Liver cirrhosis Ginès, Pere; Krag, Aleksander; Abraldes, Juan G ...
The Lancet (British edition),
10/2021, Letnik:
398, Številka:
10308
Journal Article
Recenzirano
Cirrhosis is widely prevalent worldwide and can be a consequence of different causes, such as obesity, non-alcoholic fatty liver disease, high alcohol consumption, hepatitis B or C infection, ...autoimmune diseases, cholestatic diseases, and iron or copper overload. Cirrhosis develops after a long period of inflammation that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension. The disease evolves from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis), the complications of which often result in hospitalisation, impaired quality of life, and high mortality. Progressive portal hypertension, systemic inflammation, and liver failure drive disease outcomes. The management of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation can be required in some cases. In this Seminar, we discuss the disease burden, pathophysiology, and recommendations for the diagnosis and management of cirrhosis and its complications. Future challenges include better screening for early fibrosis or cirrhosis, early identification and reversal of causative factors, and prevention of complications.
Global burden of liver disease: 2023 update Devarbhavi, Harshad; Asrani, Sumeet K.; Arab, Juan Pablo ...
Journal of hepatology,
August 2023, 2023-08-00, 20230801, Letnik:
79, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Liver disease accounts for two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men. ...Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and non-alcoholic fatty liver disease. Hepatotropic viruses are the aetiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.
There are different operating definitions for acute-on-chronic liver failure (ACLF) in different geographic regions. Consortia in Western countries have developed definitions that apply to patients ...with cirrhosis, while consortia in Asia have developed definitions that apply to patients with chronic liver diseases with or without cirrhosis. Investigators of the Chinese and Western Consortia believe that ACLF can be precipitated by acute insults that are intrahepatic (e.g. alcoholic hepatitis) or extrahepatic (e.g. bacterial infection, gastrointestinal haemorrhage), and that extrahepatic organ system failures can be used to define ACLF. In contrast, the Asia Pacific consortium believe that ACLF is only defined by an acute onset of liver failure in response to an acute hepatic insult. Of note, although ACLF has received different operating definitions, every definition recognises that ACLF is a distinct clinical entity. This article provides an updated overview of the distinctive features of ACLF according to the definitions used to characterise it. In addition, we discuss future directions for research aimed at identifying the hallmarks of ACLF.
ACG Clinical Guideline: Alcoholic Liver Disease Singal, Ashwani K; Bataller, Ramon; Ahn, Joseph ...
The American journal of gastroenterology,
02/2018, Letnik:
113, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most patients are diagnosed at advanced ...stages and data on the prevalence and profile of patients with early disease are limited. Diagnosis of ALD requires documentation of chronic heavy alcohol use and exclusion of other causes of liver disease. Prolonged abstinence is the most effective strategy to prevent disease progression. AH presents with rapid onset or worsening of jaundice, and in severe cases may transition to acute on chronic liver failure when the risk for mortality, depending on the number of extra-hepatic organ failures, may be as high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in about half of treated patients with severe AH and long-term mortality is related to severity of underlying liver disease and is dependent on abstinence from alcohol. General measures in patients hospitalized with ALD include inpatient management of liver disease complications, management of alcohol withdrawal syndrome, surveillance for infections and early effective antibiotic therapy, nutritional supplementation, and treatment of the underlying alcohol-use disorder. Liver transplantation, a definitive treatment option in patients with advanced alcoholic cirrhosis, may also be considered in selected patients with AH cases, who do not respond to medical therapy. There is a clinical unmet need to develop more effective and safer therapies for patients with ALD.
Portal hypertension is a major complication of cirrhosis, and its consequences, including ascites, esophageal varices, hepatic encephalopathy, and hepatorenal syndrome, lead to substantial morbidity ...and mortality. The past several decades have seen major improvements in the clinical management of complications of portal hypertension, resulting in substantial gains in patient outcomes. However, important challenges remain. This review focuses on the pathophysiology and diagnosis of portal hypertension and discusses general approaches in the management of patients with ascites as a result of portal hypertension.
Disorders of the mesenteric, portal, and hepatic veins and mesenteric and hepatic arteries have important clinical consequences and may lead to acute liver failure, chronic liver disease, ...noncirrhotic portal hypertension, cirrhosis, and hepatocellular carcinoma. Although literature in the field of vascular liver disorders is scant, these disorders are common in clinical practice, and general practitioners, gastroenterologists, and hepatologists may benefit from expert guidance and recommendations for management of these conditions. These guidelines represent the official practice recommendations of the American College of Gastroenterology. Key concept statements based on author expert opinion and review of literature and specific recommendations based on PICO/GRADE analysis have been developed to aid in the management of vascular liver disorders. These recommendations and guidelines should be tailored to individual patients and circumstances in routine clinical practice.
In this debate, the authors consider whether patients with acute-on-chronic liver failure grade 3 (ACLF-3) should receive higher liver transplant priority, with reference to the following clinical ...case: a 62-year-old male with a history of decompensated alcohol-associated cirrhosis, with recurrent ascites and hepatic encephalopathy, and metabolic comorbidities (type 2 diabetes mellitus, arterial hypertension and a BMI of 31 kg/m2). A few days following evaluation for liver transplantation (LT), the patient was admitted to the intensive care unit and placed on mechanical ventilation for neurological failure, FiO2 of 0.3 with a SpO2 of 98%, and started on norepinephrine at 0.62 μg/kg/min. He had been abstinent since the diagnosis of cirrhosis a year prior. Laboratory results at admission were: leukocyte count 12.1 G/L, international normalised ratio 2.1, creatinine 2.4 mg/dl, sodium 133 mmol/L, total bilirubin 7 mg/dl, lactate 5.5 mmol/L, with a MELD-Na score of 31 and a CLIF-C ACLF score of 67. On the 7th day after admission, the patient was placed on the LT waiting list. On the same day, he had massive variceal bleed with hypovolemic shock requiring terlipressin, transfusion of three red blood cell units, and endoscopic band ligation. On day 10, the patient was stabilised with a low dose of norepinephrine 0.03 μg/kg/min, with no new sepsis or bleeding. However, the patient was still intubated for grade 2 hepatic encephalopathy and on renal replacement therapy with a lactate level of 3.1 mmol/L. The patient is currently categorised as having ACLF-3, with five organ failures (liver, kidney, coagulation, circulation, and respiration). Based on the severity of his liver disease and multiorgan failure, the patient is at an exceedingly high risk of death without LT. Is it appropriate to perform LT in such a patient?
The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management ...of patients with suspected acute kidney injury in patients with cirrhosis.
This article provides practical advice for the management of patients with cirrhosis and acute kidney injury based on the best available published evidence. This best practice document is not based on a formal systematic review. This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Clinical Gastroenterology & Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Acute kidney injury (AKI) should be diagnosed when the serum creatinine increases by ≥0.3 mg/dL within 48 hours or is ≥50% from baseline or when the urine output is reduced below 0.5 mL/kg/h for >6 hours. BEST PRACTICE ADVICE 2: Preventive measures against the development of AKI in cirrhosis include (1) avoidance of potentially nephrotoxic medications like nonsteroidal anti-inflammatory drugs (NSAIDs), (2) avoidance of excessive or unmonitored diuretics or nonselective beta-blockade, (3) avoidance of large-volume paracentesis without albumin replacement, and (4) counseling patients to avoid alcohol use. BEST PRACTICE ADVICE 3: (A) Investigation is directed to determining the cause of AKI, which can be due to hypovolemic causes (volume responsive, and the most common cause of AKI in patients with cirrhosis); acute tubular necrosis; hepatorenal syndrome with AKI (HRS-AKI) (a functional renal failure that persists despite volume repletion); HRS with acute kidney disease, a type of functional renal failure of <3 months- duration in which criteria for HRS-AKI are not met; or postrenal, which occurs only rarely. (B) The specific type of AKI should be identified through a careful history, physical examination, blood biochemistry, urine microscopic examination, urine chemistry (Na+ and urea) and selected urinary biomarkers, and renal ultrasound. BEST PRACTICE ADVICE 4: A rigorous search for infection is required in all patients with AKI. A diagnostic paracentesis should be carried out to evaluate for spontaneous bacterial peritonitis; blood and urine cultures and chest radiograph are also required. There is no role for routine prophylactic antibiotics in patients with AKI, but broad-spectrum antibiotics should be started whenever infection is strongly suspected. BEST PRACTICE ADVICE 5: When AKI is diagnosed, diuretics and nonselective beta-blockers should be held, NSAIDs discontinued, the precipitating cause of AKI treated, and fluid losses replaced, administering albumin 1 g/kg/d for 2 days if the serum creatinine shows doubling from baseline. Urine output, vital signs, and when indicated, echocardiography or CVP (if there is a pre-existing central line) should be used to monitor fluid status. BEST PRACTICE ADVICE 6: When the serum creatinine remains higher than twice the baseline value despite these measures, treatment of HRS-AKI should be initiated with albumin at a dose of 1 g/kg intravenously on day 1 followed by 20-40 g daily along with vasoactive agents (terlipressin; if terlipressin is not available, either a combination of octreotide and midodrine; or norepinephrine, depending on institutional preferences) and continued either until 24 hours following the return of the serum creatinine level to within ≤0.3 mg/dL of baseline for 2 consecutive days or for a total of 14 days of therapy. BEST PRACTICE ADVICE 7: Terlipressin should be initiated as a bolus dose of 1 mg every 4-6 hours (total 4-6 mg/d). The dose should be increased to a maximum of 2 mg every 4-6 hours (total 8-12 mg/d) if there is no reduction in serum creatinine at day 3 of therapy by at least 25% compared to the baseline value. Alternatively, clinicians can administer terlipressin by continuous intravenous infusion at a lower starting dose of 2 mg/d, which may reduce ischemic side effects and increase the dose gradually every 24-48 hours up to a maximum dose of 12 mg/d, or reversal of HRS. As per Food and Drug Administration restrictions, terlipressin should not be used in patients with a serum creatinine ≥5 mg/dL, or oxygen saturation of <90%. BEST PRACTICE ADVICE 8: Oral midodrine when used should be initiated at doses of 7.5 mg and titrated upward to 12.5 mg 3 times daily with octreotide (starting with 100 μg and titrating upward to 200 μg subcutaneously 3 times daily). BEST PRACTICE ADVICE 9: Norepinephrine should be used as a continuous intravenous infusion at a starting dose of 0.5 mg/h and the dose increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h with the goal of increasing the mean arterial pressure by ≥10 mm Hg and/or the urine output to >50 mL/h for at least 4 hours. BEST PRACTICE ADVICE 10: The risks of ischemic side effects of terlipressin and norepinephrine include angina and ischemia of fingers, skin, and intestine. These side effects may be lowered by starting at the lowest dose and gradually titrating upward. BEST PRACTICE ADVICE 11: Fluid status should be closely monitored because of the risk of pulmonary edema with excessive use of albumin. BEST PRACTICE ADVICE 12: Renal replacement therapy (RRT) may be used in the management of (A) AKI secondary to acute tubular necrosis; (B) HRS-AKI in potential candidates for liver transplantation (that is, RRT should not be used in patients with HRS-AKI who are not candidates for liver transplantation); and (C) AKI of uncertain etiology in which the need for RRT may be considered on an individual basis. BEST PRACTICE ADVICE 13: Transjugular intrahepatic portosystemic shunts should not be used as a specific treatment of HRS-AKI. BEST PRACTICE ADVICE 14: Liver transplantation is the most effective treatment for HRS-AKI. Pharmacotherapy for HRS-AKI before proceeding with liver transplantation may be associated with better post-liver transplantation outcomes. Selected patients with HRS-AKI may require simultaneous liver kidney transplantation based on updated Organ Procurement and Transplantation Network listing criteria.
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