis B

The results of examination for anti-delta antibodies in the blood of 86 patients (33 children and 53 adults) with chronic persisting hepatitis (CPH) and chronic active hepatitis (CAH) verified by morphological examinations of liver biopsy specimens are presented. Delta infection was found in 43 (31.5%) of patients with CAH, only anti-HBe being demonstrable in the blood. In this group of patients, marked enzymatic disorders and more intensive changes in the morphological picture of the liver were demonstrated.