From the Editors” Desk
Hepatology for nurses. Elsevier Medicine UK, Vol 51, issue 5
(1). Marianne Samyn, et al. Liver and biliary disease in infancy. Medicine UK 2023;51(6):P375-379.
Liver disease in infancy is a relatively rare but serious cause of morbidity and mortality. Since jaundice is a common finding in the neonatal period, the immediate priority is to differentiate between unconjugated hyperbilirubinaemia, which is generally a benign developmental phenomenon, and conjugated hyperbilirubinaemia (conjugated fraction >20%), which is always pathological. Conjugated hyperbilirubinaemia, suggested by yellow urine and stools that are not yellow or green in an infant of any age, is pathognomonic of liver parenchymal or bile duct disease. It warrants prompt investigation because some of its causes require urgent treatment. Genetic counselling can also be required.
(2). Marianne Samyn, et al. Liver and biliary disease in childhood. Medicine UK 2023;51(6):P380-384.
It is estimated that around 1000 children are diagnosed with liver disease in the UK, every year. Their presentation varies from acute to more insidious, often in the context of chronic liver disease. In acute settings, the liver disease can be so severe as to cause acute liver failure, a multisystemic disease requiring urgent referral to a specialized liver centre with access to intensive care support and liver transplantation. The clotting profile is the most sensitive marker of liver disease severity and should always be checked at presentation. Whereas infectious causes are common in this age group, other conditions such as autoimmune liver disease and Wilson disease must be excluded, and rarer, metabolic and genetic conditions considered. Children can develop acute cholestasis suggesting biliary obstruction related to intra- and/or extrahepatic pathologies. Presentation with complications of chronic liver disease, such as portal hypertension and failure of synthetic function, is less common but requires specialized care and consideration for liver transplantation.
(3). Sophie Ragan, et al. Liver disease in pregnancy. Medicine UK 2023;51(6):P385-388.
Liver disease in pregnant patients often causes concern. This chapter covers both acute liver pathologies that occur in pregnancy, and pregnancy in mothers with chronic liver disease, focusing on practical diagnostic and management strategies.
(4), Sophia L. Ling, et al. Autoimmune hepatitis and overlap syndromes. Medicine UK.
Autoimmune hepatitis (AIH) is an immune-mediated liver disease that can progress rapidly to cirrhosis if left untreated. As the natural history of AIH features both acute and chronic inflammatory liver damage with fluctuating degrees of severity, clinical presentation can vary from asymptomatic to fatigue, jaundice and acute liver failure. The diagnosis is suspected by deranged liver enzymes, supported by hypergammaglobulinaemia and positive autoantibodies; it is confirmed by interface hepatitis and lymphoplasmacytic infiltration on liver biopsy. A small proportion of individuals with AIH present with or later develop an overlap syndrome, demonstrating clinical, biochemical or radiological features of concomitant primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). These patients require histological confirmation, additional therapies and additional monitoring for the direct, metabolic and iatrogenic effects of both conditions. Overlap syndrome should be suspected early in non-, insufficient or loss of response, to identify and avoid disease progression.
(5). George Mells, et al. Primary biliary cholangitis. Medicine 2023;51(6):P395-397.
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by lymphocytic destruction of the small, intrahepatic bile ducts, causing chronic cholestasis and progressive fibrosis that eventually leads to biliary cirrhosis. It is a complex disorder resulting from the interaction of genetic and environmental factors and is strongly predominant in female patients (female:male 9:1). Typical symptoms include cholestatic pruritus and the PBC fatigue symptom complex. Features of end-stage liver disease (ESLD) from PBC are the same as those of ESLD from other causes, i.e. variceal haemorrhage, ascites, jaundice and hepatic encephalopathy. First-line disease-modifying treatment for PBC is with ursodeoxycholic acid (UDCA). Individuals with an inadequate biochemical response to UDCA (e.g. defined as serum alkaline phosphatase >1.67 times the upper limit of normal measured after 12 months of treatment) are prioritized for the addition of second-line treatment with obeticholic acid or a fibrate, i.e. bezafibrate or fenofibrate. First-line treatment for PBC-related pruritus is colestyramine. If colestyramine is unpalatable or ineffective, second-line treatment of pruritus is with rifampicin. Patients with the fatigue symptom complex and prominent somnolence can benefit from modafinil. Liver transplantation is indicated for PBC patients with chronic liver failure or intractable pruritus.
(6). Jeremy S. Nayagam, et al. Primary sclerosing cholangitis. Medicine 2023;51(6):P398-404.
Primary sclerosing cholangitis (PSC) is a chronic liver disease that leads to chronic cholestasis, biliary strictures and liver fibrosis. It is considered an immune-mediated liver disease, although the exact aetiopathogenesis is not clear and there has been no clinical benefit from immunosuppression. Symptoms in PSC can be variable and include pruritus, abdominal pain, jaundice and fatigue. Diagnosis of PSC requires the exclusion of secondary causes of cholangiopathy and can usually be made on non-invasive imaging without the need for liver biopsy, which is usually reserved for variants. There is a close association with inflammatory bowel disease, which affects approximately two-thirds of patients, and all patients should undergo a screening colonoscopy at diagnosis. No currently licensed medications have proven prognostic benefit; the mainstay of management is prompt intervention for complications, such as acute cholangitis and dominant biliary strictures, and surveillance for progressive fibrosis, portal hypertension and cancers. There is a variable prognosis in PSC, but without curative medical options the median time from diagnosis to liver transplantation or death is 10-22 years. There is a significantly increased risk of hepatobiliary and colorectal malignancy in PSC; however, there is a limited role for cancer surveillance. Liver transplantation is associated with excellent outcomes but there is a risk of recurrent PSC after transplantation.
(7). Chinedu Nwaduru, et al. IgG4-related disease. Medicine UK 2023;51(6):P405-411.
Immunoglobulin G4-related disease is a rare immune-mediated systemic fibro-inflammatory condition characterised by a mass and/or thickening of the involved organ systems. The diagnosis remains challenging and requires a combination of clinical findings, serology, imaging and histological evaluation with cross-speciality input. Classification criteria have been developed with a high specificity to distinguish IgG4-related disease from disease mimics, which are essential for clinical trial design. Disease associations include occupational exposures and atopic/allergic history. Treatment dampens inflammation and shrinks masses/thickening, although relapse remains common on tapering or discontinuation of immunosuppression. Progressive fibrosclerotic disease with organ damage and failure, and an increased risk of malignancy are recognized outcomes. Our knowledge and understanding of the disease pathogenesis has expanded rapidly, leading to the discovery of circulating biomarkers that correlate with disease activity and relapse. A number of novel targeted agents are in the clinical pipeline to allow a precision medicine approach and top-down therapy.
(8). William JH. Griffiths. Haemochromatosis. Medicine UK 2023;51(6):P412-417.
Haemochromatosis is an inherited disorder of iron loading associated with significant morbidity and mortality if recognized late. Diagnosis, via HFE genotyping and confirmation of iron overload, followed by treatment with venesection, is simple to enact. Clinicians are now more attuned to thinking about haemochromatosis, with earlier presentations the norm. However, the diagnosis is still missed and irreversible joint disease in particular affects quality of life. Furthermore, men with haemochromatosis are 10 times more likely to develop primary liver cancer, highlighting the need to diagnose and treat early. C282Y homozygosity is the principal genotype and can be readily inferred in primary care. Non-invasive fibrosis testing, to exclude individuals at risk of hepatocellular carcinoma, is reducing the need for liver biopsy. Overlap with fatty liver disease is common so lifestyle changes can be required in addition to phlebotomy. Venesection services are variable in terms of their location, capacity and practice; patients in the UK can be enrolled via the National Blood Service if their serum ferritin is <500 micrograms/litre, at a frequency up to 6-weekly. Rarer forms of haemochromatosis can be identified via next-generation sequencing, readily accessible to secondary care clinicians in England via the new Genomic Laboratory Hubs.
(9). James Liu Yin, et al. Wilson disease. Medicine UK 2023;51(6):P418-421.
Wilson disease is a rare progressive genetic disorder of copper metabolism associated with hepatolenticular degeneration. Left untreated, it results in severe disability and death. The diagnosis is very easily overlooked but, if discovered early, effective treatments are available to prevent or reverse many manifestations of this disorder. The role of copper in disease pathogenesis, coupled with clinical, biochemical and genetic markers, is pivotal to establishing a clear diagnosis. Medical therapy involves chelating agents (e.g. penicillamine, trientine) and/or zinc salts. Liver transplantation corrects the underlying pathophysiology and can be life-saving. Knowledge of the Wilson disease gene has opened up a new molecular diagnostic repertoire in investigating suspected patients and first-degree relatives.
(10). Sarah Al-Shakhshir, et al. Complications of cholestasis: symptoms and extrahepatic manifestations. Medicine UK 2023;51(6):P422-426.
Cholestasis is a state of impaired or reduced bile flow, resulting from intrahepatic disease, cholangiocellular disorders or large bile duct obstruction. Although disease-modifying treatments exist, not all provide the relief that patients seek. Pruritus and fatigue are the most commonly reported symptoms, and chronic cholestatic disorders can be complicated by hepatic osteodystrophy, dyslipidaemia and hypovitaminosis. Mechanistic insights into specific biological pathways have led to a revived interest in developing symptom-specific therapies, with a resurgence of clinical trial activity directed toward improving patients” quality of life. However, with the exceptions of itch and metabolic bone disease, recommendations for managing the systemic complications of cholestasis currently lack an evidence base.
(11). Marcus Robertson et al. Management of portal hypertension, Budd- Chiari syndrome and portal vein thrombosis. Medicine UK 2023;51(6):P427-433.
Portal hypertension is associated with many of the known complications of cirrhosis and has an enormous impact on prognosis. Ascites and hepatic encephalopathy represent the most common complications of cirrhosis; both are associated with a significantly worse prognosis, with 50% survival over 1-2 years. Acute variceal bleeding remains a life-threatening complication and leading cause of death in individuals with cirrhosis. Advances in variceal bleeding management, including empirical antibiotic use, vasoactive drugs, early endoscopy and therapies such as transjugular intrahepatic portosystemic shunts (TIPS), have resulted in improved mortality rates, currently 11-20% per episode. The use of non-selective β-adrenoceptor blockers (NSBBs) in patients with clinically significant portal hypertension lowers the risk of variceal bleeding and improves patient outcomes; carvedilol is the preferred agent. Secondary prophylaxis of variceal bleeding with a combination of NSBBs and endoscopic variceal ligation also improves survival. Budd-Chiari syndrome (BCS) is a life-threatening disorder resulting from hepatic venous outflow obstruction. Myeloproliferative neoplasms represent its most common cause, although a significant proportion of patients have >1 risk factor. Therapeutic anticoagulation remains the first-line treatment for both BCS and symptomatic portal vein thrombosis. TIPS is increasingly used in the management of BCS and reduces the need for liver transplantation.
(12). Dominic Crocombe, et al. Diagnosis and management of ascites and hepatorenal syndrome (acute kidney injury) in cirrhosis. Medicine UK 2023;51(6):P434-439.
Ascites is the most common decompensation-defining complication of cirrhosis and represents a watershed moment, with median survival falling from >12 years for compensated cirrhosis to approximately 2 years. Treatment is based on reducing sodium intake and increasing renal sodium excretion with the aldosterone antagonist spironolactone at a starting dose of 100 mg daily, to which 60% respond. Renal dysfunction affects as many as 20% of hospitalized patients and is a strong predictor of mortality. Liver transplantation represents the best treatment for hepatorenal syndrome (HRS) yet is rarely available in this context; a combination of vasoconstrictors and albumin represents the mainstay of treatment. Terlipressin is the most widely utilized vasoconstrictor, leading to HRS resolution in >50%. The role of transjugular intrahepatic portosystemic shunt (TIPS) insertion or renal replacement therapy for HRS remains uncertain, with further studies needed. Many patients with cirrhotic ascites require regular ascitic drainage every 2-4 weeks, best achieved in outpatient day-case settings. Diuretic medications often require frequent dose adjustment because of coexisting renal impairment. In patients in whom ascites persists despite medical therapy, liver transplantation or TIPS should be considered. Finally, given the poor prognosis for many, it is important, where appropriate, to address end-of-life planning and palliative care in advance.
(13). Henry Kibble et al. Hepatic encephalopathy. Medicine UK 2023;51(6):P440-444.
Hepatic encephalopathy (HE) is a neurocognitive disorder associated with both acute and chronic liver injury. It manifests as a wide spectrum of neuropsychological abnormalities ranging from subtle impairments in executive higher functions through to coma. In acute liver failure, the central role of ammonia in the development of brain oedema remains undisputed. However, the gut microbiome and the presence of systemic inflammation or the development of infection have become increasingly recognized as drivers of the development of HE in cirrhosis. The development of HE is often unpredictable and its management, particularly in ward environments, remains challenging. Patients frequently require augmented levels of care in a high-dependency or intensive care area. The probability of maintaining transplant-free survival after a first episode of HE at 3 years is only 23% so referral for liver transplantation should be considered early. This review covers the practical aspects of managing HE and provides an up-to-date overview of the evidence base in this area, focusing predominantly on the management of HE in chronic liver disease.
(14). Ahmed Adel Amin et al. Acute liver failure: updates in pathogenesis and management. Medicine UK 2023;51(6): P445-449.
Acute liver failure is a life-threatening illness precipitated by an acute liver injury in patients with no pre-existing liver disease. Acute viral hepatitis and drug-induced liver injury account for most cases, the clinical course characterized by the development of coagulopathy and hepatic encephalopathy, often progressing to multi-organ disease, which is associated with high fatality rates. The outcomes have improved significantly over time with improving standards of organ system support and access to liver transplantation for very sick individuals. The King”s College criteria are the most commonly used tool for determination of prognosis and consideration for transplantation. Prompt diagnosis, immediate initiation of supportive care and aetiology-specific treatment, where applicable, as well as early discussions and transfer to a transplant centre, are the keys to successful outcome.
(15). James W. Ferguson. Liver transplantation. Medicine UK 2023;51(6):P450-452.
Liver transplantation is a successful therapy for end-stage liver disease, hepatocellular carcinoma and acute liver failure. Early referral is essential to allow time for careful assessment. The patient’s needs must be balanced against the predicted outcome after transplantation. The calcineurin inhibitor tacrolimus is the mainstay of immunosuppression in liver transplantation. Outcomes after liver transplantation are excellent but patients do not have a normal quantity or quality of life compared with an age- and sex-matched population.
(16). Ian J. Beckingham. Gallstones. Medcine UK 2023;51(6):P453-456.
Gallstone disease is one of the most common medical problems and presents to physicians and surgeons in many forms. This article discusses the cause of gallstones, their presentation and their management.