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Cirrhosis

Conventional Treatments

The first goal of cirrhosis management is preventing progression of the underlying chronic liver disease to reduce risk of decompensated cirrhosis. Once a decompensation event occurs, the focus becomes treatment of cirrhosis complications and the option of liver transplantation. The definitive treatment for decompensated cirrhosis is liver transplant (Ferri 2014).

Management of cirrhosis complications includes (Liou 2014):

  • Ascites. Therapy for ascites includes treatment of the underlying disorder (eg, cessation of alcohol use, treatment of hepatitis), sodium restriction (≤2g/day), and diuretics (“water pills;” a combination of spironolactone and furosemide has been recommended) (Liou 2014; Garcia-Tsao 2012). Patients with refractory ascites may require additional treatment with large volume paracentesis, the direct removal of ascitic fluid from the abdomen through a catheter. Correction of albumin deficiency can improve circulatory function following paracentesis, and albumin administration (6 – 8 g/L of ascitic fluid removed) is recommended when the volume of ascites fluid removed by paracentesis exceeds 5 liters (Bernardi 2012; Garcia-Tsao 2012). Paracentesis fluid can also function as a diagnostic technique for bacterial infection (spontaneous bacterial peritonitis) in hospitalized cirrhotic patients and may improve short-term survival (Orman 2014).

  • Portal hypertension. Options for the conservative management of portal hypertension are limited. Beta-blockers and nitrates may sometimes be recommended, along with diuretics in cases of ascites. However, surgical treatment involving the installation of shunts can be performed for serious cases (NIDDK 2014a; Anand 2012).

    Portal hypertension, and refractory cases of ascites, can be treated surgically with placement of a transjugular intrahepatic portosystemic shunt (TIPS). This method is less invasive than traditional surgery. In TIPS placement, artificial channels are installed that directly connect the flow of the portal vein and hepatic veins.

    In a 2014 meta-analysis of trials in which TIPS was compared to paracentesis in 390 patients, TIPS significantly reduced the need for liver transplants (39%); the incidence of recurrent ascites (85%) and hepatorenal syndrome (68%); and reduced deaths from liver disease (38%). However, in this study population, TIPS more than doubled the risk of severe hepatoencephalopathy and nearly tripled the risk of hepatoencephalopathy overall (Bai 2014).

  • Spontaneous bacterial peritonitis. Treatment with broad-spectrum oral or intravenous antibiotics (Liou 2014).

  • Hepatorenal syndrome. Therapy includes vasoconstrictors (eg, octreotide [Sandostatin] or terlipressin [Glypressin]) and albumin (to increase circulation and oxygenation of the kidneys) (Arroyo 2014; Garcia-Tsao 2012).

  • Hepatic hydrothorax. Typical treatment includes dietary sodium restriction and diuretics (Liou 2014).

  • Esophageal and gastrointestinal varices. Screening by endoscopy is recommended to check for varices. Non-selective beta-blockers (propranolol [Inderal], nadolol [Corgard]) do not prevent varices, but may reduce the risk of rupture and hemorrhage of fragile varices (Liou 2014). Endoscopic ligation of varices may also be effective.

  • Hepatic encephalopathy. Hepatic encephalopathy can be treated with non-absorbable carbohydrates (lactulose), which are fermented by colonic bacteria and help to reduce excess ammonia. Rifaximin (Xifaxan), a non-absorbable antibiotic, is effective against ammonia-producing bacteria and appears to be as effective as lactulose in the treatment of symptoms related to mild-to-moderate encephalopathy (Zullo 2012; Kimer 2014).

  • Hepatocellular carcinoma. Surgical excision of hepatocellular carcinoma is indicated when the tumor is a more important clinical concern than cirrhosis. Often only part of the tumor can be removed (Graf 2014). Even then, hepatocellular carcinoma recurs within 5 years more than 50% of the time (Liou 2014). Ablation (local destruction of the tumor) is an option in patients who are not suitable for resection. Common treatment techniques include ethanol injection and radiofrequency ablation (Graf 2014).

  • Hepatic osteodystrophy. Calcium, vitamin D, and vitamin K may be used for osteopenia; alendronate (Fosomax) is often prescribed for osteoporosis. Calcitonin has also been studied for this purpose (Lipkin 2002; Liou 2014; Yurci, Kalkan 2011; Goel 2010).

Transplantation. Liver transplantation surgery has become the standard treatment for end-stage cirrhosis and chronic liver disease over the past two decades, resulting in a marked reduction in deaths from chronic liver disease (Fox 2014; Silva Santos 2012). Liver transplantation survival rates in the United States are now greater than 74% after 5 years post-surgery (Liou 2014). There are several medical contraindications to liver transplantation: cardiac and pulmonary diseases, sepsis or active infection, cancer outside the liver, poorly-controlled HIV infection, insufficient social support or psychiatric disorders that would prevent post-transplant medical compliance, and active substance abuse. Advanced age, obesity, HIV infection, malnutrition, and a history of poor medication compliance are relative contraindications to liver transplant surgery (Fox 2014). Although transplantation can be curative for cirrhosis (and a number of chronic liver diseases), it typically requires a lifetime of immunosuppressive drug therapy to prevent “rejection” of the transplanted organ by the immune system.

Liver Transplantation in the United States

Liver transplantation, once viewed as an experimental procedure, is now the only treatment for end-stage liver disease, liver cancer, and cirrhosis that has a substantial impact on patient survival (Sanyal 2010; Wong 2002; Schuppan 2008). Almost 57 000 adult liver transplant recipients are currently alive in the United States, a number that has doubled in the last 10 years (SRTR 2012).

With the acceptance of transplantation as routine care, the demand for donor organs has increased significantly, far outpacing their availability. Metrics like the MELD score have aided in prioritizing patients for transplants in a way that addresses the most serious cases first, but many patients still die while waiting for a donor organ. According to the most recent Organ Procurement and Transportation Network Report, 6256 adults received liver transplants in 2012, with 15 308 candidates on the waiting list for a liver. While the number of new transplant candidates added to the list each year has begun to decrease, the rate of transplants has also been decreasing, and median wait times for a transplant have increased to over 18 months. The rate of pre-transplant death has also increased for the first time in several years (SRTR 2012).