Management of minimal and overt hepatic encephalopathy with branched-chain amino acids: a review of the evidence.

Hepatic encephalopathy (HE) is a challenging complication of liver disease that is associated with substantial morbidity and mortality. Branched-chain amino acid (BCAA) supplementation in the management of HE is a debated topic. This narrative review aims to provide an up-to-date review of the topic and includes studies featuring patients with hepatocellular carcinoma. A review of the literature was performed using the online databases MEDLINE and EMBASE for studies between 2002 and December 2022. Keywords 'branched-chain amino acids', 'liver cirrhosis' and 'hepatic encephalopathy' were used. Studies were assessed for inclusion and exclusion criteria. Of 1045 citations, 8 studies met the inclusion criteria. The main outcomes reported for HE was changed in minimal HE (MHE) (n = 4) and/or incidence of overt HE (OHE) (n = 7). Two of the 4 studies reporting on MHE had improvement in psychometric testing in the BCAA group, but there was no change in the incidence of OHE in any of the 7 papers in the BCAA group. There were few adverse effects of BCAA supplementation. This review found weak evidence for BCAA supplementation for MHE, and no evidence for BCAAs for OHE. However, given the relative paucity and methodological heterogeneity of the current research, there is scope for future studies to examine the effects of varying timing, dosage, and frequency of BCAAs on outcomes such as HE. Importantly, research is also needed to examine BCAAs in conjunction with standard therapies for HE such as rifaximin and/or lactulose.

Radioembolization for Treatment of Hepatocellular Carcinoma: Current Evidence and Patterns of Utilization.

Primary liver malignancy, of which hepatocellular carcinoma (HCC) is the most common type, is the second most common cause of death due to cancer worldwide. Given the historically poor prognosis of liver cancer, there has been major research on its treatment options, with significant advancements over the last decade. Transarterial radioembolization (TARE) is a locoregional treatment option for HCC that involves transarterial delivery of the ß-emitter yttrium-90 via resin or glass microspheres to arterialized tumor vasculature, delivering a tumoricidal dose to the tumor. The recent 2022 update of the Barcelona Clinic Liver Cancer (BCLC) treatment algorithm features a more prominent role for locoregional treatment, including the incorporation of radioembolization for very-early-stage (BCLC-0) and early-stage (BCLC-A) diseases. This review provides a contemporary summary of the evolving role of TARE in treatment of HCC in light of recent and upcoming trials.

Transjugular intrahepatic portosystemic shunts in portal vein thrombosis: A review.

The presence of portal vein thrombosis (PVT) has previously been considered a contraindication to the insertion of transjugular intrahepatic portosystemic shunts (TIPSS). However, patients with PVT may have portal hypertension complications and may thus benefit from TIPSS to reduce portal venous pressure. There is an increasing body of literature that discusses the techniques and outcomes of TIPSS in PVT. This review summarizes the techniques, indications and outcomes of TIPSS in PVT in published case reports, case series and comparative trials, especially regarding the reduction in portal hypertensive complications such as variceal bleeding. A comprehensive literature search was conducted using MEDLINE and PubMed databases. Manuscripts published in English between 1 January 1990 and 1 March 2021 were used. Abstracts were screened and data from potentially relevant articles analyzed. TIPSS in PVT has been reported with high levels of technical success, short-term portal vein recanalization and long-term PV patency and TIPSS patency outcomes. Several comparative studies, including randomized controlled trials, have shown favorable outcomes of TIPSS compared with non-TIPSS treatment of PVT complications. Outcomes of TIPSS with PVT appear similar to those in TIPSS without PVT. However, TIPSS may be more technically difficult in the presence of PVT, and such procedures should be performed in expert high-volume centers to mitigate the risk of procedural complications. The presence of PVT should no longer be considered a contraindication to TIPSS. TIPSS for PVT has been acknowledged as a therapeutic strategy in recent international guidelines, although further studies are needed before recommendations can be strengthened. KEY POINTS: Portal vein thrombosis (PVT) is no longer a contraindication to the insertion of transjugular intrahepatic portosystemic shunts (TIPSS) TIPSS often leads to the spontaneous dissolution of PVT, but can be combined with mechanical or pharmacological thrombectomy TIPSS reduces portal hypertensive complications of PVT, such as variceal bleeding, and can also facilitate liver transplantation where PVT may otherwise interfere with vascular anastomoses Studies have shown favorable long-term outcomes of TIPSS compared with TIPSS without PVT; as well as compared with non-TIPSS treatment of PVT complications TIPSS in PVT should be performed in high-volume specialist centers due to technical difficulties.

Inflammatory bowel disease incidence, prevalence and 12-month initial disease course in Tasmania, Australia.

BACKGROUND: High inflammatory bowel disease (IBD) rates have been reported in Australasia, but no state-wide studies have yet been performed. AIM: This study estimates the 1-year incidence and point prevalence of IBD in the state of Tasmania, Australia. It also reports clinical outcomes after 12 months of diagnosis in an incident cohort. METHODS: A prospective, population-based study was performed collecting prevalent and incident state-wide cases from 1 June 2013 to 31 May 2014. Case data were identified from specialist doctors, pathology databases and hospital records. Age-standardised rates (ASR) were calculated based on World Health Organization 2000 standard population characteristics. Incident cases were followed up 12 months after diagnosis. RESULTS: There were 1719 prevalent cases: ASR for IBD, Crohn disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBDU) prevalence rates were 303.9, 165.5, 131.4 and 6.9 per 100 000 respectively. Prevalent CD cases were younger, with greater immunomodulator/biological use and bowel resections. There were 149 incident cases: ASR for IBD, CD, UC and IBDU incidence were 29.5, 15.4, 12.4 and 1.7 per 100 000 respectively. Incident CD cases were more likely than UC or IBDU to require escalation of medical therapy, hospitalisation and bowel resection, especially among those with penetrating or stricturing disease. They had a longer duration of symptoms prior to diagnosis. CONCLUSION: IBD prevalence and incidence rates are high in Tasmania, comparable to data from other Australasian studies and those from Northern Europe and America. Poorer 12-month clinical outcomes occurred in complicated CD, with greater use of healthcare resources.

Depression, fatigue and neurocognitive deficits in chronic hepatitis C.

Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy. Therefore, intracerebral neurobiological changes associated with HCV may potentially explain these symptoms. These changes may arise from infiltration of the brain by peripherally induced cytokines, as well as direct neuropathic effects of HCV viral particles penetrating the blood-brain barrier. These phenomena parallel those reported in human immunodeficiency virus (HIV) infection. HCV-associated intracerebral changes include upregulated inflammatory responses, altered neurotransmitter levels, hormonal dysregulation, and release of neurotoxic substances. These may subsequently lead to abnormal neuronal conduction and function in areas of the brain governing affective responses, emotional processing, motivation, attention and concentration. Although direct-acting antiviral medications lead to high rates of HCV clearance, intracerebral changes may not be subsequently reversed and symptoms of depression, fatigue and neurocognitive deficits may persist. There is an ongoing role for multidisciplinary care and pharmacotherapy to manage these symptoms in HCV patients. Furthermore, there may be opportunities for future therapies to specifically target and ameliorate HCV-associated intracerebral changes.

Esophageal bezoar due to karaya gum granules used as a laxative.

Esophageal obstruction from soluble fiber laxatives, such as karaya gum, has been rarely reported in the literature. However, as such preparations are widely commercially available, it is important for gastroenterologists to be aware of their potential to form a bezoar in the esophagus due to swelling on contact with liquid. This report highlights such a case and discusses its challenging management.

Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy.

Direct acting antiviral (DAA) regimens containing ritonavir have been developed to treat hepatitis C, with fewer side effects than that by interferon-based regimens. However prescribers must be aware of drug-drug interactions. There are multiple reports of iatrogenic Cushing syndrome (CS) caused by ritonavir, when used to treat human immunodeficiency virus, increasing the bioavailability of exogenous steroids by inhibiting cytochrome p450 enzymes in the liver and gut wall and thus reducing steroid metabolism. We herein report a novel scenario of CS due to interaction between ritonavir for hepatitis C treatment and oral budesonide for autoimmune hepatitis.

A Delayed Diagnosis of Chronic Mesenteric Ischaemia: The Role of Clinicians' Cognitive Errors.

Chronic diarrhoeal illnesses with nausea and weight loss are a common indication for gastroenterology review. While many such cases have intra-luminal aetiologies, such as inflammatory bowel disease, coeliac disease or other malabsorptive conditions, with many other cases due to functional gut disorders or systemic malignancy, clinicians must also keep vascular disorders in mind. Here we report a patient with a delayed diagnosis of chronic mesenteric ischaemia after 6 months of gastrointestinal symptoms strongly mimicking an alternative diagnosis such as inflammatory bowel disease due an atypical predominance of nausea and diarrhoea rather than pain. We briefly review the literature on treatment of this condition but also discuss with particular attention the sequence of cognitive errors made by clinicians that led to a diagnostic delay, inviting readers to thus reflect on how such errors can be minimised in their practice.

Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease.

AIM: To determine characteristics and prognostic predictors of patients with hepatocellular carcinoma (HCC) in association with non-alcoholic fatty liver disease (NAFLD). METHODS: We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index (BMI), and the presence of diabetes, hypertension, or dyslipidaemia. RESULTS: Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent (8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of <25 kg/m2, 25-29 kg/m2 and ≥30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics (P=0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of HCC. CONCLUSION: HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis.

An unusual cause of biliary obstruction.

Portal biliary ductopathy (PBD) is a condition in which biliary and pancreatic ducts are extrinsically compressed by collateral branches of the portal venous system, which in turn have become dilated and varicosed due to portal hypertension. While the majority of patients with PBD are asymptomatic, a minority can present with symptoms of biliary obstruction and cholangitis with the potential of developing secondary chronic liver disease. This paper reports the case of a 29 year old male presenting with acute cholangitis, in whom PBD was diagnosed radiologically. A brief review of current literature regarding the diagnosis and management of this condition will also be presented.

Perceptions of health and diabetes in a Melbourne South Sudanese community.

This qualitative study explored how members of the Dinka South Sudanese community in West Melbourne perceive diabetes within the context of their broader health circumstances. These perceptions may guide health services aiming to prevent diabetes and chronic disease. 3 focus groups were conducted with 25 participants. Recorded discussions were transcribed and interrogated through a grounded theory approach. Diabetes and chronic diseases were familiar to participants, but issues they claimed not to understand well. The Australian social environment was seen to propagate unhealthy lifestyle changes, while experiences with Australian health services were dissatisfying. Mental distress was perceived as significantly detracting from the community's health. Preventative health interventions in this community, while emphasising education and healthy lifestyle behaviours, should also acknowledge underlying socio-historical contexts and the psychiatric burden of forced migration.