Ulcerative colitis (UC) is an auto-immune irritable bowel disease (IBD) of the large or lower intestines, which is characterized by inflammation and ulceration of the intestine walls. It presents as bloody and frequent diarrhea, cramping, fatigue and anemia. Ulcerative colitis often precedes or accompanies PSC, so elevated liver enzymes can be associated with UC. In my case UC developed after transplant, which is not the usual pattern.
About ten months post transplant, and a couple of months after I had quit taking the cortico-steroid prednisolone, my liver enzymes slowly began to increase. I suspected IBD because I was experiencing frequent diarrhea, so I scheduled a colonoscopy. I also wanted to make sure that my suppressed immune system had not allowed any incipient colon cancer. It had been six years since I had undergone sigmoidoscopy, so I was overdue for a checkup. However, in early December 1996, a week before the scheduled colonoscopy my enzyme levels took a big jump, and an ultrasound was scheduled to check for acute rejection. The report indicated everything was normal, except for an enlarged spleen, which was no big deal, having existed that way for years:
"Real-time sonography within the abdomen reveals normal appearance of the transplant liver parenchyma. The hepatic and portal veins are all patent with normal direction of flow. The hepatic artery has a normal appearing waveform with a resistive index of 62 percent. No free fluid is identified in the upper abdomen. The spleen is enlarged measuring 16.7 cm in length. Both kidneys are within normal limits with no hydronephrosis."
9/27 11/04 12/06 12/27 01/22 01/29 02/07 02/14 02/21 02/28
alk phos 77 115 365* 658* 584* 402* 360* 347* 320* 262*
GGT 78 115* 392* 600* 727* 774* 853* 803* 668* 620*
SGOT 28 38 69* 59* 112* 48 63* 46 56* 55*
SGPT 34 50* 92* 70* 151* 129* 133* 97* 98* 86*
bili 1.0 1.2 1.1 1.2 0.9 0.6 0.9 0.6 0.7 0.7
chol 136 148 193 204* 207* 170 180 172 184 174
plat 112* 125* 141 153 140 ? 93* 107* 115* 100*
asterisk indicates out of normal range.
elevated alk phos and GGT indicate inflammation.
elevated SGOT and SGPT indicate ongoing liver damage.
The scheduled colonoscopy was cancelled in favor of a liver biopsy in the same time slot (Dec 11, my birthday), since biopsy is generally considered the definitive means for obtaining a reliable diagnosis of liver disease, and the ultrasound had not turned up anything. The pathologist's report looked pretty ominous:
"Sections reveal an adequate biopsy of liver containing approximately six portal tracts. Many of the tracts contain mild to moderate amounts of mixed inflammatory infiltrate including occasional eosinophils, neutrophils, and many lymphocytes. Some activated lymphocytes and plasma cells are also present. Many of the bile ducts show evidence of epithelial damage. In the lobules, a foci of lymphoid infiltrate with rare hepatocyte dropout is also noted. There is no significant evidence of piecemeal necrosis. The current findings suggest an ongoing bile duct damage due to smoldering cellular rejection. The possibility of a recurrent PSC should also be considered. No significant cholestasis is demonstrated. There is no evidence of onion-skinning or bile duct scars. Clinical correlation is needed."
So what does this biopsy report conclude? It doesn't quite commit to chronic rejection (which is not effectively treatable), but suggests that the original disease that destroyed the first liver (Primary Sclerosing Cholangitis) is attempting to make a comeback. However, it also suggests that further study is needed. So we scheduled a percutaneous trans-hepatic cholangiogram to see if there was a stricture in the liver ducts. This means that the radiologist pokes a hole in your side at about the same place a biopsy needle would be inserted, and tries not to hit too many veins before finding a bile duct. An ERCP cholangiogram, which is preferable, could not be performed because I no longer have a common duct to provide instrumentation access to the liver via the esophagus; I have a Roux-en-Y connection between the liver and the bowel instead. The x-rays revealed the following:
". . . inserted a 22 gauge Chiba needle into a right hepatic duct from a right intercostal approach. Nonionic contrast material was injected into the biliary system. Multiple spot films were obtained. The bile ducts are nondistended. No discrete strictures are identified. The Roux-en-Y choledochojejunostomy anastomosis is widely patent and allows for prompt drainage of bile into the intestinal tract."
So, everything looked fine here, too. Except my right side and shoulder hurt for several days as a result of some bleeding. The biopsy could have had the same complication, but fortunately it went perfectly. So we still were not really sure what was going on, but in the meantime began 300 mg of actigall twice daily in case of PSC, and increased the prograf from 2 to 3 mg twice daily in case of rejection. Now the diarrhea became severe, and there was a fair amount of blood with almost every evacuation. The abdominal pain was worse than simple gas, and I began to feel pretty lousy, especially since I wasn't sleeping well. At first I thought the elevated LFTs were just a reaction to a flu shot I had taken in November, especially when I developed flu symptoms in December, never having had a sniffle since the transplant. I was getting a bit frustrated by now. I had just not been prepared for any setbacks, and I guess I got a little cocky after doing so well post transplant. When you are sick for ten years, and then suddenly you feel well for ten months straight, it is quite a shock to feel chronically ill again. But in a couple of weeks you make the necessary emotional adjustments, your attitude improves, and life goes on smoothly.
So we rescheduled the colonoscopy and found ulcerative colitis in both the ascending and descending colon Jan 17, 1997. Fortunately it stopped short of Crohn's disease, which involves the upper intestine as well. So I stopped taking the actigall, and began 15 mg of prednisone twice daily and 400 mg of asacol or mesalamine (5-ASA designed to dissolve in the lower intestine) also twice daily. So I was back on the steroids. Maybe I came off them too soon, who knows? The good news is that my symptoms were relieved overnight. The 5-ASA takes a while to become effective, but the prednisone is effective immediately, removing a lot of water from the intestines and reducing inflammation. I noticed a big increase in urine output for the same daily fluid intake. Biopsy samples of the colon revealed no virus, parasites, bacterial disease, or cancer. A week later, however, the LFTs were worse than ever, so we scheduled another liver biopsy.
On January 29th, 1997 (my 25th wedding anniversary), we performed the second liver biopsy and took the usual blood samples. Improvement in the pathology report and the LFTs was evident. Very good news indeed. At this time, I decreased my steroid dose from 30 to 20 mg daily (taking it all in the morning so I could sleep better at night), and increased the 5-ASA dose from 800 to 1600 mg daily. Here is the biopsy report from the pathologist (there was not enough tissue for a detailed analysis, and it was from the edge of the liver):
"The biopsy shows mostly dense sclerotic liver capsular membrane and attached to this there are only one or two liver lobules. The portal tract demonstrated does not show any changes of duct and there is no significant inflammation. The lobule tissue that is present is also essentially unremarkable with no cholestasis or other changes. No rejection demonstrated."
On 2-4-97 I reduced the prograf from 6 mg to 4 mg daily, thus returning to my normal level. I had begun to experience the same visual artifacts that had accompanied the 6 mg prograf level months earlier. These artifacts appear as a bright white zig-zag shape that overlays normal vision for perhaps an hour at a time and interferes with eyesight. It is probably related to episodic high blood pressure that seems to be associated with higher prograf levels.
However, the jury is still out, since the latest LFT blood lab numbers are mostly out of the normal ranges. They began to improve dramatically shortly after the prednisone was started. After the prednisone was reduced from 20 to 15 mg daily beginning 2-15-97, the rate of improvement slowed down. In fact, the GGT and alkaline phosphatase began to increase again on 3-14-97, so we returned to 20 mg of prednisone on 3-17-97. There has been a significant loss of thigh muscle mass, which may be caused by the steroid, because no change in diet or exercise could explain it. My overall weight is the same as it was before the resumption of steroids, 164 pounds on a 5 foot 11 inch frame (38 inch chest, 32 inch waist). A small increase in midriff and some gynecomastia are also probably attributable to the prednisone. It is interesting to note that the elevated LFTs, although scary in themselves, do not seem to prevent me from working a normal day. The steroids have caused the typical facial puffiness and accelerated hair loss above the forehead. High blood pressure and acid stomach are also problems associated with the prednisolone, so I began taking Imuran (another immuno-suppressant) July 6th in the hope of eventually reducing the steroid to a very small amount. The Imuran can take a couple of months to become effective. I started at 50 mg daily Imuran, and went to 75 mg as the prednisolone was reduced to 5 mg by mid September 1997. Except for GGT, all LFTs gradually returned to normal. The GGT is falling, and I expect it will enter the normal range eventually.
ulcerati.htm 9-29-97