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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2948_Библиотеки_им_академика_М_И_Перельмана
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Part IV
Hepatology Compendium
https://t.me/medicina_free
281© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
W. H. Sobin et al. (eds.), Managing Complex Cases in Gastroenterology,
https://doi.org/10.1007/978-3-031-48949-5_56
Chapter 56
Introduction to the Hepatology
Compendium
W.HarleySobin
We gastroenterologists deal with many patients with liver disease in the community
setting. We get many requests to see patients for abnormal liver enzymes or for
questions about NAFLD.Managing complications of cirrhosis continues to con-
sume a lot of our time. Treating hepatitis C used to be burdensome, but since the
development of DAA treatment, this is rarely a problem.
While community gastroenterologists continue to spend a lot of time dealing
with liver issues, we frequently curbside our hepatology experts at the regional ter-
tiary care center for help with our complicated patients. There are numerous man-
agement decisions in hepatology that are confusing or controversial. In the sections
below, we highlight how our liver specialists deal with some of these problem cases.
Oftentimes, our hepatology dilemmas start with abnormal liver enzymes. The
workup is usually launched with a battery of serologic tests. At MCW, the standard
panel of tests for evaluation of abnormal liver enzymes includes a viral hepatitis
panel, an autoimmune panel that includes ANA, ASMA, and AMA, as well as ceru-
loplasmin, Fe/TIBC, ferritin, alpha-1-antitrypsin level, and celiac panel (occasion-
ally IgG4 and others). This panel is a good starting point.
While these results often lead us to a diagnosis, the results are sometimes unre-
vealing and other times confusing. In addition, liver enzymes may be normal in
cases where patients are consuming a lot of alcohol, cases where ultrasound reveals
extensive hepatic steatosis, or even in cases of clear-cut cirrhosis. If the workup for
abnormal liver enzymes is negative, what should the next steps be? These and many
more issues are discussed in the case presentations that follow.
W. H. Sobin (*)
Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of
Wisconsin, Milwaukee, WI, USA
e-mail: hsobin@mcw.edu
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282
Below, we encounter a case of suspected hemochromatosis, where the transferrin
saturation and the ferritin are discordant. How should we proceed? And if hemo-
chromatosis is diagnosed, what is the end goal for phlebotomy?
The importance of Wilson’s disease is highlighted in two different cases. We
never want to miss Wilson’s, which can lead to severe liver disease and debilitating
neurodegenerative disease. In a case of suspected Wilson’s, how is the diagnosis
conrmed? The serum ceruloplasmin is a starting point in making the diagnosis,
which, if low, triggers investigations. But, what about a case where the ceruloplas-
min is normal? And, if Wilson’s is conrmed, how is it treated? In the community,
we may see one or two patients with Wilson’s throughout our career, but it is imper-
ative that we remain vigilant. If Wilson’s is diagnosed, we certainly need advice
about management.
A patient with abnormal LFTs and apparent alpha-1 antitrypsin deciency is
discussed. Alpha-1 antitrypsin deciency may be the primary cause of chronic liver
damage, or it can be a secondary, exacerbating factor in other cases. It is easily
missed, if not specically investigated.
We are all familiar with patients with indirect hyperbilirubinemia who have
Gilbert’s. But a case is discussed where Gilbert’s is suspected but the patient also
has an elevated direct bilirubin. How is this interpreted?
Normally, the ALT>AST, except in cases of active alcohol abuse. How do we
interpret cases where the AST > ALT and alcohol abuse is apparently absent?
Several authors discuss this phenomenon.
A case of profound hyperbilirubinemia is presented. In cases where the bilirubin
is >20, it is usually not due to obstruction alone. What other factors may be
contributing?
Community gastroenterologists are seeing more and more referrals for managing
NAFLD.This is a confusing and controversial area, and it may be difcult to know
what course of action to take. Talking to the hepatologists, there are several recom-
mendations they all agree upon, but different viewpoints exist, even among the
experts. Below, we share various approaches from several advisors with different
management styles.
While this textbook was in production, the terminology-NAFLD was accepted
by consensus. But, just prior to printing, NAFLD was replaced by MASLD.As Dr.
Sourianarayanane says, “MASLD is the current terminology for non-alcoholic fatty
liver disease (NAFLD), which is an encompassing diagnosis of those with fatty liver
with metabolic risks. Similarly, metabolic dysfunction-associated steatohepatitis
(MASH) is the replacement term for prior non-alcoholic steatohepatitis (NASH)”.
Since most of our readers are more familiar with NAFLD and NASH, we have not
gone back to edit these terms that are still present in the majority of the chapters.
There is a case where we discuss the increased susceptibility women have to
alcohol-induced liver disease. In another case, we discuss management of acute
alcoholic hepatitis. Community gastroenterologists have managed patients with
alcoholic hepatitis through the decades. We have gone through periods where pent-
oxifylline was recommended and where steroids have been advocated. Now, even
the possibility of transplant has been raised. We hear about the management of
alcoholic hepatitis in the tertiary care setting.
W. H. Sobin
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283
Another problem we commonly deal with in the community is managing ascites.
In the initial evaluation of ascites, we know to examine the ascites albumin and cell
count. We measure the SAAG (serum albumin minus ascites albumin), expecting it
to be >1.1in most cases, consistent with portal hypertension. We know that a PMN
count in uid >250 requires treatment for infection. We discuss cases of low SAAG
ascites, ascites in a patient without apparent cirrhosis, and ascites in a patient with
cirrhosis of unclear etiology. There is also a case that explores the possible etiolo-
gies of worsening ascites in an apparently stable cirrhotic.
Another issue we deal with in the community is managing bleeding esophageal
varices. But what is the best approach to dealing with bleeding from post-banding
ulcers? The other problem that may lead to a tertiary center referral is management
of gastric varices. In the segments below, we discuss both of these challenging
scenarios.
In the community, we spend a lot of time managing the complications of cirrho-
sis. Unfortunately, our therapies are themselves fraught with multiple potential
complications. We present one such case. Ultimately, many of these patients with
end-stage liver disease require a liver transplant. However, as we highlight in our
section on transplantation, getting a liver may be frustratingly slow.
Portal vein thrombosis (PVT) is a known complication of cirrhosis. Decisions on
anticoagulation for patients with PVT, who may have varices, bleeding portal
hypertensive gastropathy, or GAVE, can be challenging. This is discussed in one of
the cases.
Another complication of cirrhosis that we need to screen for is hepatocellular
carcinoma (HCC). In our community hospital, once HCC is detected, the patient
usually gets referred to the tertiary care center, where specic therapies and poten-
tial liver transplant are available. There are several cases discussing manage-
ment of HCC.
While most patients with HCC have underlying cirrhosis, it is well-known that
you can develop HCC without having cirrhosis if there is underlying chronic hepa-
titis B or hemochromatosis. Now there are reports of HCC occurring in NASH
patients who don’t have cirrhosis. With the huge numbers of patients with NAFLD
in the USA, this is potentially a huge problem. This is also discussed.
We see quite a lot of PBC in the community, patients who are referred with an
asymptomatic elevation of alkaline phosphatase. Management is often uncompli-
cated, but sometimes questions arise. We see far fewer patients with advanced
PBC in the community, and this generally warrants referral to the transplant cen-
ter. How do they approach these patients? An extensive discussion of management
follows.
In the following chapters, we have several hepatologists who discuss cases of
autoimmune hepatitis, overlap syndromes, and PSC.In PSC, of course, we need to
be vigilant in screening for cholangiocarcinoma and colon cancer.
Chronic hepatitis B is not commonly seen by most community GIs. It can be a
confusing disease to understand and treat. There are cases discussing management
of immune-tolerant and immune-active chronic HBV.Another reviews the situation
where a patient with chronic HBV stops taking his antiviral medication and disease
relapses.
56 Introduction to the Hepatology Compendium
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284
The question posed in a different case asks whether a patient once infected with
HBV will continue to have lifelong stigmata of the infection.
The management of an exacerbation of chronic HBV differs from the treatment
of acute HBV.Sometimes, it is unclear which we are dealing with. What are some
clues to making this distinction and managing this?
While long-term management of HCV used to take up a lot of our time, the
development of DAAs has made management so easy that often gastroenterologists
in the community are not even consulted. However, there are occasional confusing
cases that are sent our way. One such case is presented.
Liver failure and liver transplant are explored in several cases. A previously
healthy patient who presents with acute liver failure always necessitates an urgent
call to the transplant center. Here are some insights into their management once
transferred. In the community, we get consulted on patients with a recent Tylenol
overdose, and their management is often straightforward. But how should we man-
age patients with a delayed presentation?
Deciding who to refer for a transplant can be confusing. Four different cases
highlight the controversies that occur. And then, once a patient goes on the trans-
plant list, it can still be very frustrating for the community gastroenterologist to have
to manage the recurring complications while waiting for the transplant to happen. It
seems like the wait for a liver goes on forever.
Finally, the transplant hepatologists are the ones who commonly deal with com-
plications that may occur post-liver transplant. However, community gastroenter-
ologists may be the rst to encounter these problems and need to know what to be
on the lookout for. This is discussed in our last case.
W. H. Sobin
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285© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
W. H. Sobin et al. (eds.), Managing Complex Cases in Gastroenterology,
https://doi.org/10.1007/978-3-031-48949-5_57
Chapter 57
Liver Enzyme Elevation-negative Work-up
FranciscoDurazo
A 47-year-old female is referred for abnormal liver enzymes. She has a normal
BMI, does not drink or take street drugs, and is on no medications. Her AST is 78,
ALT is 90, Alk phos is 100 (nl<80), and bilirubin is 1.4, in which the direct is 1.0.
The US of the liver is unremarkable. ANA+1:16, ASMA negative, AMA negative,
celiac panel, ceruloplasmin, and alpha-1 Antitrypsin are all normal, and Fe/
TIBC is 24%.
How do you approach the case of a patient with elevated LFTs where
workup is negative?
My rst approach with this patient would be to corroborate the history and do a
detailed physical exam.
Is there any more information that you need to know?
It is helpful to know the time that the liver tests became abnormal and for how
long they have been abnormal. When was the last time that the patient had normal
liver tests? If we know this information, we can focus the interrogatory around that
time and look for events that may be related. Is the patient symptomatic? Any
changes in bowel habits that would suggest inammatory bowel disease with pri-
mary sclerosing cholangitis or celiac sprue? Does the patient have itching that
would suggest cholestasis? Any symptoms that would suggest heart failure such as
paroxysmal nocturnal dyspnea or dyspnea on exertion? Any joint swelling and
hyperpigmentation suggesting hemochromatosis? Does the patient have upper
abdominal pain that would indicate biliary tract disease?
F. Durazo (*)
Division of Gastroenterology and Hepatology, Department of Medicine,
Medical College of Wisconsin, Milwaukee, WI, USA
e-mail: fdurazo@mcw.edu
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286
I would check for risk factors for viral hepatitis: recent travel to endemic areas,
parenteral exposure, tattoos, blood transfusions before 1992, and eating under-
cooked pork (hepatitis E).
Other important information that is frequently not disclosed accurately is the use
of alcohol and illicit drugs. This patient apparently does not drink alcohol, but did
she drink heavily in the past? She can have alcohol-related liver disease from previ-
ous drinking. The same with street drugs. Did she take street drugs in the past? Even
if she did once, that’s enough to acquire viral hepatitis. We saw this in the baby
boomers that experimented with intravenous drugs in the 1970s and acquired hepa-
titis C.Many denied using intravenous drugs, but when asked more specically,
they confessed. Many street drugs can cause liver test abnormalities, hepatitis, and
acute liver failure.
Frequently, patients do not offer the information we are looking for. Up to two
thirds of patients taking supplements do not disclose this information to their physi-
cian. Others don’t mention them when interviewed because they do not consider
supplements to be part of their medications. Drug-induced liver injury is a frequent
cause of liver test abnormalities. This patient was not taking medications at the time
she was seen, but a thorough history of medications can be the culprit. Some medi-
cations can cause drug-induced liver injury with liver test abnormalities that persist
even months after stopping them (intrahepatic cholestasis, i.e., amoxicillin/clavu-
lanic acid, estrogens, anabolic steroids).
A detailed physical exam is most helpful. A good exam can narrow or even give
you the diagnosis you are looking for. Does this patient have stigmata of chronic
liver disease, such as palmar erythema or vascular spiders? Does she have a palpa-
ble liver? Is the liver rm and nodular? Is there a hepatic bruit suggesting alcoholic
hepatitis or hepatocellular carcinoma? Is there a venous hum present (Cruveilhier-
Baumgarten murmur, which is highly suggestive of portal hypertension)?
Are there other labs you would order?
I would like to rule out chronic viral hepatitis with hepatitis B surface antigen,
hepatitis B core antibody, and hepatitis C antibody. I would also like to check her
for type 2 and 3 autoimmune hepatitis with a liver-kidney microsomal antibody and
a soluble liver antigen. Thyroid disease can affect the liver tests, especially hyper-
thyroidism. A thyroid panel with thyroid stimulating hormone is another test I
would order.
A platelet count is helpful to assess for the presence of signicant brosis. The
AST to platelet ratio index (APRI score) or the Fib-4 score can be obtained with
simple routine laboratory tests. They have good ability to differentiate patients with
signicant brosis (F2 to F4) from those without signicant brosis (F0 to F1).
Would you do FibroScan
®
? If so, how would it help you?
A FibroScan
®
can be used as the rst-line assessment for the severity of liver
brosis in patients with chronic hepatitis. It performs best with regard to the ruling
out of cirrhosis. It is primarily used as an alternative to liver biopsy for the assess-
ment of hepatic brosis. It can also be used to predict complications in patients with
cirrhosis. However, in this patient, I would be more interested in nding out the
etiology of her liver test abnormalities. Depending on this information, I may or
may not request a FibroScan
®
and may or may not proceed with a liver biopsy.
F. D u r a z o
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287
In considering a liver biopsy, what are you looking for? What might it show,
and what are you hoping to rule out?
Doing a liver biopsy in a patient with a negative serologic workup is tempting.
However, a liver biopsy doesn’t always give you the answer. Pathologists base, to
some extent, their histologic interpretation on the clinical history and the results of
the serologic workup. If the work up is noncontributory, the histologic interpretation
of the biopsy will be less specic. A liver biopsy may help to denitively establish
the nal diagnosis in some patients. However, the results rarely change your pre-
sumptive diagnosis or inuence the patient management. On the other hand, if the
liver test abnormalities persist, then I would proceed with a percutaneous liver
biopsy. Occasionally, the liver biopsy may reveal an unsuspected diagnosis or dic-
tate a change in the patient management. In most of the cases, the liver biopsy will
reassure the patient and physician that there is no advanced liver disease.
Any other management decisions?
In the case of this patient, I would check the results of the viral hepatitis serolo-
gies and a thyroid panel. If these are noncontributory, like the rest of the workup, I
would repeat the liver tests in 1month and look at the trend. If the liver test abnor-
malities continue to get worse, I would proceed with a percutaneous liver biopsy
(not a transjugular liver biopsy). If the liver test abnormalities would get better, I
would continue to follow up the patient until these normalize.
57 Liver Enzyme Elevation-negative Work-up
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289© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
W. H. Sobin et al. (eds.), Managing Complex Cases in Gastroenterology,
https://doi.org/10.1007/978-3-031-48949-5_58
Chapter 58
Increased LFTs withIncreased Iron
JoseFranco
A 35-year-old male is being elevated for abnormal LFTs: AST, 60; ALT, 78; and
ALK PHOS,100 (nl<80). Hepatitis panel and autoimmune panel are negative, and
Fe/TIBC is 20% but ferritin is 800.
Do you think this is hemochromatosis?
The protocol that I follow is that if the transferrin saturation (TS) is > or equal to
45% and/or the ferritin is elevated, you should order a hemochromatosis genotype.
So, in this case, the ferritin is elevated, although the transferrin saturation isn’t. You
need to order the genotype, because one of them is elevated. I don’t think hemo-
chromatosis is very likely, with the TS being normal, but you do have to go that next
step. Of course, many chronic liver diseases, besides hemochromatosis, may be
associated with elevated ferritin.
What if the iron saturation was 55% and the ferritin was 250? What if the
blood draw was non-fasting?
Once again, if either the transferrin saturation or the ferritin is elevated, you need
to order a hemochromatosis genotype. In this instance, I also think it is unlikely to
be hemochromatosis, with a normal ferritin, but I would still check the genotype. In
terms of the iron level, this should be drawn fasting. Presumably, there can be some
artifactual rise in the iron level, if the draw is postprandial, although I've never been
able to nd a good reason why (except where the patient is ingesting iron).
In what cases are you seeing elevated ferritin in patients with liver disease
who don’t have hemochromatosis?
Fatty liver, alcohol, chronic viral hepatitis, chronic cholestatic diseases, pretty
much any chronic liver disease. Back in the 1990s, there was actually a movement
to consider phlebotomy in patients with chronic HCV who had elevated ferritin
J. Franco (*)
Department of Medicine-Division of Gastroenterology and Hepatology, Medical College of
Wisconsin, Milwaukee, WI, USA
e-mail: jfranco@mcw.edu
https://t.me/medicina_free
290
prior to initiating interferon therapy. The ferritin is elevated in these diseases because
of ongoing inammation, and it is an acute phase reactant.
What if the iron saturation is 55%, ferritin is 750, and the hemochromatosis
genotype is C282Y homozygote in this patient with elevated liver enzymes.
Would you bother with a liver biopsy? What if the ferritin was above 1000,
would you want a biopsy then?
In my practice, any patient who is a C282Y homozygote with a ferritin >1000
and/or elevated liver enzymes should have a liver biopsy. If the liver enzymes were
normal and the ferritin was <1000, a liver biopsy would not be required. The 1000
cutoff relates to the fact that patients with hemochromatosis and a ferritin <1000 are
unlikely to have cirrhosis. The main reason for doing a liver biopsy would be to
document the presence of cirrhosis.
It is important to look at the age in patients with suspected hemochromatosis. If
this were a 20-year-old male, he would be unlikely to have cirrhosis. At 35, it is
much more likely.
When you start your phlebotomies, what would be your goal level for TS or
ferritin? What are the numbers you aim for?
I like to follow the ferritin and I aim to get it down below 100. Some people go
as low as 50. It takes you a while to get that low, even with frequent phlebotomies,
and then once you do, you go into a maintenance phase, where the patient gets phle-
botomies quarterly. Sometimes, you are limited by the hemoglobin in some patients
who are anemic for some other reason, and then you can't be as aggressive.
Is there any signicance to patients with NASH who have an elevated
ferritin?
Once again, chronic inammatory conditions seem to be the common thread
here. We tend to do a full chronic liver disease workup in our patients with sus-
pected NASH, even when we're close to a hundred percent condent of our diagno-
sis, so we are routinely getting iron studies.
We do nd that some patients with NASH have secondary iron overload, that's
how I describe it to patients. Secondary iron overload doesn't require phlebotomy.
However, is it possible to have NASH and hemochromatosis coexist? Absolutely.
You hate to miss a potentially treatable component, and so we always check ferritin
levels in these patients, and, once again, NASH doesn't really have a serologic test.
Even though I may be dealing with somebody with a BMI of 40 who’s diabetic and
has fatty liver on imaging, I still do the autoimmune markers, the viral markers, and
the iron studies.
J. Franco
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