A 63-Year-Old Woman With Liver Disease: Epidemiology, Course, and Prognosis

Author:
Ronald N. Rubin, MD—Series Editor

A 63-year-old woman presented for further evaluation of possible liver disease. Approximately 8 months previously, she had undergone a routine physical examination with laboratory testing. Although the initial examination findings had been recorded as unremarkable, results of a biochemistry profile had shown her transaminase levels to be elevated to approximately 2 to 3 times the normal reference values. Repeated biochemistry tests had confirmed the findings. Serologic test results were negative for hepatitis C virus (HCV) infection.

Results of a thorough history and physical examination now revealed a several-year history of low-dose statin use and that she has consumed at least 3 glasses of red wine daily with dinner for many years. She was noted to be obese, with a body mass index of 30 kg/m². There was a question of a firm, nontender liver edge, but her obesity rendered the examination difficult. Laboratory tests at this visit revealed not only elevated transaminases levels, but also borderline-high glucose and hemoglobin A_1c levels. Results of a lipid panel were normal. The statin was stopped, and she was advised to lose weight, cease all alcohol intake, and repeat a biochemistry panel in 3 months.

The patient did not undergo the biochemistry testing in 3 months as directed but rather did so 1 week before presenting for her 6-month follow-up visit. The results now revealed persistent elevation of transaminases 2 to 3 times above normal, with a low-normal serum albumin level of 3.6 g/dL. Her weight had not changed since her visit 6 months previously. A detailed history revealed that there had been no change in her alcohol consumption. She was sent for abdominal ultrasonography, which revealed hepatomegaly with steatohepatitis and early cirrhotic changes. Gallbladder sludge was noted incidentally.

Answer: C is the correct statement

Cirrhosis—irreversible fibrosis of the liver—is an ancient and classic syndrome. As medical technology and therapeutics continue to advance, our ability to detect, quantify, manage, and prevent cirrhosis improves, and with time, new etiologies and new demographic trends find their way into the cirrhosis discussion. Nevertheless, many of the core findings about cirrhosis continue to serve as a sound basis for the approach to its diagnosis and management.

Liver damage caused by many various pathophysiologic mechanisms can lead to cirrhosis. In the United States, the main 3 pathophysiologies of the inflammation that leads to irreversible fibrosis are the oldest one, alcohol abuse; a newer viral etiology, HCV, with its favorite demographic of baby boomers; and the newest cause, NASH, with its ever-increasing demographic of persons with obesity and metabolic syndrome. Very frequently, combinations of all 3 factors contribute to cirrhosis in the same patient. With the advent of very effective HCV therapies¹ and the epidemic nature of obesity and metabolic syndrome, statistics clearly are predicting that NASH will become the most common indication for orthotopic liver transplantation in the United States.² This quickly makes Answer C the correct answer, although the patient presented in the vignette has a typical history of multiple etiologies (alcohol use plus steatohepatitis).

Regardless of its specific etiology, cirrhosis has established symptoms, signs, laboratory and imaging features, and prognostics. Typically, the initial finding is firm hepatomegaly, detected directly or incidentally during physical examination or with ultrasonography or computed tomography. As the fibrosis progresses, 2 separate pathophysiologies contribute to further findings and natural history. Ongoing damage to hepatocytes causes deterioration of the hepatosynthetic functions of sodium balance and hormonal metabolism and a variety of synthetic failures (eg, coagulation proteins, thrombopoietin, etc), leading to abnormal liver test results (eg, elevated transaminases, depressed albumin), spider telangiectasias, and ascites. At the same time, progressive fibrosis results in portal hypertension, which further predisposes to ascites and creates variceal dilation in a variety of involved circulation, including the stomach, esophagus, hemorrhoidal plexus, and abdominal wall, with the subsequent development of complications such as caput medusae (periumbilical abdominal-wall varices) and variceal GI hemorrhage. Overall, these findings are useful in determining prognosis using the well-validated Child-Pugh scoring system and, even more specifically, the 40-point Model for End-Stage Liver Disease (MELD) scoring system.

Some useful landmarks in the natural history of cirrhosis from any cause include the following: The average life expectancy of compensated cirrhosis is 10 to 13 years but as low as 2 years once decompensation occurs; even among the population with compensated cirrhosis, the probability of developing ascites is 47%, hepatic encephalopathy is 28%, and variceal bleeding is 25%³; once ascites has developed, the mortality rate is 15% within 1 year and 44% within 5 years; and persons with cirrhosis have an annual incidence of 5% per year for the development of hepatocellular carcinoma.³ Analysis of these numbers indicates that ascites rather than the more dramatic GI hemorrhage is the cardinal and more common complication of cirrhosis, which makes Answer B an incorrect statement.

As if the direct complications of cirrhosis were not ominous enough, the cirrhotic state also renders other medical care more difficult and dangerous. For example, invasive procedures such as intra-abdominal surgery become extremely dangerous, with perioperative mortality increasing 1% for each additional MELD score point up to 20, and 2% for each MELD score point above 20, equating to a 23.9% overall mortality rate associated with nontransplant abdominal surgery in a population with cirrhosis.³ This clearly makes Answer D an incorrect statement.

Therapeutic interventions for the specific complications of cirrhosis will be discussed in the next issue’s “What’s the ‘Take Home’?” article. For example, the advent of effective and well-tolerated therapy for HCV infection already is lowering the numbers and morbidity rates of the demographic group entering advanced cirrhosis.^1,3 However, lifestyle risk factors must be addressed and reversed if possible before such treatment is initiated. The oldest etiology, alcoholism, has the clearest and most potent effect of all. When true abstinence can be accomplished, 65% of persons with alcoholic cirrhosis will be alive at 3 years, whereas 0% who continue drinking will be alive at 3 years,^1,3 making Answer A a grossly understated and incorrect statement.

Patient Follow-Up

A very thorough evaluation of the patient was undertaken. All serologic test results were negative for hepatitis virus infection, and less-common but reversible etiologies such as hemochromatosis also were excluded. Thus, the best-fit diagnosis was cirrhosis related to the combination of obesity-related steatohepatitis and excessive alcohol intake. The initial therapeutic and management approach will include the lifestyle changes of weight loss and abstinence from alcohol. Additionally, more detailed imaging studies and endoscopy are planned. 

Ronald N. Rubin, MD, is a professor of medicine at the Lewis Katz School of Medicine at Temple University and is chief of clinical hematology in the Department of Medicine at Temple University Hospital in Philadelphia, Pennsylvania.

REFERENCES:

1. Ge PS, Runyon BA. Treatment of patients with cirrhosis. N Engl J Med. 2016;375(8):767-777.
2. Wijdicks EFM. Hepatic encephalopathy. N Engl J Med. 2016;375(17):1660-1670.
3. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44(1):217-231.