The management of cirrhosis has evolved at a rapid pace in recent years.

During an AASLD symposium on the final day of DDW® 2018, three experts reviewed the most recent developments in diuretic resistant/refractory ascites, recurrent/refractory hepatic encephalopathy and recurrent/refractory variceal bleeding. The case-based session was titled Cirrhosis: State of the Art Practical Management.

Case 1: Diuretic resistant/refractory ascites

Case 1: Diuretic resistant/refractory ascites

The first case, presented by Michael Porayko, MD, FAASLD (second from left in panel photo), professor of medicine at Vanderbilt University Medical Center, Nashville, TN, involved a 63-year-old woman with hepatitis C virus (HCV) cirrhosis who presents for follow-up of ascites and hepatic hydrothorax. Her HCV has been treated with a direct-acting antiviral and she has achieved sustained viral response.

The patient has developed moderate ascites and right hepatic hydrothorax that requires paracentesis/thoracentesis every week or two when she becomes short of breath. Diuretics are limited by symptomatic hypotension and renal insufficiency. With diuretics, her baseline serum creatinine rose from 0.6 mg/dL to 2 mg/dL. The woman has been referred for liver transplant, but her MELD-Na score is only 19.

The patient has anxiety disorder and has smoked one pack of cigarettes per day for 30 years. She is currently on furosemide 20 mg daily, spironolactone 50 mg daily and promethazine prn for nausea.

A physical exam shows a frail, malnourished, muscle-wasted patient. Her blood pressure is 86/40, pulse 115/minute, respiration 20/minute and O2 saturation 92 percent. There are decreased breath sounds from the right posterior lung fields, but otherwise clear. She has moderate ascites and hepatosplenomegaly.

Florence Wong, MD

Florence Wong, MD

“As a patient goes through the natural history of cirrhosis, she goes through an ascites-clear state and progresses to the point where ascites becomes refractory to diuretics,” said Florence Wong, MD, associate professor of medicine at the University of Toronto and affiliate scientist at Toronto General Hospital Research Institute, ON, Canada. “If we don’t take good care, the patient will continue to progress and the likelihood of mortality is very high.”

The problem, Dr. Wong explained, is that cirrhosis increases intrahepatic resistance. There are mechanical factors such as fibrous scar tissue, regenerative nodules, hepatocyte swelling and capillarization of sinusoids. As sodium retention builds, the patient becomes more responsive to vasoconstrictors and less responsive to vasodilators.

The net result is increased resistance to portal flow, leading to portal hypertension. Portal hypertension, in turn, increases renal sodium retention, contributing to ascites.

Dr. Wong recommended a stepwise approach to ascites management, starting with sodium restriction. The next steps are adding diuretics, performing large-volume paracentesis, transjugular intrahepatic portosystemic shunt (TIPS) and finally liver transplantation.

Patients should move to a no- or low-sodium diet at the earliest stage of ascites in order to reduce sodium accumulation.

“It’s important to refer the patient to a dietician, and I always explain to them why sodium retention is so important,” Dr. Wong said.

If large-volume paracentesis (removing five liters or more) becomes necessary, immediate administration of albumin can significantly reduce post-paracentesis circulatory dysfunction. Albumin is significantly more effective than other volume expanders, Dr. Wong noted.

TIPS is very effective at lowering portal pressure and restoring renal function. Between 35 and 55 percent of patients develop hepatic encephalopathy after TIPS, and it almost always develops within the first three months.

The best candidates for TIPS are younger patients, less than 65 years of age, with normal cardiac and renal function, no prior history of encephalopathy, a Child Pugh score less than 12, MELD less than 18 and no sepsis, including dental sepsis. There’s little support for TIPS in hepatic hydrothorax.

The best treatment option is liver transplant, although a MELD score of 19 makes transplant unlikely in most locations. The alfapump®, which pumps ascites out of the peritoneal cavity into the circulatory system, is available in Europe but has not been approved in the U.S.

Case 2: Recurrent/refractory hepatic encephalopathy

Case 2: Recurrent/refractory hepatic encephalopathy

The second case involved a 65-year-old man with alcoholic cirrhosis who has been abstinent for two years and has been admitted on multiple occasions for management of confusion, said Catherine Frenette, MD, FAST, AGAF (at podium in panel photo), medical director of liver transplantation and director of the hepatocellular carcinoma program at the Scripps Clinic/Green Hospital, La Jolla, CA. The man lives with his family, who help manage his condition, but they work during the day and cannot be sure of his daytime care or medication adherence.

The patient takes lactulose to have three or four bowel movements daily but has been difficult to regulate. When his stool frequency decreases, he takes more lactulose. When treated with lactulose in the hospital, he improves. He was also put on rifaximin 550 mg twice daily during his last admission.

The patient has been admitted to the hospital six times for encephalopathy. On his second episode, he also had a gastric variceal bleed with TIPS placement. He’s now arousable but falls back to sleep easily and has asterixis. The man also has degenerative joint disease of the lower spine and insomnia.

The patient’s current drug regimen includes oxycodone-acetaminophen as needed for back pain, zolpidem for sleep, furosemide 40 mg daily and spironolactone 100 mg daily.

The man is muscle-wasted with scleral icterus. Blood pressure is 118/70, pulse 90/minute, respiration 20/minute and O2 saturation 98 percent. He has moderate ascites, hepatosplenomegaly and trace peripheral edema.

Jasmohan S. Bajaj, MD, AGAF

Jasmohan S. Bajaj, MD, AGAF

Hepatic encephalopathy (HE) is brain dysfunction caused by liver insufficiency and/or porto-systemic shunting, said Jasmohan S. Bajaj, MD, AGAF, associate professor of gastroenterology, hepatology and nutrition at Virginia Commonwealth University School of Medicine, Richmond. It manifests as a wide spectrum of neurological and psychiatric abnormalities ranging from subclinical to coma.

“This doesn’t just affect your patient, it affects the whole family. And the family has to be part of the solution,” Dr. Bajaj said.

The first step is to determine if the patient actually has HE. The next steps are to figure out what precipitated it, if the patient becomes alert after treatment and, if not, why.

A differential diagnosis of HE is critical. A variety of conditions produce similar symptoms, including diabetes, alcohol intoxication or withdrawal, drugs (including sleep aids and opioids), electrolyte disorders and intracranial bleeding or stroke.

“Please do not use zolpidem in these patients,” Dr. Bajaj said. “It’s not indicated in cirrhosis. And remember that a little opioid goes a long way. Bioavailability is dramatically increased in cirrhosis.”

The patient is clearly not taking lactulose properly, Dr. Bajaj said. At appropriate doses, lactulose reduces the risk of HE while excessive doses exacerbate HE.

HE patients are a low priority for liver transplant, so other therapies must be found. In addition to adjusting medications, it helps to exercise the body and mind, Dr. Bajaj said. Aerobic training, resistance training plus balance and strength training all improve HE.

So does improved nutrition. Small meals or liquid nutritional supplements several times daily are ideal. A late night snack of a complex carbohydrate can prevent nighttime problems.

Investigational therapies include fecal microbiota transplantation and ammonia scavengers.

Case 3: Recurrent/refractory variceal bleeding

Case 3: Recurrent/refractory variceal bleeding

The final case involved a 50-year-old man with nonalcoholic steatohepatitis (NASH) cirrhosis who presents with melena. The patient had an upper endoscopy when initially diagnosed with cirrhosis and ascites a year earlier. The EGD found large, non-bleeding esophageal varices and small fundal gastric varices, Dr. Frenette reported. The patient was started on carvedilol and given a band ligation of esophageal varices.

The patient later presented with upper GI bleeding presumed to be esophageal varices. Band ligation was performed again and he was discharged on carvedilol. He is now presenting with a third GI bleed. Upper endoscopy reveals small distal esophageal varices plus blood and clots in the stomach, but no clearly identifiable bleeding site.

The patient has a body mass index of 38, type 2 diabetes controlled with diet, prior hypertension and current dyslipidemia and chronic lower back pain. His drug regimen includes furosemide 80 mg daily, spironolactone 200 mg daily and carvedilol 12.5 mg twice daily. He appears anxious.

The patient’s blood pressure is 105/65, pulse 125/minute, respiration 18/minute and O2 saturation 98 percent. He has moderate to large ascites, hepatosplenomegaly, obvious melena and multiple spots of pitting edema.

Guadalupe Garcia-Tsao, MD

Guadalupe Garcia-Tsao, MD

The management of varices and variceal hemorrhage must be considered in the context of other complications of cirrhosis, said Guadalupe Garcia-Tsao, MD, professor of medicine at Yale University and chief of digestive diseases at the VA-Connecticut Healthcare System, New Haven. This patient decompensated a year ago and has continued to decompensate. Current AASLD guidelines for patients with medium to large esophageal varices that have not bled are carvedilol, endoscopic variceal ligation or a nonselective beta blocker (propranolol or nadolol). Combination therapy is not recommended.

“I would choose a beta blocker,” Dr. Garcia-Tsao said. “Nonselective beta blockers prevent a first variceal hemorrhage, reduce rebleeding, and further decompensation is significantly lower. In patients with ascites, carvedilol is not recommended. And once you fail combination therapy, the next step is TIPS.”

Early pre-emptive TIPS dramatically reduces the risk of rebleeding and death in patients with cirrhosis and acute variceal hemorrhage, she said.