Nephrology JC078: Glomerular And Tubulo-interstitial Diseases And Acute Kidney Injury

Question 1

***Renal parenchymal disease (GN)

Answer 1

Renal parenchyma:
- Functional tissue of kidney, consisting of ***Nephrons (basic unit)

Classification of glomerulonephritis by ***glomerular cellularity (Proliferative / Non-proliferative) in kidney biopsy

Primary glomerular diseases (i.e. no cause found)
- Proliferative
1. IgA nephropathy (IgAN)
2. Membranoproliferative GN (MPGN)
3. Crescentic GN
4. IgM nephropathy

• Non-proliferative
  1. Minimal change nephrotic syndrome
  2. Membranous nephropathy
  3. Focal segmental glomerulosclerosis (FSGS)
  4. Thin membrane disease (TBMD)

—> ALL above terms are ***morphological description under microscope

Secondary glomerular diseases
- Proliferative
1. Lupus nephritis
2. Post-streptococcal GN
3. Hep B / C-related MPGN
4. Systemic vasculitis
5. Goodpasture syndrome

• Non-proliferative
  1. Diabetic nephropathy
  2. Hypertensive nephrosclerosis
  3. Amyloidosis
  4. Light/Heavy chain deposition disease
  5. Alport syndrome
  6. Infection-related membranous glomerulopathy
  7. HIV nephropathy (FSGS / Collapsing glomerulopathy)
  8. Drug-induced glomerulopathy
  9. Malignancy-associated nephropathy
  10. Reflux nephropathy

Question 2

Classification of Glomerular disease

Answer 2

Usually by different patterns of histologic injury seen on biopsy

NO single classification is ideal
- one histologic pattern can have **multiple etiologies (e.g. membranous pattern can be idiopathic / due to lupus / viral hepatitis infection)
- one etiology may produce a **variety of histologic patterns (e.g. lupus nephritis (class 1-6 with different morphological pattern), IgAN, HBV infection)
- one histologic pattern can have ***multiple clinical presentations (e.g. IgA nephropathy may present with asymptomatic microscopic haematuria / synpharyngitic gross haematuria / RPGN)

Question 3

***Clinical features of Renal parenchymal disorders

Answer 3

Glomerulonephritis (present with 1 of 6 clinical syndromes):
1. Asymptomatic microscopic haematuria / proteinuria
2. Macroscopic haematuria
3. Acute nephritic syndrome
4. Nephrotic syndrome
5. Rapidly progressive glomerulonephritis
6. Chronic glomerulonephritis / CKD

Question 4

1. Asymptomatic haematuria

Answer 4

Features:
- Either Macroscopically / Microscopically (>2 RBC per high power field in spun urine) detected blood in urine, usually **dysmorphic
—> irregularities of RBC membrane
—> **acanthocytes (with ring-formed cell bodies with blebs of different size / shape)
—> may clump together to form **RBC cast (tubular shape) when pass through tubules
- Detected through health check, pre-employment, pre-school etc.
- Usually with **normal GFR + **no evidence of systemic disease
- Variable degrees of **proteinuria may be present, usually ***<1 g/day (low-grade)

Question 5

Macroscopic haematuria

Answer 5

**Episodic **painless macroscopic haematuria associated with glomerular disease
—> often ***brown / smoky urine rather than red
—> blood clots are unusual (clots usually indicate Lower UT bleeding)

Question 6

***DDx of Haematuria

Answer 6

Urological conditions:
1. Stones
2. Tumours

Renal conditions:
1. **Glomerulonephritis
- **IgA nephropathy —> usually Gross
- **Alport syndrome (Hereditary nephritis) (hearing deficit common) —> usually Gross
- **Thin membrane disease (TBMD) (Benign familial haematuria)
2. ***Acute interstitial nephritis
3. Polycystic kidney disease

Infection:
1. Cystitis
2. TB
3. Schistosomiasis

Question 7

Alport syndrome

Answer 7

• Mutations of ***Type 4 collagen genes
• Cochlea
  —> ↓ Adhesion of Organ of Corti (auditory sensory cells) to Basilar membrane via defective alpha-3-4-5 type 4 collagen
  —> Deafness

Inheritance:
- ***X-linked in 80%
- No male-to-male transmission
- Women with X-linked Alport syndrome are heterozygous carriers of the disease mutation
—> almost all have some degree haematuria + some develop renal failure (∵ lyonisation, a random X-inactivation phenomenon)

Question 8

***Evaluation of Haematuria

Answer 8

1. IgAN
2. Alport’s syndrome (Hereditary nephritis) (hearing deficit common)
3. Thin membrane disease (Benign familial haematuria)
   —> Above conditions can be distinguished by **history + **urinalysis of family members

History taking:
1. **Gross haematuria
- common in **IgAN (haematuria often occur after an episode of mucosal infection e.g. URTI) + ***Alport syndrome
- unusual in TBMD (<10%)

2. ***Family history of CKD
   - Alport syndrome (renal failure / deafness (primarily in males), X-linked dominant mode of inheritance)
   - IgAN (run in families but no particular mode of inheritance ∵ polygenic / multi-hit theory)
3. ***Electron microscopy of Membrane thickness
   - TBMD: 150-225 nm (normal 300-400 nm) —> cannot guard against RBC leakage from blood to urine —> microscopic haematuria

Question 9

Investigations for Haematuria

Answer 9

1. RFT
2. ***Urine culture / cytology / AFB
3. ***Urinalysis
4. ***Urine microscopy (crystal for presence of stone)
5. KUB
6. ***USG / Doppler
   - stones with acoustic shadowing
7. Cystoscopy (look for bladder space occupying lesion)
8. IVP (IV pyelogram) / RP (retrograde pyelogram)
9. CT urogram (high radiation exposure: 2x IVP)
10. ***Pure tone audiometry (Alport syndrome)
11. **Renal biopsy (to ascertain cause)
    - usually not required in isolated haematuria
    - indicated with concomitant **significant proteinuria (e.g. >1 g/day)

Question 10

2. Isolated proteinuria

Answer 10

Normal <150 mg (40-80)
- ***10mg is albumin

Urine albumin:
- Normal **<20 mg/day (15 ug/min)
- Persistent microalbuminuria: **30-300 mg/day (20-200 ug/min)
- Macroalbuminuria / Overt proteinuria: ***>=300 mg/day (200 ug/min) —> standard dipstick becomes +ve

(Nephrotic syndrome: >3.5g protein / day)

Question 11

***Evaluation of Proteinuria

Answer 11

1. Dipstix
   - screening for detecting proteinuria
   - ***>=1+ should undergo confirmation by quantitative measurement
   - measures albumin concentration via a colourimetric reaction between albumin and tetrabromophenol blue —> produce different shades of green according to concentration of albumin in sample
   —> trace: 15-30 mg/dL
   —> 1+: 30-100
   —> 2+: 100-300
   —> 3+: 300-1000
   —> 4+: >1000
2. Spot urine (convenient + accurate as Timed urine)
   - **Urine protein-to-creatinine ratio
   —> Normal: <0.2 mg/mg
   —> **>3.5 mg/mg: Nephrotic range for proteinuria
   - first morning urine preferred, random sample acceptable
3. Timed urine (24 hour)

Patients with >=2 positive quantitative tests (spaced by 1-2 weeks)
—> diagnosed as ***Persistent proteinuria
—> Further evaluation needed

Monitoring proteinuria:
- by Quantitative measurements (rather than Dipstix)

Question 12

Pitfalls in Proteinuria assessment

Answer 12

False positive results:
1. **Strenuous exercise within 24 hours
2. Concomitant systemic infection
3. **UTI
4. Fever
5. **Pregnancy (kidney bloodflow markedly ↑)
6. **Marked HT
7. Haematuria

Question 13

Orthostatic proteinuria

Answer 13

• ↑ Protein excretion in upright position but not when supine
• Mechanism unclear, ?Neurohumoral activation
• ***Benign condition in young subjects
• Proteinuria <1 g/day, but may >3 g/day
• ***Split urines (Erect + Supine urine) are collected to identify this condition
• Requires no further evaluation / specific therapy —> ***resolves over time

Question 14

***3. Acute nephritic syndrome

Answer 14

Features:
- **Abrupt onset of **macroscopic haematuria
- **Oliguria
- **Acute renal failure (abrupt ↓ in renal function)
- **Fluid retention (edema + HT)
- Urinary protein **<3 g/day

Disease
1. Post-streptococcal GN

Question 15

Post-streptococcal GN

Answer 15

Children 2-10 yo predominantly

Pathogenesis:
- Streptococcal Ag “planted” in glomerulus during early phase of streptococcal infection
—> 10-14 days later by host immune response against Streptococcal Ag in glomerulus
—> formation of ***Immune complexes
—> kidney damage

Clinical picture:
- Acute, reversible disease characterised by **spontaneous recovery in vast majority
- **Gross haematuria, Oliguria, HT, Edema: develop ***7 days - 12 weeks after streptococcal infection (throat / skin)
- Spontaneous resolution of clinical manifestations generally rapid
—> diuresis resolves within 1-2 weeks
—> renal function return normal within 4 weeks

Investigation:
1. Total haemolytic complement activity / **C3 concentration ↓
- persistently low C3 >8 weeks —> possibility of **Lupus nephritis / **MPGN
2. **Anti-Streptolysin O ↑ (but not all strains produce Streptolysin O)
3. Diffuse hypercellularity on biopsy (i.e. ***Proliferative)
4. Subepithelial deposits (Immune complex) on electron microscope

Question 16

Treatment of Acute nephritic syndrome

Answer 16

Depends on etiology

Acute Post-streptococcal GN:
1. **Penicillin (may be indicated)
2. During Oliguric phase
- **Supportive therapy (fluid / salt restriction, Anti-HT)
- +/- ***Temporary dialysis may be needed (grossly edematous, high serum urea, creatinine)

Question 17

***4. Nephrotic syndrome

Answer 17

Features:
1. Massive proteinuria (>3.5 g/day or 40 mg/hr/m^2 in children)
2. Generalised edema
3. Hypoalbuminaemia (<30 g/L)
4. Hyperlipidaemia + Lipiduria (varying degrees)

Clinical presentations:
1. **Periorbital edema in early morning (resolves during day under gravity)
2. **Dependent ankle edema
3. **Xanthelasma
4. **Muehrcke’s bands (transverse white bands grew on nails during a transient period of hypoalbuminaemia)

Electron microscopy:
- Primary, Secondary, Tertiary, Quaternary processes of podocytes are lost —> ***Effacement of podocytes

Causes:
Primary renal diseases:
1. FSGS
2. Membranous GN
3. Minimal change disease
4. MPGN
5. IgAN (occasionally)

Systemic diseases:
1. DM Type 2
2. SLE
3. Secondary membranous nephropathy
- **Infection: HBV, HCV, HIV, malaria, syphilis
- **Malignancy: lymphoma, adenocarcinoma (lung, GI tract, breast), myeloma
- ***Drugs: penicillamine, gold, mercury, NSAIDs, probenecid
4. Amyloidosis
(5. Cryoglobulinaemia
6. Renal vein thrombosis
7. Kimura’s disease (JC Teaching Clinic))

Question 18

Investigation of Nephrotic syndrome

Answer 18

1. CBC
2. Renal biochemistry
3. ***Urine protein quantification (spot / 24 hour urine)
4. ***FG
5. ***Immune markers
6. Ig pattern
7. HBsAg
8. Anti-HCV
9. Anti-HIV
10. **Anti-PLA2R (Anti-Phospholipase A2 receptor: present in 70% of primary **membranous nephropathy, not present in normal people)
11. ***Tumour screening (for >50 yo): CXR, Stool OB, Other tumour markers

Question 19

***Treatment of Nephrotic syndrome

Answer 19

1. Corticosteroid (mainstay)

2nd line:
2. **Calcineurin inhibitor (steroid-resistant / steroid-dependent cases —> **steroid-sparing effects)
- Tacrolimus
- Cyclosporin

3. Other forms of treatment

Question 20

Complications of Nephrotic syndrome (JC Teaching Clinic)

Answer 20

1. Hyperlipidaemia and lipiduria
2. Infection
3. Vascular thrombosis
4. ARF
5. Protein malnutrition
6. Hypovolaemia

Question 21

***5. Rapidly progressive glomerulonephritis (RPGN)

Answer 21

Features:
- **Signs of GN (Haematuria, Proteinuria, RBC casts)
- **Rapid decline in renal function —> can lead ESRD within days to weeks

Pathological hallmark:
- Presence of ***Cellular crescents in glomerulus (severe inflammation in kidney)

• Beware of other organ system involvement e.g. pulmonary haemorrhage (Goodpasture’s) / hepatic failure (leptospirosis)

Causes:
1. **Pauci-immune GN (systemic vasculitis) (absence of immune staining)
2. **Anti-GBM disease / Goodpasture syndrome (pulmonary capillary BM also destroyed by Ab —> pulmonary haemorrhage)
3. **Crescentic IgAN
4. **Acute post-infectious GN
5. Multisystem diseases
- Systemic vasculitis
- Cryoglobulinaemia (associated with active Hep C infection / haematological diseases e.g. dysproteinaemia)
- SLE

Question 22

Investigations of RPGN

Answer 22

1. CBC
2. Renal biochemistry
3. Urine protein quantification
4. Urine sediments
5. ***Autoimmune markers
   - ANCA, Anti-GBM, ANA, Anti-dsDNA, C3/C4
6. ***CXR
7. ***DLCO (pulmonary function for Goodpasture’s)

Question 23

Treatment of RPGN

Answer 23

According to etiology
1. **Corticosteroids +/- Immunosuppressants
2. **Plasmapheresis (if Anti-GBM Ab present)

Question 24

***6. Chronic GN

Answer 24

Syndrome manifested by progressive kidney failure in patients with **glomerular inflammation, proteinuria, haematuria, HT (all previously undetected)
- Important cause of CKD
- Kidneys show variable degrees of **atrophy
- Blood tests: ***Very high creatinine
- Urinalysis: Protein + Blood

Question 25

Investigations of Chronic GN

Answer 25

Ascertain **chronic nature of disease
1. CBC
- **Normochromic normocytic anaemia

2. Renal biochemistry
   - ↑ Urea, Creatinine, **PO4
   - **↓ Ca
   - +/- ↑ K
   - Metabolic acidosis
3. Urine protein quantification
4. USG (↓ kidney size, ↑ echogenicity)
5. Renal biopsy (usually unnecessary, ∵ only show fibrosis, glomerulosclerosis —> cannot identify underlying cause anyway)

Question 26

Treatment of Chronic GN

Answer 26

1. Supportive therapy
2. Minimise metabolic disturbance + complications
3. Renal replacement therapy (if approaching stage 5 CKD)

Question 27

***Tubulointerstitial diseases (TIN)

Answer 27

• Anatomically >95% of kidney
• Acute TIN may cause important renal dysfunction (***~5-15% acute renal failure causes)
• If left unchecked, Chronic TIN is major pathway leading to ***CKD

Clinical manifestations (∵ Interstitial inflammation + Tubular dysfunction):
1. Loss of renal function
2. Abnormal urine sediment (e.g. WBC (but without infection), proteinuria)
3. **Electrolyte disturbance
4. **Acid-base disorders

Question 28

***Entities of TIN

Answer 28

1. ***Acute TIN
   - Drugs (e.g. Penicillins, NSAID, PPI, Mesalazine (delayed) (Davidson))
   - Infections (e.g. pyelonephritis, leptospirosis, TB, Hantavirus (Davidson))
   - Autoimmune disease
2. ***Chronic TIN
   - Etiology unknown
   Davidson:
   - ANY causes of Acute TIN if persistent
   - Drugs (e.g. Tenofovir, Lithium, Ciclosporin, Tacrolimus, Analgesic nephropathy)
   - Autoimmune disease (e.g. SLE, Sjogren’s)
   - Metabolic (e.g. CaPO4 crystallisation, HypoK, Hyperoxaluria)
3. K-wasting tubular disorders
4. ***Renal tubular acidosis (∵ inability of tubules to excrete H / reabsorb HCO3)

Question 29

***Acute kidney injury

Answer 29

Definition:
- Abrupt decrease in kidney function

• Even mild, reversible AKI can progress to CKD
• AKI viewed as same to Acute lung injury / ACS

Characterised by:
1. Abrupt ↓ in GFR over a period of hours / days
2. 50% ↑ SeCr
(3. ↑ in some damage markers e.g. NGAL, KIM-1, IL18)

Risk factors of AKI:
1. **Pre-existing CKD
2. **Diabetic nephropathy
3. Heart failure
4. Liver disease
5. ***Hypovolaemia
6. Age >50
7. Sepsis
8. Trauma
9. Post-operative (e.g. Post-CABG)
10. Cancer

Question 30

Causes of AKI

Answer 30

Various etiologies
- May have >=1 of below conditions

1. Pre-renal (>50%)
   - Prerenal azotaemia (Hypotension, Dehydration, Sepsis, Shock, Heart failure, Hepatorenal syndrome)
   - Renal artery (Occlusion, Vasculitis)
   - Small vessel disease (Thrombotic microangiopathy, Renal atheroembolism, Vasculitis)
2. Intrinsic (<50%)
   - Acute GN (All causes of RPGN)
   - Acute tubular necrosis (Drugs, Toxins, Ischaemia (from dehydration, hypotension, cardiogenic shock, hypovolaemic shock), Rhabdomyolysis, Radiocontrast)
   - Acute interstitial nephritis (Drugs, Infection, Autoimmune disease)
   - Intratubular obstruction (Cast nephropathy, Drugs, Crystalluria)
3. Post-renal (<10%)
   - Renal vein thrombosis
   - Obstructive causes (e.g. Ureteric stone, BPH, Neurogenic bladder)

Question 31

Management of AKI

Answer 31

General principles:
1. Rapid + Accurate diagnosis
2. Identify + Reverse underlying cause (e.g. nephrotoxins, sepsis, hypovolaemia, obstruction, cardiogenic)

Treatment:
1. Diuretics (for fluid overload, acute pulmonary edema)
2. Electrolyte disturbance (HyperK, **acidosis): **Polysulphonate (for binding K in gut), **D/I drip (drive K into cells, dextrose is buffer for insulin to prevent hypoglycaemia), **HCO3
3. HCO3 (for acidosis)
4. **Acute dialysis support
- usually **HD
- vascular access
- ICU admission if indicated

Indications for dialysis (Blue book + SpC Medicine):
1. Severe HyperK
2. Severe Metabolic acidosis
3. Fluid overload (e.g. APO)
4. Uraemia complications (Uraemic encephalopathy / pericarditis)

Question 32

Natural history and progression of Diabetic nephropathy (From GIS + MSS + HNS + HIS + ERS PBL)

Answer 32

First changes
- **Microalbuminuria
- **Glomerular BM thickening —> Microangiopathy
- Accumulation of matrix material in mesangium

Subsequent changes
- **Heavy proteinuria
- Nodular deposits
- **Glomerulosclerosis

Pathogenesis:
1. Chronic hyperglycaemia
—> ***↑ Mesangial Cell matrix production + apoptosis —> Mesangial cell expansion + injury

2. Glomerular hypertrophy (↑ Renal size)
   —> ↑ shear stress on glomerular capillary wall
3. Glomerular hyperfiltration (↑ GFR)
   —> dilatation of afferent arteriole by ***AGEs, Sorbitol, IGF-1
   —> ↑ Renal blood flow
   —> ↑ Intra-glomerular pressure (Intra-glomerular hypertension)
4. Glomerulosclerosis
   —> ∵ Intra-glomerular hypertension
   —> ∵ Hyaline narrowing of vessels supplying the glomeruli (Hyaline deposition induced by ischaemic injury)

Histology:
1. Diabetic **Glomerulosclerosis —> ECM deposition in glomeruli
2. **Mesangial expansion
3. **GBM thickening
4. **Arteriolar Hyalinosis / Arteriolosclerosis

Consequence:
Microalbuminuria

Management:
1. Protein restriction
2. Antihypertensive
3. Glycaemic control

Question 33

Contraindications to Renal biopsy (JC Teaching Clinic + SpC Teaching Clinic)

Answer 33

1. ***Uncorrectable bleeding diathesis
   - check Plt, Clotting profile
   - stop Antiplatelet, Anticoagulants
2. ***Small kidneys which are generally indicative of chronic irreversible disease
   - futile + risky due to puncturing a hard fibrotic structure —> bleeding
3. ***Severe hypertension, which cannot be controlled with antihypertensive
   - one dose of amlodipine —> wait several hours for BP to decrease
4. Multiple, bilateral cysts / renal ***tumour
5. Hydronephrosis
6. Active renal / perirenal ***infection
7. Uncooperative patient
8. Solitary kidney
   - ∵ in case of several bleeding may need embolisation / nephrectomy

Question 34

Minimal change nephrotic syndrome (MCNS)

Answer 34

“Nephrotic syndrome, normal-looking glomeruli + absence of hypertension, haematuria or azotaemia”

Epidemiology:
- ***Children: >90% of nephrotic syndrome
- Adult: 10-15% of nephrotic syndrome
- Elderly: suspect possible underlying malignancy, esp. lymphoid origin (e.g. Hodgkin’s disease)

Clinical features:
1. Heavy proteinuria
2. Onset of edema may be insidious / acute, initially affecting periorbital area upon awakening and shifting to the ankles towards the end of day
3. Ascites / Pleural effusion in severe cases

Pathology:
- Light microscopy demonstrates essentially **normal glomerular morphology
- Immunofluorescence is usually **negative for immunoglobulins
- Only detectable abnormality is **total effacement of foot processes (podocytes) of visceral epithelial cells shown on ultrastructural examination by **EM
- These morphological alterations are typical of nephrotic syndrome but not specific to MCNS
- Some patients with clinical features of MCNS have **positive mesangial IgM staining, along with mesangial **proliferative changes
- These patients, more likely to also have **microscopic haematuria and less likely to respond to steroid, are said to have **IgM nephropathy
- Relationship between MCNS, IgM nephropathy, and FSGS is **poorly defined, but responsiveness to steroid therapy is a shared feature —> **Continuum of pathology

Treatment:
1. Corticosteroid
- Adult: Prednisolone started at 1 mg/kg/day (up to max 80 mg/day)
—> slowly tailed off over a period of around 4 months
- Children: Prednisone at 60 mg/m2/day (up to max 80 mg/day) for 4 to 6 weeks
—> 40 mg/m2 every other day for 4 to 6 weeks

2nd line agents
2. Alkylating agents
3. Cyclosporine, Tacrolimus
4. Levamisole
- antihelminthic agent with immunomodulatory effects, used alone / in combination with steroid
in MCNS in children
- well tolerated
- SE: neutropenia, rash, liver toxicity

Question 35

Membranous nephropathy

Answer 35

• Most common cause of nephrotic syndrome in adults
• Defined by the presence of **subepithelial immune deposits leading to a spectrum of glomerular capillary wall alterations, most typically the formation of intervening **“GBM spikes”
• Primary vs Secondary
• Primary MN is regarded as **prototypic glomerular disease mediated by **in situ immune complex formation
• Can also occur secondary to autoimmune disease, neoplasia, infection, exposure to certain therapeutic agents

Epidemiology:
- Most common in Caucasian individuals + Adults
- Rare in infants and young children
- M:F = 2:1
- Secondary MN most commonly encountered in young children and in individuals >60 yo

Clinical features:
1. ***Proteinuria (defining clinical feature of MN)
- majority of patients have full nephrotic syndrome
2. Normal RFT (most patients at time of presentation)
3. Microhaematuria (~50%)

Secondary MN:
- 25% of cases
- 4 categories:
1. Autoimmune / Collagen vascular diseases,
- SLE (most notably, i.e. membranous lupus nephritis)
- RA
- Sjogren’s syndrome
- mCTD
- Sarcoidosis
- Grave’s disease
- Hashimoto’s thyroiditis

2. Malignancy
   - Carcinomas of the lung, prostate, breast, GI tract
3. Drugs
   - Gold
   - Penicillamine
   - NSAIDs, COX-2 inhibitors
   - Captopril
4. Infections
   - Hepatitis B / C
   - Syphilis
   - Malaria
   - Parasites

Question 36

HBV associated nephropathy

Answer 36

1. Membranous GN
2. Mesangiocapillary glomerulonephritis (MCGN)
3. IgA nephropathy

Clinical features:
1. Proteinuria, usually in the nephrotic range
2. Mild to moderate renal impairment (may be present at presentation)

Children:
- Male preponderance
- Nephrotic syndrome most frequent
- Transaminase levels are usually normal

Adults:
- Proteinuria / Nephrotic syndrome
- More likely than children to have HT, renal dysfunction, and clinical evidence of liver disease

Prognosis:
- Children: Favourable; high rates of spontaneous remission
- Adults: Worse in patients with nephrotic range proteinuria and overt hepatitis at presentation

Treatment:
1. General measures for CKD
- Optimise BP control
- Reduce proteinuria with ACEI / ARB
- Control lipid levels
- Sodium restriction
- Quit smoking
- Optimise body weight
- Regular exercise

2. Specific measures
   - Eradication of the underlying HBV by nucleoside analog e.g. Lamivudine