WEBVTT 00:00.000 --> 00:30.000 position:50% align:top line:0% *This machine-generated transcript may have errors. If remediation or a manually-generated transcript is needed, please contact NLM Support at https://support.nlm.nih.gov.* 00:00.000 --> 00:30.000 *This machine-generated transcript may have errors. If remediation or a manually-generated transcript is needed, please contact NLM Support at https://support.nlm.nih.gov.* 00:00.140 --> 00:00.350 Mhm. 00:01.140 --> 00:01.860 Well 00:13.440 --> 00:16.370 a United States Army Medical Department continuing 00:16.370 --> 00:18.260 education program, 00:18.940 --> 00:20.220 liver dysfunction, 00:20.230 --> 00:21.660 post transplantation 00:23.040 --> 00:23.770 with William A. 00:23.770 --> 00:24.230 Briggs, 00:24.230 --> 00:25.070 Lieutenant Colonel, 00:25.070 --> 00:27.700 US Army Medical Corps Chief nephrology 00:27.700 --> 00:30.220 service walter reed Army Medical center Washington, 00:30.220 --> 00:30.430 D. 00:30.430 --> 00:30.870 C. 00:32.340 --> 00:34.910 Now the insidious but 00:34.910 --> 00:37.790 progressive or abrupt and 00:37.790 --> 00:40.620 striking elevations of serum liver 00:40.620 --> 00:41.390 enzymes. 00:42.040 --> 00:44.260 With or without hyperbole room anemia 00:44.940 --> 00:47.710 or with or without clinical symptoms 00:48.340 --> 00:50.910 occur with annoying frequency 00:51.230 --> 00:53.890 In this particular population of patients 00:55.740 --> 00:58.390 and in the walter reed experience 00:59.000 --> 01:01.500 slightly more than a half of patients 01:02.040 --> 01:04.890 have demonstrated elevations of serum serum 01:04.900 --> 01:07.700 trans am in its and lactic di hydrogen is 01:08.640 --> 01:11.250 enzyme levels at some time in their course, 01:11.640 --> 01:14.410 which were not readily attributed to extra hepatic 01:14.420 --> 01:15.150 disease. 01:16.900 --> 01:19.150 This problem is particularly troublesome 01:19.740 --> 01:22.270 because in addition to the need to sort out the 01:22.270 --> 01:23.720 differential diagnosis, 01:24.220 --> 01:26.860 a number of other considerations arise. 01:28.040 --> 01:28.850 For example, 01:29.440 --> 01:31.110 is the patient infectious 01:32.640 --> 01:35.250 and is the handling of the patient's blood 01:35.940 --> 01:38.310 hazardous to the staff and other 01:38.310 --> 01:40.260 laboratory personnel of the hospital? 01:42.940 --> 01:45.360 Will alterations in drug therapy 01:45.940 --> 01:46.960 be necessary? 01:48.840 --> 01:51.670 And what effects will this development or its 01:51.670 --> 01:54.590 management have on the overall course of 01:54.590 --> 01:55.160 the patient? 01:58.440 --> 01:58.650 Well, 01:58.650 --> 02:01.460 like any problem in clinical medicine, 02:01.470 --> 02:04.430 we have to face problem of 02:04.430 --> 02:06.890 liver dysfunction with the differential 02:06.890 --> 02:07.710 diagnosis. 02:09.340 --> 02:10.360 I could have the first lot. 02:14.240 --> 02:15.070 First of all, 02:15.070 --> 02:17.750 it's necessary to consider 02:17.750 --> 02:20.360 and exclude or rule in 02:21.340 --> 02:23.650 potential sources of confusion 02:24.940 --> 02:27.210 relevant to the interpretation of 02:27.590 --> 02:29.230 abnormal elevations and S. 02:29.230 --> 02:29.420 G. 02:29.420 --> 02:29.540 O. 02:29.540 --> 02:29.940 T. 02:29.940 --> 02:30.450 Or even S. 02:30.450 --> 02:31.360 GPT. 02:31.740 --> 02:34.480 Or the LDH is so enzymes, 02:36.340 --> 02:39.260 muscle necrosis from recent surgery 02:40.040 --> 02:41.870 from intra muscular injections, 02:43.440 --> 02:45.560 our potential source of confusion 02:47.040 --> 02:49.890 resolving large hematomas as red cells 02:49.890 --> 02:52.790 break down release can release 02:52.790 --> 02:54.660 striking amounts of 02:55.140 --> 02:55.950 enzymes, 02:57.740 --> 02:59.070 pulmonary disease. 02:59.320 --> 03:02.160 Either pneumonia or infarction 03:03.040 --> 03:05.990 can cause elevations in enzymes, 03:05.990 --> 03:08.420 which might be interpreted as coming from 03:08.650 --> 03:11.640 liver renal infarction 03:11.650 --> 03:14.060 related to severe 03:14.070 --> 03:16.790 rejection or cortical necrosis 03:17.340 --> 03:19.650 may cause elevations in serum enzyme. 03:21.840 --> 03:23.360 And then interestingly enough, 03:23.940 --> 03:26.550 there are a number of drugs which have been reported 03:26.550 --> 03:29.460 to interfere with the cholera 03:29.460 --> 03:32.430 metric essay for Trans AM 03:32.430 --> 03:32.980 in Aces. 03:34.340 --> 03:37.250 And looking over the list drugs which 03:37.740 --> 03:39.970 have been reported to do this and which might 03:39.980 --> 03:42.620 be given to transplant 03:42.620 --> 03:44.850 recipients include 03:45.240 --> 03:46.350 Aretha mason, 03:47.440 --> 03:47.890 hydra, 03:47.890 --> 03:49.740 lysine ison, 03:49.740 --> 03:52.460 is it alpha methyl dopa? 03:53.240 --> 03:55.830 So for fires all and tom you know, 03:55.830 --> 03:56.160 mine. 03:57.940 --> 04:00.790 So the implication is to not only in terms of 04:00.790 --> 04:03.100 considering hepatitis cellular 04:03.100 --> 04:06.000 disease or hypersensitivity liver 04:06.000 --> 04:06.710 disease, 04:07.340 --> 04:09.560 one should look at the drugs of the patients on 04:10.240 --> 04:13.210 and then find out from the clinical pathologist running the 04:13.210 --> 04:16.140 laboratory where the particular essay or 04:16.140 --> 04:19.030 the techniques for the essay would allow 04:19.040 --> 04:21.280 a possible interference with S. 04:21.280 --> 04:21.460 A. 04:24.640 --> 04:25.800 Congestive heart failure, 04:25.800 --> 04:28.320 obviously with right sided failure, 04:28.320 --> 04:30.990 and the paddock congestion can 04:30.990 --> 04:33.740 result in striking liver function 04:33.740 --> 04:34.560 abnormalities. 04:35.640 --> 04:36.190 In addition, 04:36.190 --> 04:38.910 any patient who has recently sustained shock 04:38.910 --> 04:41.790 syndrome for many cause may 04:41.790 --> 04:44.450 have had a period of inadequate hepatic profusion 04:45.040 --> 04:45.670 in the schema, 04:45.670 --> 04:46.830 ca paddock necrosis. 04:54.240 --> 04:57.070 Now more commonly is the 04:57.080 --> 05:00.060 problem of infection 05:01.440 --> 05:02.080 Again, 05:02.080 --> 05:03.750 patients with factory MIA, 05:04.340 --> 05:06.830 predominantly gram negative bacteria, 05:06.830 --> 05:07.020 MIA, 05:07.020 --> 05:08.660 but also indo toxemia. 05:09.240 --> 05:11.250 In some cases with gram positive, 05:11.840 --> 05:13.040 back to re miA, 05:13.420 --> 05:15.560 one can get Apache non specific 05:16.440 --> 05:18.710 hepatitis cellular necrosis or 05:18.710 --> 05:21.560 infiltration with abnormal liver function. 05:21.940 --> 05:22.450 Test 05:24.820 --> 05:27.050 much more commonly considered is that 05:27.610 --> 05:30.250 infection related to 05:30.740 --> 05:33.430 viral hepatitis and its 05:33.440 --> 05:35.030 differential diagnosis. 05:38.640 --> 05:38.850 Now, 05:38.850 --> 05:39.660 first of all, 05:41.040 --> 05:43.750 a lot of attention has been given to the 05:43.750 --> 05:46.290 high incidence of cytomegalovirus 05:46.290 --> 05:48.940 infection and immuno suppressed patients. 05:48.940 --> 05:49.580 In general, 05:49.580 --> 05:52.190 patients with cancers and renal 05:52.200 --> 05:53.660 transplant patients 05:57.240 --> 05:59.820 in the walter reed experience 06:01.230 --> 06:03.710 ed Morrison of the infectious disease Service 06:05.140 --> 06:07.750 has determined that almost 1/2 06:08.340 --> 06:11.200 of the patients Show a 06:11.200 --> 06:13.700 four fold or greater rise in 06:13.700 --> 06:15.010 complement fixing 06:16.450 --> 06:17.340 anti cmv. 06:17.340 --> 06:19.640 E antibody tighter following 06:19.640 --> 06:20.560 transplantation. 06:21.940 --> 06:24.460 This including rises in 06:24.840 --> 06:25.920 antibody tigers, 06:25.920 --> 06:28.130 on the basis of both primary 06:28.130 --> 06:31.060 responses and secondary responses. 06:31.840 --> 06:34.090 A fair proportion of patients come to 06:34.090 --> 06:36.890 transplantation already with greater 06:36.890 --> 06:39.040 than 1-4 antibiotics. 06:39.040 --> 06:40.600 Fighters against c. 06:40.600 --> 06:40.730 m. 06:40.730 --> 06:41.160 v. 06:43.440 --> 06:46.250 And I mentioned earlier that slightly more than 06:46.250 --> 06:48.360 half of the patients at some point in time 06:48.740 --> 06:51.730 also have abnormalities and liver 06:51.730 --> 06:52.460 enzymes. 06:54.540 --> 06:55.160 However, 06:56.420 --> 06:58.960 in only approximately half of those 06:58.960 --> 07:01.830 patients manifesting liver 07:01.830 --> 07:04.720 function abnormalities has there 07:04.720 --> 07:07.700 been a temporal relationship between 07:07.700 --> 07:08.860 the liver dysfunction, 07:09.440 --> 07:12.090 often with clinical symptoms 07:12.920 --> 07:13.870 and C. 07:13.870 --> 07:14.030 M. 07:14.030 --> 07:14.310 V. 07:14.310 --> 07:14.410 C. 07:14.410 --> 07:17.050 Zero conversion to reasonably 07:17.050 --> 07:19.490 implicate that virus in the 07:19.490 --> 07:21.870 pathogenesis of the hepatitis. 07:25.540 --> 07:25.950 Uh huh. 07:27.640 --> 07:29.940 So in addition to cytomegalovirus, 07:29.940 --> 07:31.810 which obviously is a common cause, 07:32.440 --> 07:34.920 one must still consider other viral 07:35.250 --> 07:35.860 agents. 07:37.890 --> 07:40.450 Hepatitis A is unless one 07:40.450 --> 07:42.860 has a family source of 07:42.860 --> 07:45.590 infection or some point source 07:45.850 --> 07:47.760 of infection to determine 07:48.340 --> 07:49.660 incubation time. 07:50.840 --> 07:51.600 We, 07:51.650 --> 07:54.460 at this point in time do not have access to 07:55.340 --> 07:58.250 laboratory assays which will permit 07:58.740 --> 08:01.350 the detection of antigens associated with 08:01.840 --> 08:04.550 uh hepatitis A virus. 08:05.540 --> 08:08.420 But certainly it has to be retained in the differential 08:08.420 --> 08:09.220 diagnosis, 08:09.640 --> 08:12.460 particularly in patients who are at 08:12.460 --> 08:14.730 a negative or a G. 08:14.740 --> 08:15.060 B. 08:15.060 --> 08:17.950 Negative without evidence 08:17.960 --> 08:18.380 of C. 08:18.380 --> 08:18.560 M. 08:18.560 --> 08:19.070 V. 08:19.450 --> 08:20.460 Serial conversion. 08:23.440 --> 08:26.390 Obviously hepatitis B is an 08:26.390 --> 08:29.260 agent which requires serious consideration 08:29.740 --> 08:31.620 in this population of patients 08:33.140 --> 08:34.910 and in the walter reed experience, 08:34.910 --> 08:37.620 there have been six patients showing Ciro 08:37.620 --> 08:40.360 conversion uh or 08:41.000 --> 08:42.950 serum manifestation of 08:44.140 --> 08:44.680 A G. 08:44.680 --> 08:45.290 B. 08:45.590 --> 08:46.360 In the serum, 08:47.240 --> 08:49.840 some sub clinically others with 08:49.840 --> 08:51.200 evidence of hepatitis. 08:53.540 --> 08:56.460 Now the information is incomplete at 08:56.470 --> 08:59.100 this time on determining how many 08:59.100 --> 09:01.460 patients have evidence of 09:02.040 --> 09:04.520 zero conversion for 09:04.650 --> 09:06.150 anti AGB, 09:06.740 --> 09:09.160 evidence for the development of antibody against 09:09.540 --> 09:12.340 ah hepatitis virus 09:12.350 --> 09:12.750 B. 09:13.840 --> 09:15.470 When this information is available, 09:15.470 --> 09:18.090 perhaps a greater proportion of those patients 09:18.540 --> 09:19.530 with hepatitis, 09:19.540 --> 09:20.490 but without C. 09:20.490 --> 09:20.640 M. 09:20.640 --> 09:20.830 V. 09:20.830 --> 09:23.680 Zero conversion will be determined 09:23.940 --> 09:26.660 to have sustained infection with 09:26.670 --> 09:27.960 hepatitis B. 09:30.840 --> 09:33.640 There's another hepatitis viral agent which has 09:33.640 --> 09:36.610 been proposed and that's Hepatitis 09:37.040 --> 09:38.360 C virus. 09:39.340 --> 09:41.820 This was proposed mainly by Prince 09:42.840 --> 09:45.660 who followed patients receiving transfusions 09:46.840 --> 09:49.340 and determine among those patients 09:49.340 --> 09:51.750 with long incubation 09:52.140 --> 09:52.950 hepatitis 09:55.010 --> 09:57.630 that only approximately half of those 09:57.630 --> 10:00.120 patients had evidence 10:00.740 --> 10:03.560 for the development or infection with hepatitis 10:03.570 --> 10:04.550 B virus. 10:05.740 --> 10:07.960 In their examination of that included 10:08.640 --> 10:11.250 follow serial examinations for 10:12.130 --> 10:14.470 energy and be serial 10:14.470 --> 10:15.960 examinations for 10:16.740 --> 10:18.380 anti H. 10:18.380 --> 10:18.990 A. 10:19.200 --> 10:19.950 Antibody. 10:20.840 --> 10:23.810 And in addition in the negative patients also 10:23.810 --> 10:26.550 testing for antibody against 10:27.240 --> 10:29.700 core an urgent of hepatitis 10:30.140 --> 10:31.010 the virus. 10:34.240 --> 10:37.080 The incubation periods from the point 10:37.080 --> 10:39.400 source which was a transfusion 10:40.240 --> 10:42.060 were entirely 10:42.600 --> 10:45.420 equivalent to the incubation period 10:45.420 --> 10:48.350 seen in patients with and 10:48.410 --> 10:50.960 Hepatitis B infection. 10:51.340 --> 10:53.840 And beyond the point considered 10:53.840 --> 10:56.160 reasonable for hepatitis A. 10:57.510 --> 11:00.190 These patients were also examined for evidence of serial 11:00.190 --> 11:02.040 conversion for antibodies against C. 11:02.040 --> 11:02.180 M. 11:02.180 --> 11:02.660 V. 11:04.740 --> 11:07.490 And what the data showed 11:07.490 --> 11:10.480 was that there wasn't any difference in the rate 11:10.490 --> 11:12.060 of conversion. 11:12.440 --> 11:12.820 Again, 11:12.820 --> 11:13.070 C. 11:13.070 --> 11:13.210 M. 11:13.210 --> 11:15.750 V between uh 11:16.140 --> 11:19.120 different groups that is those not developing 11:19.120 --> 11:19.800 hepatitis, 11:20.170 --> 11:23.060 those developing long incubation hepatitis with 11:23.060 --> 11:25.660 evidence for a hepatitis B 11:25.670 --> 11:27.850 infection and then the others 11:27.860 --> 11:30.260 uh KGB negative, 11:30.270 --> 11:32.810 long incubation hepatitis. 11:33.640 --> 11:35.160 So on the basis of that, 11:36.140 --> 11:38.750 his group felt that 11:39.140 --> 11:42.050 this other group of patients could not be explained 11:42.640 --> 11:45.270 on the basis of cytomegalovirus 11:45.280 --> 11:46.070 hepatitis. 11:48.040 --> 11:50.860 That probably is open to argue, 11:53.140 --> 11:55.690 but these are the major viral 11:56.040 --> 11:58.750 agents considered at this point in time. 11:59.540 --> 12:01.760 Hepatitis and renal transplant patients, 12:02.340 --> 12:02.520 R. 12:02.520 --> 12:02.790 C. 12:02.790 --> 12:02.940 M. 12:02.940 --> 12:03.360 V. 12:03.940 --> 12:05.050 Hepatitis B. 12:05.440 --> 12:08.050 And possibly this other very interesting group 12:08.540 --> 12:11.260 who may be infected with hepatitis C. 12:13.740 --> 12:16.740 Not to be overlooked is the possibility that Epstein 12:16.740 --> 12:19.700 Barr virus may be involved in 12:19.860 --> 12:22.660 causing hepatitis in this population of patients. 12:23.640 --> 12:25.460 Few studies where 12:26.240 --> 12:28.460 examination for Ciro conversion 12:29.140 --> 12:31.150 for Epstein barr has been examined, 12:31.610 --> 12:32.460 it's been found. 12:33.540 --> 12:34.190 In addition, 12:34.190 --> 12:36.960 there have been studies demonstrating 12:37.340 --> 12:40.010 zero conversion for Herpes Simplex 12:40.010 --> 12:42.380 virus around the time of 12:42.440 --> 12:43.490 hepatitis. 12:44.840 --> 12:47.820 But the real confusing thing for me is 12:47.830 --> 12:49.950 the overlap and apparent inter 12:49.950 --> 12:51.650 relationships between 12:52.700 --> 12:55.360 simultaneous zero conversion for 12:56.740 --> 12:58.860 hepatitis and it can be 12:59.640 --> 13:00.050 C. 13:00.050 --> 13:00.240 M. 13:00.240 --> 13:00.660 V. 13:01.640 --> 13:04.570 Herpes virus so that it becomes very 13:04.570 --> 13:07.310 difficult to sort out what's the 13:07.310 --> 13:09.990 primary agent causing the hepatitis 13:10.640 --> 13:13.550 versus those which may be turned on simultaneously 13:13.550 --> 13:15.950 in some sort of animistic response 13:16.640 --> 13:19.370 we're related to the same. 13:19.380 --> 13:20.770 We're actually in fact 13:20.880 --> 13:23.660 simultaneously causing infection. 13:25.540 --> 13:27.870 So this is an area of some 13:27.870 --> 13:30.620 confusion and no doubt there will be other 13:30.620 --> 13:33.510 viruses implicated as time goes 13:33.510 --> 13:33.970 on. 13:33.980 --> 13:36.660 Coxsackie viruses et cetera, 13:37.040 --> 13:39.460 which may be involved 13:40.340 --> 13:43.110 in causing the liver 13:43.110 --> 13:46.100 dysfunction commonly seen in these patients, 13:46.120 --> 13:48.330 which cannot be specifically 13:48.330 --> 13:50.800 diagnosed and attributed to 13:50.810 --> 13:53.140 recognized agents. 13:53.150 --> 13:53.800 Uh, 13:53.810 --> 13:56.450 at this point in time for 13:56.450 --> 13:58.060 completeness sake, 13:58.940 --> 14:01.920 fungal and parasitic involvement of the liver should 14:01.920 --> 14:04.270 not be overlooked, 14:04.270 --> 14:06.560 especially in high risk 14:06.620 --> 14:09.550 patients or in the appropriate clinical setting. 14:14.440 --> 14:14.650 Now, 14:14.650 --> 14:16.920 the other major differential 14:16.920 --> 14:19.900 consideration probably besides viral 14:19.900 --> 14:20.560 infection, 14:21.240 --> 14:22.560 is drug toxicity, 14:23.740 --> 14:26.050 either geppetto cellular or cola stat. 14:28.540 --> 14:29.860 And we must, 14:30.440 --> 14:32.150 I've selected out of 14:32.840 --> 14:35.150 long lists of potential 14:35.840 --> 14:38.790 drugs capable of causing a 14:39.120 --> 14:40.150 paddock dysfunction, 14:40.940 --> 14:43.250 those which may be a 14:43.640 --> 14:46.240 utilised in or 14:46.240 --> 14:48.090 by transplant patients. 14:49.630 --> 14:52.160 Ethanol needs no further comment. 14:53.940 --> 14:54.540 He's a thigh. 14:54.540 --> 14:56.960 A prim to me is a very interesting 14:56.960 --> 14:57.750 consideration. 14:59.640 --> 15:01.950 There's always been talk about 15:03.240 --> 15:05.850 primary is a thigpen HEPA no 15:05.850 --> 15:06.550 toxicity. 15:08.540 --> 15:09.080 However, 15:09.080 --> 15:11.300 in the vast majority 15:12.340 --> 15:15.270 of reported cases or cases talked 15:15.270 --> 15:18.140 about it was very difficult for 15:18.140 --> 15:21.070 me to be sure 15:21.070 --> 15:22.060 that in fact, 15:23.540 --> 15:25.850 as a fire brown was the culprit, 15:26.540 --> 15:29.090 since they're often multi factorial 15:29.090 --> 15:31.790 considerations in the patient who develops 15:31.790 --> 15:32.750 hepatic dysfunction. 15:34.540 --> 15:35.070 However, 15:35.070 --> 15:37.950 there's no question in my mind that 15:37.950 --> 15:40.000 is a thigh a prin maybe 15:40.060 --> 15:43.060 synergistically HEPA toxic 15:43.940 --> 15:46.360 or help a toxic superimposed on 15:46.740 --> 15:48.150 previously injured liver. 15:50.540 --> 15:51.090 However, 15:51.090 --> 15:53.880 there have been cases reported and other 15:53.880 --> 15:56.700 people have seen cases 15:57.440 --> 16:00.370 where it has felt certain today is a fire 16:00.370 --> 16:02.770 pit has in fact been the 16:02.780 --> 16:05.060 primary HEPA toxic agent. 16:12.040 --> 16:14.680 Al appear in all is an agent which may be 16:14.680 --> 16:17.550 prescribed to patients with hyper 16:17.550 --> 16:20.370 euros anemia and in addition to the 16:20.380 --> 16:23.330 danger associated with its use in 16:23.330 --> 16:25.650 a patient on a South I appear in this drug also 16:26.640 --> 16:29.270 not infrequently causes liver 16:29.270 --> 16:29.850 dysfunction. 16:31.940 --> 16:34.710 Virtually all the anti tuberculosis drugs have been 16:34.710 --> 16:35.960 associated with 16:37.440 --> 16:40.260 liver enzyme elevations if not 16:40.640 --> 16:41.660 hepatic dysfunction. 16:43.540 --> 16:45.630 Almost all the anabolic steroids, 16:45.630 --> 16:48.520 which are not used very commonly but 16:48.530 --> 16:50.980 may be utilized been associated 16:50.980 --> 16:52.850 with liver dysfunction 16:53.700 --> 16:56.100 as have contraceptive medication 16:57.240 --> 16:59.470 and then young women who 17:00.140 --> 17:02.920 ah In whom birth control is 17:02.920 --> 17:03.620 exercised. 17:03.620 --> 17:06.110 This is one modality which may be 17:06.120 --> 17:08.960 associated with liver disease 17:09.740 --> 17:11.210 and a convulsant drugs. 17:11.590 --> 17:14.270 Matthias scenes alpha method opa 17:16.440 --> 17:18.590 are commonly recognized agents 17:19.340 --> 17:21.950 patient undergoes another surgical procedure. 17:22.440 --> 17:25.000 One must always look at the record to see if there's any 17:25.000 --> 17:27.470 possible association with halothane 17:27.480 --> 17:28.170 anesthesia. 17:29.440 --> 17:32.330 And then just about all these phantom I'd 17:32.330 --> 17:33.200 derivatives, 17:33.460 --> 17:34.580 antibiotics, 17:35.340 --> 17:37.160 oral hypoglycemic agents, 17:37.380 --> 17:38.340 diuretics, 17:38.490 --> 17:38.980 et cetera, 17:38.980 --> 17:39.360 et cetera, 17:39.360 --> 17:41.820 et cetera have been reported to cause 17:43.340 --> 17:45.770 hepatic injury or hispanic dysfunction. 17:46.440 --> 17:48.960 So obviously it's very important to go back and 17:49.840 --> 17:52.760 critically scrutinize the patient's drug 17:52.760 --> 17:55.540 list to see if there's any possible agent which can be 17:55.540 --> 17:58.520 removed and reverse the the 17:58.520 --> 17:59.360 paddock disorder. 18:00.940 --> 18:01.530 And again, 18:01.530 --> 18:02.770 for completeness sake, 18:03.940 --> 18:05.560 it's very important not to forget. 18:06.340 --> 18:09.160 Many of the patients who come to transplantation 18:09.740 --> 18:12.170 May at one point in time developed 18:13.040 --> 18:15.520 separate biliary tract disease 18:16.240 --> 18:19.060 and require either medical or surgical treatment for that. 18:20.040 --> 18:22.200 And of course the other common association 18:23.040 --> 18:25.890 with liver function abnormalities with or without 18:25.890 --> 18:26.400 hyper billy, 18:26.400 --> 18:26.650 Rubin, 18:26.650 --> 18:26.910 EMEA, 18:26.910 --> 18:27.450 etcetera. 18:28.040 --> 18:30.940 Is that not uncommonly seen in association 18:30.940 --> 18:31.990 with pancreatitis, 18:32.540 --> 18:35.360 which also is a problem which 18:35.840 --> 18:38.470 comes up with some frequency and post 18:38.470 --> 18:39.550 transplant patients. 18:43.200 --> 18:44.160 The other thing, 18:45.540 --> 18:48.020 assuming that one does not 18:48.020 --> 18:50.830 identify some 18:50.840 --> 18:53.620 extra hepatic disease or is unable 18:53.620 --> 18:56.550 to identify a 18:56.560 --> 18:57.690 drug which can be 18:58.940 --> 19:01.060 discontinued with resolution of the problem. 19:02.340 --> 19:04.770 The other consideration is what to do, 19:05.440 --> 19:06.270 first of all, 19:06.940 --> 19:08.560 is the liver biopsy in the kids. 19:11.240 --> 19:11.460 Now, 19:11.460 --> 19:12.090 unfortunately, 19:12.090 --> 19:14.740 I think in most people's experience liver 19:14.740 --> 19:17.360 biopsy all too frequently 19:17.940 --> 19:20.760 is not diagnostic and 19:20.760 --> 19:23.550 not terribly helpful in the absence of 19:23.550 --> 19:26.330 specific hissed a pathologic findings 19:26.390 --> 19:28.170 for certain problems. 19:30.440 --> 19:32.310 So in individual cases, 19:32.320 --> 19:35.200 liver biopsy uh 19:35.210 --> 19:36.760 is not necessarily indicated. 19:38.040 --> 19:40.490 I think probably an important role for liver 19:40.490 --> 19:42.460 biopsy with being a 19:42.940 --> 19:45.850 protocol type prospective evaluation 19:46.620 --> 19:48.580 of the paddock dysfunction in these patients. 19:49.540 --> 19:51.870 Where at the end of collecting a large amount of 19:51.870 --> 19:52.570 data, 19:52.580 --> 19:54.970 one could hope to come up with some uh 19:54.980 --> 19:56.320 correlation between history, 19:56.320 --> 19:59.110 pathologic abnormalities and certain 19:59.120 --> 19:59.860 ideology. 20:02.140 --> 20:04.760 The other consideration is whether there should be any 20:04.760 --> 20:06.550 modification in drug therapy, 20:07.540 --> 20:09.810 particularly in patients with clinical hepatitis 20:11.640 --> 20:14.190 can a disease liver metabolizes 20:14.190 --> 20:17.120 Ethiopian appropriately so that the drug 20:17.120 --> 20:18.360 is still immuno suppressive. 20:19.940 --> 20:21.770 Is there any reason to believe that 20:22.440 --> 20:25.210 discontinuing as Cynthia Perrin will speed up the 20:25.210 --> 20:27.690 recovery rate of the 20:27.700 --> 20:28.460 hepatitis. 20:29.640 --> 20:31.940 And in those patients with let's say 20:32.200 --> 20:33.520 uh H. 20:33.520 --> 20:33.760 A. 20:33.760 --> 20:36.510 Positive hepatitis will altering 20:36.510 --> 20:39.370 immuno suppressive therapy improve the patient's ability 20:39.840 --> 20:41.060 to clear the energy. 20:42.540 --> 20:44.460 Well I used to have some thoughts about all that, 20:44.460 --> 20:46.910 all of which has been annihilated by 20:46.920 --> 20:49.520 various peoples different experience 20:50.640 --> 20:53.220 such that many patients with 20:53.230 --> 20:56.220 clinical hepatitis of whatever variety with 20:56.220 --> 20:58.050 no alteration in their drug therapy, 20:58.840 --> 21:00.270 the problem resolves. 21:00.840 --> 21:03.460 And in fact I just heard this 21:03.460 --> 21:05.270 meeting that 21:06.200 --> 21:08.550 Wilford Hall group has had patients who have 21:08.550 --> 21:10.150 developed a G. 21:10.150 --> 21:10.620 B. 21:10.620 --> 21:12.670 Hepatitis with serial conversion 21:13.040 --> 21:15.990 positive and then back to negative again with no 21:15.990 --> 21:18.350 modification of the recent thigpen therapy. 21:18.740 --> 21:19.300 She's very, 21:19.300 --> 21:20.060 very interesting, 21:21.630 --> 21:22.890 liver dysfunction, 21:22.890 --> 21:24.450 post transplantation 21:26.040 --> 21:26.710 with William A. 21:26.710 --> 21:27.160 Briggs, 21:27.160 --> 21:28.120 Lieutenant Colonel, 21:28.120 --> 21:30.800 US Army Medical Corps Chief nephrology 21:30.800 --> 21:31.330 service, 21:31.330 --> 21:33.660 walter reed Army Medical Center Washington D. 21:33.660 --> 21:34.260 C. 21:36.140 --> 21:38.910 Was produced through the mobile facilities of the television 21:38.910 --> 21:39.490 division, 21:39.780 --> 21:41.270 Academy of Health Sciences, 21:41.270 --> 21:43.750 United States Army Fort SAm Houston 21:43.750 --> 21:44.390 texas.