Wilson's disease and autoimmune hepatitis coexistence: A cause of diagnostic delay

This case report describes a 27-year-old housewife who presented with a progressive and insidious onset of abdominal distension, loss of appetite, and fatigue which started 3 months before her presentation. The physical assessment showed moderate ascites and small liver size, and no other peripheral evidence of chronic liver disease was observed. A diagnosis of liver cirrhosis and was confirmed by investigations and imaging, where ascites responded well to therapy with diuretics. Investigations for the cause of cirrhosis was established through the diagnosis of autoimmune hepatitis, and she was started on steroids and azathioprine with partial improvement in liver biochemistry. She presented 8 months later with neuropsychiatric symptoms in the form of slurred speech and difficulty walking. Accordingly, Wilson's disease was suspected to be the cause and further investigations confirmed this. A chelating agent, D penicillamine, was added to her immunosuppressive treatment. Nine months later she showed slow improvement in her neurological symptoms and was referred for assessment for liver transplantation. Wilson's disease, although rare, should be suspected in patients with decompensated liver disease. The dominance of clinical and epidemiological features of autoimmune hepatitis as a common causative pathology for chronic liver disease in young and middle-aged ladies may hide the presence of other serious different pathologies such as Wilson's disease.

Nomenclature and definition of metabolic-associated fatty liver disease: a consensus from the Middle East and north Africa.

With the increasing prevalence of obesity and type 2 diabetes, fatty liver disease associated with metabolic dysfunction is a global health problem, especially because it is one of the earliest consequences of obesity and it precedes diabetes development. Fatty liver disease associated with metabolic dysfunction is of particular concern in the Middle East and north Africa, where its prevalence is greater than that in the rest of the world. Despite the magnitude of the problem, no regional guidelines have been developed to address this disease. This Review describes suggestions of redefining fatty liver disease associated with metabolic dysfunction, including its terminology and criteria for diagnosis. Experts have raised serious concerns on the current nomenclature, which labels the disease as non-alcoholic fatty liver disease (NAFLD), and its diagnostic criteria. The panel reached a consensus that the disease should be renamed as metabolic-associated fatty liver disease (MAFLD) and that the disease should be diagnosed by positive criteria. The aim is now to work with authorities across the region to implement these proposed changes and reflect them in health-care policy and to improve health care for patients in this region.

Evidence of an Exponential Decay Pattern of the Hepatitis Delta Virus Evolution Rate and Fluctuations in Quasispecies Complexity in Long-Term Studies of Chronic Delta Infection.

Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand hepatitis B e antigen seroconversion, and has helped to predict whether hepatitis C infection will resolve or become chronic. It is likely that characterization of the hepatitis delta virus (HDV) quasispecies will ultimately have similar value for the management of this infection. This study sought to determine the RNA evolution rates in serum of chronic hepatitis delta (CHD) treatment-naïve patients, using next-generation sequencing methods. The region selected for study encompassed nucleotide positions 910 to 1270 of the genome and included the amber/W codon. Amber/W is a substrate of the editing process by the ADAR1 host enzyme and is essential for encoding the 2 delta antigens (HDAg). The amber codon encodes the small (unedited) HDAg form and the W codon the large (edited) HDAg form. The evolution rate was analyzed taking into account the time elapsed between samples, the percentage of unedited and edited genomes, and the complexity of the viral population. The longitudinal studies included 29 sequential samples from CHD patients followed up for a mean of 11.5 years. In total, 121,116 sequences were analyzed. The HDV evolution rate ranged from 9.5x10-3 to 1.2x10-3 substitutions/site/year and showed a negative correlation with the time elapsed between samples (p<0.05). An accumulation of transition-type changes was found to be responsible for higher evolution rates. The percentages of unedited and edited genomes and the quasispecies complexity showed no relationships with the evolution rate, but the fluctuations in the percentages of genomes and in complexity suggest continuous adaptation of HDV to the host conditions.

Prevalence of and predictive factors for nonalcoholic fatty liver disease in Sudanese individuals with type 2 diabetes: Is metabolic syndrome the culprit?

BACKGROUND AND STUDY AIM: Non-alcoholic fatty liver disease (NAFLD) is a common global chronic liver condition. The prevalence of NAFLD among individuals with type 2 diabetes is estimated to be as high as 75%. The aim of this study was to determine the prevalence of NAFLD among individuals with type 2 diabetes in Sudan. PATIENTS AND METHODS: This was a cross-sectional hospital-based study, which was carried out at the Jabir Abu-Elizz diabetic centre in Khartoum; 167 outpatients with type 2 diabetes were enrolled. NAFLD was diagnosed based on ultrasound, following exclusion of significant alcohol intake and secondary causes of liver diseases. NAFLD was defined as hepatic steatosis in the absence of alcohol intake, medication, previous liver disease and negative results for the serological test for hepatitis B and C. Logistic regression analysis was used to determine independent risk factors for the development of NAFLD in individuals with type 2 diabetes. RESULTS: The number of female subjects was 89 (53.3%), and most subjects (145, 86.8%) were between the ages of 40 and 70 years. The overall prevalence of fatty liver among individuals with type 2 diabetes was found to be 50.3%. Age, duration of diabetes, hypertension and HbA1c levels appeared to have no impact on the prevalence of NAFLD. The possible predictors of NAFLD were overweight, obesity, central obesity, high triglyceride level and low high-density lipoprotein cholesterol (HDL-c) level. A higher prevalence of NAFLD was observed in individuals with three components of the metabolic syndrome. CONCLUSION: NAFLD was observed in half of the diabetic population, and its occurrence correlates positively with metabolic syndrome risk factors.

The association between renal stone disease and cholesterol gallstones: the easy to believe and not hard to retrieve theory of the metabolic syndrome.

Renal stone disease and gallstone disease are widely prevalent and costly disease across the globe. Both renal stone disease and gallstone disease are associated with a variety of diseases including obesity, metabolic syndrome, dyslipidemia, hypertension, insulin resistance diabetes and gout. Importantly, the presence of either renal stone disease or gallstone disease is associated with an increased risk of cardiovascular disease. In a recent study of the Atherosclerosis Risk in Communities (ARIC), individuals with a history of gallstones were 54% more likely to report a history of nephrolithiasis after adjusting for age, gender, body size and other factors. Furthermore, in three large cohorts including over 240,000 subjects: the Nurses' Health Studies (NHS) I and II and the Health Professionals Follow-up Study (HPFS), showed that gallstone disease is independently associated with nephrolithiasis. The mechanisms linking gallstone disease and renal stone disease are complex and not yet established. Insulin resistance, lithogenic diets, alterations of transporters in gallbladder and urinary system, and pH are possible potential mechanisms for future exploration. How the liver communicates with kidney in individuals with renal stone disease and gallstone disease is not well known and whether this communication is similar as in hepto-renal syndrome is subject for future research. Further research is needed to determine: (i) the underlying mechanisms of renal stone disease and gallstone disease; (ii) the potential treatment of renal stone disease and gallstone disease.

Non alcoholic fatty liver disease (NAFLD) in a Sudanese population: What is the prevalence and risk factors?

BACKGROUND AND STUDY AIMS: Non alcoholic fatty liver disease (NAFLD) is a common clinical condition associated with obesity and considered as possible precursor of more serious disease like Non alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. There is very little research work carried concerning NAFLD in African countries in relation to prevalence and risk factors. Therefore, the aim of this study is to determine the prevalence of NAFLD and risk factors among asymptomatic co-patients accompanying patients admitted to gastroenterology wards at the National Centre for GI & Liver Diseases, Ibn Sina Hospital (Khartoum, Sudan). PATIENTS AND METHODS: Subjects with liver disease, excess alcohol intake (the intake of more than 21 units of alcohol per week for men and 14 units for women per week) and pregnancy were excluded from this study. The age, sex, body mass index (BMI), history and duration of diabetes and hypertension were recorded. Ultrasound was offered followed by clinical examination and blood sample was taken for assessment of liver function from each subject (total number of participants was 100). RESULTS: NAFLD was diagnosed in 20 patients, giving prevalence of 20%. There was no statistical significance between the two sexes. The mean age of subjects with NAFLD was 53 years old and without NAFLD was 40 years (p<0.05). Importantly, the prevalence of NAFLD increased with age and BMI. Due to small number of diabetic individuals and hypertension, these two conditions were not statistically significant when related to NAFLD. CONCLUSION: The estimated prevalence of NAFLD in our study is 20% and this figure is comparable to the prevalence of NAFLD in Asian countries. Males and females were nearly equally affected and the prevalence of NAFLD increased with age and BMI, making obesity a main risk factor.

Nonalcoholic fatty liver disease and cardiovascular disease: has the time come for cardiologists to be hepatologists?

Nonalcoholic fatty liver disease (NAFLD) is prevalent in people with the metabolic syndrome and type 2 diabetes and is present in up to one-third of the general population. Evidence is now accumulating that NAFLD is associated with obesity and diabetes and may serve as a predictor of cardiovascular disease (CVD). The possible mechanisms linking NAFLD and CVD include inflammation and oxidative stress, hyperlipidaemia, insulin resistance, and direct impact of NAFLD on coronary arteries and left ventricular dysfunction. In addition, several studies suggest that NAFLD is associated with high risk of CVD and atherosclerosis such as carotid artery wall thickness and lower endothelial flow-mediated vasodilation independently of classical risk factors and components of the metabolic syndrome. It is not yet clear how treatment of NAFLD will modulate the risk of CVD. Furthermore, studies are urgently needed to establish (i) the pathophysiology of CVD with NAFLD and (ii) the benefit of early diagnosis and treatment of CVD in patients with NAFLD. In the absence of biochemical markers, it is crucial that screening and surveillance strategies are adopted in clinical practice in the growing number of patients with NAFLD and at risk of developing CVD. Importantly, the current evidence suggest that statins are safe and effective treatment for CVD in individuals with NAFLD.