From the Editors’ Desk
Hepatology for nurses. Elsevier Medicine UK, Vol 51, issue 5
(1). Neil Mistry et al. Clinical and laboratory assessment of symptomatic and asymptomatic liver disease. Medicine UK 2023;51(5):P305-310.
Chronic liver disease is rising in incidence and prevalence and carries a significant mortality as well as socioeconomic burden for individuals, their families and health services. Although the causes of liver disease are many, the vast majority of liver disease is preventable and related to excess alcohol consumption, being overweight/obese or the acquisition of hepatitis B and or C. However, less common causes of liver disease should not be overlooked, especially as effective specific therapies may be available; this is the case for autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and haemochromatosis. A major challenge in assessing liver disease is that it is typically ‘silent’ or asymptomatic until the later stages, i.e. when decompensation occurs. There are exceptions to this, such as pruritis in PBC or jaundice in acute viral or AIH, but these scenarios are very much in the minority when considering the totality of the liver disease burden in any given population. A thorough clinical history, including an accurate alcohol history, is needed, with a systematic approach using and understanding the risk factors for liver disease.
(2). Stephen M. Gregory, et al. Imaging of the liver and biliary tract. Medicine UK, 2023;51(5):P311-315.
Radiology is a rapidly evolving specialty that parallels the advances and achievements of the modern era, including state-of-the-art imaging systems, adaptive artificial intelligence and novel interventional procedures. This is particularly reflected in the imaging of the liver and biliary tract in which the full set of implements available in the radiologist’s imaging toolbox (ultrasonography, computed tomography, magnetic resonance imaging, nuclear medicine imaging, image-guided interventional procedures) are fully used and essential in both the investigative diagnostic process and image-guided treatment. This includes emergency assessment of the acute abdomen, oncological diagnosis and staging, surgical or radiotherapy planning, monitoring treatment response, surveillance scans and diagnosis of other primary hepatobiliary diseases. This article reveals the complementary role of different imaging modalities, image-guided interventional procedures and future advances in the diagnosis and treatment of common benign and malignant hepatobiliary diseases and in the acute setting.
(3). Sara Mahgoub et al. Investigation of jaundice. The Medicine, UK 2023;51(5):P321-325.
Jaundice is a clinical sign that reflects an accumulation of bilirubin in the blood. It can result from increased bilirubin production, inability of the liver to conjugate bilirubin or failure to excrete bilirubin into the biliary tree. Appropriate investigation of jaundice starts with a history of associated symptoms and risk factors for liver disease. Clinical examination should look for stigmata of chronic liver disease and signs of specific liver diseases. Initial blood tests should assess liver injury and synthetic function. A combination of urinalysis and the pattern of abnormal liver function tests can indicate whether the jaundice is likely to be hepatitic or cholestatic, and guide further investigations. This review describes bilirubin metabolism, the causes of jaundice and the appropriate investigation of jaundice.
(4). Munir Pirmohamed. Prescribing in liver disease. Medicine, UK 2023;51(5):P326-330.
Patients with liver disease often require drug therapy. As the liver is the main site of drug detoxification and elimination, each person’s need for therapy must be carefully assessed; the choice of the drug, its dose and the duration of therapy must be carefully considered to avoid adverse effects. Ideally, the chosen drug should have a high therapeutic index, be largely devoid of pharmacokinetic and pharmacodynamic interactions and hepatotoxic effects, and be renally eliminated. However, the ideal drug with these properties is often not available, so the dose and drug should be individualized to the patient, who should then be carefully monitored, with the duration of treatment kept as short as possible. The British National Formulary contains useful information on drugs that should be avoided or have their dosage modified in patients with liver disease.
(5). Linda Provan. Alcohol and the liver. Medicine UK 2023;51(5):P331-335.
Hospital admissions due to alcohol-related liver disease (ArLD) are increasing. Both the quantity and the pattern of alcohol consumption are linked to an increased risk of ArLD. However, other factors such as obesity, coexisting liver disease – particularly hepatitis C – gender, nutritional status and genetic factors also play a role. The spectrum of ArLD ranges from steatosis to alcoholic hepatitis to established cirrhosis; a progression of liver injury which involves multiple mechanisms. Excessive alcohol consumption can cause cirrhosis in the absence of alcohol dependency syndrome. The presentation is variable, and recognition requires clinicians to be aware of the significance of a history of alcohol excess, clinical stigmata of liver disease and compatible laboratory investigations. Early detection of liver injury is key. Not all people who drink to excess develop liver disease, and other causes of liver damage must be excluded. The mainstay of management is long-term abstinence, and medical interventions should be delivered in conjunction with addiction services. Nutritional issues should also be addressed. Acute alcoholic hepatitis has a high mortality, and patients with the highest risk can benefit from short-term corticosteroids. Individuals with cirrhosis require hepatoma surveillance and variceal screening; liver transplantation should be considered in selected cases.
(6). Anthony George et al. Non-alcoholic fatty liver disease. Medicine UK 2023;51(5):P336-341.
Non-alcoholic fatty liver disease (NAFLD) is a global health problem. It has an estimated prevalence of 25% among adults worldwide; predicted to increase significantly over the coming decade. It is closely related to metabolic syndrome – associated with obesity and type 2 diabetes mellitus (T2DM). NAFLD is defined histologically, ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Triglyceride droplet accumulation in hepatocytes is the first feature in the natural history, leading in some patients to oxidative stress, inflammation and the development of fibrosis. NAFLD is typically asymptomatic, often detected incidentally by abnormal liver blood tests or increased echogenicity on ultrasonography. Physicians use sequential non-invasive tests such as composite blood result scores and/or transient elastography to stratify patients according to their risk of developing advanced fibrosis or cirrhosis. Liver biopsy is used selectively to confirm disease stage where there is uncertainty or concern about hepatic co-morbidity. Treatment focuses on weight loss through dietary modification and exercise. A concurrent diagnosis of T2DM is treated by appropriate drugs that promote weight loss (e.g. GLP-1 receptor agonists, SGLT2 inhibitors). Independent risk factors for cardiovascular disease (e.g. hypertension, dyslipidaemia, diabetes mellitus) should be addressed and treatment optimized. There are currently no liver-specific therapies licensed for use in NAFLD; vitamin E and pioglitazone have shown some benefit in trials but are rarely used because of concerns about their long-term safety. Several agents are being evaluated in Phase III clinical trials.
(7). Guruprasad P. Aitha et al. Drug-induced liver injury. Medicine UK 2023;51(5):P342-346,
The lack of substantial advances in pre-clinical testing for hepatotoxicity has meant that drug-induced liver injury (DILI) remains an important issue during both the drug development and post-marketing phases. Several drug-related, genetic and non-genetic host factors influence the risk of DILI in any individual. The demonstration of human leukocyte antigen genotype as a strong risk factor for the development of DILI from a range of drugs has highlighted the role of the adaptive immune system in its pathogenesis; there is accumulating evidence that drug metabolism genes also contribute to some forms of DILI. Early recognition and prompt withdrawal of the drug is essential in preventing serious hepatic failure and is the critical step in the management of adverse reactions. The diagnosis of DILI relies upon the index of suspicion, careful evaluation of a temporal relationship between the exposure to a particular drug and the specific clinical event, and exclusion of potential alternative diagnoses. The high negative predictive value of genetic tests can be used to rule out DILI caused by specific drugs and to correctly identify the agent underlying DILI in a person exposed to two concomitant medications.
(8). Maria Fernanda Guerra Veloz, et al. Hepatitis A and E and other hepatotropic viruses. Medicine UK 2023;51(5): P347-350.
Hepatitis E and A are the major cause of acute hepatitis worldwide. Hepatitis E is also one of the major causes of chronic hepatitis in immunocompromised individuals. Both infections were initially attributed to developing countries because of poor sanitation and limited health access. However, it is now apparent that hepatitis E virus is endemic in high-income countries and is largely a zoonotic infection. Furthermore, recent hepatitis A outbreaks in high-risk populations have reinforced the necessity of scaling up the vaccination rates in these groups in developed countries.
(9). Apostolos Koffas, et al. Hepatitis B and D: an overview of the diagnosis and management. Medicine UK 2023;51(5):P351-355.
Chronic hepatitis B (CHB) represents a major global healthcare challenge with increasing morbidity and mortality because of the progression to cirrhosis and hepatocellular carcinoma (HCC). Hepatitis delta virus (HDV) is a defective virus that can propagate only in the presence of hepatitis B virus (HBV); it is the most aggressive form of viral hepatitis CHB is a dynamic disease that can be broadly categorized into four phases. HDV infection can develop after synchronous infection with HBV (co-infection) or alternatively after exposure to HDV from a patient with pre-existing CHB (superinfection). The primary treatment goal in CHB is to improve survival and quality of life by preventing disease progression and HCC development. Current treatment regimens are non-curative and, once initiated, treatment is long term in most cases. Functional cure, i.e. sustained HBsAg loss, is another goal, and novel agents in Phase II and III trial settings will contribute to achieving this target. Individuals with active HDV infection should also be offered antiviral treatment. Until recently, there were very limited options available, with conventional HBV treatments being either ineffective or poorly tolerated. More recently, the conditional approval of bulevirtide, a first-in-class HBV entry inhibitor, seems to have revolutionized the HDV treatment landscape.
(10). Ryan Buchanan. Hepatitis C. Medicine UK 2023;51(5):P356-361.
Hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease. Over 58 million people worldwide have chronic HCV infection and are at risk of developing its life-threatening complications. Acute infection is usually asymptomatic, with most patients unaware that they have contracted the virus. Some individuals clear the virus spontaneously, but most become chronic carriers. If carriers are identified, they can be treated with antiviral therapy, the main goal being the prevention of cirrhosis, liver failure and hepatocellular carcinoma by eradicating the virus. During the past decade, there has been impressive progress in the efficacy and tolerability of therapy: modern treatment regimens able to eradicate the virus in >90% of cases with minimal adverse effects, although therapy is costly. However, many infected individuals are unaware that they carry the virus, and for many there are barriers preventing them from accessing medical care. In the future, HCV could be eliminated, but to achieve this strategies to prevent infection, test for infection and treat infection in high-risk groups need to be expanded.
(11). Nick Beeching, et al. Tropical liver disease. Medcine UK 2023;51(5):P362-366.
The liver is frequently involved in infections that are prevalent in different regions of the tropics, and chronic liver disease, sometimes with multiple aetiological explanations, is an important cause of early morbidity and mortality. This article describes some hepatic and biliary problems that are seen in the tropics or can be imported from resource-poor settings. The epidemiology of hepatitis A is changing in many areas and hepatitis E is now recognized in a wide range of tropical and non-tropical settings. Vaccines have been developed against hepatitis E. Hepatitis B and C continue to cause chronic liver disease, cirrhosis and hepatocellular carcinoma, but these can be eclipsed in epidemiological importance by the sequelae of the emerging epidemic of non-alcoholic fatty liver disease in many parts of the tropics. The pathophysiology of acute and chronic liver disease caused by aflatoxins is better understood, as is the relationship of veno-occlusive disease of the liver to pyrrolizidine alkaloids. Self-poisoning with hepatotoxins is common in many countries. The diagnosis and management of cystic hydatid disease of the liver has been rationalized, based on a systematic approach to the classification of imaging findings.
(12). Stephen D. Ryder. Hepatobiliary tumours. Medicine UK 2023;51(5):P367-371.
Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the two major types of primary liver tumour. Both are increasing in incidence in the UK, for HCC because of the increasing prevalence of chronic liver disease, particularly that caused by alcohol and non-alcoholic fatty liver disease. They have a poor overall prognosis because of late presentation and the presence of underlying liver cirrhosis in patients with HCC. Patients usually present with a liver mass or jaundice. Assessment is primarily radiological by means of computed tomography and/or magnetic resonance imaging. Surgery remains the major curative option for both tumour types; liver transplantation and, rarely, resection are performed for HCC, and surgical resection for cholangiocarcinoma. However, only approximately 20% of these cancers present at a stage when surgery is possible. For non-surgical candidates with HCC, there are three potential treatment types: ablation, trans-arterial chemo-embolization or an increasing range of new systemic treatments. Chemotherapy for cholangiocarcinoma is limited to gemcitabine-based systemic chemotherapy. Surveillance for HCC could potentially enhance early diagnosis
