Colonic disease in cirrhosis

GASTBOENTEBOLOGY

lSSo;99:195-199

Colonic Disease in Cirrhosis An Endoscopic Evaluation in 412 Patients MORDECHAI RABINOVITZ, ROBERT R. SCHADE, VINCENTS J. DINDZANS, STEVEN H. BELLE, DAVID H. VAN THIEL, and JUDITH S. GAVALER Division of Gastroenterology, Department of Medicine, University of Pittsburgh School of Medicine: and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania

Colonic disease is relatively uncommon in cirrhosis. To determine the prevalence of colonic lesions in cirrhosis of all types, cirrhotics evaluated for possible liver transplantation underwent combined pan up per endoscopy and colonoscopy. The patients were divided into two main groups, 248 with parenchymal liver disease (nonviral and viral) and 184 with cholestatic liver disease. The prevalence of the various colonic lesions identified was: polyps, 8.4%; nonspecific edema, 19.9%; inflammatory changes, 11.6%; hemorrhoids, 25.2%; and rectal varices, 3.6%. Normal findings were present in 42.4%. Except for an increased prevalence (P < 0.06) of edema and a reduced prevalence (P < 0.001) of inflammatory changes in the parenchymal liver disease group, the prevalence for all other lesions was similar in the two groups. Esophageal varices were present in most patients with hemorrhoids and in all with rectal varices. The degree of portal hypertension and/or disease severity was associated with hemorrhoids but not with rectal varices. The higher prevalence of inflammatory changes in the cholestatic group was because one fourth of this group had an inflammatory bowel disease.

U

pper gastrointestinal hemorrhage is one of the more important complications of cirrhosis and is responsible for much of the considerable morbidity and mortality that occurs in individuals having this condition (I]. Based upon available data, the colon would appear to be a rare cause of either morbidity or mortality in individuals with cirrhosis. The available data, however, are few and have never been either accrued in a prospective manner or examined in a cirrhotic population other than in patients with liver disease due to alcohol abuse. Worse yet, the data

available have been obtained predominantly from patients with overt hemorrhage in the lower gastrointestinal tract (2-4) or from autopsy studies (5). The two most common sites of lower gastrointestinal bleeding reported to occur in individuals with cirrhosis are hemorrhoids and rectal varices, which have a reported prevalence of 28%-63% and Q%-4470, respectively (6-9). Only one study has prospectively investigated the prevalence of these lesions in various subtypes of cirrhosis (8). However, this study concentrated only on the anorectal area, and, like most studies, almost half the patients included were alcoholics. The objectives of the present study were to define the prevalence of lower gastrointestinal abnormalities detected as a result of a prospective endoscopic screening of cirrhotic subjects being evaluated for liver transplantation, and to relate the occurrence of these lesions to the degree of portal hypertension and the severity of the underlying liver disease. Materials and Methods Subjects Four hundred twelve adult cirrhotic patients who were admitted to the Presbyterian University Hospital, Pittsburgh, between January 1985 and June 1987 for possible orthotopic liver transplantation (OLTx) and who gave a written informed consent for upper and lower gastrointestinal endoscopy were studied. Each underwent a complete endoscopic evaluation of the colon and upper gastrointesti-

Abbreviations used in this paper: IBD, inflammatory bowel disease; OLTx, orthotopic liver transplantation; PBC, primary biliary cirrhosis; RX, primary sclerosing chol@tis. 0 1990 by the American Gastroenterological Association

0016.5065/90/$3.00

196 RABINOVITZ ET AL.

GASTROENTEROLOGY

nal tract as part of a liver protocol that had been approved by the institutional review board for human studies at the University of Pittsburgh in November 1982. The diagnosis of cirrhosis in each case was confirmed by a combination of clinical, biochemical, radiological, and pathological methods. Patients with noncirrhotic liver disease (n = 153), primary and secondary hepatic malignancy (n = 212). fulminant hepatic failure (n = 142). and prior total colectomy [usually because of inflammatory bowel disease (IBD]] [n = 39) were excluded. In addition, patients who had an inadequate colonic preparation (n = 3481, those who refused the procedure (n = 458), and those who were admitted directly to the intensive care unit because they were acutely ill (n = 318) were excluded from study. The clinical severity of the liver disease in each case was determined using the Pugh modification of Child’s original classification (101.

Endoscopic

case. All subjects were examined under conscious sedation with IV midazolam and meperidine.

Definitions A colonic polyp was defined as a mass of tissue that protruded into the lumen of the bowel; nonspecific edema was defined as endoscopic swelling of the mucosa with a resultant disappearance of the normal submucosal vascular pattern; inflammatory changes were defined as erythema, granularity, and friability of the mucosa. Hemorrhoids were defined as large venous structures at or just proximal to the anus and were subdivided into external and internal hemorrhoids. They have quite different characteristics compared with rectal varices, which extend well into the rectum often to the first rectal valve. Hemorrhoids are limited to the perianal area.

Statistical

Procedures

Each patient underwent a full colonoscopy using a Olympus CFl TlOL endoscope. In addition, each subject underwent an upper gastrointestinal endoscopy using an Olympus GIF 2TlO endoscope to determine the size of any esophageal varices present. These endoscopic procedures were performed by gastroenterology fellows under direct supervision of one of three attending physicians (D.H.V.T., R.R.S., and V.J.D.] who confirmed the findings in each

Table 1. Characteristics

Analysis

Statistical analyses of the data were performed using x2 tests to assess differences in proportions, qualitative trends, and associations.

Results shown

The characteristics of the patients studied are in Table 1. Of the 57 subjects with PSC, 30 had

of the Patients Studied

Parenchymal liver disease [n = 248) Nonviral [n = 175) CAH (n = 61)

Age”

Sex

(Yrl

W/F I

43.6i 13.9

14/47

Alcoholic [n = 53)

46.1k 10.8

35/18

Cryptogenic [n = 361

45.7f 13.1

21/15

q-Antitrypsin

38.3 + 18.0

5/5

49.0 + 11.2

5/l

Wilson’s [n = 4)

27.0 zt 9.6

l/3

Other (n = 5)

47.4 + 18.4

2/3

Child’s classification [n) B

C

(3&o]

[45?%,

(Il.&]

(28::%,

(60%*,

(1&7~]

@-.~%I

$&]

A

(Z%]

(n = 10)

Hemochromatosis

(n = 6)

Viral (n = 73) CAH (type B) [n = 53)

45.0 k 10.9

42/11

43.0 * 11.0

5/15

(lk) 0 0 (2&j 0 0

(17.&o] CAH-NANB

[n = 20)

Cholestatic liver disease (n = 164) PBC [n = 107) PSC [n = 57)

Vol. 99, No. 1

48.5i 10.1 41.2+ 11.4

CAH, chronic active hepatitis; NANB, non-A, non-B. “Mean + SD.

(5&j (d%]

(4&, (83.i%]

(2&J

(502%)

(4&r?]

(a:%,

(22Y%]

(2&J

(4&/o)

(20%)

(52?%1

(60%,) (3571~)

6/101 33/24

(27%)

COLONOSCOPY IN CIRRHOTICS

July 1990

ulcerative colitis and 8 had Crohn’s disease. Nineteen showed no evidence of IBD. All subjects with IBD had been diagnosed as having their IBD before their evaluation in Pittsburgh. The results of the lower gastrointestinal endoscopic findings in the 412 cirrhotic subjects studied are shown in Table 2. Of the 35 polyps identified, 15 were hyperplastic and 20 were adenomatous (8 were tubular adenomas; 12, tubulovillous adenomas). Most of them were less than 1 cm long. The prevalence of the various lesions did not differ significantly between the parenchymal and cholestatic liver disease groups except for the prevalence of nonspecific edema that was significantly higher (24.2% vs. 13.4%; P < 0.05) and of inflammatory changes that were significantly less (6.4% vs. 19.5%; P < 0.001) in individuals with parenchymal liver disease compared with those with cholestatic liver disease. The prevalence of the various colonic lesions as well as of normal endoscopic findings did not differ significantly between the nonviral- and viral-liverdisease groups composing the parenchymal-liverdisease group. Similarly, the prevalence of these lesions did not differ significantly between the two groups of patients making up the cholestatic disease group, with one exception. Specifically, inflammatory changes of the colon were observed more often in patients with primary sclerosing cholangitis (PSC) than in those with primary biliary cirrhosis (PBC) (52.6% vs. 1.9%; P < 0.001) because of the frequent coexistence of ulcerative colitis and Crohn’s colitis in patients with PSC. In the parenchymal liver disease group, 94% of patients with hemorrhoids and 100% of patients with rectal varices had portal hypertension as evidenced by the presence of esophageal varices. In the cholestatic group, 85’70of patients with hemorrhoids and 100% of patients with rectal varices had portal hypertension as evidenced by the presence of esophageal varices. The distributions of hemorrhoids and rectal varices relative to grade 3 + to 4 + esophageal varices, ascites, and hepatic encephalopathy are shown in Table 3. Among patients with parenchymal liver disease, there was a significant association between the presence of hemorTable 2. Prevalence

of Various Colonoscopic

Parenchymal liver disease [n = 248) Cholestatic liver disease (n = 164) Total [n = 412)

197

rhoids and the occurrence of ascites. Among patients with cholestatic liver disease, the finding of hemorrhoids was associated significantly with the presence of both encephalopathy and large esophageal varices. In neither liver disease group was there a significant association between esophageal varices, ascites, or encephalopathy and rectal varices. The prevalence of hemorrhoids and rectal varices within categories based on the severity of the underlying liver disease is shown in Table 4. A significant trend for the presence of hemorrhoids with increasing degrees of disease severity could be shown in both liver disease groups (P < 0.005). No such trend with disease severity could be shown for rectal varices. Findings of routine hematologic and biochemical tests were similar in the two disease groups, except for the serum albumin level, which was greater in the patients with cholestatic liver disease compared with the patients with parenchymal liver disease [3.l k 0.6 g/dL vs. 2.7 + 0.6 g/dL (mean + SD), respectively; P < O.OOl]. Discussion Few data are available as to the prevalence of colonic disease in cirrhotics. In contrast to all prior available data that have been obtained from patients with rectal bleeding, the patients in the present study were studied electively while hemodynamically stable. The prevalence of the various colonic lesions ranged between 3.6% and 25.2% (Table 2). The data obtained show that there are no differences in the frequency of polyps, hemorrhoids, or rectal varices among patients with different types of liver disease (Table 2). The higher percentage of subjects with IBD in the cholestatic liver disease group may account for the higher prevalence of inflammatory changes and the greater prevalence of nonspecific colitis found in patients with PSC. The reason for the higher frequency of nonspecific colonic edema in the parenchyma1 liver disease group is probably the lower serum albumin level (P < 0.001) and the greater degree of disease severity found in this group. The prevalence of rectal varices and hemorrhoids

Findings

in Patients With Cirrhosis

Colonic polyps

Nonspecific edema

Inflammatory changes

[7z%,

(zz”,,

Hemorrhoids

Rectal varices

Normal endoscopy

(2&,

(4&l

(44.0%)

r25.& 104 (25.2%)

(3.0&

(40.%, 175 (42.5%)

109

(lOC%)

(A]

I*?%]

(l&

“Significantly greater than in cholestatic liver disease (P < 0.05). bSignificantly greater than in parenchymal liver disease (P < 0.001).

(t&c ) (l&,,

198 RABINOVITZ ET AL.

Table 3. The Association

GASTROENTEROLOGY Vol. 99, No. 1

of Hemorrhoids

and Rectal Varices With Esophageal

Varices, Ascites or Encephalopathy in

Parenchvmal and Cholestatic Liver Diseases Esophageal varices, grade 3+ to 4+ With Hemorrhoids Parenchymal liver disease Cholestatic liver disease Rectal varices Parenchymal liver disease Cholestatic liver disease

Ascites

Encephalopathy

Without

With

Without

29.8%

20.9%

29.5%”

15.9%

30.6%

20.4%

36.7‘La

19.2%

32.7%

22.3%

40.5%"

21.2%

5.2%

3.0%

1.6%

3.8%

4.2% 1.9%

3.7% 3.6%

4.5% 2.7%

3.6% 3.2%

With

Without

“P < 0.02.

in cirrhotic subjects is uncertain. Although Jacobs et al. (9) report 0% and 28% prevalences for rectal varices and hemorrhoids, respectively, Hosking et al. (8) report 44% and 63% prevalences of these two lesions. Others report rectal varices in 3% of cirrhotic patients (7) compared with 0.07% of the general population (5). In the present series of patients, the prevalences of rectal varices and hemorrhoids were 3.6% and 25.2%, respectively. No difference in the prevalence of these findings was evident among subgroups of cirrhosis (Table 2). The reason for the wide variation in the occurrence of rectal varices and hemorrhoids reported by various authors is not clear. It cannot be attributed to a difference in portal pressure, because more than 85% of the patients in this study had portal hypertension. Moreover, most of the patients in this study were Child’s class C. Consequently, rectal varices cannot be considered as a prognostic sign in patients with liver disease. The pathogenesis of hemorrhoids and/or rectal varices would seem to be dependent on the venous drainage of the rectum and anal canal. The inferior rectal vein drains the distal part of the anal canal, and the middle rectal vein drains the proximal anal canal and the lower rectum. Both veins are part of the systemic venous circulation. The superior rectal vein

Table 4. Prevalence of Hemorrhoids and Rectal Varices in Cirrhotic Patients in Relationship to Disease Severity” Child’s classification @I

Hemorrhoidsb (701

Parenchymal liver disease A .(39) B (72) C(137)

Cholestatic liver disease A (531 B (761 .c WI

Rectal varices [“lo1

17.9 20.8 29.2

2.5 2.7 5.1

9.4 32.8 34.2

3.7 1.3 5.7

.

“Classified per the Pugh modification of the Child’s criteria. bSignificant (P < 0.095)trend in both liver disease categories.

drains the submucosal layer of the lower rectum and the upper part of the anal canal into the inferior mesenteric vein. Thus, the portal and caval venous systems merge just proximal to the pectinate line. This site is often the site of hemorrhoids occurring as a result of portal hypertension. Varices occur where portosystemic anastomoses are present. They do not occur in areas that lack a potential site for portosystemic shunting except in patients who have had prior abdominal surgery. Indeed, varices have been reported in the colon (2-5,1113), the duodenum (14-16), the ileum (4), and the proximal jejunum (17). About 40%-50% of all colonic varices are localized to the rectum and/or sigmoid colon (3,4). Colonic varices are less common than esophageal varices. This difference exists because of the rich coronary-azygus anastomotic system, which is better developed than other potential shunt sites in the colon and rectum. In cases in which the potential shunts between the portal and systemic circulations are more developed, colonic varices can occur even in the absence of portal hypertension (2). A diversion of flow such as occurs in esophageal variceal sclerosis may enhance the development of rectal varices (1,18). Portal hypertension was found in all cases with rectal varices in this series. In two other series, portal

hypertension was found in three fourths of the cases with rectal varices (3.19). Although an association between hemorrhoids and portal hypertension was evident in both liver disease groups studied, no association between the presence or absence of rectal varices and the degree of portal hypertension could be shown (Table 3). In contrast, other investigators report that the prevalence of rectal varices increases with increasing severity of portal hypertension, but hemorrhoids seem to be independent of portal hypertension (8). A statistically significant qualitative trend between the degree of disease severity and the presence or absence of hemorrhoids was shown in both groups (P < 0.005). Such a trend did not exist, however, in regard to the presence of rectal varices (Table 4).

July 1990

Rectal varices and hemorrhoids can lead to serious hemorrhage. When such a hemorrhage occurs, it typically is less life threatening than esophageal hemorrhage. Nonetheless, fatal hemorrhage has been reported (20). In 85% of patients presenting with rectal bleeding, the source is found in the colon. In the other l5%, the source is the upper gastrointestinal tract (21). Therefore, upper gastrointestinal endoscopy should be performed in patients with massive rectal bleeding if the results of the colonoscopic examination is negative. In summary, the prevalence of various lower gastrointestinal potential bleeding lesions in patients with advanced liver disease is reported. Of particular interest is the observation that portal hypertension was evident in most patients with hemorrhoids and in all patients with rectal varices. An association between the presence of hemorrhoids and the degree of either portal hypertension or disease severity was shown. In contrast, no association between these two parameters and rectal varices was evident. References 1. Conn HO, Atterbury CE. Cirrhosis. In: Schiff L, Schiff ER, eds. Diseases of the liver. 6th ed. Philadelphia: Lippincott, 1987:783786. 2. Wilson SE, Stone RT, Christie JP, Passaro E. Massive lower gastrointestinal bleeding from intestinal varices. Arch Surg 1979;114:1158-1161. 3. Izsak EM, Finlay JM. Colonic varices. Three case reports and review of the literature. Am J Gastroenterol1980;73:131-136. 4. Hamlyn AN, Lunzer MR. Morris JS, Purim H, Dick R. Portal hypertension with varices in unusual sites. Lancet 1974;2:15311534. 5. Feldman M, Smith VM, Warner CG. Varices of the colon. Report of three cases. JAMA 1962;179:729-730. 6. O’Brien MJ. Gottlieb LS. The liver and biliary tract. In: Robins SL, Cotran RS, eds. Pathologic basis of disease. 2nd ed. Philadelphia: Saunders, 19791048. 7. Britton RC. Influence of portal-systemic collateral patterns and distribution of varices on results of surgical treatment of bleeding esophageal varices. Surgery 1963;53:567-574.

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IN CIRRHOTICS

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8. Hodgink SW, Smart HL, Johnson AG. Triger DR. Anorectal varices, haemorrhoids, and portal hypertension. Lancet 1989;l: 349-352. 9. Jacobs DM, Bubpick MP, Onstad GR, Hitchcook CR. The relationship of hemorrhoids to portal hypertension. Dis Colon Rectum 1980;23:567-569. 10. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the esophagus for bleeding esophageal varices. Br J Surg 1973;60:646-649. 11. Geboes K, Broeckaert L, Vantrappen G. Varices of the colon. Diagnosis by colonoscopy. Gastrointest Endosc 1975;22:43-45. 12. Lopata HI, Berlin L. Colon varices: a rare cause of lower gastrointestinal bleeding. Radiology 1966;87:1048-1050. 13. Wagner M, Kiselow MC, Keats WL, Jan ML. Varices of the colon. Arch Surg 1970;100:718-720. 14. Royal HD. Papanicolaou N, Bettmann M. McNeil BJ. Scintigraphic identification of bleeding duodenal varices. Am J Gastroenterol1980;74:173-175. 15. Perchik L, Max TC. Massive hemorrhage from varices of the duodenal loop in a cirrhotic patient. Radiology 1963;80:641-644. 16. Shearburn EW, Cooper DR. Duodenal varices treated by portocaval shunt. Arch Surg 1966;93:425-427, 17. Rosen H, Silen W, Simon M. Selective portal hypertension with isolated duodenojejunal varices. N Engl J Med 1967;277:11881190. 18. Gudjonsson H, Zeiler D, Gamelli R, Kaye MD. Colonic varices. Report of an unusual case diagnosed by radionuclide scanning with review of literature. Gastroenterology 1986;91:1543-1547. 19. Doberneck RC, Janovski NA. Isolated bleeding from colonic varices in patients with liver disease. Am J Dig Dis 1970;15:834841. 20. Waxman JS. Tarkin N, Dave P, Waxman M. Fatal hemorrhage from rectal varices. Report of two cases. Dis Colon Rectum 1984:27:749-750. 21. Levinson SL, Powell DW, Callahan T, Jones JD, Kinard HB. Jackson AL, Lapis JL, and Drossman DA. A current approach to rectal bleeding. J Clin Gastroenterol1981;3(SuppI 1):9-16.

Received February 22.1989. Accepted January 26,199O. Address requests for reprints to: David H. Van Thiel, M.D., 1000 J Scaife Hall, Division of Gastroenterology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261. This work was supported in part by grants from NIDDK (DK32556) and NIAAA (AA06601 and AAO6772).