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肝硬化及其并发症的诊断与管理:综述。

Diagnosis and Management of Cirrhosis and Its Complications: A Review.

机构信息

Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor.

出版信息

JAMA. 2023 May 9;329(18):1589-1602. doi: 10.1001/jama.2023.5997.

Abstract

IMPORTANCE

Cirrhosis affects approximately 2.2 million adults in the US. From 2010 to 2021, the annual age-adjusted mortality of cirrhosis increased from 14.9 per 100 000 to 21.9 per 100 000 people.

OBSERVATIONS

The most common causes of cirrhosis in the US, which can overlap, include alcohol use disorder (approximately 45% of all cases of cirrhosis), nonalcoholic fatty liver disease (26%), and hepatitis C (41%). Patients with cirrhosis experience symptoms including muscle cramps (approximately 64% prevalence), pruritus (39%), poor-quality sleep (63%), and sexual dysfunction (53%). Cirrhosis can be diagnosed by liver biopsy but may also be diagnosed noninvasively. Elastography, a noninvasive assessment of liver stiffness measured in kilopascals, can typically confirm cirrhosis at levels of 15 kPa or greater. Approximately 40% of people with cirrhosis are diagnosed when they present with complications such as hepatic encephalopathy or ascites. The median survival time following onset of hepatic encephalopathy and ascites is 0.92 and 1.1 years, respectively. Among people with ascites, the annual incidence of spontaneous bacterial peritonitis is 11% and of hepatorenal syndrome is 8%; the latter is associated with a median survival of less than 2 weeks. Approximately 1% to 4% of patients with cirrhosis develop hepatocellular carcinoma each year, which is associated with a 5-year survival of approximately 20%. In a 3-year randomized clinical trial of 201 patients with portal hypertension, nonselective β-blockers (carvedilol or propranolol) reduced the risk of decompensation or death compared with placebo (16% vs 27%). Compared with sequential initiation, combination aldosterone antagonist and loop diuretics were more likely to resolve ascites (76% vs 56%) with lower rates of hyperkalemia (4% vs 18%). In meta-analyses of randomized trials, lactulose was associated with reduced mortality relative to placebo (8.5% vs 14%) in randomized trials involving 705 patients and reduced risk of recurrent overt hepatic encephalopathy (25.5% vs 46.8%) in randomized trials involving 1415 patients. In a randomized clinical trial of 300 patients, terlipressin improved the rate of reversal of hepatorenal syndrome from 39% to 18%. Trials addressing symptoms of cirrhosis have demonstrated efficacy for hydroxyzine in improving sleep dysfunction, pickle brine and taurine for reducing muscle cramps, and tadalafil for improving sexual dysfunction in men.

CONCLUSIONS AND RELEVANCE

Approximately 2.2 million US adults have cirrhosis. Many symptoms, such as muscle cramps, poor-quality sleep, pruritus, and sexual dysfunction, are common and treatable. First-line therapies include carvedilol or propranolol to prevent variceal bleeding, lactulose for hepatic encephalopathy, combination aldosterone antagonists and loop diuretics for ascites, and terlipressin for hepatorenal syndrome.

摘要

重要性

在美国,大约有 220 万成年人患有肝硬化。从 2010 年到 2021 年,肝硬化的年调整死亡率从每 10 万人 14.9 人增加到每 10 万人 21.9 人。

观察结果

美国肝硬化最常见的病因(可能重叠)包括酒精使用障碍(约占所有肝硬化病例的 45%)、非酒精性脂肪性肝病(26%)和丙型肝炎(41%)。肝硬化患者会出现肌肉痉挛(约 64%的患病率)、瘙痒(39%)、睡眠质量差(63%)和性功能障碍(53%)等症状。通过肝活检可以诊断肝硬化,但也可以通过非侵入性检查进行诊断。弹性成像,即通过千帕斯卡测量肝脏硬度的非侵入性评估,通常可以在 15kPa 或更高的水平上确认肝硬化。大约 40%的肝硬化患者是在出现肝性脑病或腹水等并发症时被诊断出来的。肝性脑病和腹水发病后中位生存时间分别为 0.92 年和 1.1 年。在腹水患者中,自发性细菌性腹膜炎的年发病率为 11%,肝肾综合征的年发病率为 8%;后者与中位生存时间不足 2 周相关。每年约有 1%至 4%的肝硬化患者会发展为肝细胞癌,其 5 年生存率约为 20%。在一项涉及 201 名门静脉高压患者的为期 3 年的随机临床试验中,非选择性β受体阻滞剂(卡维地洛或普萘洛尔)与安慰剂相比,降低了失代偿或死亡的风险(16%比 27%)。与序贯治疗相比,醛固酮拮抗剂和袢利尿剂联合使用更有可能解决腹水(76%比 56%),并且低钾血症的发生率更低(4%比 18%)。在随机试验的荟萃分析中,乳果糖与安慰剂相比,死亡率降低(705 名患者的随机试验中为 8.5%比 14%),复发性显性肝性脑病的风险降低(1415 名患者的随机试验中为 25.5%比 46.8%)。在一项涉及 300 名患者的随机临床试验中,特利加压素将肝肾综合征的逆转率从 39%提高到 18%。针对肝硬化症状的临床试验表明,羟嗪可有效改善睡眠功能障碍,腌制泡菜盐水和牛磺酸可减少肌肉痉挛,他达拉非可改善男性性功能障碍。

结论和相关性

大约有 220 万美国成年人患有肝硬化。许多症状,如肌肉痉挛、睡眠质量差、瘙痒和性功能障碍,都是常见且可治疗的。一线治疗包括卡维地洛或普萘洛尔预防静脉曲张出血、乳果糖治疗肝性脑病、醛固酮拮抗剂和袢利尿剂联合治疗腹水以及特利加压素治疗肝肾综合征。

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