Guidelines for the management of primary biliary cirrhosis
2014; Wiley; Volume: 44; Issue: S1 Linguagem: Inglês
10.1111/hepr.12270
ISSN1872-034X
Tópico(s)Pediatric Hepatobiliary Diseases and Treatments
ResumoHepatology ResearchVolume 44, Issue S1 p. 71-90 Special ReportFree Access Guidelines for the management of primary biliary cirrhosis The Intractable Hepatobiliary Disease Study Group supported by the Ministry of Health, Labour and Welfare of Japan Working Subgroup (English version) for Clinical Practice Guidelines for Primary Biliary Cirrhosis, Corresponding Author Working Subgroup (English version) for Clinical Practice Guidelines for Primary Biliary CirrhosisWorking Subgroup (English version) for Clinical Practice Guidelines for Primary Biliary Cirrhosis (in alphabetical order): Atsumasa Komori, Clinical Research Center, National Hospital Organization Nagasaki Medical Center; Atsushi Tanaka, Department of Medicine, Teikyo University School of Medicine; Hajime Takikawa, Department of Medicine, Teikyo University School of Medicine; §Hirohito Tsubouchi, Digestive Disease and Life-style Related Disease, Kagoshima University Graduate School of Medical and Dental Sciences and Kagoshima City Hospital; †Hiromi Ishibashi, International University of Health and Welfare/Fukuoka Sanno Hospital and Clinical Research Center, National Hospital Organization Nagasaki Medical Center; Hiroto Egawa, Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University; Junko Hirohara, Third Department of Internal Medicine, Kansai Medical University; Ken Shirabe, Department of Surgery and Science, Kyushu University; Kenichi Harada, Department of Human Pathology, Kanazawa University Graduate School of Medicine; Makoto Nakamuta, Department of Gastroenterology, National Hospital Organization Kyushu Medical Center; Mikio Zeniya, Department of Gastroenterology, Jikei University Graduate School of Medicine; Minoru Nakamura, Clinical Research Center, National Hospital Organization Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences; Nobuyoshi Fukushima, Department of Gastroenterology, National Hospital Organization Kyushu Medical Center; Shinji Shimoda, Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University; Shotaro Sakisaka, Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine; Toshio Morizane, Japan Council for Quality Health Care; Yasuaki Takeyama, Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine; ‡Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine; Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University Faculty of Medicine (†Chairperson of the Working Group, ‡Chairperson of the PBC Subcommittee, §Chairperson of the Intractable Hepatobiliary Disease Study Group).*Correspondence: Hiromi Ishibashi, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan. Email: [email protected]Search for more papers by this author Working Subgroup (English version) for Clinical Practice Guidelines for Primary Biliary Cirrhosis, Corresponding Author Working Subgroup (English version) for Clinical Practice Guidelines for Primary Biliary CirrhosisWorking Subgroup (English version) for Clinical Practice Guidelines for Primary Biliary Cirrhosis (in alphabetical order): Atsumasa Komori, Clinical Research Center, National Hospital Organization Nagasaki Medical Center; Atsushi Tanaka, Department of Medicine, Teikyo University School of Medicine; Hajime Takikawa, Department of Medicine, Teikyo University School of Medicine; §Hirohito Tsubouchi, Digestive Disease and Life-style Related Disease, Kagoshima University Graduate School of Medical and Dental Sciences and Kagoshima City Hospital; †Hiromi Ishibashi, International University of Health and Welfare/Fukuoka Sanno Hospital and Clinical Research Center, National Hospital Organization Nagasaki Medical Center; Hiroto Egawa, Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University; Junko Hirohara, Third Department of Internal Medicine, Kansai Medical University; Ken Shirabe, Department of Surgery and Science, Kyushu University; Kenichi Harada, Department of Human Pathology, Kanazawa University Graduate School of Medicine; Makoto Nakamuta, Department of Gastroenterology, National Hospital Organization Kyushu Medical Center; Mikio Zeniya, Department of Gastroenterology, Jikei University Graduate School of Medicine; Minoru Nakamura, Clinical Research Center, National Hospital Organization Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences; Nobuyoshi Fukushima, Department of Gastroenterology, National Hospital Organization Kyushu Medical Center; Shinji Shimoda, Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University; Shotaro Sakisaka, Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine; Toshio Morizane, Japan Council for Quality Health Care; Yasuaki Takeyama, Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine; ‡Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine; Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University Faculty of Medicine (†Chairperson of the Working Group, ‡Chairperson of the PBC Subcommittee, §Chairperson of the Intractable Hepatobiliary Disease Study Group).*Correspondence: Hiromi Ishibashi, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan. Email: [email protected]Search for more papers by this author First published: 07 January 2014 https://doi.org/10.1111/hepr.12270Citations: 72 AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL 1. Introduction The Japanese version of the clinical practice guidelines for primary biliary cirrhosis (PBC) was developed in 2012 by the Intractable Hepatobiliary Disease Study Group, with the support of the Ministry of Health, Labour and Welfare of Japan, for the use of general physicians, gastroenterologists and hepatologists who treat patients with PBC. In preparation for developing the guidelines, the study group reviewed recent studies that provided important evidence or that were published in leading journals with a high impact factor, in addition to considering the formal consensus of experts on PBC or related subjects. Using the core keywords "primary biliary cirrhosis," a PubMed search was conducted for English-language clinical trials, randomized clinical trials (RCTs) and meta-analyses that were published from January 1998 to December 2009 and that addressed treatment of PBC and its complications, follow-up, indication of and time of consultation for liver transplantation, or time of consultation with specialists. Medical systems and other culture-specific factors in Japan were also taken into account. Members of the task force exchanged ideas frequently during the drafting process to try and establish a consensus. The final draft was made after collecting comments from the public and all the committee members. The level of evidence (LE; Table 1) and the grade of recommendation (GR; Table 2) were based on the Medical Information Network Distribution Service in Japan (MINDS). Table 1. Level of evidence (LE) 1a Systematic review/meta-analysis of RCTs 1b Based on one or more RCTs 2a Based on non-randomized control study (prospective study) 2b Based on non-randomized control study (historical cohort study and retrospective cohort study) 3 Case control study 4 Analytical epidemiological study (cross-sectional study) 5 Descriptive study (case report or case series) 6 Opinion of expert committee, or an expert, not based on patient data Table 2. Grade of recommendation (GR) A Strong recommendation, with high level of evidence B Moderate recommendation, with certain level of evidence * Supported by an intermediate level of evidence and considered to be clinically useful * Supported by a high level of evidence but not considered to be clinically very useful * Evidence level is low, but usefulness has already been established in clinical practice C1 Recommendation to be done, without a high level of evidence C2 Recommendation not to be done, without a high level of evidence D Recommendation not to be done, as evidence indicates ineffectiveness or harm After being modified by recent literatures published since 2010, the present English version of the guidelines was developed in order to spread our ideas and exchange opinions with physicians who are involved in the management of PBC patients overseas. These clinical practice guidelines should be revised at appropriate intervals to incorporate advances in methodology and treatment. 2. Diagnosis of PBC Diagnosis of PBC: general principles PBC is an autoimmune-mediated, chronic cholestatic liver disease that predominantly affects middle-aged women. The initial symptom is most often pruritus, though the disease generally progresses insidiously without symptoms for many years. Jaundice progresses without improvement once it becomes overt, and portal hypertension occurs at a high rate. Clinically, increased levels of serum biliary enzymes [alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT)] and detection of antimitochondrial antibodies (AMAs) are characteristic. AMAs are found in 95% of patients with PBC when using the most sensitive detection techniques, and have specificity of 98% for the disease (Supporting information Memo 1). Approximately 20–30% of PBC patients are positive for anti-nuclear pore proteins, e.g., anti-gp210, and/or anti-centromere antibodies. Most patients with PBC have an elevated serum IgM concentration, although high serum IgM is not highly specific or sensitive for diagnosis of PBC. The total gamma globulin concentration remains normal until late in the disease when cirrhosis develops. Histologically, chronic non-suppurative destructive cholangitis (CNSDC) is seen in the intrahepatic small bile ducts at the level of the interlobular and septal bile ducts. Disease progression in PBC results in bile duct loss and liver fibrosis, which develop into biliary cirrhosis and, in some cases, hepatocellular carcinoma. The differential diagnosis includes autoimmune hepatitis, primary sclerosing cholangitis, drug-induced chronic cholestasis, and paucity of intrahepatic bile ducts, after excluding obstructive jaundice and cholestatic diseases of known etiologies. Recommendations: Patients with one of the following criteria should be diagnosed with PBC: (1) histologically confirmed CNSDC with laboratory findings compatible with PBC; (2) positivity for AMAs with histological findings compatible with PBC but in the absence of characteristic histological findings of CNSDC; and (3) no histological findings available, but positivity for AMAs as well as clinical findings and a course indicative of typical cholestatic PBC. (GR A) Diagnosis of PBC should be performed using the criteria endorsed by the Intractable Hepatobiliary Disease Study Group with the support of the Japanese Ministry of Health and Welfare (2010 version, Table 3). (GR A) Differential diagnosis should be performed for a spectrum of diseases that manifest chronic cholestatic liver dysfunction or immunological disorder with autoantibodies (Table 4). (GR A) Non-invasive imaging of the liver and biliary trees should be considered mandatory to exclude diseases manifesting as obstructive jaundice. (GR A) Table 3. Diagnosis of PBC endorsed by the Intractable Hepatobiliary Disease Study Group in Japan (2010 version) With histological findings 1) Biochemical evidence of cholestasis accompanied by histological evidence of CNSDC 2) Presence of AMA accompanied by histologically compatible features of PBC, even without CNSDC Without histological findings 3) Presence of AMA accompanied by clinical features and course of classical and cholestatic PBC Table 4. Differential diagnosis of PBC 1) Cholestatic liver diseases Intrahepatic cholestasis: chronic drug-induced cholestasis Primary sclerosing cholangitis IgG4-related sclerosing cholangitis Adult-onset bile duct paucity Obstructive jaundice 2) Diseases with immunological abnormalities Autoimmune hepatitis Drug-induced liver injury 3) Elevation of serum ALP and/or GGT Space occupying lesions of the liver Bone lesions Hyperthyroidism Fatty liver diseases Diagnosis of atypical PBC Pathognomonically-related but atypical PBC cases that do not fulfill the diagnostic criteria should be handled distinctively and appropriately; treatment strategies for these cases are different from those for typical PBC. Early PBC AMA may be detectable in the serum of individuals without symptoms of PBC and with normal liver tests. Histopathological changes of PBC with no or mild progression are apparent and this condition is designated early PBC. Follow-up without medication is appropriate. Autoimmune cholangitis, autoimmune cholangiopathy Patients whose clinical features are compatible with PBC may be negative for AMA but have a high titer of antinuclear antibody (ANA) in their serum. In 1987, Brunner and Klinge first described this condition as immunocholangitis, while others have used different terminology, such as autoimmune cholangiopathy, primary autoimmune cholangitis, or autoimmune cholangitis. The current understanding is that this condition is atypical PBC. AMA-negative PBC Approximately 10% of patients who have biochemical evidence of cholestasis, accompanied by histological features of PBC, are negative for AMA. Autoreactive T cells in these patients react with mitochondrial antigen, despite being negative for AMA. Special consideration for their treatment is not warranted. PBC–AIH overlap syndrome Patients with PBC who manifest clinicopathological features of autoimmune hepatitis (AIH) in conjunction with elevated levels of aminotransferases could be recognized. These cases have also been referred to as PBC with features of AIH. Prednisolone may effectively reduce aminotransferase levels in such cases. Diagnosis of PBC: symptoms, signs, and complications Approximately 70–80% of PBC cases are diagnosed in the early and asymptomatic phase. Although this phase is likely to persist for years, the clinical and histological progression precipitates several symptoms (symptomatic PBC). The symptoms and complications of PBC include cholestasis, liver injury, and comorbid autoimmune disease(s) (Table 5). Table 5. Symptoms and complications of PBC Symptoms 1) None of the following 2) General fatigue 3) Cholestasis-associated Pruritus (scratching) Jaundice 4) Liver injury and cirrhosis-associated Hematemesis and melena Abdominal fullness Consciousness disturbance 5) Comorbid autoimmune diseases -associated Sicca syndrome, etc. Complications 1) Cholestasis-associated Osteoporosis Hyperlipidemia 2) Liver injury and cirrhosis-associated Portal hypertension Hepatocellular carcinoma Ascites Hepatic encephalopathy 3) Comorbid autoimmune diseases -associated Sjögren's syndrome Rheumatoid arthritis Hashimoto thyroiditis, etc. Pruritus accompanied by cholestasis is characteristic of PBC. It may occur initially before overt jaundice. Prolonged cholestasis results in jaundice, xanthoma coupled with lipid abnormalities, and osteoporosis-related bone lesions/fractures. Persistent fatigue is another common symptom, occurring in 20–70% of Caucasian patients, although less frequently in Japanese patients. No correlation has been found between fatigue and age, sex, jaundice, liver function parameters, or histological stage of the disease. PBC patients can experience profound distress associated with fatigue. Cirrhosis-associated symptoms include esophagogastric varices. Portal hypertension is more likely to occur in PBC than in liver diseases with other etiologies, and can develop even in the non-cirrhotic stage of PBC; some patients are diagnosed by the presence of esophagogastric variceal bleeding as an initial symptom. Prevalent comorbid autoimmune diseases include Sjögren's syndrome, Hashimoto thyroiditis, and rheumatoid arthritis. aPBC may be masked by the symptoms of comorbid autoimmune diseases. Appropriate diagnosis of comorbid autoimmune diseases is important because they may influence the outcome of PBC. Diagnosis of PBC: pathological examinations PBC is histologically characterized by autoimmune-mediated progressive destruction of the intrahepatic small bile ducts, as well as by chronic intrahepatic cholestasis, hepatocellular damage, fibrosis, and septal formation. Bile duct damage PBC is histologically characterized by CNSDC and progressive bile duct loss, which preferably affects the intrahepatic small bile ducts, especially the interlobular bile ducts. Non-caseating epithelioid granuloma formation is often seen in the portal tracts. Granulomatous cholangitis consisting of CNSDC and periductal granuloma formation is valuable for pathological diagnosis. CNSDC is characterized by marked lymphoplasmacytic accumulation around the damaged bile ducts, and lymphoid cell infiltration is found in the biliary epithelial layer of CNSDC. Some biliary epithelial cells in CNSDC show eosinophilic apoptotic changes and swelling. Moreover, chronic cholangitis, which does not fulfill the criteria of CNSDC, is also found. Bile duct loss is seen during the progression of PBC, and the interlobular bile ducts are mostly lost in the terminal cirrhotic stage. The presence of arteries in the absence of bile ducts is useful for identification of bile duct loss or ductopenia. Parenchymal change In the early stage of PBC, non-specific necroinflammatory changes are found in the parenchyma. Interface hepatitis and chronic cholestatic changes are also found. During the progression of irreversible bile duct damage and loss, there are several characteristic findings that reflect cholestasis, including ductular reaction (proliferating bile ductules), copper deposition (orcein-positive granules), bile plaques, hepatocellular ballooning (cholate stasis), Mallory–Denk bodies, and feathery degeneration. These features are associated with the progression of biliary fibrosis and biliary cirrhosis. Changes similar to small cell dysplasia are also often found in zone 1 (periportal area), which is useful for the diagnosis of PBC. In addition to these cholestatic changes reflecting bile duct loss, chronic hepatitic changes resembling autoimmune hepatitis, such as interface and lobular hepatitis, are also found in most PBC cases, and are involved in the progression of hepatic fibrosis and cirrhosis. Histological staging The characteristic histological findings of PBC are heterogeneously distributed throughout the liver. Thus, in small specimens such as those taken from needle liver biopsy, sampling errors are likely to be recognized when using the classification systems of Scheuer and Ludwig, because these two systems define each stage by a sole histological feature (Supporting information Memo 2). Therefore the novel staging system of Nakanuma (2009) (Tables 6-8) is recommended for histological staging of PBC, as this system could avoid the sampling errors caused by the heterogeneous distribution of histological features. Table 6. Histological staging of PBC Stage 1 no progression Stage 2 mild progression Stage 3 moderate progression Stage 4 advanced progression Table 7. Histological staging system of PBC (Nakanuma et al.) I. Histological findings and scoring for the determination of stage of PBC A. Scoring of fibrosis Score 0 No portal fibrosis, or fibrosis limited to portal tracts Score 1 Portal fibrosis with periportal fibrosis or incomplete septal fibrosis Score 2 Bridging fibrosis with variable lobular disarray Score 3 Liver cirrhosis with regenerative nodules and extensive fibrosis B. Scoring of bile duct loss Score 0 No bile duct loss Score 1 Bile duct loss in < 1/3 of portal tracts Score 2 Bile duct loss in 1/3 to 2/3 of portal tracts Score 3 Bile duct loss in > 2/3 of portal tracts C. Scoring of deposition of orcein-positive granules Score 0 No deposition of granules Score 1 Deposition of granules in a few periportal hepatocytes in < 1/3 of portal tracts Score 2 Deposition of granules in several periportal hepatocytes in 1/3 to 2/3 of portal tracts Score 3 Deposition of granules in many hepatocytes in > 2/3 of portal tracts II. Staging by sum total of two (A and B) or three (A, B, and C) criteria Stage Sum of scores Two criteriaa Three criteriab Stage 1 (no progression) 0 0 Stage 2 (mild progression) 1–2 1–3 Stage 3 (moderate progression) 3–4 4–6 Stage 4 (advanced progression) 5–6 7–9 a Two criteria: fibrosis and bile duct loss. b Three criteria: fibrosis, bile duct loss and deposition of orcein-positive granules. Table 8. Grading of chronic cholangitis and hepatitis activity in PBC I. Cholangitis activity (CA) CA0 (no activity) No cholangitis, but mild duct damage may be present CA1 (mild activity) One bile duct with evident chronic cholangitis CA2 (moderate activity) ≥2 bile ducts with evident chronic cholangitis CA3 (marked activity) ≥1 bile duct with CNSDC (CNSDC: chronic nonsuppurative destructive cholangitis.) II. Hepatitis activity (HA) HA0 (no activity) No interface hepatitis, and no or minimum lobular hepatitis HA1 (mild activity) Interface hepatitis affecting > 10 continuous hepatocytes in 1 portal tract or fibrous septa, and mild to moderate lobular hepatitis HA2 (moderate activity) Interface hepatitis affecting > 10 continuous hepatocytes in ≥2 portal tracts or fibrous septa, and mild to moderate lobular hepatitis HA3 (marked activity) Interface hepatitis affecting > 20 continuous hepatocytes in ≥ 1/2 of portal tracts, and moderate lobular hepatitis or bridging or zonal necrosis Recommendations: The novel system for histological grading and staging of PBC proposed by Nakanuma et al. is recommended (LE6, GRC1). Diagnosis of PBC: clinical staging and disease severity Clinical staging PBC is classified into two groups depending on the absence or presence of symptoms caused by liver damage: aPBC and sPBC. aPBC is considered the non-advanced stage (stage I), while sPBC is considered the advanced stage. sPBC is further classified as s1PBC, with serum bilirubin level 10 Albumin (g/dL) 3.5< 2.8–3.5 <2.8 PT (%) 70%< 40–70% <40% INR 2.3 Ascites None Mild Moderate Encephalopathy None Grade1–2 Grade 3–4 Grade A: 5–6 points; Grade B: 7–9 points; Grade C: 10–15 points. Diagnosis of PBC: clinical type and prognosis Clinical type The progression of PBC varies among individuals, and more than 70% of those with aPBC do not progress over 10 years. PBC is largely classified into three clinical types (Fig. 1) . Many patients progress gradually and remain in the asymptomatic stage for longer than a decade (gradual progressive type). However, some patients progress to portal hypertension presenting without jaundice (portal hypertension type), and others progress rapidly to jaundice and ultimately hepatic failure (jaundice/hepatic failure type). The jaundice/hepatic failure type tends to affect relatively younger patients compared to the other two types. Patients with the jaundice/hepatic failure-type PBC are often positive for anti-gp210 antibody, while those with the portal hypertension-type PBC have anti-centromere antibodies (Supporting information Memo 3). Figure 1Open in figure viewerPowerPoint Three types of natural course of PBC. Prognosis Several models for predicting the prognosis of PBC have been proposed. In the updated Mayo Clinic Natural History Model for PBC, the key factors are age, serum total bilirubin, albumin, prothrombin time (PT), edema/ascites, and use of diuretics. This model is used worldwide to predict the prognosis of PBC patients. The updated version is better than the original one for prediction of shorter prognosis (Supporting information Memo 4). In the logistic model developed by the Japanese Liver Transplantation Study Group (Ref.VII-1) (Supporting information Memo 5), serum total bilirubin and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio are necessary. The probability of death after 6 months is calculated by means of a logistic regression formula, and transplantation is recommended if the value exceeds 50%. Finally, for the MELD (Model for End-Stage Liver Disease) score, the serum creatinine level, total bilirubin, and prothrombin time (PT) are the key factors. The MELD score is used for the evaluation of end-stage liver failure. The score is high if hepatorenal syndrome is present, and the pre-transplantation value correlates well with the likelihood and magnitude of complication after liver transplantation. Therefore, it is recommended that transplantation should be performed before complication by hepatorenal syndrome (Supporting information Memo 6). The common factor among these different schemes is serum total bilirubin. A life expectancy of 10 years is predicted for patients with a serum bilirubin level 6.0 mg/dL. Recommendations: Total bilirubin, prothrombin (INR), albumin, and the serum creatinine level, which are essential to calculate the MELD score, should be measured when considering liver transplantation. (LE 2b (2a in part), GR A) Patients with PBC should be referred to transplant hepatologists when serum total bilirubin level is >5 mg/dL. To encourage the patients to prepare for liver transplantation, an earlier and appropriate explanation of liver transplantation is desirable. (LE 4, GR B) 3. Treatment and Management of PBC Treatment and management of PBC: general principles Although there is no completely curative treatment for PBC, ursodeoxycholic acid (UDCA) is currently considered the first-line treatment for the disease. UDCA delays the progression of PBC, although it does not have a significant benefit for PBC at the advanced stage. The clinical usefulness of UDCA is evaluated according to the following factors: (i) improvement of serum biochemical markers, such as ALP, GGT, AST, ALT and total bilirubin; (ii) histological improvement of cholangitis, liver inflammation and liver fibrosis; and (iii) delay in the disease progression until end-stage liver disease, death, or liver transplantation. The following Paris and Barcelona criteria are useful for evaluating the clinical outcome of UDCA treatment. (i) Paris criteria: total bilirubin ≤1.0 mg/dL, ALP ≤3 × the upper normal limit (UNL), and AST ≤ 2 × UNL at 1 year after introduction of UDCA. (ii) Barcelona criteria: decrease of ALP ≥40% at 1 year after introduction of UDCA. Liver transplantation is the only therapeutic approach for patients in the advanced stage when medical treatment shows little improvement. Prevention and treatment strategies for comorbid autoimmune diseases, cholestasis, and cirrhosis-related symptoms and complications are required. Although the term cirrhosis is included in the name PBC, most patients (70–80%) with PBC have little clinical and histological evidence of liver cirrhosis. Patients should be informed accordingly to prevent misunderstanding of their prognoses. Currently, patients are likely to be diagnosed at earlier stages and disease progression is likely to be delayed by UDCA. Therefore, the prognosis of patients with aPBC, as long as they remain asymptomatic, is equivalent to that in the general population. No restrictions are necessary in daily life for patients with aPBC. By cont
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