Factors Associated With Hepatitis A Mortality During Person-to-Person Outbreaks: A Matched Case-Control Study-United States, 2016-2019.

BACKGROUND AND AIMS: During 2016-2020, the United States experienced person-to-person hepatitis A outbreaks that are unprecedented in the vaccine era, during which case-fatality ratios reported by some jurisdictions exceeded those historically associated with hepatitis A. APPROACH AND RESULTS: To identify factors associated with hepatitis A-related mortality, we performed a matched case-control study (matched on age [±5 years] and county of residence in a 1:4 ratio) using data collected from health department and hospital medical records of outbreak-associated patients in Kentucky, Michigan, and West Virginia. Controls were hepatitis A outbreak-associated patients who did not die. There were 110 cases (mean age 53.6 years) and 414 matched controls (mean age 51.9 years); most cases (68.2%) and controls (63.8%) were male. Significantly (P < 0.05) higher odds of mortality were associated with preexisting nonviral liver disease (adjusted odds ratio [aOR], 5.2), history of hepatitis B (aOR, 2.4), diabetes (aOR, 2.2), and cardiovascular disease (aOR, 2.2), as well as initial Model for End-Stage Liver Disease (MELD) score ≥ 30 (aOR, 10.0), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio > 2 (aOR, 10.3), and platelet count < 150,000/µL (aOR, 3.7) among hepatitis A outbreak-associated patients in the independent multivariable conditional logistic regression analyses (each model adjusted for sex). CONCLUSIONS: Preexisting liver disease, diabetes, cardiovascular disease, and initial MELD score ≥ 30, AST/ALT ratio ≥ 1, and platelet count < 150,000/µL among hepatitis A patients were independently associated with higher odds of mortality. Providers should be vigilant for such features and have a low threshold to escalate care and consider consultation for liver transplantation. Our findings support the recommendation of the Advisory Committee on Immunization Practices to vaccinate persons with chronic liver disease, though future recommendations to include adults with diabetes and cardiovascular disease should be considered.

A systematic review of the epidemiology of hepatitis A in Africa.

BACKGROUND: Hepatitis A, caused by the hepatitis A virus (HAV), is a vaccine preventable disease. In Low and Middle-Income Countries (LMICs), poor hygiene and sanitation conditions are the main risk factors contributing to HAV infection. There have been, however, notable improvements in hygiene and sanitation conditions in many LMICs. As a result, there are studies showing a possible transition of some LMICs from high to intermediate HAV endemicity. The World Health Organization (WHO) recommends that countries should routinely collect, analyse and review local factors (including disease burden) to guide the development of hepatitis A vaccination programs. Up-to-date information on hepatitis A burden is, therefore, critical in aiding the development of country-specific recommendations on hepatitis A vaccination. METHODS: We conducted a systematic review to present an up-to-date, comprehensive synthesis of hepatitis A epidemiological data in Africa. RESULTS: The main results of this review include: 1) the reported HAV seroprevalence data suggests that Africa, as a whole, should not be considered as a high HAV endemic region; 2) the IgM anti-HAV seroprevalence data showed similar risk of acute hepatitis A infection among all age-groups; 3) South Africa could be experiencing a possible transition from high to intermediate HAV endemicity. The results of this review should be interpreted with caution as the reported data represents research work with significant sociocultural, economic and environmental diversity from 13 out of 54 African countries. CONCLUSIONS: Our findings show that priority should be given to collecting HAV seroprevalence data and re-assessing the current hepatitis A control strategies in Africa to prevent future disease outbreaks.

Epidemiological shift of hepatitis A in EAGLE countries - a projection.

PURPOSE: Many world regions are developing quickly and experiencing increasing levels of sanitation, causing an epidemiological shift of hepatitis A in these areas. The shift occurs when children avoid being infected with the disease until a later age due to cleaner water sources, food, and hygiene practices in their environment; but if they are infected at later age, the disease is much more severe and lost productivity costs are higher. The purpose of this paper is to examine what could occur if an epidemiological shift of the disease continues in these regions, and what type of future burden hepatitis A may have in a hypothetical rapidly developing country. DESIGN/METHODOLOGY/APPROACH: Initially, annual hepatitis A mortality was regressed on the Human Development Index (HDI) for each country classified as an emerging and growth-leading economy (EAGLE) to provide an overview of how economic development and hepatitis A mortality related. Data from the various EAGLE countries were also fit to a model of hepatitis A mortality rates in relation to HDI, which were both weighted by each country's 1995-2010 population of available data, in order to create a model for a hypothetical emerging market country. A second regression model was fit for the weighted average annual hepatitis A mortality rate of all EAGLE countries from the years 1995 to 2010. Additionally, hepatitis A mortality rate was regressed on year. FINDINGS: Regression results show a constant decline of mortality as HDI increased. For each increase of one in HDI value in this hypothetical country, mortality rate declined by 2.3016 deaths per 100,000 people. The hypothetical country showed the HDI value increasing by 0.0073 each year. Also, results displayed a decrease in hepatitis A mortality rate of 0.0168 per 100,000 people per year. Finally, the mortality rate for hepatitis A in this hypothetical country is projected to be down to 0.11299 deaths per 100,000 people by 2030 and its economic status will fall just below the HDI criteria for a developed country by 2025. ORIGINALITY/VALUE: The hypothetical country as a prototype model was created from the results of regressed data from EAGLE countries. It is aimed to display an example of the health and economic changes occurring in these rapidly developing regions in order to help understand potential hepatitis A trends, while underscoring the importance of informed and regular policy updates in the coming years. The author believes this regression provides insight into the patterns of hepatitis A mortality and HDI as these EAGLE countries undergo rapid development.

Chronic Hepatitis B Increases Liver-Related Mortality of Patients With Acute Hepatitis E: A Territorywide Cohort Study From 2000 to 2016.

Background: The epidemiology of acute hepatitis A and E has been changing over the last 2 decades. The impact of concomitant chronic hepatitis B (CHB) on clinical outcomes remains unclear. We aimed to evaluate the morbidity and mortality of patients with acute hepatitis A or E with and without underlying CHB. Methods: We identified consecutive patients with acute hepatitis A or E based on hepatitis serology from the electronic medical records of the Hospital Authority of Hong Kong from January 2000 to December 2016. Hepatic events, all-cause mortality, and liver-related mortality within 30 days of the diagnosis of acute hepatitis were evaluated. Results: The cohort included 1068 cases of acute hepatitis A and 846 cases of acute hepatitis E. More patients with acute hepatitis E than those with acute hepatitis A had underlying CHB (13.5% vs 8.0%; P < .001). Patients with hepatitis E had more all-cause mortality (3.9% vs 0.6%; P < .001), liver-related mortality (2.0% vs 0.3%; P < .001), and hepatic events (2.8% vs 0.3%; P < .001) within 30 days from diagnosis. In patients with acute hepatitis E, underlying renal failure (adjusted hazard ratio [aHR], 3.90; P < .001) and age ≥50 years (aHR, 3.25; P = .036) were associated with 30-day all-cause mortality, whereas CHB (aHR, 3.34; P = .02) was associated with 30-day liver-related mortality. Conclusions: The mortality is higher in patients with acute hepatitis E than in those with hepatitis A. Coexisting CHB is the independent risk factor for liver-related mortality in patients with acute hepatitis E.

A Description of a Health System's Emergency Department Patients Who Were Part of a Large Hepatitis A Outbreak.

BACKGROUND: A recent hepatitis A virus (HAV) outbreak in San Diego, California represents one of the largest HAV outbreaks in the United States. The County of San Diego Health and Human Services Agency identified homelessness and illicit or injection drug use as risk factors for contracting HAV during this outbreak. OBJECTIVE: We describe those patients who presented to our Emergency Department (ED) and were identified as HAV positive. METHODS: This was a retrospective descriptive study conducted at a tertiary care university health system's EDs from November 2016 to February 2018. Included were those of all ages who tested positive for HAV immunoglobulin M antibody. Outcome measures included: 1) demographic data; 2) number of patients testing positive for HAV by week and month of the outbreak; 3) homeless status, illicit and injection drug use, and alcohol use; 4) ED chief complaint; 5) initial liver function and coagulopathy test results, hepatitis B and C test results, and initial vital signs; 6) admission status; 7) death; and 8) the 7-day ED revisit rate for nonadmitted patients and the 30-day all-cause readmission rate for admitted patients. RESULTS: We identified 57,721 patients with at least one ED visit, and 1,453 of these were tested for HAV; 133 patients (9.2%) tested positive. Average age was 45.1 years, and 91 (68.4%) were male. Eighty-six patients (64.7%) were homeless and 53 patients (39.8%) reported illicit or injection drug use; 64 patients (48.1%) had chief complaints consistent with typical HAV symptoms. Most patients (112 or 84.2%) were admitted. Nine patients (6.8%) were admitted to a critical care setting; 8 patients (6%) died. CONCLUSIONS: During this large HAV outbreak, 9% of those screened for HAV tested positive. The majority were homeless, and 40% reported illicit or injection drug use. Most required hospitalization, and 6% of patients died.

Hospitalization and mortality due to hepatitis A in Taiwan: a 15-year nationwide cohort study.

Hepatitis A virus (HAV) is the most common food-borne hepatitis in the world. The study objectives were (i) to describe the epidemiology of HAV-related hospitalizations during 1997-2011 in Taiwan, (ii) to examine the age effect on the length of stay (LOS) in hospital and (iii) to study the factors associated with death. The hospitalized cases were identified from the Taiwan National Health Insurance Research Database between 1997 and 2011 by ICD-9-CM code of 070.0/070.1. Patient sex, birthday, dates of hospitalization and death were analysed. A total of 3990 HAV-hospitalized cases, males 2467 (62%), were identified. The LOS increased as patients' age increased. The overall mortality rate was 16.8 per 1000 hospitalizations. Males had significantly higher case fatality rate than females (20.7 vs 10.5 per 1000 cases). The adjusted odds ratio (aOR) for death rose by age and increased rapidly over 40 years of age. The aOR and 95% confidence interval [95%CI] for aged 40-59 years and aged over 60 years were 7.89 (1.06-58.98) and 14.88 (2.02-109.40) compared to aged 0-19 years, respectively. Patients with chronic liver disease and cirrhosis had significantly higher risk of death (aOR=1.03 [1.01-1.04]), compared to those without liver disease. However, patients with liver disease, but no cirrhosis did not have higher risk of death (aOR=1.00 [0.99-1.01]). The aOR [95%CI] for LOS >9 day was 3.26 (1.96-5.40) compared to cases with LOS ≤9 days. Male sex, age over 40 years, cirrhotic liver and long LOS are significant factors associated with death in HAV-hospitalized cases.

Trends in disease and complications of hepatitis A virus infection in the United States, 1999-2011: a new concern for adults.

BACKGROUND: In recent years, few US adults have had exposure and resultant immunity to hepatitis A virus (HAV). Further, persons with liver disease have an increased risk of adverse consequences if they are infected with HAV. METHODS: This study used 1999-2011 National Notifiable Diseases Surveillance System and Multiple Cause of Death data to assess trends in the incidence of HAV infection, HAV-related hospitalization, and HAV-related mortality. RESULTS: During 1999-2011, the incidence of HAV infection declined from 6.0 cases/100 000 to 0.4 cases/100 000. Similar declines were seen by sex and age, but persons aged ≥80 years had the highest incidence of HAV infection in 2011 (0.8 cases/100 000). HAV-related hospitalizations increased from 7.3% in 1999 to 24.5% in 2011. The mean age of hospitalized cases increased from 36.0 years in 1999 to 45.1 years in 2011. While HAV-related mortality declined, the mean age at death among decedents with HAV infection increased from 48.0 years in 1999 to 76.2 years in 2011. The median age range of decedents who had HAV infection and a liver-related condition was 51.0 to 68.0 years. CONCLUSIONS: Although vaccine-preventable, HAV-related hospitalizations increased greatly, mostly among adults, and liver-related conditions were frequently reported among HAV-infected individuals who died. Public health efforts should focus on the need to assess protection from hepatitis A among adults, including those with liver disease.

Hepatitis A: epidemiology in resource-poor countries.

PURPOSE OF REVIEW: Transmission of hepatitis A virus (HAV) infection is primarily fecal-oral. Symptomatic hepatitis, severe disease, and death are more likely to occur when infection occurs at an older age. Improvements in socioeconomic and hygienic conditions have led to a change in its epidemiology worldwide. RECENT FINDINGS: In the last two decades, improved hygiene in several resource-poor countries has led to reduced transmission of HAV, an increase in average age at infection, and, consequently, a paradoxical increase in morbidity and mortality because of hepatitis A. In Argentina, introduction of one dose (instead of the conventional two doses, to reduce costs) of inactivated HAV vaccine at 12-month age in a universal childhood immunization program during such 'epidemiologic transition' has markedly reduced the incidence of symptomatic hepatitis A, and of fulminant hepatitis and liver transplantation caused by HAV infection. The monetary value of medical and nonmedical benefits of this strategy outweighed the expenditure on vaccination. These excellent results were possibly contingent upon a high vaccination coverage. SUMMARY: Resource-poor countries should closely monitor the epidemiology of HAV infection and periodically undertake cost-effectiveness analyses of HAV immunization strategies. This should allow timely identification of epidemiologic transition and introduction of preventive strategies before HAV infection becomes a public health problem.

Viral Hepatitis in Pregnancy--A study of its Effect on Maternal and Foetal Outcome.

BACKGROUND AND AIMS: The outcome of Hepatitis during pregnancy has been observed to be widely different by various authors, ranging from the benign to fatal. A poor outcome has increasingly been observed in pregnant women suffering from Hepatitis in Central India. Hence, this study was undertaken to study the incidence, causative organisms and chief prognostic factors affecting the outcome of viral hepatitis in pregnant women. METHODS: Sixty-eight pregnant women reporting to the hospital with jaundice were enrolled as cases and their Haematological, Biochemical and Viral profiles were studied. Sixteen non- pregnant women were enrolled as controls and a similar workup was done. A comparison was done between the two groups We also divided the cases into two groups--survivors and non- survivors and tried to find out the factors predicting mortality. The unpaired student t test and chi square test were used to find out whether the differences were statistically significant. RESULTS: Viral Hepatitis in pregnancy caused a very high maternal mortality (19.1%) and foetal wastage (42.6%). Hepatitis E virus was the commonest causative organism (77.9%) responsible for viral hepatitis during pregnancy. It also caused the highest maternal mortality due to fulminant hepatic failure. Maternal mortality was significantly higher in those women presenting with features of encephalopathy, SIRS, high bilirubin levels and prolonged prothrombin time. Vertical transmission was noted in Hepatitis B and E. CONCLUSIONS: Hepatitis E is the chief causative organism causing fulminant hepatic failure in pregnant women in Central India. It lead to very high rates of maternal mortality and foetal wastage.

Causes of death and characteristics of decedents with viral hepatitis, United States, 2010.

BACKGROUND: Previous research indicates that the mortality burden from viral hepatitis is growing, particularly among middle-aged persons. To monitor progress toward prevention goals, it is important to continue to document characteristics and comortalities of these deaths. This study sought to examine demographic characteristics and the most frequent causes of death among decedents with a viral hepatitis-related death. METHODS: A cross-sectional study was performed on approximately 2.4 million death records from 2010. We calculated mortality rates for decedents with and without hepatitis A, B, and C virus (HAV, HBV, and HCV) and relative risks for the most frequently cited conditions in decedents with and without HBV and HCV. RESULTS: In 2010, there were 18 473 (0.7%) deaths with HAV, HBV, and HCV listed among causes of death, disproportionately in those aged 45-64 years. Among the 10 frequent causes of death, decedents listing HBV or HCV died, on average, 22-23 years earlier than decedents not listing these infections. HBV- and HCV-infected decedents aged 45-64 years had an increased risk of having the following conditions reported than decedents without these infections: cancer of liver and intrahepatic bile duct; fibrosis, cirrhosis, and other liver diseases; alcohol-related liver disease; gastrointestinal hemorrhage; human immunodeficiency infection; acute and unspecified renal failure; and septicemia (HCV only). CONCLUSIONS: Decedents with other causes of death that include HBV or HCV died 22-23 years earlier than decedents not listing these infections. These data suggest and support the need for prevention, early identification, and treatment of HBV and HCV.

Determinants of poor outcome in patients with hepatitis A infection: a four-year retrospective study in Shiraz, Southern Iran.

There are 1.4 million estimated cases of hepatitis A every year worldwide. We aimed to detect the correlates of poor outcome in patients with hepatitis A virus (HAV) infection. In this four-year retrospective study, which was conducted in Shiraz, Southern Iran, data of all hospitalized HAV patients were analyzed by SPSS and STATA. Out of 110 HAV patients, 8 (7.3 %) developed hepatic encephalopathy, and 7 (6.4 %) died. The results show that 19 years of age is a cutoff level for predicting mortality, with a sensitivity of 42.9 % and specificity of 91.3 %, and with an area under the curve (AUC) of 0.595 (95 % CI, 0.309-0.881). Every one-year increase in age adds 3 % to the mortality rate from severe hepatitis A. The cutoff level of alanine aminotransferase (ALT) for predicting death is 1819.5 IU/L, with a sensitivity of 100 %, specificity of 68 %, and AUC 0.877 (95 % CI, 0.777-0.977). Every 100 IU/L increase in ALT is associated with a 0.1 % increase in the risk of death. Patients from large families (OR, 0.583, 95 % CI, 0.46-0.74) and those who are not the firstborn child of their family (OR, 0.287, 95 % CI, 0.146-0.564) have better outcome. Adult patients with hepatitis A who are first children, are from a small family, or have a very high level of ALT are more prone to a poor outcome of this infection. Public education and establishment of a national surveillance system for HAV and an HAV vaccination program for high-risk populations should be regarded among the priorities of the health system of Iran.

Clinical characteristics and outcomes of acute hepatitis a in Korea: a nationwide multicenter study.

The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.

Rising trend of symptomatic infections due to Hepatitis A virus infection in adolescent and adult age group: An observational study from a tertiary care liver institute in India.

BACKGROUND: Hepatitis A Virus (HAV) is the most common cause of Acute Viral Hepatitis (AVH) in children. It causes self-limiting illness and rarely acute liver failure. The shifting pattern in HAV endemicity is rendering adolescents and adults vulnerable to infection. METHODS: In this retrospective study, samples received from 14,807 patients with acute onset icteric illness from January 2014-December 2022 were analyzed. HAV infection was detected by anti-HAV IgM positivity. The cases were divided into 3 age groups, pediatric, adolescents and adults, and clinical presentations were compared. RESULTS: Overall, 7.72%(1144) were positive for anti-HAV IgM. Of these, 60%(690) were finally included in the study. The positive cases were divided into adults, ≥18 years (44%, 304); pediatric, <12 years (31%, 212) and adolescents (25%,174) age groups. Overall males were predominant [72.4%(500)], with a median age of 16 (IQR:9-21) years. Cases were characterised into AVH (68.1%, 470/690), Acute Liver Failure (ALF) (31.4%, 217/690) and Acute-on-Chronic Liver Failure (0.43%, 3/690). AVH in the pediatric age group was 69%(146/212), adolescents was 67%(117/174), and adults was 68%(207/304). ALF cases among the 3 groups were 30%(65/212), 33%(57/174), and 31%(95/304) respectively. Overall mortality was seen in 6.52%(45/690), maximum in adolescents with ALF presentation [10.3%(18/174)]. On molecular characterization of infection, viremia was seen in 28.9%(200/690) and all the isolates were Genotype IIIA. CONCLUSIONS: The number of adults experiencing symptomatic HAV infection was seen to increase over the years in the present study. Infection in adolescents was associated with higher mortality and ALF as the clinical presentation.

Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model.

OBJECTIVES: Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. METHODS: The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. RESULTS: As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of  ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). CONCLUSION: INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. CLINICAL TRIAL REGISTRY NUMBER: Not applicable as this is a retrospective study.

Hepatitis A virus vaccination in persons with hepatitis C virus infection: consequences of quality measure implementation.

UNLABELLED: Hepatitis A virus (HAV) superinfection in persons with hepatitis C virus (HCV) infection has been associated with a high mortality rate, and vaccination is recommended. The incidence of HAV is low, and the aim of this study was to determine the mortality risk of HAV superinfection and the consequences of routine vaccination in persons with HCV infection. To determine the mortality risk of HAV superinfection, a meta-analysis including studies reporting mortality in HCV-infected persons was performed. Data were extracted independently by two investigators and recorded on a standardized spreadsheet. The pooled mortality estimate was used to determine the number needed to vaccinate (NNV) to prevent mortality from HAV superinfection. The total vaccine cost was also calculated. A total of 239 studies were identified using a defined search strategy. Of these, 11 appeared to be relevant, and of these, 10 were suitable for inclusion in the meta-analysis. The pooled odds ratio (OR) for mortality risk in HAV superinfection of HCV-infected persons was 7.23 (95% confidence interval: 1.24-42.12) with significant heterogeneity (I(2) = 56%; P = 0.03) between studies. Using the pooled OR for mortality, this translates to 1.4 deaths per 1,000,000 susceptible persons with HCV per year. The NNV to prevent one death per year is therefore 814,849, assuming 90% vaccine uptake and 94.3% vaccine efficiency. The vaccine cost for this totals $162 million, or $80.1 million per death prevented per year. CONCLUSION: These data challenge the use of routine HAV vaccination in HCV-infected persons and its incorporation into clinical practice guidelines. HAV vaccination of all HCV-infected persons is costly and likely to expose many individuals to an intervention that is of no direct benefit.

Hepatitis mortality in Brazil and regions, 2001-2020: temporal trend and spatial analysis.

OBJECTIVE: To analyze the spatial distribution and the temporal trend of the hepatitis mortality rate in Brazil from 2001 to 2020. METHODS: Ecological, temporal, and spatial study on mortality from hepatitis in Brazil with data from the Mortality Information System (Sistema de Informações sobre Mortalidade - SIM/DATASUS). Information was stratified by year of diagnosis, region of the country, municipalities (of residence). Standardized mortality rates (SMR) were calculated. The temporal trend was estimated by Prais-Winsten regression and the spatial distribution by the Global Moran Index (GMI). RESULTS: The highest SMR means in Brazil were for Chronic viral hepatitis with 0.88 deaths per 100,000 inhabitants (SD=0.16), followed by Other viral hepatitis with 0.22/100,000 (SD=0.11). In Brazil, the temporal trend of mortality from Hepatitis A was -8.11% per year (95%CI -9.38; -6.82), while for Hepatitis B it was -4.13% (95%CI -6.03; -2.20), of Other viral hepatitis of -7.84% (95%CI -14.11; -1.11) and of Unspecified Hepatitis -5.67% per year (95%CI -6.22; -5.10). Mortality due to chronic viral hepatitis increased by 5.74% (95%CI 3.47; 8.06) in the North and 4.95% in the Northeast (95%CI 0.27; 9.85). The Moran Index (I) for Hepatitis A was 0.470 (p<0.001), for Hepatitis B 0.846 (p<0.001), Chronic viral hepatitis=0.666 (p<0.001), other viral hepatitis=0.713 (p<0.001), and Unspecified Hepatitis=0.712 (p<0.001). CONCLUSION: The temporal trend of hepatitis A, B, other viral, and unspecified hepatitis was decreasing in Brazil, while mortality from chronic hepatitis was increasing in the North and Northeast.

Clinical course and management of acute hepatitis A infection in adults.

BACKGROUND: Hepatitis A is the most common type of viral hepatitis in Mexico. The change of hepatitis A epidemiology in Mexico from high to intermediate endemicity leads to increasing susceptible adults for severe illness. OBJECTIVE: To describe the clinical characteristics and hospital outcome of adult patients with acute hepatitis A infection, and determine risk factor for mortality. MATERIAL AND METHODS: This is a retrospective observational, multicentre study in Mexico City and in Guatemala City. All inhospital patients were followed until discharge or death. Risk factors for death/acute liver failure were identified. RESULTS: Forty seven patients were analyzed, sixty percent were male, the prodrome phase was from 3 to 30 days. The three most common symptoms were fever, malaise and jaundice, with 87%, 74% and 62% respectively. The incidence of patients who were treated with antibiotics before hospital admission was up to 34%. Unnecessary imaging studies and out of guidelines drugs were used. Presence of encephalopathy, leukocytes > 19,000/mL, blood urea nitrogen > 36 mg/dL, creatinine > 2 mg/dL, albumin < 2.5 mg/dL and total bilirubin > 9.6 mg/dL, are predictors of mortality. Serum creatinine > 2 mg/dL has the best sensibility and specificity for predicting fulminant hepatitis/death. CONCLUSION: Acute hepatitis A infection in adults is associated some unnecessary diagnostic and therapeutic approach. Could be associated with fulminant hepatitis, and a creatinine value > 2 mg/dL is the best predictor for fulminant hepatitis and death.

What factors determine the severity of hepatitis A-related acute liver failure?

The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were sub-genotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare sub-genotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes.