Improvement In Prothrombin Time Research Articles

Fondaparinux sodium combined with conventional therapy improves subchorionic hematoma with protein S deficiency

BACKGROUND: Fondaparinux sodium can prevent and treat acute illnesses and venous thromboembolism in patients undergoing surgery. At present, no studies have reported on treating subchorionic hematoma combined with protein S deficiency using fondaparinux sodium. OBJECTIVE: To investigate the clinical efficacy of fondaparinux sodium in the treatment of patients with subchorionic hematoma combined with protein S deficiency. METHODS: This single-center, open-ended, and prospective study enrolled 78 patients with subchorionic hematoma and protein S deficiency. They were randomly assigned to the treatment and control groups. The control group received conventional treatment, and the observation group received subepithelial injections of fondaparinux sodium (2.5 mg/day) based on conventional treatment. After 30 days of continuous treatment, the hematoma was evaluated by ultrasonography. RESULTS: After treatment with fondaparinux sodium, a significant improvement in subchorionic hematoma was observed in the observation group compared with that in the control group (p< 0.05). A substantial improvement in prothrombin time and activated partial thromboplastin time was observed in the observation group after fondaparinux sodium treatment (p< 0.05). Furthermore, after fondaparinux sodium treatment, the duration of hematoma maintenance and incidence of adverse pregnancy outcomes were significantly reduced in the observation group compared with that in the control group (p< 0.05). CONCLUSION: With a favorable safety profile, fondaparinux sodium is effective in treating subchorionic hematoma combined with protein S deficiency. The results provide new ideas and methods for treating this disease, which is worthy of further promotion and application in clinical practice.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Title: Haematological disorders revealing a raticide suicide attempt: A case report

IntroductionSuicide attempts are common in individuals with schizophrenia. These actions are marked by a greater lethality, due to the use of more violent means in particular the intentional ingestion of rodenticides.ObjectivesTo describe the gravity of the heamatological disorders revealing suicide attempts by a rodenticides in patient with schizophrénia.MethodsWe repport the case of a patient who present a haematological disorders after an rodenticide intoxication.ResultsA 41-year-old man with schizophrénia since 2011 was brought to the department of psychiatry in july 2020 for behavioral disorders. On arrival, the patient was oriented but reticent and refuse to tell his full story. On examination, his vital signs were normals, and he did not show any externalized bleeding. Bilogical tests revealed the prothrombin time (PT) was <10% with an isolated and unexplained fall in vitamin K-factors. The etiological investigation was negative. Later,the patient admitted attempted suicide by taken 4 rodenticide packages orally three days prior admission to hospital. The initial treatment with intravenous vitamin K almost daily is effective. An improvement in PT (35%) and vitamin K-dependent factors was observed after one week of treatment. A Normalization of hemostasis disorders was obtained after two weeks of treatment.ConclusionsIt is imperative to suspect rodenticide intoxication in patient with scizophrenia with an isolated and an explained deficiency of vitamin K dependent factors. The particularity of this intoxication lies in the dangerous and prolonged side effects making the curative treatment difficult and long.DisclosureNo significant relationships.

Effectiveness and Safety of 4-factor Prothrombin Complex Concentrate (4PCC) in Neonates With Intractable Bleeding or Severe Coagulation Disturbances: A Retrospective Study of 37 Cases.

To date, clinical experience with prothrombin complex concentrate (PCC) in the neonatal population has been limited. The objective of this study was to describe our experience regarding the effectiveness and safety of PCC administration in newborns with severe bleeding or coagulopathy resistant to conventional therapy. We retrospectively analyzed data from 37 neonates with intractable bleeding or severe coagulation disturbances. All patients received intravenous bolus administration of 20 or 30 u/kg of PCC per dose, as a rescue procedure. Hemostasis was achieved in the majority of neonates and we observed statistically significant improvement in prothrombin time, international normalized ratio, and activated partial thromboplastin time (P<0.001, P=0.044, P<0.001, respectively). Thirteen neonates survived, whereas 24 did not survive. In those who survived, PCC had been administered earlier (<24 h) in the disease process compared with those who died (P=0.043). Neither acute adverse events nor thromboembolic complications were observed in all neonates. In our study, PCC seemed to be a safe and effective intervention for hemostasis and early intervention was more effective as a rescue therapy, without any adverse event. Further prospective controlled trials are required to determine optimal dose and timing of PCC administration in neonates.

Sa1840 Effects of Oral L-Carnitine on Liver Functions After Transarterial Chemoembolization (TACE) in Intermediate Stage Hepatocellular Carcinoma (HCC) Patients.

Background :Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage hepatocellular carcinoma (HCC) and usually followed by hepatic dysfunction that limits its efficacy. L-carnitine (4-N-trimethyl ammonium 3-hydroxybutyric acid) is recently studied as hepatoprotective agent. In this study, we evaluated L-carnitine effects against the deterioration in liver functions after TACE. Study design: 53 sequential patients with intermediate stage HCC at Osaka Medical College enrolled to this study. All patients were treated by TACE and assigned into two groups; L-carnitine group (26 patients) who received L-carnitine 300 mg tablet twice daily from 2 weeks before to 12 weeks after TACE and Control group (27 patients) without L-carnitine therapy. Liver functions were evaluated for all patients at 2 weeks before, 1, 4, 12 weeks after TACE. 28 of study patients received branched chain amino acids granules. Results: L-carnitine suppressed deterioration in serum albumin level at 1 week after TACE. There were significant differences between L-carnitine group and control group in mean serum albumin change from baseline to 1 week and 4 weeks after TACE (p < 0.05). L-Carnitine maintained Child-Pugh score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (p < 0.01 compared to 1 week after TACE). Conversely, control group reported significant Child-Pugh score deterioration from baseline to 1 week after TACE (p < 0.05) and 12 weeks after TACE (p < 0.05). There were significant differences between L-carnitine and control groups in mean Child-Pugh score change from baseline to 4 weeks (p < 0.05) and 12 weeks after TACE (p < 0.05). Interestingly, L-carnitine displayed improvement in prothrombin time (PT) from baseline to 1 week, 4 weeks (p < 0.05) and 12 weeks after TACE. Contrariwise, PT in control group declined less than baseline along all follow up intervals. There were significant differences between L-carnitine and control groups in PT mean change from baseline to 1 week (p < 0.05) and 4 weeks after TACE (p < 0.05). Total bilirubin in L-carnitine group decreased at 1 week post TACE while in control group, total bilirubin at 1 week significantly increased (p = 0.01). Mean total bilirubin change from baseline to 1 week after TACE reported significant differences between L-carnitine and control groups (p < 0.05). Alanine transaminase and C-reactive protein elevation at 1 week after TACE were suppressed in Lcarnitine group. The hepatoprotective effects of L-carnitine were enhanced by concomitant use of branched chain amino acids. No side effects appeared by L-carnitine administration in all clinical courses. Conclusion: L-carnitine and BCAA combination therapy maintained and improved liver functions after TACE and may be offered as a new liver support tool in HCC patients.

Efficacy of Various Combined Blood Purification Techniques for Treating Patients with Non-viral Acute Liver Failure

We sought to study the clinical efficacy of various combined blood purification techniques in patients with non-viral acute liver failure complicated by multiple organ dysfunction syndrome (MODS). For this purpose, 19 patients diagnosed of mid- or late-stage liver failure with MODS score-4 were randomly divided into 3 treatment groups of PE+HP+CVVHDF, PE+CVVHDF, and HP+CVVHDF, respectively. Pre- and post-treatment heart rate (HR), mean arterial pressure (MAP), arterial blood gases (pH, PaO2, and PaCO2), hepatic function, platelet count, and blood coagulation were determined. The data show significant improvement in HR, MAP, PaO2/FiO2, total bilirubin (TBIL), and alanine aminotransferase (ALT) levels after treatment (P < 0.05). TBIL decreased more significantly after treatment in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.01). Significant improvement in prothrombin time and albumin was observed only in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.05). The decrease of TBIL and improvement of PaO2/FiO2 ratio were more pronounced in PE+HP+CVVHDF than in HP+CVVHDF group (P < 0.05). To conclude, liver function was relatively improved by all the three combined blood purification techniques used; however, PE+HP+CVVHDF approach was found more efficient in the removal of toxic metabolites, especially bilirubin. The data suggest that the combined blood purification techniques used were effective and involved minor side effects.

Hepatic vein waveform and splenomegaly predict improvement of prothrombin time after splenectomy in hepatitis C virus‐related cirrhotic patients

Whether hepatic function can recover in cirrhotic patients after splenectomy remains controversial. All consecutive Japanese patients with hepatic cirrhosis due to hepatitis C who had undergone elective splenectomy in Kyushu University Hospital between January 2008 and December 2009 were included in this retrospective study. Prothrombin time, serum albumin and total bilirubin concentrations were reviewed before and after splenectomy and analyzed to clarify whether splenectomy improves hepatic function in patients with cirrhosis and to determine the factors predictive of improvement in hepatic function. Prothrombin time and total serum bilirubin concentration improved after splenectomy; however, serum albumin concentrations did not increase significantly. Twelve months after splenectomy, total serum bilirubin had decreased by over 0.3 mg/dL in 52.3% of patients and prothrombin time had improved by over 10% in 52.3% of patients. Multiple linear regression analysis identified hepatic vein waveform (HVWF) type I (P = 0.0174) and spleen weight (P = 0.0394) as independent predictors of improvement in prothrombin time and preoperative total serum bilirubin (P = 0.0002) as the only independent predictor of decrease in total bilirubin. Total bilirubin and prothrombin time were significantly improved after splenectomy in patients with HVWF type I, however, they were not improved in patients with HVWF type II. Prothrombin time and total bilirubin improve in approximately half of cirrhotic patients within a year after splenectomy. HVWF type I and splenomegaly may be predictive factors for improvement in prothrombin time after splenectomy in patients with cirrhosis due to hepatitis C.

The requirement for a sufficient period of corticosteroid treatment in combination with nucleoside analogue for severe acute exacerbation of chronic hepatitis B

The prognosis of severe acute exacerbation of chronic hepatitis B is very poor if signs of liver failure appear. We have reported the efficacy of the early introduction of sufficient doses of corticosteroids (CSs) and nucleoside analogues (NAs), but the optimal period of immunosuppressive therapy has not been well demonstrated. In this study, we analyzed patients with severe acute exacerbation of chronic hepatitis B treated with CSs and NAs, prospectively, in order to clarify the factors affecting their outcome. Ten patients, admitted to our liver unit between 2000 and 2009, were defined as having severe exacerbation of chronic hepatitis B based on our uniform criteria, and were enrolled in this study. NAs and sufficient doses of CS were introduced as soon as possible after making the diagnosis of severe disease prospectively. Seven of the 10 patients recovered. The absence of fulminant hepatitis on admission, the improvement of prothrombin time (PT) activity and the decline of hepatitis B virus (HBV) DNA during the first 2 and 4 weeks, respectively, were significant in the recovered patients, while the worsening of total bilirubin level during 4 weeks, especially between week 2 and week 4, was significant in those who died. In severe acute exacerbation of chronic hepatitis B, more than a few weeks of CS treatment in combination with an NA is required in the early stage, whereas a short period of conventional pulse therapy would be insufficient for treating this condition.

Use of Prothrombin Complex Concentrate (Beriplex/Octaplex) in Acquired Bleeding Disorders: A Two-Year Single Centre Experience.

Abstract 3160Poster Board III-97The major challenges in acquired bleeding disorders are accurate assessment of bleeding risk and subsequent effective correction of the haemostatic imbalance without increasing the risk of thrombotic complications. The response to Fresh Frozen Plasma (FFP) is extremely variable when used in acquired bleeding disorders. The administration of higher doses of FFP is more effective (Chowdhury et al., Br J Haematology. 2004 Apr; 125(1):69-73), but is limited by the potential risk of fluid overload. In addition, as with the use of all blood products, the risk of transmitting infection and concerns regarding allergic reactions, anaphylaxis and transfusion-related lung injury remain. With the increasing availability of prothrombin complex concentrates (PCCs), it has become possible to give a defined dose of factor II, VII, IX, X and proteins C & S in a small volume. Its efficacy has been well described in patients requiring warfarin reversal, but the indication for its use in other acquired bleeding disorders is less clear and data published on the subject is very limited. Concerns remain regarding the thrombotic risk associated with its use and, as a plasma-derived product, there is also the potential of transmitting blood borne infections. Here we present our two-year experience of the use of PCCs in a wide range of acquired coagulopathies. We collected retrospective data on a total of 200 (n=200) administration events, which we subdivided as follows: (1) Warfarin reversal (n=54), (2) Gastrointestinal bleeding on the background of coagulopathy secondary to chronic liver disease (n=62), (3) Liver transplantation complicated by massive blood loss or renal impairment requiring volume restriction (n=31), (4) Massive haemorrhage (n=10), (5) Coagulopathy due to underlying malignancy (n=10), (6) Correction of coagulopathy prior to procedures (n=20), (7) Miscellaneous (n=13). Dosing of PCCs was decided based on weight of patient, severity of acquired coagulopathy, rate of blood loss and underlying pathology. If required the PCCs were administered in conjunction with fibrinogen concentrate, blood products (packed red cells, platelets, FFP, cryoprecipitate) and antifibrinolytic agents such as aprotinin or tranexamic acid. Our PCC dosing regime of 20 -30 units/kg usually led to an improvement in prothrombin time (PT) and international normalised ratio (INR) in all the above listed clinical settings. No excessive blood loss was noted during the procedures for which PCCs were given. In addition, we did not see a significant increase in thrombotic complications in our cohort of patients, but these findings have to be confirmed in larger studies. At our institution, patients requiring warfarin reversal with an INR >4.0 receive a universal dose of 30u/kg of PCCs based on a previous study (Gatt et al., J. Thrombosis and Haemostasis. 2009 Jul; 7(7); 1123-7), which demonstrated that sufficient thrombin generation is achieved with this dose and the retrospective analysis of our clinical data supports this. In patients with acute and chronic liver failure, the capacity to generate thrombin is probably not significantly impaired in steady state despite a prolonged PT and INR (Gatt et al., Blood, vol.112, No. 11, abstract 1826). However, these patients are more vulnerable to disturbances caused by major blood loss requiring large volume transfusion. We found that administration of PCC in this setting led to improvement of prothrombin time/INR and clinical outcome. We were able to correlate these findings to improvement in the thromboelastogram curves in patients undergoing liver transplant. We conclude that use of PCCs and their dosing must be tailored to the clinical setting. Administration of PCCs can be considered when rapid correction of clotting factors to haemostatic levels is required and/or if there is a significant restriction to volume that can be safely transfused. A comprehensive approach to the management of acquired coagulopathies should also include the addition of FFP, cryoprecipitate, fibrinogen concentrate, antifibrinolytics and recombinant factor VIIa. The correlation between bleeding tendency and standard coagulation tests remains unclear and has to be further investigated to help with future changes of clinical practice. DisclosuresNo relevant conflicts of interest to declare.

Is the Use of rFVIIa Safe and Effective in Bleeding Neonates?

Recombinant activated factor VII (rFVIIa), originally developed for the treatment of life-threatening bleeding in hemophilic patients with inhibitors to factors VIII or IX, has been increasingly used to control hemorrhage unresponsive to conventional treatment, in the absence of a defined coagulopathy or thrombocytopathy. To date, clinical experience of rFVIIa administration in neonates, especially preterms, is rather limited, because of the lack of controlled studies and based solely on some published case reports and 1 prospective pilot study. The objective of this study was to retrospectively evaluate the clinical outcome of newborns treated with recombinant activated factor VII for intractable bleeding or severe coagulation disturbances, resistant to conventional hemostatic therapy. The medical records of 8 neonates treated with rFVIIa (100 micro g/kg) were retrospectively reviewed for the course of hemorrhage and the hemostatic interventions performed before and up to 24 hours after the administration rFVIIa. Coagulation parameters of 3 different time-points were assessed and compared: before administration of any blood product (time-point 1), before administration of the first dose of rFVIIa (time-point 2), and 4 hours after the administration of the last dose of rFVIIa (time-point 3). The safety and tolerability profile of rFVIIa in bleeding neonates was also evaluated. Six preterm and 2 term patients were included in the study. Seven patients presented with refractory bleeding and 1 was diagnosed with severe coagulopathy unresponsive to the conventional treatment. Prompt hemostasis was achieved in half of the patients with their coagulation profile being restored within 4 hours after the administration of the first dose of rFVIIa. Improvement in prothrombin time, activated partial thromboplastin time, and fibrinogen after rFVIIa administration was statistically significant, as compared with that observed after conventional treatment. No major safety issues were observed during the study. All 8 patients survived and had their hemorrhage or coagulopathy controlled within 4 hours after transfusion of the last dose of rFVIIa. In this study, the hemostatic agent rFVIIa was well-tolerated and behaved in a safe and efficacious manner in all infants treated for life-threatening bleeding and coagulation disorders. Future prospective controlled trials are needed to determine the efficacy, safety, tolerability, and possibly the optimal dose and timing of rFVIIa administration.

Evaluation of vitamin K deficiency in children with acute and intractable diarrhea

The purposes of this study were to determine the frequency of vitamin K deficiency and to assess its effects on bleeding in patients with acute and intractable diarrhea. A total of 90 children with diarrhea and 30 healthy children (group C) were included in this study. Patients were divided into 2 groups, according to the duration of diarrhea. Complete blood count; prothrombin time (PT); activated prothrombin time (APTT); Factors II, VII, IX, and X; and protein C levels were studied in all patients. A total of 3 mg of vitamin K was administrated to patients with prolonged PT and/or APTT. Coagulation parameters were restudied 8 to 12 h after vitamin K was administered. Mean age, sex, weight, and breastfeeding percentage, as well as history of fever and vitamin K administration at birth, were similar in the 2 groups. The duration of antibiotic administration in group B (intractable diarrhea) was significantly longer than that in group A (acute diarrhea). Gastrointestinal (GI) bleeding was observed in 3 (4.9%) infants in group A and 6 (20.7%) in group B (P<.05). The duration of diarrhea was significantly longer in infants with GI bleeding. Intracranial bleeding occurred in 1 infant with intractable diarrhea. Prolonged PT levels were noted in groups A and B. Significant improvement in PT and APTT and an increase in coagulation factors were observed after vitamin K had been administered. Investigators in this study conclude that coagulation parameters can be improved by the administration of vitamin K to children with deranged PT and APTT and diarrheal illness.

The use of recombinant factor VIIa for severe intractable bleeding during spine surgery.

A report on the use of recombinant activated factor VII in 4 patients who developed severe intractable bleeding and coagulopathy during spine surgery. To describe the role of recombinant activated factor VII for hemostasis during spine surgery. Recombinant activated factor VII is indicated for the treatment of bleeding episodes and the prevention of bleeding during surgery in patients with hemophilia with inhibitors. However, its use in adults undergoing spine surgery has not yet been reported. Four patients who underwent multilevel spine surgery through an anterior approach incurred massive bleeding and subsequently became coagulopathic. Standard hemostatic techniques were performed and blood products were transfused. Persistence of the bleeding prompted the use of recombinant activated factor VII. Treatment with recombinant activated factor VII led to an improvement in prothrombin time and partial thromboplastin time and brought about cessation in gross, nonsurgical bleeding intraoperatively. No clinically relevant thrombotic complications related to the drug were noted. Recombinant activated factor VII is promising as an adjunctive hemostatic agent for patients with perioperative bleeding problems during spine surgery. Efficacy is seen even at low doses.

Treatment of liver failure in rats with end-stage cirrhosis by transplantation of immortalized hepatocytes

The shortage of organ donors has impeded the development of human hepatocyte transplantation. Immortalized hepatocytes could provide an unlimited supply of transplantable cells. To determine whether immortalized hepatocytes could provide global metabolic support in end-stage liver disease, 35 immortalized rat hepatocyte clones were developed by transduction with the gene encoding the simian virus 40 T antigen (SV40Tag). The SV40Tag sequence and a suicide gene, herpes simplex virus thymidine kinase (HSV-tk), were flanked by loxP sequences so that they could be excised by Cre/ lox recombination. When transplanted into the spleens of portacaval-shunted rats, 3 of the 35 immortalized hepatocyte clones prevented the development of hyperammonemia-induced hepatic encephalopathy. The protection was reversed by treatment with ganciclovir, which kills HSV-tk–expressing cells. Transplantation of alginate-encapsulated, immortalized hepatocytes into the spleens of cirrhotic rats resulted in significant improvement in prothrombin time, serum albumin and bilirubin levels, hepatic encephalopathy score, and duration of survival. The metabolic support provided by the immortalized cells equaled that observed after transplantation of primary rat hepatocytes. In conclusion, immortalized hepatocytes can function as well as primary hepatocytes following transplantation and can be engineered to contain safeguards that could make them clinically useful. Further investigation is warranted regarding the mechanisms of loss of mass or function of the transplanted hepatocytes over time and how the relatively few engrafted hepatocytes can ameliorate liver decompensation in cirrhosis. (H EPATOLOGY 2002;36:386-394.)

The use of silymarin in the treatment of liver diseases.

The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability, inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression, for example, via suppression of nuclear factor (NF)-kappaB. Pooled data from case record studies involving 452 patients with Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered, do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by -4.2% [odds ratio (OR) 0.75 (0.5 - 1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual trial reported a reduction in the number of patients with encephalopathy of -8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by -25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the 'final' evidence of the efficacy of silymarin.

A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis

We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites.

Effect of simultaneous administration of glucagon and insulin on renal function in patients with liver cirrhosis and ascites.

Since glucagon and insulin (G/I) have been suggested to be hepatotrophic substances, the effect of G/I infusion on the ability to excrete water and sodium was tested in seven patients with cirrhosis and ascites (decompensated group), and compared with that in seven cirrhotics without ascites (compensated group). A constant infusion of 1 U glucagon and 10 U regular insulin over 2 hours daily for 14 days resulted in a significant improvement of prothrombin time in the decompensated group. Concomitantly, an increase in urine volume (62%, p less than 0.02) and a tendency toward an increase in urinary sodium excretion (68%, 0.05 less than p less than 0.1) were observed only in the decompensated group after the G/I infusion. In addition, these were associated with increases in creatinine clearance and osmotic clearance. These results suggest that glucagon and insulin merit further study in hepatorenal syndrome cases.