Oral ulcers produced by mycophenolate mofetil in two liver transplant patients.

Oral ulcers are a frequent problem in transplant medicine. It is important to consider infectious etiologies, exacerbated by the immunosuppressive treatment, but other etiologies are also possible, like adverse drug reactions. Mycophenolate mofetil (MMF) is an immunosuppressive medication that has been used in combination with calcineurin inhibitors and steroids. Reports of renal transplant patients with oral ulcers related to MMF have appeared lately and herein we have described 2 cases in liver transplant patients. Their oral ulcers resolved quickly after suspension of the medication. Our 2 cases in liver transplant patients represented a unique setting for this type of complication.

Daño hepático por fármacos: características clínicas e histológicas en 33 casos / Drug induced liver disease: clinical and pathological patterns in 33 cases

BACKGROUND: Drug induced liver disease (DILD) is common and of difficult diagnosis. AIM: To report the clinical, laboratory and pathological findings in 33 patients with DILD. PATIENTS AND METHODS: We revised 1,164 liver biopsies and 57 were selected as suspicious of DILD. In these, the scale proposed by Maria et al was applied to assess the possibility of hepatotoxicity reactions and 33 were selected. RESULTS: The 33 cases had a mean age of 48 +/- 18 years and 14 were male. Forty eight medications were involved, with an average of 1.4 drugs per patient. The main drugs were antimicrobials, antineoplastics-immunosuppressives and non-steroidal antiinflammatory drugs. The clinical presentations in order of frequency were cholestasis, hepatitis, asymptomatic, fulminant hepatitis and cirrhosis. The laboratory alterations observed in cases with hepatitis were 20 fold transaminase and bilirubin elevation. In cholestasis, moderate elevations of alkaline phosphatases and gamma glytamyl transferase were observed. Pathology showed hepatocellular damage, cholestasis and mixed damage, but also submassive necrosis and cirrhosis in one case. CONCLUSIONS: The present study confirms that DILD is frequently unpredictable and that it can cause a wide variety of clinical and pathological presentations, that can even evolve to chronicity.

Transmisión familiar del virus de la hepatitis C en un grupo de población chilena / Familial transmission of hepatitis C virus infection in Chilean subjects

BACKGROUND: Intravenous drug use, sexual promiscuity and a longer cohabitation period are considered risk factors for familial transmission of hepatitis C virus. The relative importance of this type of transmission is a subject of controversy. AIM: To study familial clustering of hepatitis C virus infection and its risk factors. MATERIAL AND METHODS: HCV positive patients (91 with chronic hepatitis, 88 with cirrhosis, nine with hepatic carcinoma and 29 hemophiliacs) were the index cases. HCV antibodies were measured by ELISA and the type of relationship with the index case was investigated in 317 family members. RESULTS: Positive anti HVC antibodies were detected in 12 of 243 family members of patients with chronic liver disease and in none of the family members of patients with hemophilia. Of these, five were couples of an index case with a long cohabitation period. Ten members had an index case with a severe liver disease (three with Child C cirrhosis and seven with liver carcinoma). CONCLUSIONS: Family transmission of HCV infection is uncommon in Chile. The association of severe liver disease and family transmission could be due to a higher viral load as responsible for transmission during the early periods of a long lasting disease.

Colecistectomía laparoscópica y clásica en pacientes con cirrosis hepática / Laparoscopic and classic cholecystectomy in patients with liver cirrhosis

BACKGROUND: The prevalence of gallstones is increased in patients with cirrhosis. However the presence of cirrhosis has been generally considered a relative contraindication to cholecystectomy. AIM: To investigate the complications and the outcomes of laparoscopic and open cholecystectomy in patients with cirrhosis. PATIENTS AND METHODS: Sixty seven patients with gallstones with well-documented cirrhosis undergoing cholecystectomy (laparoscopic cholecystectomy (LC) in 35 and open cholecystectomy (OC) in 32), were studied. The mean age was 57.7 + 10.3 years for LC and 58.9 + 11.6 years for OC. In the LC group, 26 were classified as Child-Pugh class A, 8 as Child's B class and 1 as Child's class C. In the OC group, 12 were classified as Child's class A, 15 as Child's B and 5 as Child's C. RESULTS: Complications occurred in 4 of 35 (12.3 per cent) LC patients (1 patients was Child A and 3 were B). In the OC group 14 of 32 patients had complications (4 Child A, 7 B and 3 C, 43.7 per cent p < 0.05 as compared with LC group). Three patients in the OC group died (9.4 per cent). Mean hospital stay was 2.8 + 1.9 and 13 + 12 days in LC and OC patients, respectively (p < 0.05). CONCLUSIONS: LC has a lower rate of complications than OC and is a reasonable option for Child's class A and B patients with cirrhosis and gallstones.

[Endoscopic coagulation with argon plasma, a therapeutic option in gastric antral vascular ectasia]. / Coagulación endoscópica con Plasma de Argón, una opción terapéutica en la ectasia vascular antral.

BACKGROUND: Gastric Antral Vascular Ectasia or Watermelon stomach is a rare cause of chronic gastrointestinal bleeding, often presenting as a chronic iron deficiency anemia. This condition can be associated with some other diseases such as cirrhosis, autoimmune diseases and others. We report two patients treated with Argon Plasma Coagulation, a 68 years old male with an ethanol related cirrhosis and a 72 years old female with an idiopathic Gastric Antral Vascular Ectasia. The characteristic endoscopic features were mistaken for many years as gastritis. Both patients presented with severe anemia requiring multiple transfusions as treatment. Due to the poor operative risk, both patients were treated with Argon Plasma Coagulation with good results.

[heparin and insulin treatment of acute pancreatitis caused by hypertriglyceridemia. Experience of 5 cases]. / Heparina e insulina en el tratamiento de la pancreatitis aguda por hipertrigliceridemia. Experiencia en 5 casos.

BACKGROUND: Hypertriglyceridemia over 1,000 mg/dl can provoke acute pancreatitis and its persistence can worsen the clinical outcome. On the contrary, a rapid decrease in triglyceride level is beneficial. Plasmapheresis has been performed in some patients to remove chylomicrons from the circulation, while heparin and/or insulin have been administered in some other cases to rapidly reduce blood triglycerides. Heparin and insulin stimulate lipoprotein-lipase activity and accelerate chylomicron degradation. AIM: To report five patients with acute pancreatitis treated with heparin and insulin. PATIENTS AND METHODS: Five patients (4 females and 1 male) seen in the last two years, who suffered acute pancreatitis induced by hypertriglyceridemia are reported. Initial blood triglyceride levels were above 1,000 mg/dl (range 1,590-8,690 mg/dl). Besides the usual treatment of acute pancreatitis, heparin and/or insulin were administered intravenously in continuous infusion. Heparin dose was guided by usual parameters of blood coagulation, and insulin dose, by serial determinations of blood glucose. Pancreatic necrosis was demonstrated in 4 patients. RESULTS: Serum triglyceride levels decreased to < 500 mg/dl within 3 days in all cases. No complication of treatment was observed and all patients survived. Early and late complications of pancreatitis occurred in one patient. CONCLUSION: Administration of heparin and/or insulin is an efficient alternative to reduce triglyceride levels in patients with acute pancreatitis and hypertriglyceridemia.

[Retractile mesenteritis. Report of 4 cases]. / Mesenteritis retráctil. Comunicación de cuatro casos.

Retractile mesenteritis is a rare condition in which the inflammation process of the mesentery is the characteristic pathological. The histologic changes are variable proportions of fat necrosis, chronic inflammation and fibrosis. The clinical presentation of this process is diverse, also the natural history is variable, ranging from a benign to fatal disease. We reviewed 4 cases of retractile mesenteritis and evaluated the clinical manifestations. There was no gender predominance. The patients aged range was 63-69 years (average 65) Patients more often presented with abdominal mass (cases n: 1 and n: 4), and chronic diarrhea (cases n: 1 and 3). The etiology is unknown, the treatment is empirical, including corticosteroids, colchicine, immunosuppressive drugs and oral progesterone.

[Severe Henoch-Schonlein purpura in a patient with multiple myeloma]. / Púrpura de Schönlein-Henoch grave en un paciente con mieloma múltiple.

A Multiple Myeloma (MM), IgG-lambda stage III-A was diagnosed in a 41-year-old-man. After VAD cycles IgG decreased from 7.5 to 2.4 g/dL. were mobilized with cyclophosphamide and 10 micrograms/Kg G-CSF. Three days after the collection of peripheral stem cell, the patient had fever, nausea, vomiting, liquid stools, shoulder and knee arthralgia and dehydration. Upper GI endoscopy showed esophageal candidiasis and ulcerative necrotic lesions both in stomach and duodenum; the biopsy confirmed necrosis. Simultaneously, the appearance of purpura with maculopapular lesions of diverse sizes appeared in the feet progressing to the limbs and trunk. Hematuria and proteinuria were also observed. Skin biopsy showed leukocytoclastic vasculitis. Renal biopsy showed focal and segmental glomerulonephritis. Serum ANCA, cryoglobulins, anti-HCV and RF were negative, and serum monoclonal IgG was 1290 mg/dL. Daily treatment with i.v. methylprednisolone pulses for 3 days improved skin lesions and digestive involvement. Macroscopic hematuria and proteinuria improved after two months of steroid treatment.

Dilinoleoylphosphatidylcholine decreases hepatic stellate cell activation.

The prevention of cirrhosis in alcohol-fed baboons by the administration of a soybean extract-43% to 50% of which was dilinoleoyl-phosphatidylcholine (DLPC) and 24% of which was 1,palmitoyl 2,linoleoyl-phosphatidylcholine (PLPC)-was associated with a significant reduction in the number of stellate cells transformed to myofibroblast-like cells. To study whether these two major phospholipids affect the similar transformation that occurs by culturing stellate cells on uncoated plastic, we assessed their effects on proliferation (by (methyl-3H)-thymidine incorporation into DNA), expression of alpha-smooth muscle actin and type I procollagen (by densitometry of Western blots), and collagen synthesis (by incorporation of tritiated proline into collagenase-digestible proteins). These manifestations of stellate cell activation were decreased by 10 micromol/L DLPC but not by 10 micromol/L PLPC when compared with controls incubated either with 17 mmol/L ethanol (used as solvent for the phospholipids) or without addition. These agents did not affect cell viability, contamination with other cells, or the capacity of stellate cells to synthesize protein. Thus DLPC specifically decreases the in vitro activation of stellate cells, as judged by the decreases in proliferative activity, alpha-smooth muscle actin and procollagen I expressions, and collagen synthesis, whereas PLPC did not show such effects. alpha-Procollagen (type I) mRNA was not affected by DLPC, suggesting a post-translational effect. The reduction in the activation of hepatic stellate cells by DLPC may be responsible for, or at least contribute to, the prevention of fibrosis by the polyenylphosphatidylcholine mixture administered in vivo.

[Cholestatic hepatitis associated with piroxicam use. Case report]. / Hepatitis colestásica por piroxicam: caso clínico.

Most nonsteroidal antiinflammatory drugs can produce hepatotoxicity. We report a 22 years old female who presented with an acute cholestatic hepatitis after a prolonged period of piroxicam use. Hepatitis was attributed to this drug since all markers for hepatitis virus (A, B, C, E, Epstein Barr, Cytomegalovirus and Herpex Simplex) were negative, autoimmune markers were negative, serum iron and ceruloplasmin were normal, there was a temporal relationship between the administration of piroxicam and the hepatitis, the histological picture was compatible with this etiology and the patient had a favorable evolution after the discontinuance of the drug. This type of hepatotoxicity is not common but it must be born in mind when patients must receive nonsteroidal antiinflammatory drugs for prolonged periods.

Collagen synthesis by liver stellate cells is released from its normal feedback regulation by acetaldehyde-induced modification of the carboxyl-terminal propeptide of procollagen.

Acetaldehyde stimulates collagen synthesis in stellate cells and forms adducts with procollagen in the liver of alcoholics. To assess the possibility that modification of the carboxyl-terminal propeptide by acetaldehyde affects its capacity to exert a feedback inhibition of collagen synthesis after splitting from procollagen, the propeptide was prepared by gel filtration of the bacterial collagenase digests of procollagen type I (obtained from 10(9) calvaria fibroblasts of newborn rats) and reacted with either 250 mM acetaldehyde and 100 mM CNBH3 or with 170 microM acetaldehyde without reducing agents, to mimick in vivo conditions. The unmodified propeptide produced a concentration-dependent inhibition of collagen synthesis by Ito cells. By contrast, the acetaldehyde-modified propeptide produced a lesser inhibition of procollagen synthesis in the cells, associated with a greater accumulation of collagen in the media. The incubation with 170 microM acetaldehyde and, to a lesser extent, 50 mM ethanol produced collagenase-digestible adducts in stellate cells. Thus, the formation of acetaldehyde adducts with the carboxyl-terminal propeptide of procollagen may account, at least in part, for the stimulatory effect of acetaldehyde on collagen synthesis by stellate cells and may lead to collagen accumulation through a decrease of the normal feedback regulation of collagen synthesis by the propeptide.

The role of laparoscopy in the diagnosis of cirrhosis.

BACKGROUND: A definitive diagnosis of cirrhosis is important in the prognosis and management of patients with chronic liver disease. The diagnosis of cirrhosis is made either by histologic examination of a biopsy specimen or upon visualization of a diffusely nodular and firm surface of the liver at laparotomy or laparoscopy. A liver biopsy, however, may not demonstrate the histologic features of cirrhosis in some cirrhotic patients. Our goal in this study was to compare the accuracy of liver descriptions made during laparoscopy with liver histology found by laparoscopic biopsy in patients with chronic liver disease. METHODS: A retrospective review of paired laparoscopy and histology reports was performed on 434 consecutive patients who underwent laparoscopy between 1992 and 1994. (M:F ratio, 1.3:1; mean age, 48 +/- 14 years). ETIOLOGY: 52% hepatitis C, 8% hepatitis B, 8% fatty liver, 4% primary biliary cirrhosis, 3% autoimmune hepatitis, and 25% miscellaneous (cancer patients were excluded). RESULTS: One hundred sixty-nine patients had laparoscopic evidence of cirrhosis; 115 were confirmed by histology, representing a 32% sampling error. Two of 265 patients with histologic evidence of cirrhosis (0.8%) had no macroscopic evidence of cirrhosis at laparoscopy. CONCLUSIONS: (1) There was a 32% histologic sampling error among patients documented to have cirrhosis by laparoscopy. (2) Using laparoscopy as a gold standard, the sensitivity of liver biopsy was 68% and the specificity was 99%.

[Correlation between serum globulin levels and hepatitis C virus antibody]. / Correlación entre niveles de globulinas séricas y anticuerpo anti-virus C de la hepatitis.

BACKGROUND: some studies have suggested that the elevation of serum globulins in patients with chronic autoimmune hepatitis, paraproteinemias and rheumatoid arthritis could affect the determination of false positive hepatitis C virus antibodies (anti-HCV). AIM: to study the relationship between positive anti-HCV and serum levels of globulins in patients with liver disease. PATIENTS AND METHODS: one hundred thirty one patients with liver disease, 49 alcoholic, 38 cryptogenetic, 17 autoimmune and 27 with other causes, were studies prospectively measuring simultaneously anti-HCV and serum levels of total, gamma and immuno-globulins (IgA, IgG and IgM). These levels were compared between anti-HCV positive and negative groups and correlated with the ratio between serum optical density/cutoff optical density of the anti HCV assay. RESULTS: Twenty eight patients (21.3%) were anti-HCV positive, no differences in serum globulins between these patients and anti-HCV negative patients and no correlations between serum globulins and anti-HCV optical densities were observed. CONCLUSIONS: the hypergamma-globulinemia observed in these patients with liver diseases would not be responsible for positive hepatitis C virus antibodies.

[Post sinusoidal obstruction of the hepatic venous flow associated with antiphospholipid syndrome in 3 cases]. / Obstrucción postsinusoidal del flujo venoso hepático asociado a síndrome antifosfolípido en 3 casos.

Three cases of post-sinusoidal hepatic blood flow obstruction as the main feature of antiphospholipid syndrome are reported. Clinically, these patients developed jaundice, malaise, ascites and hepatomegaly. Ultrasonography-Doppler and hepatic venography showed small hepatic vein disease in two and partial occlusion in the suprahepatic segment of inferior vena cava in the remaining patient. In all, anticardiolipin antibodies were positive and activated partial thromboplastin time was prolonged. This experience emphasizes that in patients with post sinusoidal portal hypertension, a systematic search for antiphospholipid syndrome must be carried out.

[Microscopic colitis and collagenous colitis. An entity not yet reported in Chile]. / Colitis microscopica y colitis colagena. Una entidad clinica no descrita en Chile.

Collagenous and microscopic colitis have been described as causes for abundant watery diarrhea with a normal radiologic and endoscopic aspect of the colonic mucosa. Microscopic colitis is characterized by diffuse intraepithelial lymphocytic infiltration and collagenous colitis by thickening of subepithelial collagen layer greater than 15 microns with or without inflammatory changes of the mucosa. Here are reported 5 patients with microscopic colitis and 4 with collagenous colitis. The mean age was 52 years (range 40 to 68) with an equal sex distribution. Diarrhea was of longstanding duration without weight loss, anemia or hypoalbuminemia. Occasionally the volume of diarrhea was over 1 L a day. One patient had steatorrhea that proved resistant to a gluten free diet. Endoscopic and radiologic findings were normal in every patient and the diagnosis was based on typical histology. Azulfidine therapy was successful in 7 patients and prednisone in another. Colonic biopsy should be performed in every patient with chronic diarrhea.

S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results.

S-Adenosyl-L-methionine has been reported to induce beneficial effects in intrahepatic cholestasis of pregnancy. Because cholestasis of pregnancy has a high prevalence in Chile and a deleterious effect on fetal prognosis, we decided to verify the efficacy of S-adenosyl-L-methionine in this disease. Eighteen patients with pruritus that appeared during pregnancy and with elevated serum levels of bile salts (68.1 +/- 15.9 mumol/L; mean +/- S.E.M.) and ALT (226 +/- 50 KU/L) were enrolled in a prospective double-blind study comparing the effects of the drug with a placebo. S-Adenosyl-L-methionine, 900 mg, or placebo was administered in daily intravenous infusions for 20 days. Every 5 days liver function tests were done and pruritus was assessed using a preestablished score. No significant differences in pruritus or in serum levels of bile salts, ALT, bilirubin and alkaline phosphatases were seen during or after treatment between patients who received S-adenosyl-L-methionine (n = 9) or placebo (n = 9). No relevant adverse reactions were detected. Most patients had cesarean sections because of reasons unrelated to the therapeutic trial. All newborns had Apgar scores greater than 7 and normal postnatal development. Our patients had moderately severe to severe cholestasis of pregnancy as indicated by the onset of pruritus before wk 32 of pregnancy. Seven of nine multiparous patients had a past history of recurrent cholestasis of pregnancy. In this study, the administration of S-adenosyl-L-methionine during 20 days did not improve intrahepatic cholestasis of pregnancy.

[Spontaneous bacterial peritonitis: a frequent and recurrent complication in cirrhotic patients with ascites]. / Peritonitis bacteriana espontánea: una complicación frecuente y recurrente en pacientes cirróticos con ascitis.

One hundred and twenty consecutive patients with liver cirrhosis and ascites were prospectively studied in order to analyze the frequency, clinical and bacteriological features, recurrence, and prognosis of spontaneous bacterial peritonitis (SBP). Two variants of SBP were defined: culture positive SBP and culture negative neutrocytic ascites (CNNA). During a follow-up of 6 +/- 2 months, thirty three episodes in 23 patients were identified. Nineteen episodes had ascites positive cultures (58%). The total mortality rate associated with SBP was 39%. (47% for culture positive form and 29% for CNNA). Seven of 15 cirrhotics who had recovered from a first episode of SBP (46%) had 10 recurrences. Mortality associated with SBP recurrence was 50%. Six-month survival probability was 65% in patients with sterile ascites and 33% in SPB (p < 0.05). Impairment of liver function was present in 23 episodes (70%) but abdominal complaints occurred only in one/third and 4 (12%) were asymptomatic. E coli was the most frequent agent involved in culture positive SBP. We confirm that SBP is a frequent, recurrent and severe complication of ascites in cirrhotics. Episodes of SBP without abdominal symptoms or with a silent course are not infrequent. Then, SBP recognition requires ample use of diagnostic paracentesis.