The Authors
REPORTS from German literature 1 show that high doses of vitamin C are beneficial in epidemic hepatitis in children. These beneficial effects were clearly observed in 63 cases of epidemic hepatitis treated with high doses of vitamin C in doses of 10 grams daily for an average of five days given either by rectal infusion or intravenously, or both. The patient’s hospital days and the appearance of urobilinogen in the urine were reduced as much as 50 per cent and the number of days that the liver remained palpable was reduced as much as 75 per cent as compared to the control group. Diuresis, weight gain, increase in appetite and feeling of general well-being, as well as absence of herpes labialis and furunculosis, were noticed in these patients.
The present case is reported because of the remarkable improvement that followed the institution of 5 grams of vitamin C daily for a period of 24 days, after a trial with Meticorten®, antibiotics, repeated paracentesis, mercurial diuretics, blood transfusions and general supportive measures such as bed rest and high caloric diet had proved futile.
The patient, a 44 year old Negro laborer, was admitted for the third time to White Cross Hospital, Columbus. on October 8, 1958, because of ascites. Two weeks prior to admission, he started to notice gradual swelling of his abdomen which became much worse a few days prior to admission. At the same time, he noticed shortness of breath and his appetite had become poor. He complained of easy bloating on eating. He denied any hematemesis, tarry or bloody stool. He never had any jaundice.
He had had previous admissions to this hospital for urethral stricture and chronic recurrent perineal fistula with occasional abscess formation; and for a circumcision. On his last admission, he was found to have hepatomegaly, but no splenomegaly, and a liver biopsy on April 10, 1957, showed cirrhosis with superimposed acute hepatitis. He had been drinking excessively for several years prior to this admission.
Physical Examination: On examination, his blood pressure was 104/70; pulse rate 118 per minute; respiratory rate 20 per minute and temperature 100° F. He appeared chronically ill, but did not appear icteric. There were no spider angiomata. His lungs were clear, except for dullness in both bases. The heart was normal. The abdomen was markedly distended with a positive fluid wave, and shifting dullness. The liver was felt 5 fingerbreadths below the right costal margin and the spleen was palpable 3 fingerbreadths below the left costal margin. Collateral veins over the abdomen were prominent. His fingers were clubbed but patient claims they had been that way since birth. There was no edema in the extremities. Rectal and neurologic examinations were normal.
Laboratory Data: The laboratory examinations on admission showed: hemoglobin 9.2 Gm. per 100 ml.; hematocrit 31 ml. per 100 ml.; white blood cell count 17.500 with 85 neutrophils. 11 lymphocytes and 4 eosinophils. Urinalysis showed many white blood cells and bacteria. Liver function tests were: prothrombin time 18.5 seconds or 65 per cent of normal; total proteins 5.9 grams and A/G ratio 3.3/2.5 grams; thymol turbidity 1.6 units; cephalin flocculation 2 plus and bromsulfalein test was 17.5 per cent retention in 45 minutes. Total bilirubin was 0.75 milligrams per 100 ml. in 30 minutes with direct reaction 0.45 mg. per 100 ml. in 1 minute and 0.55 mg/100 ml. in 10 minutes.
The platelet count was 227,000 per cu. mm. and the reticulocyte count was 2.6 per cent. Red cell survival time by radiochromium study was normal. Blood urea nitrogen was 14 mg. per 100 ml. (A bone marrow biopsy done on previous admission, May 11, 1957, showed a hyperplastic marrow.) Chest x-ray was normal and an upper gastrointestinal series showed no definite esophageal varices; marked hypertrophic gastritis; and one area in the base of the duodenal cap which suggested a small ulcer crater.
On October 10, 1958, a liver biopsy was done and this showed numerous foci of neutrophilic infiltration diffusely scattered throughout the liver tissues, with increased portal and periportal fibrosis. A few areas of fatty vacuolization were seen. Areas of necrosis with some remaining liver cells containing pink staining hyaline droplets were present. A diagnosis of active hepatitis with cirrhosis was then made.
The patient was treated with bed rest; mercurial diuretics intramuscularly; and a 3000 calorie diet with high carbohydrate and high protein and low fat content. He continued to run a low grade temperature with peaks to 100 degrees F. His appetite remained poor, improving only slightly and temporarily after each abdominal paracentesis. He required repeated abdominal paracentesis which were done on October 8th. 14th, 20th, 29th and on November 4th and 5th, to relieve his shortness of breath, increase his appetite and improve his general well being. The ascitic fluid was straw-colored and the amount ranged from 1680 cc. to as much as 3700 cc. per tap. He was given 5 pints of blood from October 14 to October 31, 1958. Occult blood determinations in the stool remained positive until the last week of his hospital stay.
He was treated with Gelusil® drams 2 after meals and ounces 1 at bedtime for his ulcer; and Gantrisin®, 0.5 grams and Chloromycetin® 50 milligrams every six hours for his urinary tract infection. On October 15, 1958, he was started on prednisolone with an initial dose of 60 milligrams, followed with ~ mg. four times a day. This dose was continued up to October 27, with no appreciable results. On October 28 his hemoglobin was 9.6 grams per 100 ml., hematocrit 31.5 ml. per 100 ml., white blood cell count 23,500 with 91 neutrophils and 9 lymphocytes. Urinalysis showed 0 to 5 leukocytes and moderate bacteria.
Vitamin C in a dose of 5 grams in 1000 cc. of 5 per cent glucose in water was started on October 28. This infusion was given daily; each was allowed to run about four hours until November 21, 1958 (25 consecutive days). Urine culture showed E. intermedium and this was sensitive to Chloromycetin.
On November 3, hemoglobin was 9.6 Gm./100 ml.; hematocrit 29 ml./100 ml.; white blood cell count 14,800 with 80 neutrophils, 14 lymphocytes and 6 eosinophils. Repeat blood counts on November 17th and 21st showed: hemoglobin 11.6 Gm.; hematocrit 35 ml.; white blood cell count 12,800 with 85 neutrophils, 12 lymphocytes, 1 monocyte and 2 eosinophils; hemoglobin 11.3 Gm.; hematocrit 37 ml.; white blood cell count 8,900 with 76 neutrophils, 23 lymphocytes, and 1 eosinophil.
Liver function tests were repeated including a liver biopsy on November 21. These showed: prothrombin time 15 seconds or 100 per cent of normal; total protein 7.2 grams; A/G ratio 4.4/2.8 grams; thymol turbidity 1.7 units; cephalin flocculation negative; and serum bilirubin 0.5 milligrams per 100 ml. in 30 minutes. Liver biopsy showed only portal cirrhosis with disappearance of the diffuse neutrophilic infiltration present in the two previous liver biopsies.
Increase in appetite and general well-being was noticed within the first week of vitamin C therapy. The last blood transfusion was given on October 31, 1958 (three days after onset of vitamin C therapy) and the last paracentesis was done on November 5 (eight days after onset of vitamin C therapy) and this yielded only 1800 cc. of ascitic fluid. From here on, diuresis continued and on November 21 his abdomen was soft with no clinical evidence of ascites. His temperature remained normal after the second week with vitamin C therapy and stayed normal up to the day he was discharged on November 23, 1958.
Table 1 is a summary of treatment.
In 1951 and 1952, McCormick 2 underlined the chemotherapeutic value of ascorbic acid as comparable to sulfonamide compounds or mycelial antibiotics in acute infections and emphasized the additional advantage of freedom from toxic or allergic reactions. He attributed the chemotherapeutic action of vitamin C to its chemical action as a reducing or oxidizing agent. Both endogenous and exogenous toxins are supposedly neutralized by vitamin C.
Ralli and Sherry 3 have found that vitamin C is higher in white blood cells than in the red blood cells or plasma and in the same theme, Crandon 4 et al. have found that the white-cell-platelet layer is the last fraction of the blood to be depleted of its vitamin content. To this effect, Nungester 5 has shown experimentally, in guinea pigs, that the white blood cells in the vitamin C poor peritoneal exudates showed increased fragility and decreased phagocytic activity.
Specific action of vitamin C on the liver has been studied by Willis 6 who found that ascorbic acid reverses fatty degeneration and acute non-fatty hepatocellular degeneration; and promotes the laying of reticulin and collagen in the liver of scorbutic guinea pigs. The main reservoir of vitamin C in the body is in the liver. A deficiency of vitamin C leads to fatty metamorphosis and this in turn has been implicated as the probable cause of the altered metabolism of amino acids that is associated with the state of vitamin C deficiency. 7
It has been found that the ascitic fluid contains the same concentration of vitamin C as does the plasma. 8 The procedure of doing repeated paracentesis, as in our patient, will readily deplete the patient of his vitamin C and this may produce a state of vitamin C subnutrition.
The etiology of the acute hepatitis in the case presented is not definitely known. It is possible that the chronic urinary tract infection has kept the hepatitis smoldering from April 1957 to October 1958. The two liver biopsies taken on these dates look very much alike (Figs. 1 and 2). Control of the urinary infection in the hospital did not bring any clinical improvement in the patient. Likewise, a trial with prednisolone for 12 days proved ineffective in relieving or alleviating clinical signs and symptoms.
TABLE 1. Summmary of Treatment
|
Date |
Paracentesis |
Liver Biopsy** |
Blood Transfusion |
Meticorten |
Vitamin C |
|
10/ 8/58 |
3700 cc. |
||||
|
10/14/58 |
2650 cc. |
active hepatitis |
500 cc. |
||
|
10/15/58 |
500 cc. |
60mg. initial dose; |
|||
|
10/17/58 |
500 cc. |
||||
|
10/20/ 58 |
1900 cc. |
500 cc. |
|||
|
10/27/ 58 |
|||||
|
10/28/58 |
5 gm. vitamin C |
||||
|
10/29/58 |
3300 cc. |
||||
|
10/31/58 |
500 cc. |
||||
|
11/ 4/58 |
1680 cc. |
||||
|
11/ 5/58 |
1800 cc. |
||||
|
11/20/58 |
|||||
|
11/21/58 |
moderate cirrhosis |
||||
| ** Liver biopsy on 4/10/57 showed also active hepatitis with cirrhosis. | |||||
Mainly because of the good results obtained in epidemic hepatitis in children with high doses of vitamin C, we decided to try this treatment in our patient. We used 5 grams of vitamin C (Cevalin© in 1000 cc. of 5 per cent glucose in water given intravenously in four to five hours daily for 24 days. The salutary effects from this treatment were dramatic. The anemia was corrected; the leukocyte count and differential returned to normal; the ascites disappeared; the patient gained weight, and his appetite improved. A feeling of general well-being was evident after the first few days of treatment. The liver function tests which were deranged prior to treatment returned to normal except the bromsulphalein test which dropped down to 8.5 per cent in 45 minutes. This latter abnormality is consistent with his moderate portal cirrhosis. The absence of neutrophilic infiltration in the last liver biopsy done immediately after the termination of treatment with vitamin C was striking (Fig. 3).
(Figure not Available for this version)
FIG. 1. Liver biopsy taken on April 10, 1957.
(Figure not Available for this version)
FIG. 2. Liver biopsy taken on October 14, 1958. Both biopsies show
neutrophilic infiltration with a background of portal cirrhosis.
(Figure not Available for this version)
FIG. 3. Liver biopsy taken on November 21, 1958. Note striking disappearance
of neutrophilic infiltration. Portal cirrhosis remains.
The disappearance of ascites was particularly encouraging in view of the fact that repeated paracentesis and mercurial infections [“infusions ”?-ed] had failed earlier. This diuretic effect of vitamin C has been observed in previous studies, including the experimental study of Barac. 9 It has been suggested that the diuretic effect of vitamin C is due to the inhibition of the antidiuretic hormone. Schaffer and Chapman 10 use 500 milligrams of vitamin C to potentiate mercurial diuretics in congestive failure.
It is hoped that this case report of our patient will serve to stimulate further trial of this treatment in acute hepatitis.
A case of acute hepatitis, treated with 5 grams of vitamin C in 1000 cc. of 5 per cent glucose in water given intravenously daily for 24 days, is reported. Among other things, the liver biopsy after treatment provided the strongest single evidence of the efficacy of the treatment.
From The Ohio State Medical Journal, Volume 56, June, 1960, pp. 821-823
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