Unusual clinical spectra of childhood severe malaria during malaria epidemic in eastern Uganda: a prospective study.

BACKGROUND: In sub-Saharan Africa (SSA), malaria remains a public health problem despite recent reports of declining incidence. Severe malaria is a multiorgan disease with wide-ranging clinical spectra and outcomes that have been reported to vary by age, geographical location, transmission intensity over time. There are reports of recent malaria epidemics or resurgences, but few data, if any, focus on the clinical spectrum of severe malaria during epidemics. This describes the clinical spectrum and outcomes of childhood severe malaria during the disease epidemic in Eastern Uganda. METHODS: This prospective cohort study from October 1, 2021, to September 7, 2022, was nested within the 'Malaria Epidemiological, Pathophysiological and Intervention studies in Highly Endemic Eastern Uganda' (TMA2016SF-1514-MEPIE Study) at Mbale Regional Referral Hospital, Uganda. Children aged 60 days to 12 years who at admission tested positive for malaria and fulfilled the clinical WHO criteria for surveillance of severe malaria were enrolled on the study. Follow-up was performed until day 28. Data were collected using a customized proforma on social demographic characteristics, clinical presentation, treatment, and outcomes. Laboratory analyses included complete blood counts, malaria RDT (SD BIOLINE Malaria Ag P.f/Pan, Ref. 05FK60-40-1) and blood slide, lactate, glucose, blood gases and electrolytes. In addition, urinalysis using dipsticks (Multistix® 10 SG, SIEMENS, Ref.2300) at the bedside was done. Data were analysed using STATA V15.0. The study had prior ethical approval. RESULTS: A total of 300 participants were recruited. The median age was 4.6 years, mean of 57.2 months and IQR of 44.5 months. Many children, 164/300 (54.7%) were under 5 years, and 171/300 (57.0%) were males. The common clinical features were prostration 236/300 (78.7%), jaundice in 205/300 (68.3%), severe malarial anaemia in 158/300 (52.7%), black water fever 158/300 (52.7%) and multiple convulsions 51/300 (17.0%), impaired consciousness 50/300(16.0%), acidosis 41/300(13.7%), respiratory distress 26/300(6.7%) and coma in 18/300(6.0%). Prolonged hospitalization was found in 56/251 (22.3%) and was associated with acidosis, P = 0.041. The overall mortality was 19/300 (6.3%). Day 28 follow-up was achieved in 247/300 (82.3%). CONCLUSION: During the malaria epidemic in Eastern Uganda, severe malaria affected much older children and the spectrum had more of prostration, jaundice severe malarial anaemia, black water fever and multiple convulsions with less of earlier reported respiratory distress and cerebral malaria.

Characteristics and outcomes of acute hepatitis of unknown etiology in Egypt: first report of adult adenovirus-associated hepatitis.

PURPOSE: Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt. METHODOLOGY: Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson's disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A-E viruses, cytomegalovirus, Epstein-Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus. RESULTS: A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease. CONCLUSION: This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens.

HEPATITIS A. THE FEATURES OF DISEASE COURSE IN ADULTS.

OBJECTIVE: The aim: To analyze the incidence of Hepatitis A in Ukraine and Poltava region and to study the clinical and epidemiological features of the course of Hepatitis A in adult patients. PATIENTS AND METHODS: Materials and methods: The course of HA in 96 hospitalized patients was analyzed. The diagnosis of HA was established on the basis of clinical and epide¬miological data and confirmed by the results of laboratory studies (serological and molecular biological). RESULTS: Results: In 2019, in the Poltava region, there was an increase in the incidence of Hepatitis A with a predominance among sick people of working age, among the urban population. This part of people aged from 60 to 75 years old constitutes 9.4%. This study showed that the waterway was the dominant way of HA transmission. The course of the disease in most hospitalized patients was typical and cyclic, with a predominance of a mixed variant of the pre-jaundice period and jaundice. One third of patients survey that they had fever, which persisted with jaundice. CONCLUSION: Conclusions: The findings of this study indicates that the patients older than 40 years were more likely to have concomitant chronic pathology than younger patients, and Hepatitis A was more severe with the development of prolonged cholestasis, wave-like course and recurrence. In most patients under the age of 40, the course of Hepatitis A was mild, but splenomegaly and severe cytolytic syndrome were more common.

Prevalence of hepatitis B & C infections in prospective blood donors deferred due to history of jaundice.

Background & objectives: As per national guidelines, prospective blood donors with a history of jaundice of unknown cause are deferred permanently to prevent the transmission of hepatitis B and C. The validity of this guideline was tested by comparing prevalence rates of hepatitis B and C in prospective blood donors deferred due to a history of jaundice, with that of donors who were found fit. Methods: Blood samples of 212 consecutive donors (male, n=203) deferred due to a history of jaundice were studied for hepatitis B and C by rapid test kits as well as by chemiluminescence (n=115) or ELISA (n=97). Consecutive healthy donors (n=549; male, n=518) were also studied by ELISA (n=266) or chemiluminescence (n=283). Results: The cumulative prevalence detected by rapid test kit and ELISA/chemiluminescence tests of hepatitis B (n=10) and C (n=2) among donors deferred due to a history of jaundice (n=212) was 5.7 per cent [95% confidence interval (CI): 2.9, 9.9]. The prevalence of reactive results among healthy donors (n=549) by ELISA/chemiluminescence tests was 3.3 per cent (95% CI: 1.9, 5.2), which included hepatitis B (n=15) and hepatitis C (n=3) cases. Compared to healthy donors, the odds of seropositivity among jaundice-deferred donors was 1.7 (95% CI: 0.8, 3.6), P=0.15. For rapid test-negative deferred donors, the odds of seropositivity by ELISA/chemiluminescence declined to 0.4 (0.1, 1.5), P=0.19. Interpretation & conclusions: The prevalence rates of hepatitis B and C in prospective blood donors deferred due to a history of jaundice of unknown aetiology did not differ significantly from that in healthy donors. The current practice of permanently deferring such donors depletes valuable donor pool. A strategy of rejecting only those donors who are found reactive on pre-donation testing by rapid test needs further validation.

Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Serious liver injury induced by Nimesulide: an international collaborative study.

Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and Latin American DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a twofold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was ≤ 15 days in 12 patients (21%) and one patient developed ALF within 7 days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (≤ 15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable.

Clinical Decompensation and Outcomes in Patients With Compensated Cirrhosis and a Hepatic Venous Pressure Gradient ≥20 mm Hg.

INTRODUCTION: Hepatic venous pressure gradient (HVPG) of ≥10 mm Hg predicts clinical decompensation (CD) in compensated cirrhosis. A proportion of cirrhotic patients at presentation have high HVPG (≥20 mm Hg) and are compensated. The natural history, spectrum of CD, and mortality in this group is largely unknown. METHODS: Consecutive compensated cirrhotic patients with HVPG ≥6 mm Hg (n = 741) were followed up for 3-6 months for the development of any CD. Patients were classified based on the baseline HVPG (6 to <12 mm Hg [low HVPG, Gr.A, n = 163], 12 to <20 mm Hg [intermediate HVPG, Gr.B, n = 437] and ≥20 mm Hg [high HVPG, Gr.C, n = 141]). We analyzed the predictors of first CD, HVPG response to carvedilol, and mortality in these groups. RESULTS: CD developed in 217 (29.3%) patients during a mean follow-up of 1.6 ± 0.4 years, and those who developed CD had higher baseline HVPG (17.02 ± 4.79 vs 14.28 ± 4.86; P < 0.001). First CD was seen earlier (1.3 ± 0.7 years vs 1.5 ± 0.6 years and 1.6 ± 0.5 years, P = 0.02) and more frequently (44.7% vs 11% and 31.1%, P < 0.01) in high HVPG groups compared with low and intermediate HVPG groups, with higher mortality rates. Patients in the high HVPG group compared with the low HVPG group more often had NASH-cirrhosis (35.5% vs 19.6%; P 0.001), higher liver stiffness values (45.06 ± 20.46 vs 20.09 ± 5.47 kPa, P < 0.001), and lower platelet counts (113.37 ± 72.57 vs 151.7 ± 87.30/cmm, P < 0.001). Patients with HVPG ≥12 mm Hg received carvedilol, and a repeat HVPG performed in a proportion after 9.3 ± 2.4 months showed response (≥20% reduction in HVPG or <12 mm Hg) in 31.6% patients (Gr. B, 44.9% > Gr. C, 22.2%, P < 0.05). Baseline HVPG (HVPG ≥12 to <20 mm Hg [Hazard ratio: 2.73] and HVPG ≥20 mm Hg [Hazard ratio: 4.48], P < 0.001) independently predicted CD. DISCUSSION: HVPG ≥20 mm Hg in patients with compensated cirrhosis independently predicts early and more frequent CD and poor outcomes. These patients should be labeled as "high-risk compensated cirrhosis," and early and effective interventions to reduce portal pressure should be initiated to improve long-term outcomes.

Caution With the Use of Lopinavir/Ritonavir in Severely Ill Patients for the Treatment of SARS-CoV-2: A Report of Severe Jaundice.

INTRODUCTION: We investigated the potential hepatotoxicity of lopinavir/ritonavir recently used in the treatment of Severe Acute Respiratory Syndrome Coronavirus. METHODS: This is a retrospective cohort of critical patients in a teaching hospital: 12 treated with lopinavir/ritonavir and 30 in the standard-of-care group. RESULTS: Elevation occurred more frequently in patients treated with lopinavir/ritonavir (33% vs 6.7%). DISCUSSION: Caution is advised regarding the use of lopinavir/ritonavir in the most severe cases of Severe Acute Respiratory Syndrome Coronavirus.

Plants used for the treatment of icterus (jaundice) in Central India: A review.

Jaundice is one of the most common medical condition affecting infants, children, and adults. Jaundice is not a disease but it is a visible sign and symptom of liver disease which occurs when there is an increase in the amount of bilirubin circulating in the blood due to the abnormal metabolism and excretion in the urine. Medicinal plants are being used long ago by our ancestors for the treatment of jaundice. At the present era, consumption of these herbal medicines is increasing at a high speed, due to its less or no side effect and cost-effectiveness as compared to synthetic medicines. This review describes approximately 55 medicinal plants which are used by rural and tribal people of different area of Chhattisgarh for curing jaundice. The data was collected from different kinds of literature survey from the year 1993 to 2018. This review has been conferred in a systematic way which includes plant's vernacular name, botanical name along with its family, part used and ethnomedicinal uses in a tabulated form and also the description of scientific evidence behind the folklore uses of some medicinal plants along with their mechanism of action which have been reported in different kinds of literature. The current study may be useful for the development of new medicines for the treatment of jaundice.

Jaundice outbreak likely caused by HEV in Amritsar, Punjab, India, 2013.

BACKGROUND: Hepatitis-E Virus (HEV) infection is endemic in Punjab, India. On 4th April 2013, public officials of Labour Colony, Amritsar reported > 20 jaundice cases occurring within several days. METHODS: We performed a case-control study to identify the cause and prevent additional cases of jaundice cases in Amritsar, Punjab, India in 2013. RESULTS: A total of 159 cases (attack rate 3.6%) and 1 death were identified in Labour and 5 adjoining colonies from January 1 to June 5, 2013. Persons with jaundice were more likely to report foul-smelling piped water (adjusted odds ratio [AOR], 4.0, 95% confidence interval [CI], 2.2-7.2) and used piped water for drinking (AOR, 5.1; 95% CI, 2.2-11.4) than persons without jaundice. Among 14 cases tested, all had anti-hepatitis E virus IgM, and none had anti-hepatitis A virus IgM. Additionally, 21/23 tap water samples from affected households had detectable fecal coliforms. An environmental investigation found that water pipelines were damaged during sewer construction and likely led to contamination of drinking water with hepatitis E virus. CONCLUSIONS: Hepatitis E outbreaks are common in India, to curb future outbreaks of hepatitis E; measures to ensure safe drinking water are urgently needed.

Autoimmune pancreatitis not otherwise specified (NOS): Clinical features and outcomes of the forgotten type.

BACKGROUND: Autoimmune pancreatitis (AIP) is a well-recognized fibroinflammatory disease of the pancreas. Despite the significant number of studies published on AIP type 1 and 2, no studies have been focused on AIP type not otherwise specified (NOS) and therefore very little is known about clinical features and long-term outcomes of these patients. The aim of this study was to investigate clinical and radiological features of AIP type NOS-patients. METHODS: Patients classified as AIP type NOS at clinical onset included in our database prospectively maintained since 1995 were evaluated. Epidemiological, clinical data were collected and analyzed. RESULTS: Forty-six patients were included in the study. The clinical onset was mainly characterized by weight loss, jaundice and acute pancreatitis. Eight patients (17.4%) were reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. Seven patients (15.2%) experienced relapse after steroid treatment but only one (2.2%) needed immunosuppressive drugs because of recurrent relapses. CONCLUSIONS: AIP type NOS shares clinical features similar to AIP type 2 and a relevant proportion of patients was reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. The risk of relapse is low but not irrelevant.

Leptospirosis as Cause of Febrile Icteric Illness, Burkina Faso.

Patients in Burkina Faso who sought medical attention for febrile jaundice were tested for leptospirosis. We confirmed leptospirosis in 27 (3.46%) of 781 patients: 23 (2.94%) tested positive using serologic assays and 4 (0.51%) using LipL32 PCR. We further presumed leptospirosis in 16 (2.82%) IgM-positive specimens.

19th-century and early 20th-century jaundice outbreaks, the USA.

Historical enquiry into diseases with morbidity or mortality predilections for particular demographic groups can permit clarification of their emergence, endemicity, and epidemicity. During community-wide outbreaks of hepatitis A in the pre-vaccine era, clinical attack rates were higher among juveniles rather than adults. In community-wide hepatitis E outbreaks, past and present, mortality rates have been most pronounced among pregnant women. Examination for these characteristic predilections in reports of jaundice outbreaks in the USA traces the emergence of hepatitis A and also of hepatitis E to the closing three decades of the 19th century. Thereafter, outbreaks of hepatitis A burgeoned, whereas those of hepatitis E abated. There were, in addition, community-wide outbreaks that bore features of neither hepatitis A nor E; they occurred before the 1870s. The American Civil War antedated that period. If hepatitis A had yet to establish endemicity, then it would not underlie the jaundice epidemic that was widespread during the war. Such an assessment may be revised, however, with the discovery of more extant outbreak reports.

Evidence of human leptospirosis cases in a cohort of febrile patients in Bangui, Central African Republic: a retrospective study, 2012-2015.

BACKGROUND: In spite of a local favorable environment, leptospirosis has never been described in Central African Republic so far mainly because of the weakness of diagnostic tests and differential diagnostic strategy for febrile jaundice cases negative for yellow fever virus. Here we bring a complementary insight to conclusions of Gadia CLB et al. regarding the presence of leptospirosis in Central African Republic in YFV-negative febrile icteric patients. METHODS: Our study included 497 individuals presenting with fever and jaundice but negative for yellow fever infection, retrospectively selected from the national surveillance biobank for yellow fever in Institut Pasteur de Bangui, Central African Republic. A combination of serological (ELISA, agglutination) and molecular biology techniques (quantitative real-time polymerase chain reaction) was used to identify Leptospira or the patient's immune response to the bacteria. Statistical analyses were done using the non parametric Mann-Withney U test with a 5% statistical threshold. RESULTS: ELISA test results showed 46 positive serum samples while 445 were negative and 6 remains equivocal. In addition, the reference microscopic agglutination test for leptospirosis diagnostic confirmed that 7 out of 32 samples tested were positive. Unfortunately, all 497 serum samples tested for leptospirosis were negative using the molecular techniques. CONCLUSIONS: Unlike Gadia et al., we confirmed that leptospirosis is circulating in Central African Republic and therefore may be responsible for some of the unexplained cases of febrile jaundice in the country. Thus, leptospirosis needs to be investigated to improve identification of aetiological pathogens. Our study also suggests a need to improve sample transportation and storage conditions.

Hepatitis due to Epstein-Barr virus and cytomegalovirus: clinical features and outcomes.

OBJECTIVE: To determine the frequency of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) hepatitis among those with acute CMV and EBV infection in a population based setting and to compare these two types of hepatitis and analyze the outcomes. METHODS: A retrospective search was undertaken on all patients with IgM antibodies to CMV and EBV during the period of 2006-2015 in the virological database of the University Hospital of Iceland covering the metropolitan area of Reykjavík (population 202,255). Patients with available liver tests at the University Hospital and/or admitted to this institution were included and relevant clinical data obtained from medical records. RESULT: Overall, 190 patients had acute EBV infection during the study period and 118 patients were diagnosed with acute CMV. Overall, 82% of patients with acute EBV infection had hepatitis, males 43%, median age 17 years, 15% had jaundice and 26% hospitalized. Among those with acute CMV infection, 69% had elevated liver tests, 63% males, median age 33 years, 9% had jaundice and also 26% hospitalized. Overall, 17% of those with CMV hepatitis were immunosuppressed, 6% were pregnant and 4% developed Guillain-Barré syndrome following the infection. CONCLUSION: A high proportion of patients with acute CMV and EBV developed hepatitis and jaundice, most of those patients have good prognosis. Patients with CMV hepatitis were more often immunosuppressed, required hospitalization or were pregnant in comparison with patients with EBV hepatitis.

Impact of maternal nutrition in hepatitis E infection in pregnancy.

BACKGROUND AND AIM: The basis of host response in hepatitis E virus (HEV)-related liver disease during pregnancy-is still unclear. The study aims to evaluate anthropometric parameters and biochemical nutritional parameters in hepatitis E infection during pregnancy and correlate it with severity of the disease. METHODS: A total of consecutive 267 pregnant women with jaundice were recruited. The jaundiced patients were classified as acute viral hepatitis (AVH) or acute liver failure (ALF). The study group included 144 pregnant women with HEV infection and 144 healthy asymptomatic age and gestational age-matched pregnant women as controls. Nutritional factors were evaluated on basis of anthropometric parameters and biochemical factors. Serum prealbumin and folate were assayed by ELISA kit. RESULTS: All nutritional parameters were significantly lower in pregnant women with HEV infection as compared with healthy pregnant controls. Some of the nutritional parameters significantly lower in ALF pregnant patients compared to AVH pregnant patients in HEV group. Linear regression analysis of the AVH group showed that serum total protein and mid-upper arm circumference (MUAC) were significant predictors for bilirubin, body mass index (BMI) could significantly predict viral load level, and total protein, prealbumin, folate, and tricep skin fold thickness (TSFT) could significantly predict prothrombin time. In ALF group, serum prealbumin could significantly predict bilirubin levels and MUAC could significantly predict prothrombin time. CONCLUSION: Malnutrition might confer a higher predisposition for HEV infection during pregnancy and is associated with increased severity of disease in terms of occurrence of ALF.

Severe Childhood Anaemia and Blood Transfusion in a Nigerian Secondary Level Facility.

This study aimed to describe the pattern and immediate outcome of severe childhood anaemia requiring blood transfusion at a secondary level of care in Nigeria. A cross-sectional survey of children hospitalized in a secondary health facility in Ogun State, Nigeria, with packed cell volume <20% and who received blood transfusion was done. Of the 253 children admitted between March 2013 and June 2014, 79 (31.2%) had severe anaemia and were transfused with blood. Two-thirds had multiple transfusions. Higher rates of blood transfusion were obtained among underweight children. Fever (98.7%), hypoglycaemia (65.8%) and tender liver (54.4%) were the leading co-morbidities. The case fatality rate was 21.5%. Respiratory distress, convulsions and altered sensorium were significantly associated with mortality. In conclusion, severe anaemia was associated with major morbidities and mortality at the secondary level of paediatric care in Nigeria.

Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.

BACKGROUND & AIMS: Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS: We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS: Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS: When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF.

Baseline Analysis of a Young α-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension.

OBJECTIVES: α-1-Antitrypsin (A1AT) deficiency is a common genetic disease with an unpredictable and highly variable course. The Childhood Liver Disease Research and Education Network is a National Institutes of Health, multicenter, longitudinal consortium studying pediatric liver diseases, with the objective of prospectively defining natural history and identifying disease modifiers. METHODS: Longitudinal, cohort study of A1AT patients' birth through 25 years diagnosed as having liver disease, type PIZZ or PISZ. Medical history, physical examination, laboratory, imaging, and standardized survey tool data were collected during the provision of standard of care. RESULTS: In the present report of the cohort at baseline, 269 subjects were enrolled between November 2008 and October 2012 (208 with their native livers and 61 postliver transplant). Subjects with mild disease (native livers and no portal hypertension [PHT]) compared to severe disease (with PHT or postliver transplant) were not different in age at presentation. A total of 57% of subjects with mild disease and 76% with severe disease were jaundiced at presentation (P = 0.0024). A total of 29% of subjects with native livers had PHT, but age at diagnosis and growth were not different between the no-PHT and PHT groups (P > 0.05). Subjects with native livers and PHT were more likely to have elevated bilirubin, ALT, AST, INR, and GGTP than the no-PHT group (P << 0.001), but overlap was large. Chemistries alone could not identify PHT. CONCLUSIONS: Many subjects with A1AT presenting with elevated liver tests and jaundice improve spontaneously. Subjects with PHT have few symptoms and normal growth. Longitudinal cohort follow-up will identify genetic and environmental disease modifiers.

Feto-Maternal Outcome of Jaundice in Pregnancy in a Tertiary Care Hospital.

Acute viral hepatitis is the most common cause of jaundice in pregnancy. Amongst hepatitis E bears a deadly combination with pregnancy, leading to loss of very young lives. There is almost no data available in this aspect documenting prevalence, profile and effect of jaundice on outcome of pregnancy in Bangladesh. This observational study was done to determine and analyze the frequency, cause and outcome of jaundice in pregnancy among the admitted patients in the feto-maternal medicine wing of Bangabandhu Sheikh Mujib Medical University, for a 2 years period from August 2009 to July 2011. Management was done in collaboration with the hepatologists, hematologists and intensive care unit specialist. Outcome was noted in terms of the mode of delivery, maternal complications, need of blood transfusion and fresh frozen plasma and maternal end result. Fetal outcome was assessed by birth weight, Apgar score, neonatal admission, and perinatal mortality. Prevalence of jaundice was found 2.5% among all high risk and 1.3% among all obstetric admissions. Hepatitis E was the commonest cause and responsible for 80.4% cases of jaundice and next was cholestatic jaundice. Almost half of the patients (43.4%) faced complications like post partum haemorrhage (15.3%), hepatic encephalopathy (10.8%), ante partum hemorrhage (6.5%). Preterm delivery was noted in 71.1% cases. Out of 46 patients with jaundice four (4) mothers died due to hepatic encephalopathy in hepatitis E group. Regarding perinatal outcome 55.8% were of low birth weight, 35.3% had low Apgar score and perinatal mortality was 6.4%.