Alpha-1 antitrypsin deficiency

α-1 antitrypsin is synthesised in the liver and protects lung alveolar tissues from destruction by neutrophil elastase. α-1 antitrypsin deficiency is a common autosomal recessive condition (1:1600 to 1:1800) in which liver disease results from retention of abnormal polymerised α-1 antitrypsin in the endoplasmic reticulum of hepatocytes, and emphysema results from alveolar wall damage. The clinical consequences of α-1 antitrypsin deficiency in childhood are haemorrhagic disease in infancy, cholestasis in infancy, or chronic liver disease. Lung disease attributable to α-1 antitrypsin deficiency does not occur in childhood, but is closely linked to smoking in adults. Membranoproliferative glomerulonephritis, panniculitis, and necrotising vasculitis are associations with α-1 antitrypsin deficiency in adult life

Demographic and clinical profile of adult Sri Lankans having hepatocellular carcinoma admitted to medical units of a tertiary referral center; 4 years experience

Objective: To study the demographic and clinical profile of adult Sri Lankans having hepatocellular carcinoma. Methods: Clinical notes of 42 patients having hepatoma admitted to medical units at Sri Jayawardenepura General Hospital, Kotte, Sri Lanka from January 2008 to January 2012 were retrospectively analyzed to obtain the required data. Results: The age range was 43-91 years with a mean age of 65.5+/- 11.1 SD. Sex distribution was male: female; 38:4 (9:1). 90.5% were alcoholics. 57.1% had established liver disease at the time of diagnosis. 27.7% of patients with undiagnosed liver disease at presentation had radiological evidence of cirrhosis. On presentation ascites, abdominal pain, hepatic encephalopathy, anorexia and weight loss were found in 38.1%, 19%, 19%, 16.7% and 14.7% respectively. Uni-focal tumors were found in 61.9%. Secondaries were seen in 11.9%. The detectable sites were lymph nodes, bones, lungs, and the inferior vena cava extending into the right atrium. Hepatitis B and C infection were not seen. The available curative therapeutic modalities were minimal. Conclusions:A marked male dominance was seen. Alcohol etiology was the dominant cause. Hepatoma may be the first presentation in undiagnosed liver disease. In all patients the diagnosis had been made at an advanced stage of the tumor thus resulting in a poor prognosis. We recommend that ultrasound scanning of the abdomen and alpha-feto protein estimation to be done at every six months interval in chronic liver disease patients

Familial haemophagocytic lymphohistiocytosis: rare cause of acute liver failure in a neonate--a case report

Familial haemophagocytic lymphohistiocytosis (FHLH) is a rare lifethreatening disorder of the immune system characterized by proliferation and infiltration of hyperactivated macrophages and T-lymphocytes and manifesting as acute illness with prolonged fever, cytopenias, and hepatosplenomegaly. We describe a one-month-old female with FHLH and rapidly progressing liver failure. To conclude, FHLH should be included in the differential diagnosis of acute liver failure in neonates and young infants.Keywords: Familial haemophagocytic lymphohistiocytosis; Acute liver failure; Neonate; Case repor

Development and validation of a model to predict incident chronic liver disease in the general population: the CLivD score

BACKGROUND & AIMS: Current screening strategies for chronic liver disease focus on detection of subclinical advanced liver fibrosis but cannot identify persons at high future risk for severe liver disease. Our aim was to develop and validate a risk prediction model for incident chronic liver disease in the general population based on widely available factors. METHODS: Multivariable Cox regression analyses were used to develop prediction models for liver-related outcomes with and without laboratory measures (Modellab and Modelnon-lab) in 25,760 individuals aged 40-70 years. Their data were sourced from the Finnish population-based health examination surveys FINRISK 1992-2012 and Health 2000 (derivation cohort). The models were externally validated in the Whitehall II (n = 5058) and Copenhagen City Heart Study (CCHS) (n = 3049) cohorts. RESULTS: The absolute rate of incident liver outcomes per 100,000 person-years ranged from 53 to 144. The final prediction model included age, sex, alcohol use (drinks/week), waist-hip ratio, diabetes, and smoking, and Modellab also included gamma-glutamyltransferase values. Internally-validated Wolbers' C-statistics were 0.77 for Modellab and 0.75 for Modelnon-lab, while apparent 15-year AUCs were 0.84 (95% CI 0.75-0.93) and 0.82 (95% CI 0.74-0.91). The models identified a small proportion (10% absolute 15-year risk for liver events. Of all liver events, only 10% occurred in participants in the lowest risk category. In the validation cohorts, 15-year AUCs were 0.78 (Modellab) and 0.65 (Modelnon-lab) in the CCHS cohort, and 0.78 (Modelnon-lab) in the Whitehall II cohort. CONCLUSIONS: Based on widely available risk factors, this Chronic Liver Disease (CLivD) score can be used to predict risk for future advanced liver disease in the general population. LAY SUMMARY: Liver disease often progresses silently without symptoms and thus the diagnosis is often delayed until severe complications occur and prognosis becomes poor. In order to identify individuals in the general population who have high risk of developing severe liver disease in the future, we developed and validated a Chronic liver disease (CLivD) risk prediction score, based on age, sex, alcohol use, waist-hip ratio, diabetes, smoking, with or without gamma-glutamyltransferase (GGT). The CLivD score can be used as part of health counseling, and for planning further liver investigations and follow-up

Development and validation of a model to predict incident chronic liver disease in the general population : The CLivD score

Background & Aims: Current screening strategies for chronic liver disease focus on detection of subclinical advanced liver fibrosis but cannot identify those at high future risk of severe liver disease. Our aim was to develop and validate a risk pre-diction model for incident chronic liver disease in the general population based on widely available factors. Methods: Multivariable Cox regression analyses were used to develop prediction models for liver-related outcomes with and without laboratory measures (Modellab and Modelnon-lab) in 25,760 individuals aged 40-70 years. Their data were sourced from the Finnish population-based health examination surveys FINRISK 1992-2012 and Health 2000 (derivation cohort). The models were externally validated in the Whitehall II (n = 5,058) and Copenhagen City Heart Study (CCHS) (n = 3,049) cohorts. Results: The absolute rate of incident liver outcomes per 100,000 person-years ranged from 53 to 144. The final prediction model included age, sex, alcohol use (drinks/week), waist-hip ratio, diabetes, and smoking, and Modellab also included gamma-glutamyltransferase values. Internally validated Wolbers' C -sta-tistics were 0.77 for Modellab and 0.75 for Modelnon-lab, while apparent 15-year AUCs were 0.84 (95% CI 0.75-0.93) and 0.82 (95% CI 0.74-0.91). The models identified a small proportion ( 10% absolute 15-year risk for liver events. Of all liver events, only 10% occurred in participants in the lowest risk category. In the validation cohorts, 15-year AUCs were 0.78 (Modellab) and 0.65 (Modelnon-lab) in the CCHS cohort, and 0.78 (Modelnon-lab) in the Whitehall II cohort. Conclusions: Based on widely available risk factors, the Chronic Liver Disease (CLivD) score can be used to predict risk of future advanced liver disease in the general population. Lay summary: Liver disease often progresses silently without symptoms and thus the diagnosis is often delayed until severe complications occur and prognosis becomes poor. In order to identify individuals in the general population who have a high risk of developing severe liver disease in the future, we developed and validated a Chronic Liver Disease (CLivD) risk prediction score, based on age, sex, alcohol use, waist-hip ratio, diabetes, and smoking, with or without measurement of the liver enzyme gamma-glutamyltransferase. The CLivD score can be used as part of health counseling, and for planning further liver investigations and follow-up. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.Peer reviewe

Acute liver failure due to primary angiosarcoma: A case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Hepatic angiosarcoma is a primary sarcoma of the liver, accounting for only 2% of all primary hepatic malignancies. Acute liver failure is an extremely rare presentation of a primary liver tumour.</p> <p>Case presentation</p> <p>We report a case of a seventy year-old man who presented with a very short period of jaundice leading to fulminant hepatic failure (FHF). On further investigation he was found to have primary angiosarcoma of liver.</p> <p>Conclusion</p> <p>The treatment outcomes for hepatic angiosarcoma are poor, we discuss the options available and the need for prompt investigation and establishment of a diagnosis</p

Tuberculosis and Hepatic Steatosis Are Prevalent Liver Pathology Findings among HIV-Infected Patients in South Africa

Liver disease epidemiology in sub-Saharan Africa has shifted as a result of HIV and the increased use of antiretroviral therapy leading to a need for updated data on common causes of liver disease. We retrospectively reviewed records from all hospitalized patients who had liver biopsy at a single hospital in South Africa from 2001 to 2009 and compared diagnosis by HIV status. During the period of study 262 patients had liver biopsy, 108 (41%) were HIV-infected, 25 (10%) were HIV-sero-negative, and 129 (49%) had unknown or unrecorded HIV status. Overall 81% of biopsies provided additional diagnostic data. Malignancy was the most common finding reported on 56 (21%) biopsies followed by granuloma or TB, hepatic steatosis, and fibrosis or cirrhosis. HIV-infected patients were more likely to have granulomas and steatosis. Half of patients with granulomas were already on TB treatment, suggesting paradoxical reactions or drug induced liver injury may have been important causes of liver inflammation among these patients. We note that TB, paradoxical reactions during TB treatment, possible drug induced liver injury, and hepatic steatosis are important causes of liver pathology among HIV-infected hospitalized patients with unclear etiology of liver disease after initial assessment. Among HIV sero-negative patients, malignancy was the major cause of liver disease. Our findings re-enforce the importance of TB as a diagnosis among HIV-infected individuals.\ud \u

Live birth after fresh embryo transfer vs elective embryo cryopreservation/frozen embryo transfer in women with polycystic ovary syndrome undergoing IVF (FreFro-PCOS): study protocol for a multicenter, prospective, randomized controlled clinical trial

BACKGROUND: Polycystic ovary syndrome (PCOS) patients are at increased risk of pregnancy complications, which may impair pregnancy outcome. Transfer of fresh embryos after superovulation may lead to abnormal implantation and placentation and further increase risk for pregnancy loss and complications. Some preliminary data suggest that elective embryo cryopreservation followed by frozen–thawed embryo transfer into a hormonally primed endometrium could result in a higher clinical pregnancy rate than that achieved by fresh embryo transfer. METHODS/DESIGN: This study is a multicenter, prospective, randomized controlled clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be enrolled and randomized into two parallel groups. Participants in group A will undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants in group B will undergo elective embryo cryopreservation after oocyte retrieval and frozen–thawed embryo transfer in programmed cycles. The primary outcome is the live birth rate. Our study is powered at 80 to detect an absolute difference of 10 at the significance level of 0.01 based on a two-sided test. DISCUSSION: We hypothesize that elective embryo cryopreservation and frozen–thawed embryo transfer will reduce the incidence of pregnancy complications and increase the live birth rate in PCOS patients who need IVF to achieve pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0184152

Transient Elastography in Community Alcohol Services: Can It Detect Significant Liver Disease and Impact Drinking Behaviour?

Introduction: Alcohol is the leading cause of cirrhosis in Western populations. The early identification of high-risk drinkers followed by intervention is an effective way to reduce harm. We aim to assess the feasibility of integrating transient elastography (TE) into community alcohol services, and to determine its impact on modifying drinking behaviours. Method: A prospective cohort study was conducted at a community alcohol clinic in Nottingham, UK (April 2012 to March 2014). Patients (>18 years) with a primary alcohol problem were recruited. Those known to liver services or those known to have chronic liver disease were excluded. Significant liver fibrosis was defined by a liver stiffness of >8 kilopascal (kPa). Follow-up was for a minimum of six months. Data were descriptively analysed for significant differences between patients with a normal liver stiffness versus raised liver stiffness. Results: 156 patients were invited; n = 87 attended and n = 86 underwent successful TE. The majority were male (n = 53, 70.0%), and the mean age was 46.3 years (SD ± 9.8). Median liver stiffness was 6.9 kPa (range 3.1–75.0kPa). Clinically significant liver fibrosis was identified in n = 33 (38.4%), of which n = 6 were in the cirrhotic range (≥15 kPa). The baseline median self-reported alcohol intake for normal stiffness was 126 units per week (range 24–378) and in raised stiffness was 149.0 units per week (range 39.0–420.0); this difference was nonsignificant (p = 0.338). The median reduction in self-reported alcohol intake in the whole cohort was 65.0 units per week (range 27.0–88.0, p < 0.001); in the normal liver stiffness group it was 25.0 units per week (range 18.0–75.0, p = 0.154), and in the raised liver stiffness group it was 78.5 units per week (range 36.0–126.0, p < 0.001). Conclusion: The study demonstrated that transient elastography is a feasible tool to stratify clinically significant liver disease in community alcohol services. It can stimulate a change in high-risk drinking behaviour and a normal liver stiffness result does not provide false reassurance to participants