Recurrent Pyroglutamic Acidosis in the Context of Undiagnosed Liver Cirrhosis-A Case Report.

Metabolic associated fatty liver disease, previously known as nonalcoholic fatty liver disease, is the most common cause of chronic liver disease across all ethnic groups; however, it remains enormously underestimated.1 , 2 Sepsis, hepatotoxic medications and malnutrition in the acute settings on top of unknown cirrhosis can lead to decompensation and various metabolic complications. Pyroglutamic acidosis is a rarely recognised cause for unexplained high anion gap metabolic acidosis that is felt to be frequently underdiagnosed. Particular patients at risk include women, the elderly, those on regular paracetamol and those suffering with malnourishment or sepsis. Other risk factors include alcohol abuse and chronic liver disease (3). We present the case of a patient with recurrent episodes of pyroglutamic acidosis and encephalopathy in the context of undiagnosed nonalcoholic fatty liver disease with cirrhosis.

Increased Incidence of Post-transplant Lymphoproliferative Disorder in Autoimmune Liver Disease: An Irish National Experience.

BACKGROUND: Post-Transplant Lymphoproliferative Disorder (PTLD) is a well-recognized complication post solid organs transplant. PTLD represents a broad spectrum of abnormalities ranging from an infectious mononucleosis like illness to malignant lymphoma. METHODS: A retrospective study was performed by collecting data of orthotopic liver transplant (OLT) patients in the National Liver Unit in Ireland from December 1993 to December 2014. Data was analyzed to identify PTLD patients and determine their demographic details, the indication for liver transplant, presenting symptoms, immunosuppression regimens, Epstein"Barr virus (EBV) status and PTLD outcome. RESULTS: From a total of 756 liver transplants recipients, 20 patients (2.6%) were diagnosed with PTLD. The median time from OLT to PTLD diagnosis was 83 months. The main primary indication for OLT of the PTLD cohort was Autoimmune Liver Disease (AiLD) (n = 13, 65%, mainly primary sclerosing cholangitis (PSC) n = 8, 40%). The combined group of auto-immune hepatitis, PSC and primary biliary cholangitis had a significantly higher incidence of PTLD compared to other etiologies (P < 0.01). In AiLD PTLD subgroup, 61.5% were positive for EBV. Five patients (38.5%) had extra-nodal disease and 3 patients had CNS disease. 61% of PTLD AiLD patients (n = 8) achieved complete response following their treatment. CONCLUSION: PTLD has high mortality however early diagnosis and complete remission are achievable. Our study suggests that the incidence of PTLD is increased in AiLD and notably PSC patients.

The Metabolic Role of the Microbiome: Implications for NAFLD and the Metabolic Syndrome.

Nonalcoholic fatty liver disease (NAFLD) has rapidly emerged as one of the most prevalent liver diseases worldwide and is set to achieve virtually epidemic proportions if current trends in obesity continue. A considerable volume of data from animal experiments has revealed the magnitude of the metabolic contribution of the gut microbiome and how a disordered microbial population could contribute to the development of obesity and its complications, including NAFLD. Although considerable progress has been made in developing a role for the microbiome in NAFLD and nonalcoholic steatosis (NASH), there are still many issues to be resolved, including the nature and location of the altered microbiome (i.e., small intestine or colon, or both); the specificity of deficits in intestinal integrity to NAFLD/NASH versus liver disease in general; the metabolic pathways, in man, that are key to the influence of the microbiome; and finally, the therapeutic interventions that are likely to be of benefit to our patients.As always, the situation in man is somewhat more complex than in animal models, but the role of the microbiota and of interventions that modulate the microbiome, though not yet ready for clinical practice, continue to be fertile areas for basic and clinical research.

Homozygosity for HLA group 2 alleles predicts treatment failure with interferon-α and ribavirin in chronic hepatitis C virus genotype 1 infection.

Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).

The role of the gut microbiota in nonalcoholic fatty liver disease.

Important metabolic functions have been identified for the gut microbiota in health and disease. Several lines of evidence suggest a role for the gut microbiota in both the etiology of nonalcoholic fatty liver disease (NAFLD) and progression to its more advanced state, nonalcoholic steatohepatitis (NASH). Both NAFLD and NASH are strongly linked to obesity, type 2 diabetes mellitus and the metabolic syndrome and, accordingly, have become common worldwide problems. Small intestinal bacterial overgrowth of Gram-negative organisms could promote insulin resistance, increase endogenous ethanol production and induce choline deficiency, all factors implicated in NAFLD. Among the potential mediators of this association, lipopolysaccharide (a component of Gram-negative bacterial cell walls) exerts relevant metabolic and proinflammatory effects. Although the best evidence to support a role for the gut microbiota in NAFLD and NASH comes largely from animal models, data from studies in humans (albeit at times contradictory) is accumulating and could lead to new therapeutic avenues for these highly prevalent conditions.

Small intestinal bacterial overgrowth.

Despite the current increase in interest in the role of the microbiota in health and disease and the recognition, for over 50 years, that an excess of colonic-type flora in the small intestine could lead to a malabsorption syndrome, small intestinal overgrowth remains poorly defined. This lack of clarity owes much to the difficulties that arise in attempting to arrive at consensus with regard to the diagnosis of this condition: there is currently no gold standard and the commonly available methodologies (the culture of jejunal aspirates and a variety of breath tests) suffer from considerable variations in their performance and interpretation, leading to variations in the prevalence of overgrowth in a variety of clinical contexts. Treatment is similarly supported by a scant evidence base and the most commonly used antibiotic regimens owe more to custom than clinical trials.

Diagnosis of small intestinal bacterial overgrowth: the challenges persist!

Small intestinal bacterial overgrowth was originally defined in the context of an overt malabsorption syndrome and diagnostic tests were developed and validated accordingly. More recently, the concept of intestinal contamination with excessive numbers of bacteria, especially those of colonic type, has been extended beyond the bounds of frank maldigestion and malabsorption to explain symptomatology in disorders as diverse as irritable bowel syndrome, celiac sprue and nonalcoholic fatty liver disease. Owing to a lack of consensus with regard to the optimal diagnostic criteria (the 'gold standard') for the diagnosis of bacterial overgrowth, the status of these new concepts is unclear. This review sets out to critically appraise the various diagnostic approaches that have been taken and are currently employed to diagnose small intestinal bacterial overgrowth.