Methods: Consecutive patients 0f Ulcerative colitis admitted to Gastroenterology Department SCB Medical College, Cuttack from 0ct 2013 to April 2015 were included in the study. Patients with history of liver diseases were excluded. All patients were subjected to clinical examination, liver function tests and ultrasonography for evaluation of hepatobiliary alterations.MRCP was performed in selected patients. Controls were recruited from healthy subjects (n=100)
Results: A total of 112 patients [73(65.1 %%) male; 39(34.9%) female] with ulcerative colitis were included. The mean age and BMI were 40.2±14.01years and 21.3±3.5kg/m2 respectively. Patients with mild, moderate and severe disease activity were 22(19.6%), 67(59.8%) and 23(20.5%) respectively. The median duration of illness was 24 months (IQR: 6.5-48). Extra intestinal manifestations were found in 68 patients(60.7%).40(35.7%) patients had arthralgia,6(5.3%) had arthritis, 13(11.6%) had episcleritis,2(1.7%) had stomatitis, 3(2.6%) had Erythematic Nodosum, 1(0.9%) had pyoderma Gangrenosum. 60 (53.8%) patients developed hepatobiliary alterations.2(1.7%) had jaundice, pruritus and clay colored stool in whom MRCP revealed primary sclerosing cholangitis. 22(19.6%) had hepatic steatosis, 42(37.5%) had asymptomatic transaminitis, 17(15.1%) had elevated alkaline phosphatase and 67(60%) had hypoalbuminmia.In control groups 17(17%) had hepatic steatosis,28(28%) had transaminitis, 8(8%) had elevated alkaline phosphatase.
Conclusion: The study revealed that approximately 61% of Ulcerative colitis patients had extra intestinal manifestations.Hepatobiliary alterations are the most common (53.5%) extra intestinal manifestations in Ulcerative colitis and asymptomatic transaminitis is the most common hepatobiliary alterations in the patients with Ulcerative colitis in the present study.
Key Words: Inflammatory bowel disease (IBD); Chronic ulcerative colitis (CUC); CRP(C-Reactive protein); Primary sclerosing cholangitis(PSC); Autoimmune hepatitis (AIH); ALT(Alanine transaminase) Autoimmunesclerosingcholangitis (ASC); ALP (Alkaline transferase); Gamma Glutamyl Transferase (GGT); pANCA(peri nuclear anti neutrophilic antibody); Ulcerative Colitis Disease Activity Index (UCDAI); EIM (Extraintestinal manifestations); Pyoderma Gangrenosum (PG); ErythemaNodosum (EN); ASA (Aminosalysilic acid);
In 80% cases EIM appear after the development of UC clinical symptoms and signs, in 10% they begin synchronically whereas in theremaining 10%, they precede clinical manifestations of the basic bowel disease. With their symptomatology, they can conceal the existing bowel disease and, at one point, become dominant disorder [9-11] in the last 50years; extensive literature has shown that the existence of one EIM increases the risk of the development of other EIM [12]. Although the prevalence of hepatobiliary disease in patients withIBD varies widely in different series from 2%-95%, clinically significant liver disease occurs in only 5%- 10% of patients [13]. Such a discrepancy between the various series occurs because of a number of factors which include (a) on aggressively diagnostic studies are pursued; (b) the number of patients included with mild, moderate and severe disease; (c) whether the disease was active or in remission and (d)the type of bowel involvement i.e., extensive or limited. There is no consistent temporal relationship between the onset of symptoms and hepatobiliary abnormalities [14]. Hepatobiliary involvement in ulcerative colitis is a spectrum that ranges from transient abnormalities in laboratory values (asymptomatictransaminitis), to liver diseases that can require transplantation. Hepatobiliarydiseases associated with IBD include Primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and autoimmune sclerosingcholangitis (ASC, an overlap syndrome in which features of both PSC and AIH are detected on laboratory, histological and cholangiographic investigations). Medications used in IBD treatment can also cause significant hepatotoxicity, and thus require close monitoring during their administration. Other hepatobiliary manifestations reported in the IBD literature include cholangiocarcinoma, cholelithiasis, hepatic abscess, hepatic or portal vein thrombosis, fatty liver, and amyloidosis. Because the etiologic and pathogenesis of UC and the associated Hepatobiliary complications remain elusive and speculative in the large part, and the hepatobiliary complications are on the rise[ 15-17]. It is important to find out if such increase rate of complications is seen inpatients of ulcerative colitis in our setup and to determine the features related or unrelated to the disease process leading to development of such complications. Again there is paucity of data available on prevalence of hepatobiliary manifestations in ulcerative colitis patients in Indian scenario. Hence the present study is aimed to evaluate the hepatobiliary alterations in ulcerative colitis patients referred to a tertiary care centre in Odisha.
Those who signed or gave informed consent were included in the study.Relevant clinical and demographic information in all ulcerative colitispatients was collected by questionnaire such as: Gender, age at diagnosis, familial aggregation, smoking, dietary habits, history of gluten Sensitivity, disease evolution, extension, extra intestinal manifestation, medical or surgical treatment and clinical course of disease. All patients included in the study had to undergo complete blood count, liver function test, ESR, CRP, serum protein, albumin globulin ratio, urea, and creatinine. Electrolytes stool routine, microscopic and occult blood test and chest x-ray. The prevalence of abnormal liver biochemistries (as defined by any elevation of serum AST, ALT and/or ALP above upper limit of normal i.e. AST>40 U/ml, ALT>40 U/ml, ALP> 360 U/ml) was determined amongst the study population. GGT was estimated in all patients having raised ALP to determine hepatic source of raised ALP and GGT value > ULN were taken as confirmatory. The Liver function Test (LFT) abnormalities we reconsidered transient if the liver enzymes returned to normal level within a period of 3 months during follow up. Patients, who had abnormal LFTs, repeat LFTs done every 3 months. If LFTs didn’t normalise and the values were persistently abnormal the highest values of LFTs were taken into consideration. All patients with abnormal liver biochemistry underwent abdominal USG examination and subsequently MRCP, particularly in patients having persistent elevation of ALP for more than 3 months. All patients with a persistent rise in transaminase activities and without a previously established hepatobiliary diagnosis were examined with conventional laboratory tests and questioned regarding intake of alcohol or drugs and exposure to other hepatotoxic agents. Laboratory tests including assessment of serum GGT, calcium. Serum Ceruloplasmin, ferritin, pANCA were assessed inselected cases. Immunofluorescence analyses of smooth muscle antinuclear and anti mitochondrial antibodies were made in selectedcases. Serological tests for Hepatitis B and Hepatitis C and HIV were done routinely. Abdominal ultrasonography was done in all patients. In those patients having inconclusive imaging findings and labratoryinvestigations, liver biopsy was planned after taking informed consent.The Montreal classification of disease extent of ulcerative colitis was used in all patients. The activity of disease was calculated using Ulcerative Colitis Disease Activity Index (UCDAI) (Southerland Index), which consists of four parameters such as stool frequency, rectal bleeding, mucosal appearance and physician´s rating of disease activity.
All patients were followed up 3 monthly. The clinical details including the complications, treatment were recorded as per the specified perform a prepared for the study. The treatment principles were generally homogenous therapy with combination of Mesalamine, Folic acid, Proton pump inhibitor and Prednisolone (for moderate to severe UC) for out-patients. Patients who had severe disease and required hospitalization were treated with parenteral steroids (Hydrocortisone succinate) initially along with antimicrobials – ciprofloxacin and metronidazole. In case of failure of medical therapy, the patients were evaluated for surgery. Patients were followed-up for their disease course and relapse of the disease, or complete remission or Steroid dependant or steroid resistant pattern were documented.
Complete remission was defined as clinical improvement with absence of symptoms of active disease (rectal bleeding, stool frequency)with endoscopic appearance of grade 0 or 1, [grade-0 normal mucosa, 1-granular oedematous mucosa with loss of vascular pattern, 2- Bleeding to light touch, 3-spontaneous bleeding]. Relapse was defined as worsening of symptoms recognized by the patients (rectal bleeding, loose stools and bowel frequency) with endoscopic appearance of active colitis (granularity, friability and/or spontaneous bleeding) in previously remitted patients. Patient with UC was defined as steroid dependant ifglucocorticoid can not be tapered to less than 10mg/day within 3 months of starting treatment without recurrent disease or if relapse occurs within3 months of stopping glucocorticoid therapy. Patients who do not have meaningful clinical response to glucocorticoid up to a dose of prednisolone 40-60 mg/day within 30 days of oral therapy or 7-10 days of IV therapy were said to have steroid resistant or refractory ulcerative colitis.
Parameters |
Minimum |
Maximum |
Mean |
Standard Deviation |
Age(in years) |
18 |
80 |
40.3 |
14.0 |
Duration of Ulcerative Colitis (in months) |
1 |
240 |
36.2 |
42.6 |
Onset to diagnosis of UC(months) |
1 |
48 |
7.5 |
8.5 |
Height(cm) |
132 |
178 |
156.9 |
7.6 |
Weight(kg) |
30 |
72 |
52.6 |
9.9 |
BMI(k g/m2) |
13 |
32 |
21.3 |
3.5 |
UCDAI |
2 |
12 |
7.9 |
2.2 |
Hb(%) |
6 |
13 |
10.1 |
1.6 |
TLC(/cumm) |
4000 |
17800 |
8068.8 |
2410.9 |
TPC(lakhs/cmm) |
1 |
4 |
2.3 |
0.5 |
ESR(mm/hr) |
10 |
146 |
40.9 |
27.5 |
CRP(u/1) |
3 |
86 |
27.1 |
20.2 |
Urea(mg/dl) |
10 |
34 |
19.7 |
5.2 |
Creatinine(mg/dl) |
0 |
1 |
0.7 |
0.2 |
Na+(MEq/L) |
126 |
143 |
134.9 |
4.2 |
K+(MEq/L) |
2 |
5 |
3.9 |
0.6 |
Ca++ (MEq/L) |
0 |
1 |
1.0 |
0.2 |
Mg++(MEq/L) |
0 |
1 |
1.0 |
0.2 |
FBS(mg/dl) |
65 |
174 |
104.4 |
15.9 |
Total Bilirubin(mg/dl) |
0 |
4 |
0.7 |
0.4 |
Direct Bilirubin(mg/dl) |
0 |
3 |
0.4 |
0.4 |
AST(IU/L) |
12 |
209 |
39.6 |
29.8 |
ALT(IU/L) |
10 |
128 |
36.3 |
24.7 |
Alkaline Phophatase (U/L) |
60 |
1500 |
240.6 |
170.1 |
GGT(U/L) |
15 |
85 |
68.3 |
16.7 |
Protein(gm/dl) |
4 |
8 |
6.2 |
0.9 |
Albumin(gm/dl) |
2 |
5 |
3.8 |
0.8 |
Globulin(gm/dl) |
1 |
4 |
2.4 |
0.8 |
Parameters |
Male (n=73) |
Female (n=39) |
p Value |
Age(in years) |
41.6 ± 14.3 |
37.8 ± 13.2 |
0.18 |
Height(in cm) |
158.79+6.650 |
153.56±8.071 |
0.00 |
Weight(in kg) |
55.05 ± 7.860 |
47.92 ± 11.588 |
0.00 |
BMI(kg/m2) |
21.84±2.943 |
20.21±4.299 |
0.02 |
Duration of UC (in months) |
Median=24 (IQR:6.5-48) |
Median=24 |
0.82* |
Onset of symptoms to diagnosis of UC interval(in months ) |
Median=6 (IQR:2-12) |
Median=4 (IQR:2-12) |
0.48* |
UCDAI |
7.82±2.071 |
7.82±2.311 |
0.34 |
Hb(gm %) |
10.05±1.463 |
10.10±1.779 |
0.87 |
TLC(no./cumm) |
7826.03±2112.859 |
8523.08±2862.596 |
0.15 |
TPC(lakhs/cumm) |
2.27±.453 |
2.41±.544 |
0.16 |
ESR(mm/hr) |
40.33±24.865 |
41.87±41.87 |
0.78 |
CRP(u/l) |
27.92±20.923 |
25.45±18.786 |
0.54 |
Urea(mg/dl) |
20.36±5.256 |
18.36±4.831 |
0.05 |
Creatinine(mg/dl) |
.72±.245 |
.67±.220 |
0.23 |
Na+(meq/l) |
135.00±3.933 |
134.92±4.625 |
0.93 |
K+ (meq/l) |
3.98±.564 |
3.67±.662 |
0.01 |
Ca++(meq/1) |
.97±.195 |
.98±.195 |
0.70 |
Mg++(meq/l) |
.96±.192 |
1.00±.184 |
0.31 |
FBS(mg/dl) |
106.21±15.734 |
101.08±15.895 |
0.10 |
Total Bilirubin(mg/dl) |
.75±.260 |
.71±.665 |
0.71 |
Direct Bilirubin(mg/dI) |
.34±.176 |
.39±.376 |
0.54 |
AST(u/l) |
37.70±27.543 |
43.10±33.775 |
0.36 |
ALT(u/l) |
38.23±24.671 |
32.69±24.626 |
0.26 |
ALP(u/l) |
228.41±111.048 |
263.49±245.656 |
0.30 |
GGT (u/l) |
67±17.3 |
44±19.2 |
0.31 |
Protein(gram/dl) |
6.25±.878 |
6.10±.968 |
0.40 |
Albumin(gram/d) |
3.80±.829 |
3.65±.743 |
0.35 |
Globulin(gram/dl) |
2.44±.733 |
2.41±.847 |
0.84 |
Rest P values were calculated by Independent Sample T test
Age(years) |
Study Group |
n |
Mean |
Std. Deviation |
P value |
Controls |
100 |
40.88 |
13.536 |
0.744 |
|
Cases |
1112 |
40.26 |
14.014 |
Cases(n=112) |
Controls(n=100) |
||
Religion |
Hindu |
108(96.4%) |
90(90%) |
Muslim |
4(3.6%) |
10(10%) |
|
Diet |
Vegetarian |
12(10.7%) |
19(19%) |
Non-vegetarian |
100(89.3%) |
81(81%) |
|
Smoking |
8(7.1%) |
20(20%) |
|
Gluten sensitivity |
8(7.1%) |
6(6%) |
Sex |
Total |
|||
Females |
Males |
|||
Disease Duration |
< 2 years |
25(22.3%) |
41(36.6%) |
66(58.9%) |
15-10 years |
5(4.4%) |
6(5.4%) |
11(9.8%) |
|
I> 10 years |
1(0.9%) |
4(3.5%) |
5(4.4%) |
|
Total |
39 |
73 |
112 |
Sex |
Total |
|||
Females |
Males |
|||
Severity of uc |
Mild |
6(5.4%) |
16(14.2%) |
22(19.6%) |
Moderate |
24(21.5%) |
43(38.3%) |
67(59.8%) |
|
Severe |
9(8%) |
14(12.5%) |
23(20.5%) |
|
Total |
39 |
73 |
112 |
Extension of uc |
|
sex |
Total |
|
Females |
Males |
|||
Proctitis |
5(4.46%) |
23(20.54%) |
28(25%) |
|
Left side colitis |
9(8.04%) |
19(16.96%) |
28(25%) |
|
Pancolitis |
25(22.4%) |
31(27.6%) |
56(50%) |
|
Total |
39 |
73 |
112 |
Extra intestinal manifestation of uc: n=68 (60.7%) |
Frequency |
Percent (%) |
Arthralgia |
40 |
35.7 |
Arthritis |
6 |
5.3 |
Episcleritis |
13 |
11.6 |
Stomatitis |
2 |
1.7 |
Skin Manifestations (PG-1.EN-3) |
4 |
3.5 |
HepatobiliaryAlterations |
60 |
53.5 |
ALP with MRCP showing alternate stricture and dilatation in both intrahepatic and extrahepatic biliary radicles with beaded appearance. During follow-up 35 (83.3%) of 42 patients had transient transaminitis i.e Transaminase levels normalised within 3 months whereas 7 (16.7%) of 42 had persistently abnormal transaminitis. 17patients had elevated ALP, out of which 14 (82.3%) had transient elevations where as the rest 3 patients (17.7%) had persistent elevations.
Hepatobiliary alterations |
Cases |
Controls |
P value |
PSC |
2 (1.7%) |
0 |
0.18 |
Transaminitis |
42(37.5%) |
28(28%) |
0.14 |
Increased .ALP |
17(15.1%) |
8(8%) |
0.11 |
Increased GGT |
17(15.1%) |
7(7%) |
0.10 |
Fatty liver |
22(19.6%) |
17(17%) |
0.49 |
Demographic factors |
Hepatobiliary alterations |
P Value |
|
Present(n=60) |
Absent(n=52) |
||
Age(in years) |
39.32±13.022 |
41.35±15.133 |
0.45 |
BMI(Kg/m2) |
21.14±3.696 |
21.42±3.388 |
0.67 |
Duration of UC (in months) |
34.45±34.313 |
38.29±50.850 |
0.64 |
Onset of symptoms to diagnosis of UC |
7.75±9.015 |
7.27±8.030 |
0.77 |
UCDAI |
8.28±2.076 |
7.60±2.207 |
0.09 |
Hb(Gm %) |
9.91±1.554 |
10.25±1.588 |
0.25 |
TLC(No./Cumm) |
8401.67±2480.260 |
7684.62±2291.877 |
0.12 |
TPC(lakhs/cumm) |
2.41±.517 |
2.22±.439 |
0.04 |
ESR(mm/hr) |
41.17±28.827 |
40.52±26.112 |
0.9 |
CRP(u/L) |
28.06±18.493 |
25.90±22.042 |
0.57 |
Urea(mg/dl) |
19.55±5.157 |
19.79±5.252 |
0.81 |
Creatinine(mg/dl) |
.72±.230 |
.69±.247 |
0.48 |
NA+(meq/l) |
134.45±3.933 |
135.58±4.381 |
0.15 |
K+( meq/l) |
3.82±.613 |
3.94±.617 |
0.29 |
Ca++( meq/l) |
.96±.180 |
.98±.223 |
0.69 |
Mg++( meq/l) |
.96±.180 |
.98±.201 |
0.57 |
FBS(mg/dl) |
107.10±13.951 |
101.33±17.535 |
0.05 |
Total Bilirubin(mg/dl |
.82±.535 |
.63±.274 |
0.02 |
Direct Bilirubin(mg/dl) |
.43±.370 |
.27±152 |
0.02 |
AST(U/L) |
52.32±35.826 |
24.89±6.305 |
0.00 |
ALT(U/L) |
49.38±27.365 |
21.20±5.137 |
0.00 |
ALP(U/L) |
297.10±209.290 |
175.46±65.054 |
0.00 |
Protein(mg/dl) |
6.06±.823 |
6.36±.984 |
0.09 |
Albumin (mg/dl) |
3.64±.750 |
3.88±.843 |
0.11 |
Globulin (mg/dl) |
2.38±.806 |
2.48±.732 |
0.47 |
Parameters |
OR (95% C1)4 |
P Value |
AOR (95% CI)** |
P Value |
Age |
0.99 |
0.444 |
0.99 |
0.499 |
Sex |
1.02 |
0.966 |
1.56 |
0.362 |
Severity of Ulcerative Colitis |
2.22 |
0.014 |
3.11 |
0.003 |
Duration of illness |
0.99 |
0.634 |
0.99 |
0.471 |
Extent of Colonic involvement |
0.90 |
0.648 |
0. 93 |
0.790 |
Course of disease |
0.59 |
0.036 |
0.63 |
0.129 |
Smoking |
0.67 |
0.601 |
1.09 |
0.917 |
Other extra-intestinal involvement |
1.17 |
0.347 |
0.92 |
0.661 |
Response to various treatments |
0.67 |
0.077 |
0.45 |
0.015 |
**Calculated by multivariate logistic regression analysis
Outcome |
Number |
Percentage (%) |
Mesalamine responders |
48 |
42 |
Mesalamine plus Steroid responders |
51 |
45.5 |
Steroid dependant |
4 |
3.5 |
Steroid resistant |
4 |
3.5 |
Surgery |
4 |
3.5 |
Death |
5 |
4.4 |
UC is slightly more common in men than in women, especially in the age groups after peak incidence (Shivananda et al. 1996). However epidemiological study conducted by Sivaram Gunisetty et al 2008 in south of India showed males and females were equally affected in UC which was in line with those reported by Langan et al [25] but study by Ajit Sood et al [21] in a North Indian hospital showed males were affected slightly more than females, the ratio being 1.04:1. Similarly the present study showed males were affected slightly more than females, the ratio being 1.8:1. In the present study 96.4% patients found to be Hindu, the rest3.6% patients are Muslims, but religion was not found to be risk factor for UC in present study (p=0.059). In the present study 89.3% patients took non-vegetarian diet and10.7% patients took vegetarian diet. However such dietary difference in study population was not found to be a predisposing factor for UC(P=0.088), similar to study conducted by Sivaram Gunisetty et al (2008). Active tobacco smoking has been recognised as one of the most prominent protective factors against UC and ex-smokers have an increased risk of UC [26] The present study found UC to be more prevalentamong non-smokers than smokers for development of UC (92.9% vs 7.1%, p= 0.005). These findings are well in line with the study done byLindberg E et al [27]. One of the reasons attributed to this may be nicotine which increases mucin synthesis in colon and rectum in UC patients and hence may impart protection to the epithelium. Many prospective studies have already demonstrated that patients with UC, who avoid gluten rich food products have less number of relapse per year, and exposure to gluten significantly increases the number of UC relapse, as demonstrated by Gillberg et al [28] However present study showed 7.1% patients (cases) were allergic to gluten rich diet compared to 6% healthy controls and this was found to be statistically insignificant (p=0.735). When these patients were followed with gluten restricted diet, the disease course was not influenced and duodenal biopsy and TTG results of such patients were inconclusive. In the present study 4.46% patients had family history of UC which is in accordance with the study by Peeters et al [29]. In the present study The average duration of symptoms prior to diagnosis of UC was 6 months (1-48 months, IQR: 2-12months) with average duration of illness 24 months (1-240 months, IQR:6-48 months),and 66 patients (58.9%) had duration of less than 2 years, 30 (26.7%)had 2-5 years, 11 (9.8%) had 5-10 years and 5(4.4%) had disease of more than 10 years. A study by Sood A et al [21] from a north Indian hospital showed the average duration of symptoms prior to hospital entry was 2.7 Years, with 48.34% patients had disease duration of less than 2 years, 25% had 2-5 years, 18.34% had 5-10 years and 8.34% had disease of more than 10 years. The delay in diagnosis in our patient may be due to lack of awareness about the disease amongst the patient as well as empirical treatment by primary care physician in the locality without prompt referral and few patients hesitate to attend hospitals for rectal bleeding due to social and cultural reasons. In the present study the disease activity was moderate in majority of patients (59.8%), severe in 20.5% patients with mean MAYO score 7.96±2.1, a pattern which is contrary to the belief that UC in India runs mild course [30]. This may reflect a changing pattern of the disease here. This pattern is quite similar to one reported by Sivaram Gunisetty et al in a epidemiological study in south of India showing 60.5% patients had moderate UC and 39.4% had severe UC with mean MAYO score 8.3±1.7. Half of the patients in the present study had pan colitis (50%), with left sided colitis in 25% and proctitis in 25% patients. This is in accordance to the Indian Task Force data, 18%, 38% and 42% of 724 patients with UC had Proctitis, Left side colitis and Pancolitis respectively. 29 Similarly Walker et a [31] reported that 63% of south Asian patients with UC are pancolitis compared with 42.5% of the indigenous European population (p< 0.0001). In the present study Extraintestinal manifestations were present in 68 (60.7%) UC patients. Various authors report different values for the occurrence of extra intestinal manifestations in UC making it is somewhat difficult to identify the most prevalent extra intestinal manifestations. The prevalence of these manifestations in the study of Das et al is 21% [32] Study by Ozdil et al 2004 showed approximately 42% of UC patients had extra intestinal manifestations. Gumaste et al analysed group of 1274 UC patients and diagnosed extra intestinal manifestations in 21 patients [33] It has been noted that extra intestinal manifestations prevalence is significantly lower in Asia and Africa, [34,35] in contrast, the present study showed higher prevalence. Whether different geographical area is having varying dietary, environmental and other factors have anything bearing on the development of extra intestinal manifestations still not known. In the present study 76% patients developed extraintestinal manifestations after diagnosis of UC, whereas 15% developed synchronically and 9% before diagnosis of UC, similar to study by Biljana Radovanovic- Dinic et al which showed 77% patients developed extraintestinal manifestations after diagnosis of UC where as 9% synchronically and 14% before diagnosis of UC. In the present study Peripheral arthritis/arthralgia is the second (41%) most common extra intestinal manifestations next to Hepatobiliaryalterations (53.5%). However in the study by Tromm et al arthritis was the most frequent (28.8%) associated extraintestinal manifestations [36]. In the present study the clinical course of peripheral arthritis paralleled UC activity, as effective therapy of UC was associated with the remission of both UC and peripheral arthritis. The present study showed ocular manifestation in the form of Episcleritis in 11.6% patients, which is similar to a study by Billsonet et al 1997 (9.7%). In the present study ocular manifestations followed UC activity and disappeared during UC remission. Therefore in view of significant prevalence of changes in Eyes in this study as well as in other studies, regular ophthalmic examinations in all UC patients [37]. Should be mandatory. In the present study skin manifestations were present in 4 (3.5%) patients in the form of Pyoderma Gangrenosum (PG) in 1 (0.9%) and ErythemaNodosum (EN) in 3(2.6%) patients. This was in accordance with the study by Aresia and Garcia Esilva 1987, Evan and Pardi 2007which showed EN present in 3% patients and PG in 1.4-5% patients of UC. However in contrast to the data from literature, in the present study both EN and PG correlated with UC activity as both the skin lesions disappeared within one month of treatment of UC patients with remission. Although the prevalence of Hepatobiliary manifestations in patients with IBD varies widely in different series from 2-95%, clinically significant liver disease occurs in only 5-10% of patients. In the presentstudy 53.5% patients developed hepatobiliary alterations, signifying that they are the most common extraintestinal manifestations. In the present study hepatobiliary alterations were found to be more prevalent in patients with pancolitis than distal colitis (25.8% vs14.28%), although the difference did not reach statistical significance. (p=0.89) Majority of patients with Hepatobiliary manifestations in present study had moderate severe UC (46.4% vs 7.1%, p=0.03.In the present study 1.7% patients developed Primary sclerosingcholangitis (PSC). This finding is almost similar to observation in a study by Olson et al where out of 1500 patients of ulcerative colitis 3.7% have developed PSC[38] The outcome of PSC did not relate at all to the activity and clinical course of UC in either present study or others.238. 19.6% patients in the study had fatty liver, contrary to controls having 17% fatty liver, which was not statistically significant (p=0.486). Bargiggia et al evaluated the prevalence of fatty liver in large IBD population and found these abnormalities > 35% of UC patients, a higher prevalence than among healthy controls. The prevalence of abnormal Liver Function Test (LFT) in the present study cohort was asymptomatic transaminitis in 37.5% of cases and 28% in controls(p=0.142), Elevation of Alkaline Phosphatase (ALP)was noted in 15.1% of UC cases and 8% in control(p=0.11), Elevated Gamma Glutamyl Transferase (GGT) in15.1% of cases & 7% in controls (p = 0.10). Similarly the prevalence of abnormal LFTs in study by Maria Cappello et al was 20.9% in asymptomatic patients. An epidemiologic study conducted in the country of Stockholm enrolling more than 1000UC patients, followed for15years reported an 11% prevalence of altered LFT, Gisbert et al [39] observed LFTs abnormalities in 15% IBD patients at sometime during five years study. In the present study83.3%patients had transient transaminitis and 16.7% had persistently abnormaltransaminitis, similarly 82.3% had transient elevated ALP and 17.7% had persistently elevated ALP. These findings were similar to a large Swedish follow up study[40] Similarly persistent LFTs alterations were found by Schrum pf et al in 3-15% of IBD patients[41] The cause of transienttransaminitis and elevated ALP may be related to disease activity, use of antibiotics, corticosteroids and persistent transaminitis may be related to fatty liver, disease activity, use of ASA. The cause of persistent elevated ALP in present study mostly related to coexistence of PSC and Fatty Liver. On univariate analysis risk factors associated with hepatobiliaryalterations were severity of ulcerative colitis, and course of disease, where as in Multivariate analysis risk factors were severity of ulcerative colitis and response to various treatments like mesalamine, corticosteroid and Azathioprine. Age, sex, duration of illness, colonic extension, smoking and other extra intestinal involvement were not associated as risk factors for hepatobiliary alterations in patients with ulcerative colitis in the present study. In the present study the course of the disease was characterised by relapse and remission in majority (75.8%) with only 21.4% pursuing a chronic continuous course, similar to study by Ajit Sood et a[21] showing relapses ad remission in 90% with only10% had chronic continuous course. In the present study it was found that, drug compliance was not strictly adhered, as patients had a tendency to omit or reduce drugs on their own once the symptomatic recovery occurred, indicating that proper awareness of the disease is necessary to ensure compliance. In the present study 46.4% patients suffered more than two relapses per year, similar to study by Ajit Sood et al[21] showing 45% relapses within one year. Various factors incriminated by patients as precipitating cause for relapses such as stoppage of drugs by self, emotional disturbances like family feuds, death of family members, academic Examinations, dietary factors, infections and use of other drugs. The complication rate in the present study was less (5.2%) as compared to reports 17.5% in other Indian study by Ajit Sood etal [21] and31-40% in western countries. 243 2.6% patients developed Toxic Megacolon, 0.9% developed perforation, 1.7% developed dyselectrolytemia, no patients found to have carcinoma colon. In the present study majority patients responded to Mesalamine (42%) and Mesalamine plus corticosteroid (45.5%). The clinical response to glucocorticoid was very dramatic at first use of drug while patients who had chronic active disease showed less prompt response, so that in the present study 3.5% patients became steroid dependant and they were maintained on Azathioprine (AZA), while 3.5% patients became steroid refractory and underwent proctocolectomy as they could not afford for Biological like Infliximab. During study period 5 patients (4.46%) died out of which 3 patients had toxic megacolon and 2 patients presented with fulminant colitis.
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