Cirrhosis

I gave a lecture at the refresher course last Monday. Two days later, I received a list of questions from a student. I have never answered questions in my blog before, but then I have never received so many questions from a student all at once either. The questions are practical and insightful and should be shared with other students.

1. I was told that in liver cirrhosis progression, it usually starts with deranged clotting profile, then albumin, then bilirubin, then ascites and finally encephalopathy. Is that true that when patient developed, let's say, ascites or encephalopathy, it indicates a more severe cirrhosis?

Answer: The sequence of laboratory changes is not absolute. However, it is true that clinical complications such as ascites and encephalopathy usually indicate more severe disease and are associated with poor prognosis.

2. In monitoring patients with cirrhosis, do we monitor by Child-Pugh grading + HCC surveillance + varices screening + hepatorenal syndrome screening? Do we need to repeat ultrasound for progression of features?

Answer: You have included different concepts here: assessment of the severity of cirrhosis and complications screening. Currently, most doctors use the Child-Pugh score or the model for end-stage liver disease (MELD) score to assess the severity of cirrhosis. The purpose is to predict the prognosis and prioritize patients for liver transplantation.

HCC surveillance is performed to detect early HCC so that patients may receive curative treatment. That said, this should only be done in patients who are candidates for curative treatment. For example, a patient with Child’s C cirrhosis and multiple comorbid illnesses cannot undergo liver resection or locoregional therapy even if a small HCC is detected. Surveillance would not be helpful.

Screening for varices is also recommended to reduce the risk of variceal bleeding.

Finally, the main role of ultrasound is for HCC surveillance. We use other parameters to assess the severity of cirrhosis.

3. Once patient is diagnosed to have liver cirrhosis, when should we start screening for varices? and by what mean? Ultrasound or endoscopy?

Answer: Unless the patient is moribund, all cirrhotic patients should be screened for varices by OGD.

4. When we say ultrasound imaging to look for presence of varices, do we mean hepatic doppler ultrasound that the flow in different hepatic vasculature may suggest the presence of esophageal varices?

Answer: In good hands, splenic varices may be visualized by ultrasound. While this feature confirms the presence of portal hypertension, it cannot replace OGD. It is bleeding from esophageal or gastric varices that we want to prevent.

5. For HCC surveillance, do you mean serum AFP + LFT + CT (or USG?) scan regularly?

Answer: Good question. For some hepatologists, this means 6-monthly USG and AFP testing. Liver function test does not detect HCC. CT is more accurate but involves radiation and has not been tested in the screening setting. Triphasic CT is usually reserved for confirming the diagnosis of HCC when a liver nodule is identified by USG. Interestingly, the current American guidelines only suggest USG surveillance and discourage the use of AFP. This is highly debatable.

6. In bleeding esophageal varices, do we need to give both octreotide and terlipressin together? What is the usual dosage given and are they given as IV infusion or bolus?

Answer: Either somatostatin analog (e.g. octreotide) or vasopressin analog (e.g. terlipressin) would do. The dosage we are using is octreotide 50 mcg iv stat, followed by 50 mcg/h infusion; and terlipressin 2 mg Q4-6H iv. There have also been studies showing that terlipressin infusion may be better than bolus injections.

7. In variceal bleeding, do we need to correct the deranged clotting profile by transfusing fresh frozen plasma? and also correct any platelet derangement?

Answer: Many doctors do so, but this practice is not adequately tested.

8. Do we need to prophylactically give lactulose to all cirrhotic patients with variceal bleeding to prevent development of hepatic encephalopathy? or do we give only when patients develop symptoms and signs of HE?

Answer: Because patients with variceal bleeding are at high risk of developing hepatic encephalopathy and lactulose carries few side effects, we usually give it prophylactically.

9. In secondary prophylaxis of variceal bleeding, you mentioned an option of endoscopic variceal ligation, but I thought you have already banded all varices during last variceal bleeding? or do you mean those new varices developed? Also, do we need to start beta blocker +/- nitrate immediately after first episode of variceal bleeding?

Answer: It takes an average of 5 sessions to eradicate all esophageal varices. A clinical trial from Spain showed that pharmacological therapy is more effective than endoscopic variceal ligation for secondary prevention of variceal bleeding and result in less complications (N Engl J Med 2001;345:647-55). However, a subsequent meta-analysis showed that combining endoscopic variceal ligation and pharmacological therapy would further reduce the chance of rebleeding (Aliment Pharmacol Ther 2012;35:1155-65). At our center, we do both.

Immediately after variceal bleeding, the patient should still be on vasoactive drugs such as octreotide or terlipressin. You do not need to start beta-blockers yet. Besides, it is a bad idea to give a drug that would lower the blood pressure right after active bleeding. Instead, beta-blockers and/or nitrates may be started after the acute episode settles.

10. If we are to give lactulose to patient during variceal bleeding, since patients are kept NPO, can he still tolerate an oral lactulose? How about in the case when patient is drowsy and confused as in grade 2-3 encephalopathy or patient in hemorrhagic shock, is it still safe to give oral lactulose?

Answer: We can keep the patient nil by mouth except medications. If the patient has aspiration risk, medications should be delivered via nasogastric tube instead.

11. In patients with ascites with deranged renal function (creatinine >133), do we routinely stop diuretics or paracentesis for 2 days to assess hepatorenal syndrome?
And even with albumin infusion, ascites will still come back right? And is this because hypoalbuminemia is not related to pathophysiology of ascites? And in this case, do we just leave the ascites untreated and observe?

Answer: It is important to stop diuretics and paracentesis in cirrhotic patients with acute kidney injury. They may well be the culprit.

Albumin infusion is for the prevention of paracentesis-induced circulatory dysfunction, not ascites. Therapeutic paracentesis relieves ascites rapidly but does not alter the underlying pathophysiology of portal hypertension and salt retention. Therefore, ascites will recur after paracentesis unless the patient is well controlled with salt restriction and diuretics. However, some patients will still have refractory ascites and require either repeated paracentesis or TIPS.

12. I'm sorry to complicate the case further. What if the patient has co-morbid cardiovascular condition (eg. hypertension, heart failure) that requires the use of diuretics? Do we still stop it for assessment? If patient is on ACEI, do we need to stop it for HRS assessment?

Answer: You have to assess the fluid status. If the patient is having fluid overload, you do not have much choice. For your last question, cirrhotic patients are very sensitive to ACEI because renal perfusion is often suboptimal. In case of renal deterioration, we have low threshold to stop ACEI.