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Best of Times in Liver Diseases
There has been an explosion of diagnostic and therapeutic discoveries affecting the liver. In this slide show: key points on 5 important clinically relevant areas.
There has been an explosion of diagnostic and therapeutic discoveries affecting the liver -- an essential organ and common target of diseases seen in primary care. I recently detailed the brave, new world of interferon-free treatments for Hepatitis C.1 Not long ago, I had the privilege of attending a “Liver Update” at the Cleveland Clinic. 2 Here, I expand on 5 important areas that were -- and will continue to be -- clinically relevant.
1. Rutecki G. Five top papers from 2014 that will impact your practice. Consultantlive.com. December 4, 2014..2. Carey WD, Gholam PM. Thirteenth Annual Liver Update: A Report from the American Association for the Study of Liver Disease Annual Meeting. December 5, 2014; Cleveland Clinic.
With all the attention paid to Hepatitis C, we run the risk of minimizing the second leading cause of liver injury serious enough to result in liver transplantation. As with other etiologies for cirrhosis, the pathology is also a risk factor for hepatocellular carcinoma (HCC). It affects up to one third of the population in developed nations!3 That disease is Non-Alcoholic Fatty Liver Disease (NAFLD).
3. Firneisz G. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age? WJG. 2014;20:9072-9089.
NAFLD represents a spectrum of diseases from NAFLD (not so bad) through Non-Alcoholic Steatohepatitis (NASH can be bad) to end-stage cirrhosis and HCC.
Why is NAFLD under-diagnosed, dangerous, and epidemic?
There is no validated screening test in primary care.2 NAFLD-NASH is suspected after liver ultrasound. Estimates suggest that 19% of Americans may harbor NAFLD!3 With our persisting epidemic of obesity and diabetes mellitus, 85% of obese persons and 65%-75% of diabetics have fatty livers of variable degree.2
2. Carey WD, Gholam PM. Thirteenth Annual Liver Update: A Report from the American Association for the Study of Liver Disease Annual Meeting. December 5, 2014; Cleveland Clinic.
3. Firneisz G. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age? WJG. 2014; 20:9072-9089.
Treatment strategies seem to abound -- pioglitazone, Vitamin E, controlling A1C in diabetes and cholesterol in lipid disorders.4 But a critical question remains: do they really work? More work is necessary in this area. Bariatric surgery may become the #1 choice in the future.
4. Dyson JK, Anstee QM, McPherson S. Non-Alcoholic Fatty Liver Disease: a practical approach to treatment. Frontline Gastroenterology 2014; 5:277-286.
If NAFLD/NASH is discovered on ultrasound, how do you appraise the degree of liver injury? Do you have to biopsy all comers? The most important finding suggesting serious liver damage is the presence of fibrosis. Predicting fibrosis non-invasively is our next area of study.
Predicting Liver Fibrosis Without or Before a Biopsy 5-7
The last year validated some non-invasive modalities designed to uncover occult liver fibrosis. There are formulas such as the FIB-4 Index:
(age [years] x AST [IU/L] platelet count [platelets x 109/L] x (ALT1/2[IU/L]) 5
or
“APRI” (AST to Platelet Ratio Index).6
The key is that many high risk patients identified by formula would not have been otherwise diagnosed or referred for a liver biopsy. With novel, successful treatments for hepatitis C, for example, the cohort with liver fibrosis should be identified and treated.
5. Butt AA, Yan P, Lo Re V, et. al. Liver fibrosis progression in Hepatitis C virus infection after seroconversion. JAMA Intern Med. 2014; Published online December 8, 2014.6. Dvorak K, Stritesky J, Petrtyl J, et al. Use of non-invasive parameters of non-alcoholic steatohepatitis and liver fibrosis in daily practice-an exploratory case-control study. PLOS ONE 2014; Published online October 28, 2014.7. Yada N, Sakurai T, Minami T, et. al. Ultrasound elastography correlates treatment response by antiviral therapy in patients with chronic hepatitis C. Oncology. 2014; 87 (Supp. 1):118-123.
Another important “non-invasive” diagnostic method is ultrasound elastography.7 The velocity of shear waves is measured during ultrasonography and correlated with liver “stiffness,” a sign of fibrosis. In this way, patients with significant liver damage can be identified and treated more aggressively.
7. Yada N., Sakurai T, Minami T. et. al. Ultrasound Elastography correlates Treatment Response by Antiviral Therapy in patients with Chronic Hepatitis C. Oncology 2014; 87 (Supp. 1) 118-123.
A Quality Arena for Liver Disease: Where can we do better?8,9
Paracentesis is a simple and relatively safe procedure. When should it be performed? Any patient with cirrhosis admitted to the hospital should undergo the procedure.8 That guideline is not consistently followed (40% of those eligible do not undergo the potentially lifesaving procedure).8,9 What is the downside? In-hospital mortality is decreased in cirrhotic individuals who have a paracentesis (5.7% vs. 8.1%). Paracentesis is also a cost saver. Patients who have the procedure have a 14% shorter hospital stay and 29% less in hospital charges.8 The diagnosis of spontaneous bacterial peritonitis can be a life saver!
2. Carey WD, Gholam PM. Thirteenth Annual Liver Update: A Report from the American Association for the Study of Liver Disease Annual Meeting. December 5, 2014; Cleveland Clinic. 8. Orman ES, Hayashi PH, Bataller R, et. al. Paracentesis is associated with reduced mortality in patients hospitalized with cirrhosis and ascites. Clin. Gastroenterol. Hepatol. 2014;12:496-503.9. Brooling J. Ghaoui R., Lindenauer PK, et. al. Use of paracentesis in hospitalized patients with decompensated cirrhosis and ascites: opportunities for quality improvement. J Hosp Med. 2014;9:797-799.
Another similar forgotten recommendation is endoscopy in all diagnosed cirrhotics to identify and treat varices.2
2. Carey WD, Gholam PM. Thirteenth Annual Liver Update: A Report from the American Association for the Study of Liver Disease Annual Meeting. December 5, 2014; Cleveland Clinic.
Forget Hepatitis B at your Patient’s Peril!10,11
Hepatitis C receives a lot of press. However, like NAFLD, Hepatitis B (HBV) should not be forgotten in the rush. In contemporary practice, we see so many patients who will receive a biological agent. Reactivation of Hepatitis B can be a serious problem in this specific context. There guidelines for who to treat and agents to utilize are available and are straightforward.
If patients are Hepatitis B positive or negative (American Association for the Study of Liver Diseases), and have an HBV load of > 20,000 IU/mL and an ALT >2x the upper limit of normal they should receive treatment with lamivudine, adefovir, entecavir, or tenofovir. (The last 2 are preferred because of lower rates of resistance).10
10. You CR, Lee SW, Jang JW, et. al. Update on Hepatitis B virus infection. WJG. 2014; 20:13294-13305.
11. Uribe LA, O’Brien CG, Wong RJ, e. al. Current Treatment guidelines for chronic Hepatitis B and their applications. J Clin Gastroenterol. 2014; 48:773-783.
When should we talk “TIPS”?12
Some of our patients with cirrhosis will have been treated with a “TIPS” (that is a Transjugular Intrahepatic Portosystemic Shunt). Indications for placement of a TIPS are secondary prophylaxis of esophageal variceal hemorrhage and treatment of refractory ascites as well rescue therapy for portal hypertensive gastropathy. Placement of TIPS may become more common as other indications arise in the future. Possible additional indications may include: esophageal variceal hemorrhage, Budd-Chiari Syndrome, ectopic varices, and portal vein thrombosis.
Hepatic encephalopathy is a complication of TIPS. 90% of episodes occur within the first 3 months after placement. Patients with a MELD score of above 18 have a higher mortality after placement of a TIPS.
12. Copelan A, Kapoor B, Sands M. Transjugular intrahepatic portosystemic shunt: indications, contraindications, and patient work-up. Semin. Intervent Radiol. 2014;31:235-242.
There has been an explosion of diagnostic and therapeutic discoveries affecting the liver -- an essential organ, and common target of diseases seen in primary care. In this arena, it's the best of times.Leading a distinguished list of advances is the brave new world of interferon-free treatments for Hepatitis C.1I recently had the privilege of attending a “Liver Update”2 at the Cleveland Clinic. Here, I summarize 5 important areas that were-- and will continue to be -- clinically relevant.