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\begin{document}

\title{Leukocyte chemotactic factor 2 related amyloidosis presented with severe
jaundice and hepatic encephalopathy.}



\author[1]{Hussam Almasri}%
\author[1]{Abdo Lutf}%
\author[1]{Almurtada Razok}%
\author[1]{Ahmed Badi}%
\author[1]{Muneera Almohannadi}%
\author[1]{Mahir  Petkar}%
\author[1]{Abdel-Naser Elzouki}%
\affil[1]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
One of the most recently identified types is Leukocyte chemotactic
factor 2 amyloidosis (LECT 2) which was found to be common in certain
ethnic backgrounds. It is suggested that the diagnosis of this type is
vital to prevent any therapy-related complications when it is
erroneously diagnosed as AL amyloidosis.%
\end{abstract}%



\sloppy


\textbf{Introduction:}

Leukocyte chemotactic factor 2 amyloidosis (ALect2) is a recently
recognized type of amyloidosis, common involvement of the kidneys with
infrequent proteinuria and slow progression, rare involvement of the
heart, relatively benign course and ethnic distribution are special
characteristics that differentiate Alect2 from other types of
amyloidosis (1).

Most cases of Alect2 were diagnosed in patients of Hispanic descent,
also it was described to be common in Punjabi and native American ethnic
groups (1,2).

Liver involvement is usually subclinical and likely to be underdiagnosed
in Alect2, more commonly seen in autopsy studies. The presentation of
hepatic disease is usually mild hepatocellular injury or isolated
elevation of alkaline phosphatase and rarely severe disease (1).

Diagnosis of this disorder usually is made with special stain done on
kidney or liver biopsies (3).

The management is usually supportive of the renal disease and there is
no definite treatment, however, it is important to identify this type of
amyloidosis to avoid unnecessary and sometimes toxic treatment if it is
erroneously diagnosed as AL or AA which are more common amyloidosis
subtypes (3).

We encountered a case of a Punjabi-descent man who presented with
jaundice and hepatic encephalopathy and was diagnosed with liver biopsy.

\textbf{Case presentation:}

A 53-year-old Indian gentleman with a history of hypothyroidism,
systemic hypertension, and diabetes mellitus type II complicated by
retinopathy and presumably nephropathy under conservative and follow-up
management, presented to our hospital with a chief complaint of
jaundice. The patient noticed yellowish discoloration of his eyes and
skin that gradually progressed over one week. Other complaints included
generalized, intermittent pruritus that started one month before and was
more noticeable in the palms and soles, in addition to passing
dark-colored urine.

There was no history of abdominal pain, nausea, vomiting, fever, weight
loss, or altered bowel habits. The patient is a never smoker with no
history of alcohol consumption or use of any kind of recreational drugs.

There was no history of recent travel or change in dietary habits. He
worked as a truck driver. Family history was negative. His home
medications were sodium bicarbonate, linagliptin, levothyroxine,
irbesartan, hydralazine, and furosemide.

Physical examination revealed generalized jaundice in the skin and
sclerae. No organomegaly.

Laboratory workup revealed direct hyperbilirubinemia and elevated
alkaline phosphatase and aminotransferases Table 1. The patient was
admitted as a case of painless jaundice for investigation. Ultrasound of
the abdomen and Magnetic resonance cholangiopancreatography (MRCP)
revealed cholecystolithiasis with unremarkable liver texture, no
intrahepatic and extrahepatic duct dilation.

The importance of identifying this disease is to avoid toxic
chemotherapy when it is diagnosed as AL amyloidosis. This case is to
raise awareness about this type of amyloidosis and the possibility of
severe hepatic disease presentation.

As the patient's liver and kidney function tests were gradually
worsening over one week, this prompted more invasive investigations.
Endoscopic ultrasound was done to rule out a pancreatic mass that was
not detected on MRCP and revealed a lymph node with a size of 18x15 mm
at the porta hepatis. Fine needle aspiration biopsy of the lymph node
showed reactive lymphocytosis otherwise not suggestive of a specific
pathology.

A percutaneous ultrasound-guided liver biopsy was done. Unfortunately,
the liver biopsy was complicated by acute hemoperitoneum which
necessitated admission into the medical intensive care unit and
initiation of hemodialysis due to acute worsening of his renal function.

The liver biopsy revealed prominent globular eosinophilic deposits, seen
in the portal tracts and the sinusoids. These deposits were positive for
Congo red staining, displaying apple-green birefringence. Background
cholestasis was noted. The appearances were in keeping with globular
hepatic amyloid, which is considered to be highly sensitive and specific
for LECT2 amyloidosis (4) Figure 1, 2.

After disclosure of the diagnosis to the patient and explanation of the
nature of the disease and its progressive course, he chose to go back to
his home country as he wanted to spend more time with his family. He was
discharged from our hospital after a four-week course in a stable
condition.

We were not able to follow the patient after his travel.

Table 1: Lab investigations:\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
At Admission\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
After two weeks\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
After four weeks (Time of discharge)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Reference Range\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Hb (gm/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8.3\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
10.6 (post transfusion)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
13.5-17.5\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Platelet (K/uL)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
304\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
315\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
241\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
150-400\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
INR\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.6\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.1 (post FFP administration)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.8-1.1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Total Bilirubin (umol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
116\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
357\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
650\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2-17\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Direct Bilirubin (umol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
110\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
325\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
400\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0-5.1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Alkaline phosphatase (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
687\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
561\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1644\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
40-130\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Gamma glutamyl transferase (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
478\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
398\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N/A\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
10-71\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
ALT (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
176\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
70\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
30\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0-40\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
AST (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
107\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
72\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
188\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0-37\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Lactic acid (mmol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.9\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N/A\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N/A\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.5-2.2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Albumin (gm/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
32\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
22\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
35-52\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Urea (mmol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
18.2\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
26.7\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
13\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.76-8.07\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Creatinine (umol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
269\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
372\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
226\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
70-115\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Discussion:

Amyloid is a term was first adopted in 1854 by Rudolph Virchow, first
described by a German botanist Mattias Schleiden in 1838 as a plant
starch, to refer to starch like bodies in the nervous system when
exposed to iodine (5,6).

Amyloidosis is a spectrum of disorders that share the pathology of
misfolded protein accumulation in various organs in the body originating
from diverse etiology. 30 types of protein were identified to cause
amyloid formation which causes a toxic effect in the tissues (3).

The most common type of these proteins in the developed countries is
derived from the immunoglobulin light chain namely AL, there is also the
amyloid protein that is derived from amyloid A namely AA, and amyloid
derived from transthyretin.

Another type, known to cause accumulation in patients with chronic
kidney disease, is derived from B2 microglobulin. A minor percentage of
amyloidosis cases are hereditary.

Large case series showed that the most common type of amyloidosis is AL
and AA in the US, but in the last few years, more case series emphasized
that Lect2 amyloidosis is more common in the Hispanic population.
Studies outside the US showed a common prevalence of Lect2 amyloidosis
in middle eastern, Egyptian, Sudanese, Pakistani-Kashmiri and
Punjabi-Indian, populations (2,3,7), our patient was Punjabi descent.

Lect2 is a chemotactic factor for neutrophils and it has a role in
chondrocytes and osteoblasts stimulation. It is mainly produced by the
liver and it is overexpressed in hepatocellular carcinoma and other
liver diseases, it was suggested that Lect2 is an acute phase reactant
produced as a response to hepatic inflammation and it plays a role in
hepatic regeneration (1,3).

Lect2 amyloidosis is not hereditary although some familial cases were
described, the gene of this protein is located on chromosome 5
(5q31.1-q32) but abnormality on chromosome 7 was also reported. All
cases in one case series by Rezk et al. except for one were found to be
homozygous for the G allele and the other case was heterozygous (1,7).

Said et al., reported a case series of 72 patients with renal Alect2
were mostly from the Hispanic population showed that nephrotic syndrome
and haematuria were rare, up to one-third of the patients developed
end-stage renal disease in the duration of 26 months due to glomerular
involvement (8).

Rezk et al. studied 24 patients with Lect2 amyloidosis and found that
hepatic involvement was not associated with significant liver function
derangement and none with cardiac involvement. This may be the reason
behind its benign course in most cases (1).

The diagnosis is usually made by kidney or liver biopsy.

There is no specific treatment for Lect2 amyloidosis, most of the time,
the treatment is supportive mainly directed for kidney disease (9).

The importance of identifying this disease is to avoid toxic
chemotherapy when it is diagnosed as AL amyloidosis. More studies are
needed to identify this subtype of amyloidosis and the possibility of
severe hepatic disease presentation.

Author Contributions:

\begin{enumerate}
\tightlist
\item
  Hussam Almasri: corresponding author, manuscript writing
\item
  Abdo Lutf: clinical follow up
\item
  Almurtada Razok: manuscript writing
\item
  Ahmed Badi: clinical supervision
\item
  Muneera Almohannadi: clinical supervision
\item
  Mahir Petkar: pathology input
\item
  Abdelnaser Elzouki: manuscript review
\end{enumerate}

References

1. Rezk T, Gilbertson JA, Rowczenio D, Bass P, Lachmann HJ, Wechalekar
AD, et al. Diagnosis, pathogenesis and outcome in leucocyte chemotactic
factor 2 (ALECT2) amyloidosis. Nephrol Dial Transplant. 2018 Feb
1;33(2):241--7.

2. Leukocyte cell-derived chemotaxin 2 (LECT2)-associated amyloidosis is
a frequent cause of hepatic amyloidosis in the United States - PubMed
{[}Internet{]}. {[}cited 2021 Sep 12{]}. Available from:
https://pubmed.ncbi.nlm.nih.gov/24415538/

3. Picken MM. Alect2 amyloidosis: primum non nocere (first, do no harm).
Kidney Int. 2014 Aug;86(2):229--32.

4. Chandan VS, Shah SS, Lam-Himlin DM, Petris GD, Mereuta OM, Dogan A,
et al. Globular hepatic amyloid is highly sensitive and specific for
LECT2 amyloidosis. Am J Surg Pathol. 2015 Apr;39(4):558--64.

5. Kyle RA. Amyloidosis: a convoluted story. Br J Haematol.
2001;114(3):529--38.

6. Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJM, et
al. Amyloid fibril protein nomenclature: 2012 recommendations from the
Nomenclature Committee of the International Society of Amyloidosis.
Amyloid Int J Exp Clin Investig Off J Int Soc Amyloidosis. 2012
Dec;19(4):167--70.

7. A C, P S, J C. Amyloidosis: The Newer Discovered ALECT2 Associated
with der7q add(7). J Clin Diagn Res JCDR. 2016 Sep 1;10(9):ED04--5.

8. Said SM, Sethi S, Valeri AM, Chang A, Nast CC, Krahl L, et al.
Characterization and outcomes of renal leukocyte chemotactic factor
2-associated amyloidosis. Kidney Int. 2014 Aug;86(2):370--7.

9. Jim\selectlanguage{ngerman}énez-Zepeda VH, Leung N. ALECT2 amyloidosis: a new type of
systemic amyloid highly prevalent in the Hispanic population. Rev
Investig Clin Organo Hosp Enfermedades Nutr. 2014 Jun;66(3):269--73.

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